Isolation of Adipose Tissue Immune Cells

The discovery of increased macrophage infiltration in  the adipose tissue (AT) of obese rodents and humans has led to an  intensification of interest in ...

Vanderbilt University School of Medicine

We tested the hypothesis that modest, overfeeding-induced weight gain would increase sympathetic neural activity in nonobese humans. Twelve healthy males (23 +/- 2 years; body mass index, 23.8 +/- 0.7) were overfed approximately 1,000 kcal/day until a 5-kg weight gain was achieved. Muscle sympathetic nerve activity (MSNA, microneurography), blood pressure, body composition (dual energy X-ray absorptiometry), and abdominal fat distribution (computed tomography) were measured at baseline and following 4 wk of weight stability at each individual's elevated body weight. Overfeeding increased body weight (73.5 +/- 3.1 vs. 78.4 +/- 3.2 kg, P < 0.001) and body fat (14.9 +/- 1.2 vs. 18 +/- 1.1 kg, P < 0.001) in 42 +/- 8 days. Total abdominal fat increased (220 +/- 22 vs. 266 +/- 22 cm(2), P < 0.001) with weight gain, due to increases in both subcutaneous (158 +/- 15 vs. 187 +/- 12 cm(2), P < 0.001) and visceral fat (63 +/- 8 vs. 79 +/- 12 cm(2), P = 0.004). As hypothesized, weight gain elicited increases in MSNA burst frequency (32 +/- 2 vs. 38 +/- 2 burst/min, P = 0.002) and burst incidence (52 +/- 4 vs. 59 +/- 3 bursts/100 heart beats, P = 0.026). Systolic, but not diastolic blood pressure increased significantly with weight gain. The change in MSNA burst frequency was correlated with the percent increase in body weight (r = 0.59, P = 0.022), change in body fat (r = 0.52, P = 0.043) and percent change in body fat (r = 0.51, P = 0.045). The results of the current study indicate that modest diet-induced weight gain elicits sympathetic neural activation in nonobese males. These findings may have important implications for understanding the link between obesity and hypertension.

Modest weight gain is associated with sympathetic neural activation in nonobese humans.

Nous avons test&eacute; l&#39;hypoth&egrave;se que le gain de poids modeste, induite par la suralimentation augmenterait sympathique activit&eacute; neuronale chez l&#39;&ecirc;tre humain non ob&egrave;ses. Douze hommes en bonne sant&eacute; (23 +/-2 ans ; indice de masse corporelle, 23,8 +/-0,7) ont &eacute;t&eacute; gav&eacute;es environ 1 000 kcal/jour, jusqu&#39;&agrave; ce qu&#39;un gain de poids de 5 kg a &eacute;t&eacute; atteint. Muscle nerf sympathique activit&eacute; (ANSM, microneurographie), tension art&eacute;rielle, composition corporelle (absorptiom&eacute;trie double &eacute;nergie &agrave; rayons x) et r&eacute;partition de la graisse abdominale (tomodensitom&eacute;trie) ont &eacute;t&eacute; mesur&eacute;s au d&eacute;part et apr&egrave;s 4 semaines de stabilit&eacute; du poids &agrave; chaque individu d&#39;&eacute;lev&eacute; de poids corporel. Suralimentation accrue du poids corporel (73,5 +/-3,1 vs 78,4 &plusmn; 3,2 kg, P 0,001 &lt;) et corps gras (14,9 +/-1.2 vs 18 &plusmn; 1,1 kg, P &lt; 0,001) dans 42 +/-8 jours. Total a augment&eacute; de graisse abdominale (220 +/-22 vs 266 +/-22 cm(2), P 0,001 &lt;) avec gain de poids, due &agrave; la hausse dans les deux sous-cutan&eacute;e (158 +/-15 vs 187 +/-12 cm(2), P &lt; 0,001) et la graisse visc&eacute;rale (63 +/-8 vs 79 +/-12 cm(2), P = 0,004). Augmentations ont incit&eacute; comme l&#39;hypoth&egrave;se, prise de poids dans la fr&eacute;quence ANSM (32 + /-2 vs 38 +/-2 rafale/min, P = 0,002) et de l&#39;incidence de l&#39;&eacute;clatement (52 +/-4 vs 59 +/-3 rafales/100 coeur bat, P = 0,026). La pression art&eacute;rielle systolique, mais pas diastolique augmente significativement avec gain de poids. Le changement de fr&eacute;quence de rafale ANSM est corr&eacute;l&eacute; avec l&#39;augmentation du poids corporel (r = 0,59, P = 0,022), changement de graisse corporelle (r = 0,52, P = 0,043) et variation en pourcentage de graisse corporelle (r = 0,51, P = 0,045). Les r&eacute;sultats de cette &eacute;tude indiquent que le modeste poids induite par l&#39;alimentation provoque l&#39;activation neuronale sympathique chez les m&acirc;les non ob&egrave;ses. Ces r&eacute;sultats peuvent avoir des implications importantes pour comprendre le lien entre l&#39;ob&eacute;sit&eacute; et l&#39;hypertension.

Gain de poids modeste est associ&eacute;e &agrave; l&#39;activation neuronale sympathique chez l&#39;homme non ob&egrave;ses.

Abbiamo testato l&#39;ipotesi che guadagno di peso modesto, indotta da sovralimentazione aumenterebbe simpatico attivit&agrave; neurale in nonobese degli esseri umani. Dodici uomini sani (23 + /-2 anni; indice di massa corporea, 23,8 + /-0,7) erano sovralimentate circa 1.000 kcal/giorno fino a quando &egrave; stato raggiunto un guadagno di peso di 5 kg. Muscolo nervo simpatico attivit&agrave; (MSNA, microneurography), pressione, composizione corporea (dual energy x-ray absorptiometry), il sangue e distribuzione del grasso addominale (tomografia computerizzata) sono stati misurati al basale e dopo 4 sett di stabilit&agrave; di peso ad ogni individuo di elevato peso corporeo. Sovralimentazione aumento di peso corporeo (73,5 + 3.1 vs 78.4 + 3,2 kg, P &lt; 0,001) e grasso del corpo (14,9 + 1.2 vs 18 + /-1,1 kg, P 0.001 &lt;) 42 + /-8 giorni. Totale grasso addominale aumentata (220 + 22 vs 266 + 22 cm(2), P 0.001 &lt;) con aumento di peso, a causa di aumenti in entrambi sottocutaneo (158 + /-15 vs 187 + /-12 cm(2), P &lt; 0,001) e grasso viscerale (63 + /-8 vs 79 + /-12 cm(2), P = 0,004). Come ipotizzato, aumento di peso aumenta raccolse in MSNA burst frequenza (32 + 2 vs 38 + 2 burst/min, P = 0.002) e incidenza di burst (52 + 4 vs 59 + 3 burst/100 cuore batte, P = 0,026). Pressione arteriosa sistolica e diastolica non aumentato significativamente con l&#39;aumento di peso. Il cambiamento nella frequenza di burst MSNA &egrave; stato correlato con l&#39;aumento percentuale di peso corporeo (r = 0,59, P = 0,022), cambiare in grasso corporeo (r = 0.52, P = 0.043) e cambia per cento di grasso corporeo (r = 0,51, P = 0,045). I risultati di questo studio indicano che guadagno modesto peso dieta indotta induce attivazione neurale simpatico in nonobese maschi. Questi risultati possono avere importanti implicazioni per comprendere il legame tra obesit&agrave; e l&#39;ipertensione.

