measuring-vivo-adipose-tissue-kinetics-humans-using-deuterium-2h

Measuring <em>In Vivo</em> Adipose Tissue Kinetics in Humans Using the Deuterium (<sup>2</sup>H)-Labeling Approach

White adipose tissue is a highly plastic organ that is necessary to maintain whole-body energy homeostasis. The adipose tissue mass and changes in the fat ...

University of California at Berkeley

Adipose tissue (AT) expansion occurs by hypertrophy and hyperplasia. Impaired hyperplasia, or adipogenesis, has been associated with obesity-related diseases.

Association of In Vivo Adipose Tissue Cellular Kinetics With Markers of Metabolic Health in Humans.

The storage of lipids in the form of triglycerides (TGs) and the de novo synthesis (lipogenesis) of fatty acids from nonlipid precursors [de novo lipogenesis (DNL)] are important functions of adipose tissue (AT) that influence whole-body metabolism. Yet, few studies have reported in vivo estimates of adipose lipid kinetics in humans. Fifty-two women with obesity (27 African-American and 25 Caucasian; 29.7 ± 5.5 years; BMI 32.2 ± 2.8 kg/m; 44.3 ± 4.0% body fat) were enrolled in the study. In vivo synthesis (or replacement) of TGs (f) as well as the synthesis of the fatty acid, palmitate [a measure of adipose DNL (f)], were assessed using an 8 week incorporation of deuterium into lipids (glycerol and palmitate moieties of TGs) in subcutaneous abdominal (scABD) and subcutaneous femoral (scFEM) AT. We report, for the first time, significant race differences in both TG synthesis and absolute DNL, with Caucasians having higher f and f as compared with African-Americans. The DNL contribution to newly synthesized TG (corrected f) was not different between races. Interestingly, our findings also show that the scFEM adipose depot had higher TG replacement rates relative to the scABD. Finally, the replacement rate of TG (f) was negatively correlated with changes in body weight over the 8 week labeling period. Our results provide the first evidence that in vivo TG replacement (synthesis and breakdown) rates differ by ethnicity. In addition, TG turnover varies by depot location in humans, implying an increased capacity for TG storage and higher lipolytic activity in the scFEM AT.

Racial differences in in vivo adipose lipid kinetics in humans.

Cell proliferation plays a central role in the pathogenesis of every neoplastic disease as well as many other types of illness. Labeling of newly replicated DNA with deuterium (H), a nonradioactive isotope of hydrogen, administered to the patients in drinking water (HO) is a safe and reliable method to measure the in vivo birth rates of cells. Here, we describe a protocol to measure chronic lymphocytic leukemia B-cell birth/proliferation and death rates over time using this approach.

Measurement of Leukemic B-Cell Growth Kinetics in Patients with Chronic Lymphocytic Leukemia.

Patterns of abdominal fat distribution (for example, a high vs. low visceral adipose tissue [VAT]/[VAT + subcutaneous adipose tissue (SAT)] ratio), independent of obesity, during adolescence carry a high risk for insulin resistance and type 2 diabetes. Longitudinal follow-up of a cohort of obese adolescents has recently revealed that a high ratio (high VAT/[VAT + SAT]) is a major determinant of fatty liver and metabolic impairment over time, with these effects being more pronounced in girls than in boys. To unravel the underlying metabolic alterations associated with the unfavorable VAT/(VAT + SAT) phenotype, we used the HO labeling method to measure the turnover of adipose lipids and cells in the subcutaneous abdominal and gluteal/femoral adipose tissue (SAT) of weight-stable obese adolescent girls with a similar level of obesity but discordant VAT/(VAT + SAT) ratios. Girls with the unfavorable (high VAT/[VAT + SAT]) phenotype exhibited higher in vivo rates of triglyceride (TG) turnover (representing both lipolysis and synthesis at steady state), without significant differences in de novo lipogenesis in both abdominal and gluteal depots, compared with obese girls with the favorable phenotype. Moreover, mature adipocytes had higher turnover, with no difference in stromal vascular cell proliferation in both depots in the metabolically unfavorable phenotype. The higher TG turnover rates were significantly correlated with higher intrahepatic fat stores. These findings are contrary to the hypothesis that impaired capacity to deposit TGs or proliferation of new mature adipocytes are potential mechanisms for ectopic fat distribution in this setting. In summary, these results suggest that increased turnover of TGs (lipolysis) and of mature adipocytes in both abdominal and gluteal SAT may contribute to metabolic impairment and the development of fatty liver, even at this very early stage of disease.

Altered In Vivo Lipid Fluxes and Cell Dynamics in Subcutaneous Adipose Tissues Are Associated With the Unfavorable Pattern of Fat Distribution in Obese Adolescent Girls.

In vitro and rodent studies suggest that pioglitazone, a thiazolidinedione, can promote adipogenesis in adipose tissue (AT); however, there is a lack of in vivo studies in humans to support these findings. The objectives of this randomised, placebo-controlled, parallel-arm trial were to test if pioglitazone stimulates in vivo adipogenesis in the subcutaneous adipose tissue depots and if these measures were related to metabolic health outcomes in women with obesity.

Adipose depot-specific effects of 16 weeks of pioglitazone on in vivo adipogenesis in women with obesity: a randomised controlled trial.

Exercise has beneficial effects on metabolism and health. Although the skeletal muscle has been a primary focus, exercise also mediates robust adaptations in white adipose tissue. To determine if exercise affects in vivo adipocyte formation, fifty-two, sixteen-week-old C57BL/6J mice were allowed access to unlocked running wheels [Exercise (EX) group; n = 13 males, n = 13 females] or to locked wheels [Sedentary (SED) group; n = 13 males, n = 13 females] for 4-weeks. In vivo adipocyte formation was assessed by the incorporation of deuterium (2H) into the DNA of newly formed adipocytes in the inguinal and gonadal adipose depots. A two-way ANOVA revealed that exercise significantly decreased new adipocyte formation in the adipose tissue of mice in the EX group relative to the SED group (activity effect; P = 0.02). This reduction was observed in male and female mice (activity effect; P = 0.03). Independent analysis of the depots showed a significant reduction in adipocyte formation in the inguinal (P = 0.05) but not in the gonadal (P = 0.18) of the EX group. We report for the first time that exercise significantly reduced in vivo adipocyte formation in the adipose tissue of EX mice using a physiologic metabolic 2H2O-labeling protocol.

Article	Year
Association of In Vivo Adipose Tissue Cellular Kinetics With Markers of Metabolic Health in Humans. The Journal of clinical endocrinology and metabolism\| PubMed ID: 28323935	2017
Racial differences in in vivo adipose lipid kinetics in humans. Journal of lipid research\| PubMed ID: 29910190	2018
Measurement of Leukemic B-Cell Growth Kinetics in Patients with Chronic Lymphocytic Leukemia. Methods in molecular biology (Clifton, N.J.)\| PubMed ID: 30350203	2019
Altered In Vivo Lipid Fluxes and Cell Dynamics in Subcutaneous Adipose Tissues Are Associated With the Unfavorable Pattern of Fat Distribution in Obese Adolescent Girls. Diabetes\| PubMed ID: 30936147	2019
Adipose depot-specific effects of 16 weeks of pioglitazone on in vivo adipogenesis in women with obesity: a randomised controlled trial. Diabetologia\| PubMed ID: 33001232	2021
Exercise reduced the formation of new adipocytes in the adipose tissue of mice in vivo. PloS one\| PubMed ID: 33471817	2021

Mark Fitch

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