isolation-cryopreservation-culture-human-amnion-epithelial-cells-for

Isolation, Cryopreservation and Culture of Human Amnion Epithelial Cells for Clinical Applications

Human amnion epithelial cells (hAECs) derived from term or pre-term amnion membranes have attracted attention from researchers and clinicians as a ...

Wake Forest University Health Sciences

Leucine is recognized as a nutrient signal; however, the long-term in vivo consequences of leucine signaling and the role of branched-chain amino acid (BCAA) metabolism in this signaling remain unclear. To investigate these questions, we disrupted the BCATm gene, which encodes the enzyme catalyzing the first step in peripheral BCAA metabolism. BCATm(-/-) mice exhibited elevated plasma BCAAs and decreased adiposity and body weight, despite eating more food, along with increased energy expenditure, remarkable improvements in glucose and insulin tolerance, and protection from diet-induced obesity. The increased energy expenditure did not seem to be due to altered locomotor activity, uncoupling proteins, sympathetic activity, or thyroid hormones but was strongly associated with food consumption and an active futile cycle of increased protein degradation and synthesis. These observations suggest that elevated BCAAs and/or loss of BCAA catabolism in peripheral tissues play an important role in regulating insulin sensitivity and energy expenditure.

Disruption of BCATm in mice leads to increased energy expenditure associated with the activation of a futile protein turnover cycle.

Elevations in branched-chain amino acids (BCAAs) in human obesity were first reported in the 1960s. Such reports are of interest because of the emerging role of BCAAs as potential regulators of satiety, leptin, glucose, cell signaling, adiposity, and body weight (mTOR and PKC). To explore loss of catabolic capacity as a potential contributor to the obesity-related rises in BCAAs, we assessed the first two enzymatic steps, catalyzed by mitochondrial branched chain amino acid aminotransferase (BCATm) or the branched chain alpha-keto acid dehydrogenase (BCKD E1alpha subunit) complex, in two rodent models of obesity (ob/ob mice and Zucker rats) and after surgical weight loss intervention in humans. Obese rodents exhibited hyperaminoacidemia including BCAAs. Whereas no obesity-related changes were observed in rodent skeletal muscle BCATm, pS293, or total BCKD E1alpha or BCKD kinase, in liver BCKD E1alpha was either unaltered or diminished by obesity, and pS293 (associated with the inactive state of BCKD) increased, along with BCKD kinase. In epididymal fat, obesity-related declines were observed in BCATm and BCKD E1alpha. Plasma BCAAs were diminished by an overnight fast coinciding with dissipation of the changes in adipose tissue but not in liver. BCAAs also were reduced by surgical weight loss intervention (Roux-en-Y gastric bypass) in human subjects studied longitudinally. These changes coincided with increased BCATm and BCKD E1alpha in omental and subcutaneous fat. Our results are consistent with the idea that tissue-specific alterations in BCAA metabolism, in liver and adipose tissue but not in muscle, may contribute to the rise in plasma BCAAs in obesity.

Obesity-related elevations in plasma leucine are associated with alterations in enzymes involved in branched-chain amino acid metabolism.

The efficacy of barrier precautions to prevent influenza transmission is unknown.

Transocular entry of seasonal influenza-attenuated virus aerosols and the efficacy of n95 respirators, surgical masks, and eye protection in humans.