Aumento di peso modesto &egrave; associato con attivazione neurale simpatico in nonobese degli esseri umani.

To determine whether the consumption of water 30 minutes before an ad libitum meal reduces meal energy intake in young and older adults.

Pre-meal water consumption reduces meal energy intake in older but not younger subjects.

Pour d&eacute;terminer si la consommation d&#39;eau 30 minutes avant un repas ad libitum r&eacute;duit l&#39;apport &eacute;nerg&eacute;tique repas chez les adultes jeunes et plus &acirc;g&eacute;s.

Consommation d&#39;eau pr&eacute;-prandiales r&eacute;duit l&#39;apport &eacute;nerg&eacute;tique repas chez les sujets &acirc;g&eacute;s mais pas plus jeunes.

Per determinare se il consumo d&#39;acqua 30 minuti prima di un pasto ad libitum riduce apporto energetico pasto negli adulti giovani e anziani.

Consumo di acqua bella riduce apporto energetico pasto nei soggetti pi&ugrave; anziani, ma non pi&ugrave; giovane.

The purpose of this investigation was to determine if energy intake compensation is more accurate in males compared to females matched for age, habitual physical activity, cardiorespiratory fitness, and dietary cognitive restraint. Healthy, nonobese young men (n=12) and women (n=12) were provided with an ad libitum lunch meal on two occasions. Thirty minutes prior to the lunch meals, subjects were given either a yogurt preload (YP; 500 mL, 1988 kJ, men; 375 mL, 1507 kJ, women) or no preload (NP). Energy intake at the two lunch meals was measured. Visual analog scales were used to assess changes in hunger and fullness. Blood glucose concentrations were also determined. Energy intake compensation for the YP was significantly more accurate in the male compared to the female subjects (86.2+/-5.0 vs. 73.6+/-4.8% compensation). There were no sex differences in perceptions of hunger and satiety. In the pooled sample, hunger ratings were significantly higher in the NP condition, but there were no significant differences in fullness ratings between test meals. In the YP condition, glycemic response to the preload and the ad libitum meal was significantly higher in males compared to females. These results suggest that under acute test meal conditions, energy intake regulation is more accurate in males. Relative inability to regulate energy intake may predispose females to gain weight over time.

Sex differences in acute energy intake regulation.

Le but de cette &eacute;tude &eacute;tait de d&eacute;terminer si la r&eacute;mun&eacute;ration de l&#39;apport &eacute;nerg&eacute;tique est plus pr&eacute;cise chez les m&acirc;les que chez les femmes, appari&eacute;es pour l&#39;&acirc;ge, l&#39;activit&eacute; physique habituelle, cardiorespiratoire et la restriction cognitive alimentaire. Des hommes jeunes en bonne sant&eacute;s, non ob&egrave;ses (n = 12) et femmes (n = 12) ont re&ccedil;u un repas ad libitum &agrave; deux reprises. Trente minutes avant les repas de midi, les sujets ont re&ccedil;u soit un yaourt de pr&eacute;charge (YP ; 500 mL, 1988 kJ, hommes ; femmes 375 mL, 1507 kJ,) ou aucun pr&eacute;charge (NP). L&#39;apport &eacute;nerg&eacute;tique sur les deux repas de midi a &eacute;t&eacute; mesur&eacute;e. Les &eacute;chelles analogiques visuelles ont &eacute;t&eacute; utilis&eacute;es pour &eacute;valuer les changements dans la faim et la pl&eacute;nitude. Les concentrations de glucose de sang ont &eacute;t&eacute; &eacute;galement d&eacute;termin&eacute;es. Compensation de l&#39;apport &eacute;nerg&eacute;tique pour le YP &eacute;tait beaucoup plus pr&eacute;cise chez le m&acirc;le, compar&eacute; aux sujets f&eacute;minins (86,2 +/-5,0 vs 73.6+/-4.8% compensation). Il n&#39;y a aucune diff&eacute;rence de sexe dans la perception de la faim et la sati&eacute;t&eacute;. Dans l&#39;&eacute;chantillon, les cotes de la faim &eacute;taient significativement plus &eacute;lev&eacute;s dans la condition de NP, mais il n&#39;y a pas de diff&eacute;rences significatives dans les cotes de pl&eacute;nitude entre les repas test. Dans la condition YP, r&eacute;ponse glyc&eacute;mique &agrave; la pr&eacute;contrainte et le repas ad libitum &eacute;tait significativement plus &eacute;lev&eacute;e chez les m&acirc;les que chez les femmes. Ces r&eacute;sultats sugg&egrave;rent que dans des conditions de test de toxicit&eacute; aigu&euml; de repas, la r&eacute;gulation de l&#39;apport &eacute;nerg&eacute;tique est plus pr&eacute;cise chez les m&acirc;les. Relative incapacit&eacute; &agrave; r&eacute;guler l&#39;apport &eacute;nerg&eacute;tique peut pr&eacute;disposer les femmes &agrave; prendre du poids au fil du temps.

Diff&eacute;rences de sexe dans le r&egrave;glement de l&#39;apport &eacute;nerg&eacute;tique aigu&euml;.

Lo scopo di questa indagine &egrave; stato per determinare se la compensazione di apporto di energia &egrave; pi&ugrave; accurata nei maschi rispetto alle femmine, abbinate per et&agrave;, attivit&agrave; fisica abituale, fitness cardiorespiratoria e dietetica ritenuta cognitiva. Sani, nonobese giovani (n = 12) e donne (n = 12) sono stati forniti con un pasto pranzo ad libitum in due occasioni. Trenta minuti prima dei pasti pranzo, soggetti erano dato uno yogurt precarico (YP; 500 mL, 1988 kJ, uomini; donne 375 mL, 1507 kJ,) o nessun precarico (NP). Apporto energetico ai due pasti pranzo &egrave; stata misurata. Visual analog scale sono state utilizzate per valutare i cambiamenti nella fame e pienezza. Inoltre sono state determinate concentrazioni di glucosio del sangue. Compensazione apporto energetico per il YP era significativamente pi&ugrave; accurata nel maschio rispetto ai soggetti femminili (86.2 + 5.0 vs 73.6+/-4.8% compensazione). C&#39;erano differenze di sesso nella percezione della fame e della saziet&agrave;. Nell&#39;esempio in pool, fame valutazioni erano significativamente pi&ugrave; alti nella condizione di NP, ma c&#39;erano differenze significative nelle valutazioni di pienezza tra i pasti test. Nella condizione di YP, glycemic response to il precarico e il pasto ad libitum era significativamente pi&ugrave; alta nei maschi rispetto alle femmine. Questi risultati suggeriscono che in condizioni di pasto prova acuta, regolamento di assunzione di energia &egrave; pi&ugrave; preciso nei maschi. Relativa incapacit&agrave; di regolare assunzione di energia possono predisporre le femmine ad aumentare di peso nel tempo.

Differenze di sesso nel regolamento assunzione acuta di energia.

We tested the hypothesis that with similar weight gain the increase in blood pressure (BP) would be smaller in men with higher cardiorespiratory fitness (HCRF) than in men with lower cardiorespiratory fitness (LCRF).

Cardiorespiratory fitness influences the blood pressure response to experimental weight gain.

