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.
Document Type
Article
Publication Date
6-2019
Keywords
JGM
JAX Source
Diabetes 2019 Jun; 68(6):1168-1177.
Volume
68
Issue
6
First Page
1168
Last Page
1177
ISSN
1939-327X
PMID
30936147
DOI
https://doi.org/10.2337/db18-1162
Abstract
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 2H2O 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.
Recommended Citation
Nouws J,
Fitch M,
Mata M,
Santoro N,
Galuppo B,
Kursawe R,
Narayan D,
Vash-Margita A,
Pierpont B,
Shulman G,
Hellerstein M,
Caprio S.
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 2019 Jun; 68(6):1168-1177.