&#x91CD;&#x91CF;&#x635F;&#x5931;&#x8865;&#x5145;&#x5171;&#x8F6D;&#x4E9A;&#x6CB9;&#x9178; (CLA) &#x7531;&#x8DE8; 10&#x3001; &#x72EC;&#x8054;&#x4F53; 12 (10,12) &#x548C;&#x72EC;&#x8054;&#x4F53; 9&#x3001; &#x8DE8; 11 (9,11) &#x5F02;&#x6784;&#x4F53;&#x7684;&#x76F8;&#x7B49;&#x6DF7;&#x5408;&#x7EC4;&#x6210;&#x3002;&#x4F46;&#x662F;&#xFF0C;&#x9AD8;&#x6C34;&#x5E73;&#x7684;&#x6DF7;&#x5408;&#x5171;&#x8F6D;&#x4E9A;&#x6CB9;&#x9178;&#x5F02;&#x6784;&#x4F53;&#x6216; 10,12 &#x7684;&#x540C;&#x5206;&#x5F02;&#x6784;&#x4F53;&#xFF0C;&#x4F1A;&#x5BFC;&#x81F4;&#x6162;&#x6027;&#x708E;&#x75C7;&#x3001; &#x8102;&#x4EE3;&#x8C22;&#x5F02;&#x5E38;&#x6216;&#x80F0;&#x5C9B;&#x7D20;&#x62B5;&#x6297;&#x3002;&#x6211;&#x4EEC;&#x4EE5;&#x524D;&#x8868;&#x73B0;&#x4EE5;&#x53CA;&#x4E30;&#x5BCC;&#x7684; 10,12 &#x5171;&#x8F6D;&#x4E9A;&#x6CB9;&#x9178;&#x8DCC;&#x5E45; de novo &#x8102;&#x8D28;&#x5408;&#x6210;&#x548C;&#x6D3B;&#x6027;&#x7684;&#x786C;&#x8102;&#x9170; CoA &#x53BB;&#x9971;&#x548C;&#x9176; (SCD)-1&#x3001; &delta; 9 &#x53BB;&#x9971;&#x548C;&#x9176;&#x7684;&#x5355;&#x4E0D;&#x9971;&#x548C;&#x8102;&#x80AA;&#x9178; (&#x7A46;&#x6CD5;&#xFF09; &#x5408;&#x6210;&#x7684;&#x5FC5;&#x8981;&#x6761;&#x4EF6;&#x3002;&#x56E0;&#x6B64;&#xFF0C;&#x6211;&#x4EEC;&#x5047;&#x8BBE; 10,12 &#x4ECB;&#x5BFC;&#x5171;&#x8F6D;&#x4E9A;&#x6CB9;&#x9178;&#x51CF;&#x5C11; SCD-1 &#x4E2D;&#x7684;&#x7A46;&#x6CD5;&#xFF0C;&#x968F;&#x540E;&#x8DCC;&#x5E45;&#x662F;&#x8D1F;&#x8D23;&#x89C2;&#x5BDF;&#x5230;&#x7684;&#x5F71;&#x54CD;&#x3002;&#x82E5;&#x8981;&#x6D4B;&#x8BD5;&#x8FD9;&#x79CD;&#x5047;&#x8BBE;&#xFF0C;&#x5F97;&#x5230;&#x8865;&#x5145;&#xFF0C;10,12 &#x5171;&#x8F6D;&#x4E9A;&#x6CB9;&#x9178;&#x6CBB;&#x7597;&#x4EBA;&#x7C7B;&#x8102;&#x80AA;&#x6CB9;&#x9178; 12 &#x5C0F;&#x65F6;&#x81F3; 7 &#x5929;&#xFF0C;&#x548C;&#x6D4B;&#x91CF;&#x4E86;&#x708E;&#x75C7;&#x57FA;&#x56E0;&#x8868;&#x8FBE;&#x3001; &#x80F0;&#x5C9B;&#x7D20;&#x523A;&#x6FC0;&#x8461;&#x8404;&#x7CD6;&#x548C;&#x8102;&#x80AA;&#x542B;&#x91CF;&#x3002;&#x6CB9;&#x9178;&#x5242;&#x91CF;&#x4F9D;&#x8D56;&#x6027;&#x7684;&#x65B9;&#x5F0F;&#xFF0C;&#x51CF;&#x5C11;&#x708E;&#x75C7;&#x57FA;&#x56E0;&#x7684;&#x8868;&#x8FBE;&#xFF0C;&#x800C;&#x4E14;&#x5982;&#x679C;&#x4E0D;&#x6539;&#x5584;&#x80F0;&#x5C9B;&#x7D20;&#x523A;&#x6FC0;&#x8461;&#x8404;&#x7CD6;&#x5438;&#x6536;&#x6062;&#x590D; 10,12 &#x5171;&#x8F6D;&#x4E9A;&#x6CB9;&#x9178;&#x6CBB;&#x7597;&#x8102;&#x80AA;&#x7EC6;&#x80DE;&#x7684;&#x8102;&#x80AA;&#x542B;&#x91CF;&#x3002;&#x76F8;&#x6BD4;&#x4E4B;&#x4E0B;&#xFF0C;&#x4E0E;&#x786C;&#x8102;&#x9178;&#x3001; &#x57FA;&#x677F;&#x7684; SCD-1 &#x6216; 9,11 &#x5171;&#x8F6D;&#x4E9A;&#x6CB9;&#x9178;&#x7684;&#x8865;&#x5145;&#x5E76;&#x4E0D;&#x59A8;&#x788D;&#x708E;&#x75C7;&#x57FA;&#x56E0;&#x8868;&#x8FBE;&#x7684; 10,12 &#x5171;&#x8F6D;&#x4E9A;&#x6CB9;&#x9178;&#x3002;&#x503C;&#x5F97;&#x6CE8;&#x610F;&#x7684;&#x662F;&#xFF0C;10,12 &#x5171;&#x8F6D;&#x4E9A;&#x6CB9;&#x9178;&#x7684;&#x5F71;&#x54CD;&#x53D7;&#x4F53; G &#x86CB;&#x767D;&#x52A0;&#x4E0A;&#x51E0;&#x4E2A;&#x51CF;&#x6BD2;&#x7684;&#x6CB9;&#x9178;&#x7684;&#x8868;&#x8FBE;&#x5F0F;&#x3002;&#x96C6;&#x4F53;&#xFF0C;&#x8FD9;&#x4E9B;&#x6570;&#x636E;&#x663E;&#x793A;&#x6CB9;&#x9178;&#x6291;&#x5236; 10,12 &#x5171;&#x8F6D;&#x4E9A;&#x6CB9;&#x9178;&#x8BF1;&#x5BFC;&#x7684;&#x708E;&#x75C7;&#x57FA;&#x56E0;&#x8868;&#x8FBE;&#x4E0E;&#x78F7;&#x8102;&#x548C;&#x4E2D;&#x6027;&#x8102;&#x8D28;&#x5408;&#x6210;&#x6240;&#x9700;&#x7684;&#x5185;&#x5BB9;&#xFF0C;&#x53EF;&#x80FD;&#x7531;&#x51CF;&#x8F7B;&#x7EC6;&#x80DE;&#x538B;&#x529B;&#x5F15;&#x8D77;&#x7684;&#x7A46;&#x6CD5;&#x6291;&#x5236;&#x8102;&#x8D28;&#x3002;

&#x6CB9;&#x9178;&#x51CF;&#x8F7B;&#x8DE8; 10&#x3001; &#x72EC;&#x8054;&#x4F53; 12 Conjugated Linoleic Acid-Mediated &#x708E;&#x75C7;&#x57FA;&#x56E0;&#x8868;&#x8FBE;&#x4EBA;&#x7C7B;&#x8102;&#x80AA;&#x7EC6;&#x80DE;&#x3002;

The weight loss supplement conjugated linoleic acid (CLA) consists of an equal mixture of trans-10,cis-12 (10,12) and cis-9,trans-11 (9,11) isomers. However, high levels of mixed CLA isomers, or the 10,12 isomer, causes chronic inflammation, lipodystrophy, or insulin resistance. We previously demonstrated that 10,12 CLA decreases de novo lipid synthesis along with the abundance and activity of stearoyl-CoA desaturase (SCD)-1, a Î´-9 desaturase essential for the synthesis of monounsaturated fatty acids (MUFA). Thus, we hypothesized that the 10,12 CLA-mediated decrease in SCD-1, with the subsequent decrease in MUFA, was responsible for the observed effects. To test this hypothesis, 10,12 CLA-treated human adipocytes were supplemented with oleic acid for 12Â h to 7Â days, and inflammatory gene expression, insulin-stimulated glucose uptake, and lipid content were measured. Oleic acid reduced inflammatory gene expression in a dose-dependent manner, and restored the lipid content of 10,12 CLA-treated adipocytes without improving insulin-stimulated glucose uptake. In contrast, supplementation with stearic acid, a substrate for SCD-1, or 9,11 CLA did not prevent inflammatory gene expression by 10,12 CLA. Notably, 10,12 CLA impacted the expression of several G-protein coupled receptors that was attenuated by oleic acid. Collectively, these data show that oleic acid attenuates 10,12 CLA-induced inflammatory gene expression and lipid content, possibly by alleviating cell stress caused by the inhibition of MUFA needed for phospholipid and neutral lipid synthesis.