Nous avons test&eacute; l&#39;hypoth&egrave;se selon laquelle, avec le gain de poids similaire l&#39;augmentation de la pression art&eacute;rielle (PA), serait plus faible chez les hommes avec sup&eacute;rieur cardiorespiratoire (r&egrave;glement) que chez les hommes avec inf&eacute;rieur cardiorespiratoire (curateurs).

Cardiorespiratoire influe sur la r&eacute;ponse de la pression art&eacute;rielle au gain de poids exp&eacute;rimentale.

Abbiamo testato l&#39;ipotesi che con un simile aumento di peso, l&#39;aumento della pressione sanguigna (BP) sarebbe pi&ugrave; piccolo in uomini con superiore cardiorespiratoria fitness (HCRF) rispetto a uomini con bassa fitness cardiorespiratoria (LCRF).

Fitness cardiorespiratoria influenza la risposta di pressione arteriosa per aumento di peso sperimentale.

We tested the hypothesis that weight gain would increase arterial stiffness in healthy nonobese adults. To address this, we overfed 14 nonobese men (age: 23+/-1 years) approximately 1000 kcal/d for 6 to 8 weeks until a 5-kg weight gain was achieved. Carotid diameters (high-resolution ultrasound) and pressures (applanation tonometry), body composition (dual energy x-ray absorptiometry), and abdominal fat distribution (computed tomography) were measured at baseline and following 4 weeks of weight stability at each individual's elevated body weight. Overfeeding increased body weight 5.1+/-0.1 kg and body fat 3.4+/-0.4 kg (both P<0.001) in 45+/-7 days. Total abdominal fat increased 46+/-7 cm(2) with weight gain due to increases in both subcutaneous (30+/-6 cm(2)) and visceral fat (15+/-4 cm(2); all P<0.01). As hypothesized, weight gain increased arterial stiffness 13+/-6% and decreased arterial compliance 21+/-4% (both P<0.05). Furthermore, those individuals above the median increase in abdominal visceral fat demonstrated a significantly greater increase in arterial stiffness (0.97+/-0.29 versus 0.06+/-0.36 U; P<0.05) compared with those below the median. Consistent with these observations, the only correlates of the changes in arterial stiffness with weight gain were the increases in total abdominal fat (r=0.794), abdominal visceral fat (r=0.651), and waist circumference (r=0.470; all P<0.05). Taken together, these findings suggest that modest weight gain is associated with increases arterial stiffness in nonobese men. The degree of large artery stiffening with weight gain seems to be determined, in part, by the amount of abdominal visceral fat gain. Importantly, this relation is independent of the amount of total body fat gained.

Large artery stiffening with weight gain in humans: role of visceral fat accumulation.

Nous avons test&eacute; l&#39;hypoth&egrave;se que le gain de poids augmenterait rigidit&eacute; art&eacute;rielle chez l&#39;adulte non ob&egrave;ses en bonne sant&eacute;. Pour ce faire, nous avons noy&eacute; 14 hommes non ob&egrave;ses (&acirc;ge : 23 +/-1 ans) environ 1000 kcal/j pendant 6 &agrave; 8 semaines jusqu&#39;&agrave; ce qu&#39;un gain de poids de 5 kg a &eacute;t&eacute; atteint. Diam&egrave;tres carotides (&eacute;chographie haute r&eacute;solution) et pressions (tonom&eacute;trie d&#39;aplanation), composition corporelle (absorptiom&eacute;trie double &eacute;nergie &agrave; rayons x) et r&eacute;partition de la graisse abdominale (tomodensitom&eacute;trie) ont &eacute;t&eacute; mesur&eacute;s au d&eacute;part et suivants 4 semaines de stabilit&eacute; de poids au poids &eacute;lev&eacute; de chaque individu. La suralimentation accrue du corps poids 5.1+/-0.1 kg et corps gras 3.4+/-0.4 kg (les deux P &lt; 0,001) dans 45 +/-7 jours. La graisse abdominale totale a augment&eacute; de 46 +/-7 cm(2) avec prise de poids due &agrave; la hausse dans les deux sous-cutan&eacute;e (30 + /-6 de cm(2)) et de la graisse visc&eacute;rale (15 +/-4 cm(2) ; tous les P &lt; 0,01). Comme l&#39;hypoth&egrave;se, gain de poids augmente la rigidit&eacute; art&eacute;rielle 13 +/-6 % et une diminution de la compliance art&eacute;rielle 21 &plusmn; 4 % (les deux P &lt; 0,05). En outre, les personnes ci-dessus l&#39;augmentation m&eacute;diane de la graisse visc&eacute;rale abdominale ont d&eacute;montr&eacute; une augmentation significativement plus &eacute;lev&eacute;e de rigidit&eacute; art&eacute;rielle (0,97 +/-0,29 contre 0.06+/-0.36 U ; P &lt; 0,05) comparativement &agrave; ceux inf&eacute;rieurs &agrave; la m&eacute;diane. Conform&eacute;ment &agrave; ces observations, les corr&eacute;lats seuls des changements dans la rigidit&eacute; art&eacute;rielle avec gain de poids ont &eacute;t&eacute; les augmentations dans la graisse abdominale totale (r = 0,794), la graisse visc&eacute;rale abdominale (r = 0,651) et le tour de taille (r = 0,470 ; tous les P &lt; 0,05). Pris ensemble, ces r&eacute;sultats sugg&egrave;rent que la prise de poids modeste est associ&eacute; par augmente la rigidit&eacute; art&eacute;rielle chez les hommes non ob&egrave;ses. Le degr&eacute; de grosses art&egrave;res raidissement avec gain de poids semble &ecirc;tre d&eacute;termin&eacute;, en partie, par le montant du gain de graisse visc&eacute;rale abdominale. Ce qui est important, cette relation est ind&eacute;pendante de la quantit&eacute; de graisse corporelle totale acquise.

Grosse art&egrave;re durcissant avec gain de poids chez l&#39;homme : r&ocirc;le de l&#39;accumulation de graisse visc&eacute;rale.

Abbiamo testato l&#39;ipotesi che il guadagno di peso aumenterebbe la rigidit&agrave; arteriosa in adulti sani nonobese. Per risolvere questo problema, abbiamo sovralimentate 14 uomini nonobese (et&agrave;: 23 + 1 anni) circa 1000 kcal/d per 6-8 settimane fino a quando &egrave; stato raggiunto un guadagno di peso di 5 kg. Carotidei diametri (ultrasuoni ad alta risoluzione) e pressioni (tonometria di applanation), composizione corporea (dual energy x-ray absorptiometry) e la distribuzione del grasso addominale (tomografia computerizzata) sono stati misurati al basale e seguenti 4 settimane di stabilit&agrave; di peso al peso elevato del corpo di ogni individuo. Sovralimentazione maggiore corpo peso 5.1+/-0.1 e corpo 3.4+/-0.4 grasso kg (entrambi P &lt; 0.001) 45 + /-7 giorni. Grasso addominale totale aumentato 46 + 7 cm(2) con aumento di peso a causa di aumenti in entrambi sottocutaneo (30 + 6 cm(2)) e grasso viscerale (15 + 4 cm(2); P tutti &lt; 0,01). Come ipotizzato, aumento di peso aumentata rigidit&agrave; arteriosa 13 + /-6% e ridotta compliance arteriosa 21 + /-4% (entrambi P &lt; 0,05). Inoltre, quegli individui sopra l&#39;aumento del grasso viscerale addominale mediano ha dimostrato un incremento significativamente maggiore di rigidit&agrave; arteriosa (0,97 + 0,29 versus 0.06+/-0.36 U; P &lt; 0,05) rispetto a quelli di sotto della mediana. Coerentemente con queste osservazioni, la correla solo dei cambiamenti di rigidit&agrave; arteriosa con aumento di peso sono stati gli aumenti in totale grasso addominale (r = 0.794), grasso viscerale addominale (r = 0.651) e la circonferenza della vita (r = 0.470; tutti P &lt; 0,05). Presi insieme, questi risultati suggeriscono che guadagno di peso modesto &egrave; associato con aumento della rigidit&agrave; arteriosa in nonobese uomini. Il grado di grande arteria di irrigidimento con aumento di peso sembra essere determinato, in parte, dalla quantit&agrave; di guadagno di grasso viscerale addominale. Importante, questo rapporto &egrave; indipendente dalla quantit&agrave; di grasso corporeo totale guadagnato.