Oleic Acid Attenuates trans-10,cis-12 Conjugated Linoleic Acid-Mediated Inflammatory Gene Expression in Human Adipocytes.

L&#39;acide linol&eacute;ique poids perte suppl&eacute;ment conjugu&eacute; (CLA) se compose d&#39;un m&eacute;lange &eacute;gal de trans-10, cis-12 (10,12) et cis-9, trans-11 isom&egrave;res (9,11). Cependant, des niveaux &eacute;lev&eacute;s de m&eacute;langes d&#39;isom&egrave;res CLA ou l&#39;isom&egrave;re 10,12, provoque la r&eacute;sistance chronique de l&#39;inflammation, lipodystrophie ou insuline. Nous avons d&eacute;montr&eacute; pr&eacute;c&eacute;demment que 10,12 CLA diminue synth&egrave;se de novo de lipides ainsi que l&#39;abondance et l&#39;activit&eacute; de st&eacute;aroyl-CoA d&eacute;saturase (SCD) -1, une d&eacute;saturase &delta;-9 essentiel pour la synth&egrave;se des acides gras monoinsatur&eacute;s (AGMI). Ainsi, nous avons &eacute;mis l&#39;hypoth&egrave;se que la diminution induite par le CLA 10,12 SCD-1, avec la baisse ult&eacute;rieure des AGMI, &eacute;tait responsable des effets observ&eacute;s. Pour tester cette hypoth&egrave;se, 10,12 adipocytes humains trait&eacute;s CLA ont &eacute;t&eacute; compl&eacute;t&eacute;es avec de l&#39;acide ol&eacute;ique de 12 h &agrave; 7 jours, et l&#39;expression des g&egrave;nes inflammatoires, l&#39;absorption du glucose stimul&eacute;e par l&#39;insuline et le contenu en lipides ont &eacute;t&eacute; mesur&eacute;es. Acide ol&eacute;ique r&eacute;duit l&#39;expression des g&egrave;nes inflammatoires de mani&egrave;re dose-d&eacute;pendante et restaur&eacute; la teneur en lipides de 10,12 impr&eacute;gn&eacute;es de CLA adipocytes sans pour autant am&eacute;liorer l&#39;absorption du glucose stimul&eacute;e par l&#39;insuline. En revanche, une suppl&eacute;mentation en acide st&eacute;arique, un substrat pour le SCD-1 ou 9, 11 CLA n&#39;a pas emp&ecirc;ch&eacute; l&#39;expression des g&egrave;nes inflammatoires par CLA 10,12. Notamment, le CLA 10,12 impact&eacute; l&#39;expression de plusieurs r&eacute;cepteurs G-prot&eacute;ine a coupl&eacute; qui a &eacute;t&eacute; att&eacute;nu&eacute;e par l&#39;acide ol&eacute;ique. Collectivement, ces donn&eacute;es montrent que l&#39;acide ol&eacute;ique att&eacute;nue l&#39;expression de g&egrave;ne inflammatoire induite par le CLA 10,12 et lipides, &eacute;ventuellement de soulager le stress cellulaire provoqu&eacute;e par l&#39;inhibition d&#39;AGMI n&eacute;cessaires pour les phospholipides et la synth&egrave;se des lipides neutres.

Acide ol&eacute;ique att&eacute;nue trans-10, cis-12 Conjugated Linoleic Acid-Mediated inflammatoire Expression g&eacute;nique dans les Adipocytes humains.

Gewicht Verlust Erg&auml;nzung konjugierte Linols&auml;ure (CLA) besteht aus einer Kombination der Trans-10, Cis-12 (10,12) und Cis-9, Trans-11 (9,11) Isomere. Bewirkt jedoch, dass hohe Konzentrationen von gemischten CLA-Isomere oder das 10,12-Isomer, chronische Entz&uuml;ndungen, Lipodystrophie oder Insulin-Resistenz. Wir zuvor bewiesen, dass 10,12 CLA verringert de Novo Lipid Synthese zusammen mit der F&uuml;lle und Aktivit&auml;t von Stearoyl-CoA-Desaturase (SCD)-1, ein &delta;-9-Desaturase unerl&auml;sslich f&uuml;r die Synthese von einfach unges&auml;ttigten Fetts&auml;uren (Schl&uuml;sselindizierte). So wir die Hypothese, dass die 10,12 CLA-vermittelte Abnahme der SCD-1, mit der anschlie&szlig;enden R&uuml;ckgang der Schl&uuml;sselindizierte, f&uuml;r die beobachteten Effekte verantwortlich war. Um diese Hypothese zu testen, 10,12 CLA-behandelten menschliche Adipozyten wurden erg&auml;nzt mit &Ouml;ls&auml;ure f&uuml;r 12 h 7 Tage und entz&uuml;ndliche Genexpression, Insulin stimuliert Glukoseaufnahme und Lipidgehalt gemessen wurden. &Ouml;ls&auml;ure entz&uuml;ndliche Genexpression in einer Dosis-abh&auml;ngigen Weise reduziert und der Lipidgehalt der 10,12 CLA-behandelten Adipozyten ohne Verbesserung der Insulin stimuliert Glukoseaufnahme wiederhergestellt. Im Gegensatz dazu hat eine Supplementierung mit Stearins&auml;ure, ein Substrat f&uuml;r SCD-1 oder 9,11 CLA nicht entz&uuml;ndliche Genexpression von 10,12 CLA verhindert. 10,12 CLA beeinflusst insbesondere den Ausdruck mehrere G-Protein-gekoppelte Rezeptoren, der durch &Ouml;ls&auml;ure abgeschw&auml;cht wurde. Zusammenfassend zeigen diese Daten, dass &Ouml;ls&auml;ure 10,12 CLA induziert entz&uuml;ndliche-Genexpression d&auml;mpft und Lipid Inhalt, m&ouml;glicherweise durch die Zelle Stress durch die Hemmung der Schl&uuml;sselindizierte Linderung f&uuml;r Phospholipid und neutral Lipid-Synthese notwendig.

&Ouml;ls&auml;ure d&auml;mpft Trans-10, Cis-12 Conjugated Linoleic Acid-Mediated entz&uuml;ndliche Genexpression in menschlichen Adipozyten.

Il peso perdita supplemento coniugata coniugata acido linoleico (CLA) &egrave; costituito da una miscela uguale di trans-10, cis-12 (10,12) e cis-9, trans-11 isomeri (9,11). Tuttavia, livelli elevati di isomeri misti di CLA, o l&#39;isomero 10,12, provoca resistenza di insulina, lipodistrofia o infiammazione cronica. Abbiamo precedentemente dimostrato che 10,12 CLA diminuzioni de novo lipido sintesi insieme con l&#39;abbondanza e attivit&agrave; di stearoil-CoA desaturasi (SCD) -1, un &delta;-9 desaturasi essenziale per la sintesi di acidi grassi monoinsaturi (MUFA). Cos&igrave;, abbiamo ipotizzato che il 10,12 diminuzione CLA-mediata in SCD-1, con la conseguente diminuzione di MUFA, era responsabile degli effetti osservati. Per verificare questa ipotesi, 10,12 adipociti umani trattati con CLA sono state completate con acido oleico per 12 h per 7 giorni, ed espressione genica infiammatoria, assorbimento del glucosio insulino-stimolato e lipidi contenuti sono stati misurati. Acido oleico ridotta espressione del gene infiammatorio in modo dose-dipendente e ripristinato il contenuto lipidico degli adipociti trattati con CLA 10,12 senza migliorare l&#39;assorbimento del glucosio insulino-stimolata. Al contrario, la supplementazione con acido stearico, un substrato per SCD-1 o 9,11 CLA non ha impedito espressione genica infiammatoria da 10,12 CLA. In particolare, CLA 10,12 influenzato l&#39;espressione di vari recettori accoppiato a proteina di G che &egrave; stato attenuato da acido oleico. Collettivamente, questi dati dimostrano che l&#39;acido oleico attenua 10,12 espressione genica infiammatoria indotta da CLA e lipidi contenuti, possibilmente di alleviare lo stress cellulare causato tramite l&#39;inibizione di MUFA necessari per la sintesi di lipidi neutri e fosfolipidi.

Acido oleico attenua trans-10, cis-12 Conjugated Linoleic Acid-Mediated infiammatoria espressione genica negli adipociti umani.