Grande arteria di irrigidimento con guadagno di peso in esseri umani: il ruolo dell&#39;accumulo di grasso viscerale.

The sympathetic nervous system (SNS) plays an essential role in the regulation of metabolic and cardiovascular homeostasis. Low SNS activity has been suggested to be a risk factor for weight gain and obesity development. In contrast, SNS activation is characteristic of a number of metabolic and cardiovascular diseases that occur more frequently in obese individuals. Until recently, the relation between obesity and SNS behavior has been controversial because previous approaches for assessing SNS activity in humans have produced inconsistent findings. Beginning in the early 1990s, many studies using state of the art neurochemical and neurophysiological techniques have provided important insight. The purpose of the present review is to provide an overview of our current understanding of the region specific alterations in SNS behavior in human obesity. We will discuss findings from our own laboratory which implicate visceral fat as an important depot linking obesity with skeletal muscle SNS activation. The influence of weight change on SNS behavior and the potential mechanisms and consequences of region specific SNS activation in obesity will also be considered.

Sympathetic nervous system behavior in human obesity.

Le syst&egrave;me nerveux sympathique (SNS) joue un r&ocirc;le essentiel dans la r&eacute;gulation de l&#39;hom&eacute;ostasie m&eacute;tabolique et cardiovasculaire. Activit&eacute; faible SNS a &eacute;t&eacute; sugg&eacute;r&eacute;e d&#39;&ecirc;tre un facteur de risque pour le d&eacute;veloppement de l&#39;ob&eacute;sit&eacute; et de gain de poids. En revanche, l&#39;activation de la SNS est caract&eacute;ristique d&#39;un certain nombre de maladies cardiovasculaires et m&eacute;taboliques qui se produisent plus fr&eacute;quemment chez les personnes ob&egrave;ses. Jusqu&#39;&agrave; r&eacute;cemment, la relation entre l&#39;ob&eacute;sit&eacute; et le comportement de la SNS a &eacute;t&eacute; controvers&eacute;e, car les pr&eacute;c&eacute;dentes approches d&#39;&eacute;valuation activit&eacute; SNS chez les humains ont produit des conclusions contradictoires. Depuis le d&eacute;but des ann&eacute;es 1990, de nombreuses &eacute;tudes utilisant des techniques de pointe neurochimiques et neurophysiologiques ont fourni importante insight. La pr&eacute;sente r&eacute;vision vise &agrave; donner un aper&ccedil;u de notre compr&eacute;hension actuelle de la r&eacute;gion des alt&eacute;rations particuli&egrave;res dans le comportement de la SNS dans l&#39;ob&eacute;sit&eacute; humaine. Nous allons discuter des conclusions de notre propre laboratoire qui impliquent la graisse visc&eacute;rale, comme un d&eacute;p&ocirc;t important reliant l&#39;ob&eacute;sit&eacute; avec le muscle squelettique activation SNS. L&#39;influence du changement de poids sur le comportement de la SNS et le potentiel des m&eacute;canismes et cons&eacute;quences de l&#39;activation de la SNS sp&eacute;cifique r&eacute;gion dans l&#39;ob&eacute;sit&eacute; seront &eacute;galement consid&eacute;r&eacute;es.

Comportement du syst&egrave;me nerveux sympathique dans l&#39;ob&eacute;sit&eacute; humaine.

Il sistema nervoso simpatico (SNS) svolge un ruolo essenziale nella regolazione dell&#39;omeostasi metabolica e cardiovascolare. Attivit&agrave; bassa SNS &egrave; stato suggerito per essere un fattore di rischio per lo sviluppo di obesit&agrave; e guadagno di peso. Al contrario, attivazione del SNS &egrave; caratteristica di un certo numero di malattie metaboliche e cardiovascolari che si verificano pi&ugrave; frequentemente in individui obesi. Fino a poco tempo fa, la relazione tra l&#39;obesit&agrave; e il comportamento SNS &egrave; stata controversa perch&eacute; precedenti approcci per valutare attivit&agrave; SNS in esseri umani hanno prodotto risultati inconsistenti. Cominciando negli anni novanta, molti studi utilizzando tecniche all&#39;avanguardia di neurochimici e neurofisiologici hanno fornito importanti insight. Lo scopo della presente rassegna &egrave; di fornire una panoramica della nostra attuale comprensione della regione specifiche alterazioni nel comportamento di SNS nell&#39;obesit&agrave; umana. Discuteremo i risultati dal nostro laboratorio che coinvolgono il grasso viscerale come un deposito importante che collega l&#39;obesit&agrave; con muscolo scheletrico attivazione del SNS. Saranno inoltre considerate l&#39;influenza del cambiamento di peso sul comportamento SNS e potenziali meccanismi e conseguenze dell&#39;attivazione del SNS specifica regione nell&#39;obesit&agrave;.

Comportamento del sistema nervoso simpatico nell&#39;obesit&agrave; umana.

We hypothesized that atorvastatin (ATOR) treatment would reduce arterial stiffness in overweight and obese middle-aged and older adults. Twenty-six (11 men and 15 women) overweight or obese (body mass index: 31.6+/-0.7 kg/m(2)) middle-aged and older adults (age: 54+/-2 years) were randomly assigned to receive either ATOR (80 mg/d) or placebo for 12 weeks. Arterial stiffness (beta-stiffness and pulse wave velocity) was measured before and after the intervention. At baseline, the ATOR (n=16) and placebo (n=10) groups did not differ with respect to age, body mass index, blood pressure, serum lipid and lipoprotein concentrations, high-sensitivity C-reactive protein, indices of arterial stiffness, or compliance (all P>0.05). After the 12-week treatment period, the ATOR group experienced a 47% reduction in low-density lipoprotein cholesterol (149+/-6 to 80+/-8 mg/dL) and a 42% reduction in high-sensitivity C-reactive protein (3.6+/-0.8 to 2.1+/-0.5 mg/L; both P<0.05). In addition, beta-stiffness (9.4+/-0.6 to 7.6+/-0.5 U) and aortic pulse wave velocity (1096+/-36 to 932+/-32 cm/s), but not brachial pulse wave velocity, decreased (both P<0.05) with ATOR. In contrast, there were no significant changes in beta-stiffness (9.1+/-0.8 to 9.1+/-0.7 U) or aortic pulse wave velocity (1238+/-89 to 1191+/-90 cm/s; both P>0.05) in the placebo group. There were no relations between the reductions in arterial stiffness indices and any of the baseline cardiometabolic risk factors (all P>0.05). However, the reductions in arterial stiffness were correlated with the reduction in low-density lipoprotein cholesterol but not high-sensitivity C-reactive protein or any other cardiometabolic variables (all P<0.05). Taken together, these findings suggest that ATOR reduces arterial stiffness in overweight and obese middle-aged and older adults, and these favorable changes occur irrespective of baseline cardiometabolic risk factors.