&#x91CD;&#x91CF;&#x640D;&#x5931;&#x30B5;&#x30D7;&#x30EA;&#x30E1;&#x30F3;&#x30C8;&#x5171;&#x5F79;&#x30EA;&#x30CE;&#x30FC;&#x30EB;&#x9178; (CLA) &#x30C8;&#x30E9;&#x30F3;&#x30B9; 10&#x3001;cis-12 (10,12) &#x304A;&#x3088;&#x3073; cis 9, &#x30C8;&#x30E9;&#x30F3;&#x30B9;-11 (9,11) &#x306E;&#x7570;&#x6027;&#x4F53;&#x306E;&#x7B49;&#x91CF;&#x6DF7;&#x5408;&#x7269;&#x3067;&#x69CB;&#x6210;&#x3055;&#x308C;&#x3066;&#x3044;&#x307E;&#x3059;&#x3002;&#x305F;&#x3060;&#x3057;&#x3001;&#x9AD8;&#x30EC;&#x30D9;&#x30EB;&#x306E;&#x6DF7;&#x5408; CLA &#x306E;&#x7570;&#x6027;&#x4F53;&#x3001;&#x307E;&#x305F;&#x306F; 10,12 &#x306E;&#x7570;&#x6027;&#x4F53;&#x3001;&#x6162;&#x6027;&#x708E;&#x75C7;&#x3001;&#x30EA;&#x30DD;&#x30B8;&#x30B9; &#x30C8;&#x30ED;&#x30D5;&#x30A3;&#x30FC;&#x3001;&#x307E;&#x305F;&#x306F;&#x30A4;&#x30F3;&#x30B9;&#x30EA;&#x30F3;&#x62B5;&#x6297;&#x304C;&#x767A;&#x751F;&#x3057;&#x307E;&#x3059;&#x3002;&#x6211;&#x3005; &#x306F;&#x4EE5;&#x524D;&#x305D;&#x306E; 10,12 CLA &#x6E1B;&#x5C11; de novo &#x8102;&#x8CEA;&#x5408;&#x6210;&#x3068;&#x4E00;&#x7DD2;&#x306B;&#x8C4A;&#x304B;&#x3055;&#x3068;&#x30B9;&#x30C6;&#x30A2;&#x30ED;&#x30A4;&#x30EB; CoA &#x30C7;&#x30B5;&#x30C1;&#x30E5;&#x30E9;&#x30FC;&#x30BC; (SCD)-1 &#x306E;&#x6D3B;&#x52D5;&#x306F;&#x3001;&#x4E00;&#x4FA1;&#x4E0D;&#x98FD;&#x548C;&#x8102;&#x80AA;&#x9178; &#xFF08;MUFA&#xFF09; &#x306E;&#x5408;&#x6210;&#x306E;&#x305F;&#x3081;&#x306B;&#x4E0D;&#x53EF;&#x6B20;&#x306E; &delta; 9 &#x30C7;&#x30B5;&#x30C1;&#x30E5;&#x30E9;&#x30FC;&#x30BC;&#x3092;&#x8A3C;&#x660E;&#x3057;&#x307E;&#x3057;&#x305F;&#x3002;&#x3057;&#x305F;&#x304C;&#x3063;&#x3066;&#x3001;SCD-1 &#x3067; 10,12 CLA &#x3092;&#x4ECB;&#x3057;&#x305F;&#x6E1B;&#x5C11; MUFA &#x306E;&#x5F8C;&#x7D9A;&#x306E;&#x6E1B;&#x5C11;&#x3092;&#x89B3;&#x5BDF;&#x3057;&#x305F;&#x52B9;&#x679C;&#x306E;&#x8CAC;&#x4EFB;&#x304C;&#x3042;&#x3063;&#x305F;&#x3053;&#x3068;&#x3092;&#x4EEE;&#x5B9A;&#x3057;&#x307E;&#x3057;&#x305F;&#x3002;&#x3053;&#x306E;&#x4EEE;&#x8AAC;&#x3092;&#x30C6;&#x30B9;&#x30C8;&#x3059;&#x308B;&#x306B;&#x306F;&#x3001;10,12 CLA &#x6271;&#x308F;&#x308C;&#x308B;&#x4EBA;&#x9593;&#x306E;&#x8102;&#x80AA;&#x7D30;&#x80DE;&#x3067;&#x30AA;&#x30EC;&#x30A4;&#x30F3;&#x9178;&#x3092; 7 &#x65E5;&#x9593;&#x3001;12 h &#x3092;&#x6DFB;&#x52A0;&#x3057;&#x305F;&#x3057;&#x3001;&#x708E;&#x75C7;&#x6027;&#x306E;&#x907A;&#x4F1D;&#x5B50;&#x767A;&#x73FE;&#x3001;&#x30A4;&#x30F3;&#x30B9;&#x30EA;&#x30F3;&#x523A;&#x6FC0;&#x306B;&#x3088;&#x308B;&#x30B0;&#x30EB;&#x30B3;&#x30FC;&#x30B9;&#x53D6;&#x308A;&#x8FBC;&#x307F;&#x304A;&#x3088;&#x3073;&#x8102;&#x8CEA;&#x542B;&#x91CF;&#x3092;&#x6E2C;&#x5B9A;&#x3057;&#x307E;&#x3057;&#x305F;&#x3002;&#x30AA;&#x30EC;&#x30A4;&#x30F3;&#x9178;&#x306F;&#x3001;&#x708E;&#x75C7;&#x6027;&#x306E;&#x907A;&#x4F1D;&#x5B50;&#x767A;&#x73FE;&#x306F;&#x7528;&#x91CF;&#x4F9D;&#x5B58;&#x7684;&#x306B;&#x6E1B;&#x5C11;&#x3057;&#x3001;&#x30A4;&#x30F3;&#x30B9;&#x30EA;&#x30F3;&#x523A;&#x6FC0;&#x306B;&#x3088;&#x308B;&#x30B0;&#x30EB;&#x30B3;&#x30FC;&#x30B9;&#x53D6;&#x308A;&#x8FBC;&#x307F;&#x3092;&#x6539;&#x5584;&#x305B;&#x305A; CLA &#x6271;&#x308F; 10,12 &#x8102;&#x80AA;&#x7D30;&#x80DE;&#x306E;&#x8102;&#x8CEA;&#x542B;&#x91CF;&#x3092;&#x5FA9;&#x5143;&#x3057;&#x307E;&#x3059;&#x3002;&#x5BFE;&#x7167;&#x7684;&#x306B;&#x3001;&#x30B9;&#x30C6;&#x30A2;&#x30EA;&#x30F3;&#x9178;&#x3001;SCD 1 &#x7528;&#x57FA;&#x677F;&#x307E;&#x305F;&#x306F; 9,11 CLA &#x3068;&#x88DC;&#x5145; 10,12 CLA &#x306B;&#x3088;&#x308B;&#x708E;&#x75C7;&#x6027;&#x306E;&#x907A;&#x4F1D;&#x5B50;&#x767A;&#x73FE;&#x3092;&#x4E88;&#x9632;&#x3057;&#x306A;&#x304B;&#x3063;&#x305F;&#x3002;&#x7279;&#x306B;&#x3001;10,12 CLA &#x30AA;&#x30EC;&#x30A4;&#x30F3;&#x9178;&#x306B;&#x3088;&#x3063;&#x3066;&#x6E1B;&#x8870;&#x3055;&#x308C;&#x305F;&#x3044;&#x304F;&#x3064;&#x304B;&#x306E; G &#x30BF;&#x30F3;&#x30D1;&#x30AF;&#x8CEA;&#x5171;&#x5F79;&#x53D7;&#x5BB9;&#x4F53;&#x306E;&#x767A;&#x73FE;&#x306E;&#x5F71;&#x97FF;&#x3002;&#x7DCF;&#x79F0;&#x3057;&#x3066;&#x3001;&#x3053;&#x308C;&#x3089;&#x306E;&#x30C7;&#x30FC;&#x30BF;&#x306F;&#x30AA;&#x30EC;&#x30A4;&#x30F3;&#x9178; 10,12 CLA &#x8A98;&#x767A;&#x708E;&#x75C7;&#x6027;&#x306E;&#x907A;&#x4F1D;&#x5B50;&#x767A;&#x73FE;&#x3092;&#x6E1B;&#x8870;&#x3055;&#x305B;&#x308B;&#x3057;&#x3001;&#x30EA;&#x30F3;&#x8102;&#x8CEA;&#x304A;&#x3088;&#x3073;&#x4E2D;&#x6027;&#x8102;&#x8CEA;&#x5408;&#x6210;&#x8102;&#x8CEA;&#x304A;&#x305D;&#x3089;&#x304F; MUFA &#x306E;&#x963B;&#x5BB3;&#x306B;&#x3088;&#x3063;&#x3066;&#x5F15;&#x304D;&#x8D77;&#x3053;&#x3055;&#x308C;&#x308B;&#x7D30;&#x80DE;&#x306E;&#x30B9;&#x30C8;&#x30EC;&#x30B9;&#x3092;&#x8EFD;&#x6E1B;&#x3059;&#x308B;&#x3053;&#x3068;&#x306B;&#x3088;&#x3063;&#x3066;&#x3001;&#x30B3;&#x30F3;&#x30C6;&#x30F3;&#x30C4;&#x306B;&#x5FC5;&#x8981;&#x306A;&#x8868;&#x793A;&#x3057;&#x307E;&#x3059;&#x3002;

&#x30AA;&#x30EC;&#x30A4;&#x30F3;&#x9178;&#x3092;&#x6E1B;&#x8870;&#x3055;&#x305B;&#x308B;&#x30C8;&#x30E9;&#x30F3;&#x30B9; 10, cis 12 Conjugated Linoleic Acid-Mediated &#x708E;&#x75C7;&#x6027;&#x907A;&#x4F1D;&#x5B50;&#x767A;&#x73FE;&#x3072;&#x3068;&#x8102;&#x80AA;&#x7D30;&#x80DE;&#x3002;

&#xD2B8;&#xB79C;&#xC2A4; 10, cis-12 (10,12) &#xBC0F; cis 9, &#xD2B8;&#xB79C;&#xC2A4;-11 (9,11) &#xC131;&#xCCB4;&#xAC00; &#xB611;&#xAC19;&#xC774; &#xD63C;&#xD569; &#xBB34;&#xAC8C; &#xC190;&#xC2E4; &#xBCF4;&#xCDA9; conjugated linoleic &#xC0B0; (CLA)&#xC5D0; &#xC758;&#xD558;&#xC5EC; &#xC774;&#xB8E8;&#xC5B4;&#xC838; &#xC788;&#xB2E4;. &#xADF8;&#xB7EC;&#xB098;, &#xD63C;&#xD569;&#xB41C; CLA &#xC131;&#xCCB4;&#xC758; &#xC0C1;&#xBD80; &#xB610;&#xB294; 10,12 &#xC774;&#xC131;&#xC9C8;&#xCCB4; &#xB9CC;&#xC131; &#xC5FC;&#xC99D;, lipodystrophy, &#xB610;&#xB294; &#xC778;&#xC290;&#xB9B0; &#xC800;&#xD56D;&#xC744; &#xBC1C;&#xC0DD;&#xD569;&#xB2C8;&#xB2E4;. &#xC6B0;&#xB9AC;&#xB294; &#xC774;&#xC804;&#xC5D0; &#xADF8; 10,12 CLA &#xAC10;&#xC18C; &#xB4DC; &#xB178; &#xBCF4; &#xC9C0;&#xC9C8; &#xD569;&#xC131; &#xD48D;&#xC694;&#xB85C;&#xC6C0; &#xD568;&#xAED8; &#xBC0F; stearoyl CoA desaturase (SCD)-1&#xC758; &#xD65C;&#xB3D9;, &#xBD88;&#xD3EC;&#xD654; &#xC9C0;&#xBC29;&#xC0B0; (MUFA)&#xC758; &#xD569;&#xC131;&#xC5D0; &#xD544;&#xC218;&#xC801;&#xC778; &delta; 9 desaturase &#xC2DC;&#xC5F0; &#xD588;&#xB2E4;. &#xB530;&#xB77C;&#xC11C;, &#xC6B0;&#xB9AC;&#xAC00; &#xAC00;&#xC124; 10,12 CLA &#xC911;&#xC7AC; &#xAC10;&#xC18C; SCD 1 MUFA, &#xD6C4;&#xC18D; &#xAC10;&#xC18C;&#xC640; &#xAD00;&#xCC30; &#xB41C; &#xD6A8;&#xACFC; &#xB300; &#xD55C; &#xCC45;&#xC784;&#xC744; &#xC9C0;&#xC9C0; &#xD588;&#xC2B5;&#xB2C8;&#xB2E4;. &#xC774; &#xAC00;&#xC124;&#xC744; &#xD14C;&#xC2A4;&#xD2B8; &#xD558;&#xB824;&#xBA74; 10,12 CLA &#xCDE8;&#xAE09; &#xC778;&#xAC04;&#xC758; adipocytes &#xC62C;&#xB808;&#xC0B0; 7 &#xC77C;&#xC5D0; 12 h&#xC5D0; &#xB300; &#xD55C; &#xBCF4;&#xC644; &#xD588;&#xB2E4; &#xBC0F; &#xC5FC;&#xC99D; &#xC131; &#xC720;&#xC804;&#xC790; &#xBC1C;&#xD604;, &#xC778;&#xC290;&#xB9B0; &#xC790;&#xADF9; &#xD3EC;&#xB3C4; &#xB2F9; &#xD1B5;&#xD48D; &#xAD00;, &#xADF8;&#xB9AC;&#xACE0; &#xC9C0;&#xC9C8; &#xCF58;&#xD150;&#xCE20; &#xCE21;&#xC815;. &#xC62C;&#xB808;&#xC0B0; &#xBCF5;&#xC6A9;&#xB7C9; &#xC758;&#xC874; &#xBC29;&#xC2DD;&#xC73C;&#xB85C; &#xC5FC;&#xC99D; &#xC131; &#xC720;&#xC804;&#xC790; &#xBC1C;&#xD604;&#xC744; &#xAC10;&#xC18C; &#xD558; &#xACE0; &#xC778;&#xC290;&#xB9B0; &#xC790;&#xADF9; &#xD3EC;&#xB3C4; &#xB2F9; &#xD1B5;&#xD48D; &#xAD00;&#xC744; &#xAC1C;&#xC120; &#xD558;&#xC9C0; &#xC54A;&#xACE0; 10,12 CLA &#xCDE8;&#xAE09; adipocytes&#xC758; &#xC9C0;&#xC9C8; &#xCF58;&#xD150;&#xCE20;&#xB97C; &#xBCF5;&#xC6D0;. &#xBC18;&#xBA74;, &#xC2A4; &#xD14C;&#xC544; &#xB974; &#xC0B0;, SCD 1 &#xAE30;&#xD310; &#xB610;&#xB294; 9,11 CLA &#xBCF4;&#xCDA9; 10,12 CLA&#xC5D0; &#xC758;&#xD574; &#xC5FC;&#xC99D; &#xC131; &#xC720;&#xC804;&#xC790; &#xBC1C;&#xD604;&#xC744; &#xBC29;&#xC9C0; &#xD558;&#xC9C0; &#xC54A;&#xC558;&#xB2E4;. &#xD2B9;&#xD788;, 10,12 CLA &#xC62C;&#xB808;&#xC0B0;&#xC73C;&#xB85C; &#xAC10;&#xC1E0;&#xB294; &#xBA87; G-&#xB2E8;&#xBC31;&#xC9C8; &#xACB0;&#xD569; &#xC218;&#xC6A9; &#xCCB4;&#xC758; &#xD45C;&#xD604;&#xC5D0; &#xC601;&#xD5A5;&#xC744;. &#xC0E8; &#xB2E4;, &#xC774;&#xB7EC;&#xD55C; &#xB370;&#xC774;&#xD130;&#xB294; &#xC62C;&#xB808;&#xC0B0; &#xC57D;&#xD654; 10,12 CLA &#xC720;&#xB3C4; &#xB41C; &#xC5FC;&#xC99D; &#xC131; &#xC720;&#xC804;&#xC790; &#xBC1C;&#xD604; &#xBC0F; &#xC9C0;&#xC9C8; &#xC138;&#xD3EC; &#xC2A4;&#xD2B8;&#xB808;&#xC2A4; MUFA&#xC758; &#xC800;&#xD574;&#xC5D0; &#xC758;&#xD574; &#xBC1C;&#xC0DD; &#xACBD;&#xAC10;&#xC73C;&#xB85C; &#xCF58;&#xD150;&#xCE20; &#xC778;&#xC9C0;&#xC9C8;&#xACFC; &#xC911;&#xC131; &#xC9C0;&#xC9C8; &#xD569;&#xC131;&#xC5D0; &#xD544;&#xC694;&#xD55C;&#xC744; &#xBCF4;&#xC5EC;&#xC900;&#xB2E4;.