Arterial destiffening with atorvastatin in overweight and obese middle-aged and older adults.

Nous avons &eacute;mis l&#39;hypoth&egrave;se que l&#39;atorvastatine (teur) traitement r&eacute;duirait la rigidit&eacute; art&eacute;rielle chez des adultes d&#39;&acirc;ge moyen et plus &acirc;g&eacute;s en surpoids et ob&egrave;ses. Vingt-six (11 hommes et 15 femmes) en surpoids ou ob&egrave;ses (indice de masse corporelle : 31.6+/-0.7 kg/m(2)) des adultes d&#39;&acirc;ge moyen et plus &acirc;g&eacute;s (&acirc;ge : 54 +/-2 ans) ont &eacute;t&eacute; assign&eacute;s au hasard &agrave; recevoir soit ATOR (80 mg/j) ou un placebo pendant 12 semaines. Rigidit&eacute; art&eacute;rielle (vitesse des ondes b&ecirc;ta-rigidit&eacute; et pouls) a &eacute;t&eacute; mesur&eacute;e avant et apr&egrave;s l&#39;intervention. Au d&eacute;part, le ATOR (n = 16) et le placebo (n = 10) groupes ne diff&eacute;raient pas en ce qui concerne l&#39;&acirc;ge, indice de masse corporelle, pression art&eacute;rielle, lipides et lipoprot&eacute;ines s&eacute;riques, prot&eacute;ine C - r&eacute;active ultrasensible, indices de rigidit&eacute; art&eacute;rielle, ou de conformit&eacute; (tous P &gt; 0,05). Apr&egrave;s la p&eacute;riode de traitement de 12 semaines, le groupe ATOR a connu une r&eacute;duction de 47 % de cholest&eacute;rol des lipoprot&eacute;ines de basse densit&eacute; (149 +/-6 &agrave; 80 +/-8 mg/dL) et une r&eacute;duction de 42 % de prot&eacute;ine C - r&eacute;active ultrasensible (3.6 +/-0,8 &agrave; 2.1+/-0.5 mg/L; les deux P &lt; 0,05). En addition, b&ecirc;ta-rigidit&eacute; (9,4 +/-0,6 &agrave; 7.6+/-0.5 U) et vitesse d&#39;onde de pouls aortique (1096 +/-36 &agrave; 932 +/-32 cm/s), mais la vitesse d&#39;onde de pouls brachial pas, diminu&eacute; (les deux P &lt; 0,05) avec ATOR. En revanche, il n&#39;y a pas des changements significatifs dans la b&ecirc;ta-rigidit&eacute; (9.1 +/-0,8 &agrave; 9.1+/-0.7 U) ou la vitesse d&#39;onde de pouls aortique (1238 +/-89 &agrave; 1191 de +/-90 cm/s; les deux P &gt; 0,05) dans le groupe placebo. Il n&#39;y a aucune relation entre les r&eacute;ductions dans les indices de rigidit&eacute; art&eacute;rielle et l&#39;un des facteurs de risque cardiom&eacute;tabolique r&eacute;f&eacute;rence (tous P &amp;gt; 0,05). Toutefois, les r&eacute;ductions de rigidit&eacute; art&eacute;rielle sont en corr&eacute;lation avec la r&eacute;duction du cholest&eacute;rol des lipoprot&eacute;ines de faible densit&eacute; mais pas haute sensibilit&eacute; prot&eacute;ine C - r&eacute;active ou toutes les autres variables cardiom&eacute;tabolique (tous P &lt; 0,05). Pris ensemble, ces r&eacute;sultats sugg&egrave;rent que ATOR r&eacute;duit la rigidit&eacute; art&eacute;rielle chez des adultes d&#39;&acirc;ge moyen et plus &acirc;g&eacute;s en surpoids et ob&egrave;ses, et ces changements favorables se produisent ind&eacute;pendamment de facteurs de risque cardiom&eacute;tabolique de base.

Art&egrave;re destiffening avec l&#39;atorvastatine chez des adultes d&#39;&acirc;ge moyen et plus &acirc;g&eacute;s en surpoids et ob&egrave;ses.

Abbiamo ipotizzato che atorvastatina (ATOR) trattamento ridurrebbe la rigidit&agrave; arteriosa negli adulti di mezza et&agrave; e anziani in sovrappeso e obesi. Ventisei (11 uomini e 15 donne) in sovrappeso o obesi (indice di massa corporea: 31.6+/-0.7 kg/m(2)) adulti di mezza et&agrave; e anziani (et&agrave;: 54 + /-2 anni) sono stati assegnati in modo casuale a ricevere ATOR (80 mg/d) o placebo per 12 settimane. Rigidit&agrave; arteriosa (velocit&agrave; delle onde beta-rigidit&agrave; e impulso) &egrave; stata misurata prima e dopo l&#39;intervento. Al basale, il ATOR (n = 16) e placebo (n = 10) gruppi non differiscono per quanto riguarda l&#39;et&agrave;, indice di massa corporea, pressione arteriosa, concentrazioni di lipidi e lipoproteine del siero, proteina C - reattiva ad alta sensibilit&agrave;, indici di rigidit&agrave; arteriosa o di conformit&agrave; (tutti P &amp;gt; 0.05). Dopo il periodo di trattamento di 12 settimane, il gruppo ATOR sperimentato una riduzione del 47% del colesterolo lipoproteine a bassa densit&agrave; (149 + /-6-80 + /-8 mg/dL) e una riduzione del 42% nella proteina C - reattiva ad alta sensibilit&agrave; (3.6 + /-0,8 mg/l 2.1+/-0.5; entrambi P &lt; 0,05). In aggiunta, beta-rigidit&agrave; (9,4 + 0,6 a 7.6+/-0.5 U) e velocit&agrave; delle onde pulsazione aortica (1096 + 36 a 932 + 32 cm/s), ma la velocit&agrave; delle onde impulso non brachiale, diminuito (entrambi P &lt; 0,05) con ATOR. In contrasto, ci erano cambiamenti significativi nella beta-rigidit&agrave; (9.1 + /-0.8 a 9.1+/-0.7 U) o velocit&agrave; delle onde pulsazione aortica (1238 + /-89 a 1191 + /-90 cm/s; entrambi P &amp;gt; 0.05) nel gruppo placebo. Non c&#39;erano le relazioni tra le riduzioni in indici di rigidit&agrave; arteriosa e uno qualsiasi dei fattori di rischio cardiometabolico baseline (tutti P &amp;gt; 0.05). Tuttavia, la riduzione della rigidit&agrave; arteriosa erano correlata con la riduzione del colesterolo lipoproteine a bassa densit&agrave;, ma non ad alta sensibilit&agrave; proteina C - reattiva o qualsiasi altre variabili cardiometabolico (tutti P &lt; 0,05). Presi insieme, questi risultati suggeriscono che ATOR riduce la rigidit&agrave; arteriosa negli adulti di mezza et&agrave; e anziani in sovrappeso e obesi, e questi cambiamenti favorevoli si verificano indipendentemente dalla linea di base fattori di rischio cardiometabolico.

Arteriosa destiffening con atorvastatina negli adulti di mezza et&agrave; e anziani in sovrappeso e obesi.

We tested the hypothesis that weight loss via a hypocaloric diet would reduce arterial stiffness in overweight and obese middle-aged and older adults. Thirty-six individuals were randomly assigned to a weight loss (n=25; age: 61.2+/-0.8 years; body mass index: 30.0+/-0.6 kg/m(2)) or a control (n=11; age: 66.1+/-1.9 years; body mass index: 31.8+/-1.4 kg/m(2)) group. Arterial stiffness was measured via carotid artery ultrasonography combined with applanation tonometry and carotid-femoral pulse wave velocity via applanation tonometry at baseline and after the 12-week intervention. Body weight, body fat, abdominal adiposity, blood pressure, beta-stiffness index, and carotid-femoral pulse wave velocity were similar in the 2 groups at baseline (all P>0.05). Body weight (-7.1+/-0.7 versus -0.7+/-1.1 kg), body fat, and abdominal adiposity decreased in the weight loss group but not in the control group (all P<0.05). Brachial systolic and diastolic blood pressures declined (P<0.05) only in the weight loss group. Central systolic and pulse pressures did not change significantly in either group. beta-Stiffness index (-1.24+/-0.22 versus 0.52+/-0.37 U) and carotid-femoral pulse wave velocity (-187+/-29 versus 15+/-42 cm/s) decreased in the weight loss group but not in the control group (all P<0.05). The reductions in carotid-femoral pulse wave velocity were correlated with reductions in total body and abdominal adiposity (r=0.357-0.602; all P<0.05). However, neither total body nor abdominal adiposity independently predicted reductions in arterial stiffness indices. In summary, our findings indicate that weight loss reduces arterial stiffness in overweight/obese middle-aged and older adults, and the magnitudes of these improvements are related to the loss of total and abdominal adiposity.

Arterial destiffening with weight loss in overweight and obese middle-aged and older adults.

Nous avons test&eacute; l&#39;hypoth&egrave;se que la perte de poids par un r&eacute;gime hypocalorique r&eacute;duirait la rigidit&eacute; art&eacute;rielle chez des adultes d&#39;&acirc;ge moyen et plus &acirc;g&eacute;s en surpoids et ob&egrave;ses. Trente-six personnes ont &eacute;t&eacute; assign&eacute;s au hasard &agrave; une perte de poids (n = 25 ; age : 61.2+/-0.8 ans ; indice de masse corporelle : 30.0+/-0.6 kg/m(2)) ou un contr&ocirc;le (n = 11 ; age : 66.1+/-1.9 ans ; indice de masse corporelle : 31.8+/-1.4 kg/m(2)) groupe. Rigidit&eacute; art&eacute;rielle a &eacute;t&eacute; mesur&eacute;e par &eacute;chographie carotidienne combin&eacute;e avec la tonom&eacute;trie d&#39;aplanation et vitesse d&#39;onde de pouls carotidien-f&eacute;moral par tonom&eacute;trie d&#39;aplanation au d&eacute;part et apr&egrave;s l&#39;intervention de 12 semaines. Poids corporel, masse grasse, adiposit&eacute; abdominale, tension art&eacute;rielle, index de b&ecirc;ta-rigidit&eacute; et vitesse d&#39;onde de pouls carotidien-f&eacute;moral ont &eacute;t&eacute; similaires dans les 2 groupes au d&eacute;part (tous les P &amp;gt; 0,05). (-7,1 +/-0,7 Contre-0.7+/-1.1 kg) de poids corporel, masse grasse et une adiposit&eacute; abdominale a diminu&eacute; dans le groupe de perte de poids, mais pas dans le groupe t&eacute;moin (P tous &lt; 0,05). Les pressions systolique et diastoliques brachiales diminu&eacute; (P &lt; 0,05) que dans le groupe de perte de poids. Centrale systolique et pressions d&#39;impulsions ne changent pas significativement dans les deux groupes. index de b&ecirc;ta-rigidit&eacute; (1.24 +/-0,22 versus 0.52+/-0.37 U) et pouls carotidien-f&eacute;moral vague vitesse (-187 +/-29 contre 15 +/-42 cm/s) a diminu&eacute; dans le groupe de perte de poids, mais pas dans le groupe t&eacute;moin (P tous &lt; 0,05). Les r&eacute;ductions de la vitesse d&#39;onde de pouls carotidien-f&eacute;moral &eacute;taient corr&eacute;l&eacute;es &agrave; la r&eacute;duction totale du corps et de l&#39;adiposit&eacute; abdominale (r = 0,357-0,602 ; tous les P &lt; 0,05). Toutefois, le total ni corps, ni adiposit&eacute; abdominale pr&eacute;dit ind&eacute;pendamment des r&eacute;ductions dans les indices de rigidit&eacute; art&eacute;rielle. En r&eacute;sum&eacute;, nos r&eacute;sultats indiquent que la perte de poids r&eacute;duit la rigidit&eacute; art&eacute;rielle en surpoids ou ob&egrave;ses adultes d&#39;&acirc;ge moyen et plus &acirc;g&eacute;s, et les amplitudes de ces am&eacute;liorations sont li&eacute;s &agrave; la perte de l&#39;adiposit&eacute; abdominale et de totale.

Art&egrave;re destiffening avec perte de poids chez des adultes d&#39;&acirc;ge moyen ou &acirc;g&eacute;es en surpoids et ob&egrave;ses.

Abbiamo testato l&#39;ipotesi che la perdita di peso attraverso una dieta ipocalorica ridurrebbe rigidit&agrave; arteriosa negli adulti di mezza et&agrave; e anziani in sovrappeso e obesi. Trenta-sei individui sono stati assegnati in modo casuale ad una perdita di peso (n = 25; et&agrave;: anni 61.2+/-0.8; indice di massa corporea: 30.0+/-0.6 kg/m(2)) o un controllo (n = 11; et&agrave;: anni 66.1+/-1.9; indice di massa corporea: 31.8+/-1.4 kg/m(2)) gruppo. Rigidit&agrave; arteriosa &egrave; stata misurata tramite ecografia dell&#39;arteria carotidea combinata con tonometria di applanation e velocit&agrave; delle onde polso carotideo-femorale tramite tonometria di applanation al basale e dopo l&#39;intervento di 12 settimane. Peso corporeo, grasso corporeo, adiposit&agrave; addominale, pressione arteriosa, indice beta-rigidit&agrave; e velocit&agrave; delle onde polso carotideo-femorale sono stati simili nei 2 gruppi al basale (tutti P &amp;gt; 0.05). (7,1 + 0,7 Versus-0.7+/-1.1 kg) di peso corporeo, massa grassa e adiposit&agrave; addominale &egrave; diminuito nel gruppo di perdita di peso, ma non nel gruppo di controllo (tutti P &lt; 0,05). Brachiale sistole e diastole pressione sanguigna diminuita (P &lt; 0.05) solo nel gruppo di perdita di peso. Centrale sistolica e pressione di impulso non cambia significativamente in entrambi i gruppi. indice di rigidit&agrave;-beta (-1.24 + 0,22 versus 0.52+/-0.37 U) e polso carotideo-femorale wave velocity (-187 + 29 versus 15 + 42 cm/s) &egrave; diminuito nel gruppo di perdita di peso, ma non nel gruppo di controllo (tutti P &lt; 0,05). Le riduzioni di velocit&agrave; delle onde polso carotideo-femorale sono state correlate con riduzioni in total body e adiposit&agrave; addominale (r = 0.357-0.602; P tutti &lt; 0,05). Tuttavia, n&eacute; totale corpo n&eacute; adiposit&agrave; addominale indipendente previsto riduzioni in indici di rigidit&agrave; arteriosa. In sintesi, i nostri risultati indicano che perdita di peso riduce la rigidit&agrave; arteriosa in sovrappeso/obesi adulti di mezza et&agrave; e anziani, e la grandezza di questi miglioramenti &egrave; correlati alla perdita di adiposit&agrave; addominale e totale.