&#xC62C;&#xB808;&#xC0B0; &#xC57D;&#xD654; &#xD2B8;&#xB79C;&#xC2A4;-10, cis-12 Conjugated Linoleic Acid-Mediated &#xC5FC;&#xC99D; &#xC131; &#xC720;&#xC804;&#xC790; &#xBC1C;&#xD604; &#xC778;&#xAC04;&#xC758; Adipocytes&#xC5D0;&#xC11C;.

El &aacute;cido de linoleico peso p&eacute;rdida suplemento conjugado (CLA) consiste en una mezcla de trans-10, cis-12 (10,12) y cis-9, trans-11 is&oacute;meros (9,11). Sin embargo, altos niveles de is&oacute;meros CLA mixtos, o el is&oacute;mero 10,12, causa resistencia de insulina, lipodistrofia o inflamaci&oacute;n cr&oacute;nica. Hemos demostrado previamente 10,12 CLA disminuye s&iacute;ntesis de novo de l&iacute;pidos junto con la abundancia y la actividad de estearoil-CoA desaturasa (SCD) -1, un &delta;-9 desaturasa esencial para la s&iacute;ntesis de los &aacute;cidos grasos monoinsaturados (MUFA). As&iacute;, presumimos que el CLA-mediada de 10,12 disminuci&oacute;n en SCD-1, con la subsiguiente disminuci&oacute;n en MUFA, era responsable de los efectos observados. Para probar esta hip&oacute;tesis, 10,12 adipocitos humanos tratados con CLA se complementaron con &aacute;cido oleico por 12 h a 7 d&iacute;as, y expresi&oacute;n de genes inflamatorios, absorci&oacute;n de la glucosa estimulado por insulina y contenido en l&iacute;pidos se midieron. &Aacute;cido oleico redujo la expresi&oacute;n de genes inflamatorios en forma dosis dependiente y restaurar el contenido de l&iacute;pidos de adipocitos 10,12 CLA-tratados sin mejorar la captaci&oacute;n de glucosa estimulado por insulina. En contraste, la suplementaci&oacute;n con &aacute;cido este&aacute;rico, un substrato para SCD-1 o 9,11 CLA no impidi&oacute; expresi&oacute;n g&eacute;nica inflamatoria por CLA 10,12. En particular, 10,12 CLA hab&iacute;a impactado la expresi&oacute;n de varios receptores acoplados a prote&iacute;nas-G que fue atenuada por el &aacute;cido oleico. Colectivamente, estos datos demuestran que el &aacute;cido oleico aten&uacute;a la expresi&oacute;n de genes inflamatoria inducida por CLA 10,12 y contenido, posiblemente por aliviar el estr&eacute;s celular causado por la inhibici&oacute;n de la MUFA de l&iacute;pidos necesitan para los fosfol&iacute;pidos y la s&iacute;ntesis de l&iacute;pidos neutros.

&Aacute;cido oleico aten&uacute;a trans-10, cis-12 Conjugated Linoleic Acid-Mediated inflamatoria expresi&oacute;n g&eacute;nica en adipocitos humanos.