Arteriosa destiffening con perdita di peso negli adulti di mezza et&agrave; e anziani in sovrappeso e obesi.

Mice with CCR2 deficiency are protected from insulin resistance but only after long periods of high-fat diet (HFD) feeding, despite the virtual absence of circulating inflammatory monocytes. We performed a time course study in mice with hematopoietic and global CCR2 deficiency to determine adipose tissue-specific mechanisms for the delayed impact of CCR2 deficiency on insulin resistance.

Aberrant accumulation of undifferentiated myeloid cells in the adipose tissue of CCR2-deficient mice delays improvements in insulin sensitivity.

Macrophage inflammatory protein-1Î± (CCL3) plays a well-known role in infectious and viral diseases; however, its contribution to atherosclerotic lesion formation and lipid metabolism has not been determined. Low density lipoprotein receptor deficient (LDLR(-/-)) mice were transplanted with bone marrow from CCL3(-/-) or C57BL/6 wild type donors. After 6 and 12 weeks on western diet (WD), recipients of CCL3(-/-) marrow demonstrated lower plasma cholesterol and triglyceride concentrations compared to recipients of C57BL/6 marrow. Atherosclerotic lesion area was significantly lower in female CCL3(-/-) recipients after 6 weeks and in male CCL3(-/-) recipients after 12 weeks of WD feeding (P<0.05). Surprisingly, male CCL3(-/-) recipients had a 50% decrease in adipose tissue mass after WD-feeding, and plasma insulin, and leptin levels were also significantly lower. These results were specific to CCL3, as LDLR(-/-) recipients of monocyte chemoattractant protein(-/-) (CCL2) marrow were not protected from the metabolic consequences of high fat feeding. Despite these improvements in LDLR(-/-) recipients of CCL3(-/-) marrow in the bone marrow transplantation (BMT) model, double knockout mice, globally deficient in both proteins, did not have decreased body weight, plasma lipids, or atherosclerosis compared with LDLR(-/-) controls. Finally, there were no differences in myeloid progenitors or leukocyte populations, indicating that changes in body weight and plasma lipids in CCL3(-/-) recipients was not due to differences in hematopoiesis. Taken together, these data implicate a role for CCL3 in lipid metabolism in hyperlipidemic mice following hematopoietic reconstitution.

Impact of macrophage inflammatory protein-1Î± deficiency on atherosclerotic lesion formation, hepatic steatosis, and adipose tissue expansion.

Prot&eacute;ine inflammatoire de macrophage-1&alpha; (CCL3) joue un r&ocirc;le bien connu dans les maladies infectieuses et virales ; Cependant, sa contribution &agrave; la formation de l&eacute;sions ath&eacute;roscl&eacute;reuses et m&eacute;tabolisme lipidique n&#39;a pas &eacute;t&eacute; d&eacute;termin&eacute;e. R&eacute;cepteur de lipoprot&eacute;ines de basse densit&eacute; d&eacute;ficient (LDLR(-/-)) souris ont &eacute;t&eacute; transplant&eacute;es avec la moelle osseuse provenant de donneurs de type sauvage CCL3(-/-) ou C57BL/6. Apr&egrave;s 6 et 12 semaines sur l&#39;alimentation occidentale (WD), b&eacute;n&eacute;ficiaires de moelle CCL3(-/-) d&eacute;montr&eacute; inf&eacute;rieurs cholest&eacute;rol et triglyc&eacute;rides plasmatiques par rapport aux b&eacute;n&eacute;ficiaires de moelle C57BL/6. Zone de l&eacute;sion ath&eacute;roscl&eacute;reuse &eacute;tait significativement plus faible chez les femmes CCL3(-/-) receveurs apr&egrave;s 6 semaines et chez les m&acirc;les CCL3(-/-) receveurs apr&egrave;s 12 semaines d&#39;alimentation WD (P &lt; 0,05). &Eacute;tonnamment, hommes CCL3(-/-) b&eacute;n&eacute;ficiaires ont pr&eacute;sent&eacute; une diminution de 50 % dans la masse de tissu adipeux apr&egrave;s WD-alimentation et insuline plasmatique et taux de leptine est &eacute;galement significativement plus faibles. Ces r&eacute;sultats &eacute;taient sp&eacute;cifiques &agrave; CCL3, comme LDLR(-/-) b&eacute;n&eacute;ficiaires de moelle de monocyte chemoattractant protein(-/-) (CCL2) n&#39;&eacute;taient pas prot&eacute;g&eacute;s contre les cons&eacute;quences m&eacute;taboliques de l&#39;alimentation en mati&egrave;res grasses &eacute;lev&eacute;. Malgr&eacute; ces am&eacute;liorations chez les receveurs LDLR(-/-) de CCL3(-/-) de moelle dans le mod&egrave;le de transplantation (BMT) de la moelle osseuse, double des souris knock-out, globalement d&eacute;ficients dans les deux prot&eacute;ines, n&#39;avaient pas de diminution du poids corporel, lipides plasmatiques ou l&#39;ath&eacute;roscl&eacute;rose par rapport aux t&eacute;moins LDLR(-/-). Enfin, il n&#39;y a aucune diff&eacute;rence de prog&eacute;niteurs my&eacute;lo&iuml;des ou populations de leucocytes, indiquant que changements de poids et plasma lipidiques chez les receveurs CCL3(-/-) n&#39;&eacute;tait pas due aux diff&eacute;rences dans l&#39;h&eacute;matopo&iuml;&egrave;se. Pris ensemble, ces donn&eacute;es impliquent un r&ocirc;le pour CCL3 dans le m&eacute;tabolisme lipidique chez des souris hyperlipid&eacute;miques reconstitution h&eacute;matopo&iuml;&eacute;tique.

Impact de l&#39;insuffisance de prot&eacute;ines inflammatoires-1&alpha; macrophage sur la formation de l&eacute;sions ath&eacute;roscl&eacute;reuses, st&eacute;atose h&eacute;patique et l&#39;expansion du tissu adipeux.