Diacylglycerol kinases (DGK) convert diacylglycerol to phosphatidic acid, which has been reported to stimulate calcium release from the endoplasmic reticulum. Based on our published data showing that trans-10, cis-12 conjugated linoleic acid (t10,c12 CLA)-mediated intracellular calcium accumulation is linked to inflammation and insulin resistance, we hypothesized that inhibiting DGKs with R59022 would prevent t10,c12 CLA-mediated inflammatory signaling and insulin resistance in human adipocytes. Consistent with our hypothesis, R59022 attenuated t10,c12 CLA-mediated i) increased gene expression and protein secretion of interleukin (IL)-8, IL-6, and monocyte chemoattractant protein-1 (MCP-1); ii) increased activation of extracellular signal-related kinase (ERK), cJun-NH2-terminal kinase (JNK), and cJun; iii) increased intracellular calcium levels; iv) suppressed mRNA or protein levels of peroxisome proliferator activated receptor γ, adiponectin, and insulin-dependent glucose transporter 4; and v) decreased fatty acid and glucose uptake and triglyceride content. DGKη was targeted for investigation based on our findings that i) DGKη was highly expressed in primary human adipocytes and time-dependently induced by t10,c12 CLA and that ii) t10,c12 CLA-induced DGKη expression was dose-dependently decreased with R59022. Small interfering RNA (siRNA) targeting DGKη decreased t10,c12 CLA-induced DGKη, IL-8, and MCP-1 gene expression, as well as activation of JNK and cJun. Taken together, these data suggest that DGKs mediate, in part, t10,c12 CLA-induced inflammatory signaling in primary human adipocytes.

Diacylglycerol kinase inhibitor R59022 attenuates conjugated linoleic acid-mediated inflammation in human adipocytes.

The objective of this study was to examine the mechanism by which conjugated linoleic acid (CLA) reduces body fat. Young male mice were fed three combinations of fatty acids at three doses (0.06%, 0.2%, and 0.6%, w/w) incorporated into AIN76 diets for 7 weeks. The types of fatty acids were linoleic acid (control), an equal mixture of trans-10, cis-12 (10,12) CLA plus linoleic acid, and an equal isomer mixture of 10,12 plus cis-9, trans-11 (9,11) CLA. Mice receiving the 0.2% and 0.6% dose of 10,12 CLA plus linoleic acid or the CLA isomer mixture had decreased white adipose tissue (WAT) and brown adipose tissue (BAT) mass and increased incorporation of CLA isomers in epididymal WAT and liver. Notably, in mice receiving 0.2% of both CLA treatments, the mRNA levels of genes associated with browning, including uncoupling protein 1 (UCP1), UCP1 protein levels, and cytochrome c oxidase activity, were increased in epididymal WAT. CLA-induced browning in WAT was accompanied by increases in mRNA levels of markers of inflammation. Muscle cytochrome c oxidase activity and BAT UCP1 protein levels were not affected by CLA treatment. These data suggest a linkage between decreased adiposity, browning in WAT, and low-grade inflammation due to consumption of 10,12 CLA.

Conjugated linoleic acid reduces adiposity and increases markers of browning and inflammation in white adipose tissue of mice.

Recent studies have highlighted the relation between high-fat (HF) diets, the gut microbiota, and inflammation. However, the role of sulfidogenic bacteria in mediating these effects has been explored only recently. Therefore, we tested the hypothesis that an HF diet rich in saturated fat stimulates sulfidogenic bacteria and that these increases correlate with intestinal and systemic inflammatory responses. Forty C57BL/6J male mice were fed a low-fat (LF; 10% of energy) or an HF lard-based (60% of energy) diet for 6 or 20 wk. Mucosa samples were collected from the ileum, cecum, and colon and used for measuring 16S ribosomal RNA and functional genes of sulfidogenic bacteria. Matching intestinal samples and visceral and subcutaneous white adipose tissue (WAT) depots were used to measure mRNA abundance for inflammatory genes. Mice fed the HF diet had greater (P < 0.05) abundance of 3 types of sulfidogenic bacteria, primarily in colonic mucosa, compared with LF-fed mice at week 20. Although HF feeding did not increase intestinal inflammation at week 6, ileal markers of macrophage infiltration and inflammation were upregulated (P < 0.05) 1- to 6-fold at week 20. HF feeding impaired the localization of the tight junction protein zonula occludens 1 at the apical area of the ileal epithelium at weeks 6 and 20. Mice fed the HF diet had 1- to 100-fold greater (P < 0.05) mRNA levels of markers of macrophage infiltration in visceral and subcutaneous WAT at week 20, but not at week 6, compared with LF-fed mice. These results provide evidence that chronic, but not acute, consumption of an HF lard-based diet may be linked with pathways of microbial metabolism that potentially contribute to chronic intestinal and systemic inflammation. Such linkage provides further support for reducing consumption of saturated fats.

Article	Year
Disruption of BCATm in mice leads to increased energy expenditure associated with the activation of a futile protein turnover cycle. Cell metabolism\| PubMed ID: 17767905	2007
Obesity-related elevations in plasma leucine are associated with alterations in enzymes involved in branched-chain amino acid metabolism. American journal of physiology. Endocrinology and metabolism\| PubMed ID: 17925455	2007
Transocular entry of seasonal influenza-attenuated virus aerosols and the efficacy of n95 respirators, surgical masks, and eye protection in humans. The Journal of infectious diseases\| PubMed ID: 21673029	2011
Oleic Acid Attenuates trans-10,cis-12 Conjugated Linoleic Acid-Mediated Inflammatory Gene Expression in Human Adipocytes. Lipids\| PubMed ID: 22941440	2012
Diacylglycerol kinase inhibitor R59022 attenuates conjugated linoleic acid-mediated inflammation in human adipocytes. Journal of lipid research\| PubMed ID: 23264678	2013
Conjugated linoleic acid reduces adiposity and increases markers of browning and inflammation in white adipose tissue of mice. Journal of lipid research\| PubMed ID: 23401602	2013
Intestinal and systemic inflammatory responses are positively associated with sulfidogenic bacteria abundance in high-fat-fed male C57BL/6J mice. The Journal of nutrition\| PubMed ID: 24919690	2014

Tanya Reid

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