Proteina infiammatoria del macrofago-1&alpha; (CCL3) svolge un ruolo ben noto in malattie infettive e virali; Tuttavia, non &egrave; stato determinato il contributo alla formazione della lesione aterosclerotica e metabolismo dei lipidi. Del ricevitore della lipoproteina a bassa densit&agrave; carenza (LDLR(-/-)) topi sono stati trapiantati con midollo osseo da donatori di tipo selvatico CCL3(-/-) o C57BL/6. Dopo 6 e 12 settimane di dieta occidentale (WD), i destinatari del midollo CCL3(-/-) dimostrato pi&ugrave; bassa colesterolo e trigliceridi concentrazioni plasmatiche rispetto ai destinatari del midollo C57BL/6. Lesione aterosclerotica era significativamente pi&ugrave; basso nel femminili CCL3(-/-) destinatari dopo 6 settimane e nel maschi CCL3(-/-) destinatari dopo 12 settimane di alimentazione WD (P &lt; 0,05). Sorprendentemente, maschi CCL3(-/-) destinatari ha avuto un calo di 50% in massa di tessuto adiposo dopo WD-alimentazione e insulina al plasma e i livelli di leptina sono stati anche significativamente inferiori. Questi risultati erano specifici per CCL3, come destinatari LDLR(-/-) del midollo osseo di monocyte chemoattractant protein(-/-) (CCL2) non erano protetti dalle conseguenze metaboliche di alta alimentazione grasso. Nonostante questi miglioramenti in LDLR(-/-) destinatari del midollo CCL3(-/-) nel modello bone marrow transplantation (BMT), doppio topi knockout, globalmente carenti di entrambe le proteine, non hanno avuto una riduzione di peso, lipidi del plasma o aterosclerosi rispetto ai controlli LDLR(-/-). Infine, c&#39;erano differenze nei progenitori mieloidi o popolazioni leucocitarie, che indica che le modifiche nei lipidi di peso e plasma corpo in CCL3(-/-) destinatari non era a causa delle differenze nell&#39;ematopoiesi. Presi insieme, questi dati implicano un ruolo per CCL3 nel metabolismo dei lipidi nei topi iperlipidemici dopo ricostituzione ematopoietica.

Impatto del deficit 1&alpha;-proteina infiammatoria macrofagica sulla formazione della lesione aterosclerotica, steatosi epatica e l&#39;espansione del tessuto adiposo.

Obesity is characterized by adipose tissue (AT) macrophage (ATM) accumulation, which promotes AT inflammation and dysfunction. Toll-like receptor 4 (TLR4) deficiency attenuates AT inflammation in obesity but does not impede the accumulation of ATMs. The purpose of the current study was to determine whether TLR4 deficiency alters ATM polarization. TLR4(-/-) and wild-type mice were fed a low-fat, high-monounsaturated fat (HF(MUFA)), or a high-saturated fat (HF(SFA)) diet for 16 weeks. Further, we used a bone marrow transplant model to determine the influence of hematopoietic cell TLR4 signaling. The metabolic and inflammatory responses to high-fat feeding and ATM phenotype were assessed. Global and hematopoietic cell TLR4 deficiency, irrespective of recipient genotype, produced a shift in ATM phenotype toward an alternatively activated state, which was accompanied by reduced AT inflammation. Despite the observed shift in ATM phenotype, neither global nor hematopoietic cell TLR4 deficiency influenced systemic insulin sensitivity after high-fat feeding. Results of the current study suggest that TLR4 directly influences ATM polarization but question the relevance of TLR4 signaling to systemic glucose homeostasis in obesity.

Toll-like receptor 4 deficiency promotes the alternative activation of adipose tissue macrophages.

L&#39;ob&eacute;sit&eacute; est caract&eacute;ris&eacute;e par le tissu adipeux (AT) accumulation de macrophages (ATM), qui favorise l&#39;inflammation et le dysfonctionnement. Toll-like receptor 4 (TLR4) carence en att&eacute;nue &agrave; l&#39;inflammation dans l&#39;ob&eacute;sit&eacute; mais n&#39;entrave pas l&#39;accumulation de guichets automatiques. Le but de cette &eacute;tude &eacute;tait de d&eacute;terminer si TLR4 carence modifie polarisation de l&#39;ATM. TLR4(-/-) et sauvage souris ont re&ccedil;u un faible teneur en gras, acides gras mono-insatur&eacute;s-haute (HF(MUFA)), ou une graisse satur&eacute;e en haut (HF(SFA)) di&egrave;te pendant 16 semaines. De plus, nous avons utilis&eacute; un mod&egrave;le de greffe de moelle osseuse pour d&eacute;terminer l&#39;influence de la signalisation de cellules h&eacute;matopo&iuml;&eacute;tiques TLR4. Les r&eacute;ponses m&eacute;taboliques et inflammatoires &agrave; l&#39;alimentation riche en mati&egrave;res grasses et le ph&eacute;notype de l&#39;ATM ont &eacute;t&eacute; &eacute;valu&eacute;es. Cellule mondiale et h&eacute;matopo&iuml;&eacute;tique TLR4 carence, quel que soit le g&eacute;notype destinataire, produit un changement dans le ph&eacute;notype ATM vers un &Eacute;tat alternativement activ&eacute;, qui &eacute;tait accompagn&eacute; par r&eacute;duit &agrave; l&#39;inflammation. Malgr&eacute; le changement observ&eacute; dans le ph&eacute;notype de l&#39;ATM, cellule h&eacute;matopo&iuml;&eacute;tique ni global TLR4 carence influenc&eacute; la sensibilit&eacute; &agrave; l&#39;insuline syst&eacute;mique apr&egrave;s un repas riche en graisses. R&eacute;sultats de la pr&eacute;sente &eacute;tude sugg&egrave;rent que TLR4 influence directement &agrave; polarisation ATM mais question la pertinence de TLR4 signalisation &agrave; l&#39;hom&eacute;ostasie du glucose syst&eacute;mique dans l&#39;ob&eacute;sit&eacute;.

Carence en Toll-like receptor 4 favorise l&#39;alternative activation des macrophages de tissu adipeux.

L&#39;obesit&agrave; &egrave; caratterizzata da tessuto adiposo (AT) accumulo di macrofagi (ATM), che promuove l&#39;infiammazione e la disfunzione. Recettore toll-like 4 (TLR4) deficit attenua all&#39;infiammazione dell&#39;obesit&agrave; ma non impediscono l&#39;accumulo di sportelli bancomat. Lo scopo di questo studio era di determinare se il deficit di TLR4 altera polarizzazione ATM. TLR4(-/-) e topi wild-type sono stati alimentati a basso contenuto di grassi, grassi monoinsaturi high (HF(MUFA)), o un grasso saturo ad alta (dieta HF(SFA)) per 16 settimane. Inoltre, abbiamo utilizzato un modello di trapianto di midollo osseo per determinare l&#39;influenza della segnalazione delle cellule ematopoietiche TLR4. Sono state valutate le risposte metaboliche e infiammatorie ad alimentazione ricca di grassi e fenotipo ATM. Cellule ematopoietiche e globale TLR4 deficit, a prescindere dal genotipo del destinatario, ha prodotto un cambiamento nel fenotipo ATM verso uno stato in alternativa attivato, che era accompagnato da ridotta all&#39;infiammazione. Nonostante il cambiamento osservato nel fenotipo ATM, n&eacute; globali n&eacute; hematopoietic cell deficit TLR4 influenzato la sensibilit&agrave; all&#39;insulina sistemica dopo l&#39;alimentazione ricca di grassi. Risultati di questo studio suggeriscono che TLR4 direttamente influenza polarizzazione ATM ma domanda la pertinenza di TLR4 segnalazione all&#39;omeostasi sistemica glucosio nell&#39;obesit&agrave;.

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Jeb S. Orr

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