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.

Jessica Nouws
Mark Fitch
Mariana Mata
Nicola Santoro
Brittany Galuppo
Romy Kursawe, The Jackson Laboratory
Deepak Narayan
Alla Vash-Margita
Bridget Pierpont
Gerald I Shulman
Marc Hellerstein
Sonia Caprio


Patterns of abdominal fat distribution, [for example: a high vs low VAT/(VAT+SAT) ratio] independent of obesity, during adolescence carry a high risk for insulin resistance (IR) 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 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 turnover (representing both lipolysis and synthesis at steade state), without significant differences in de novo lipogenesis (DNL) in both abdominal and gluteal depots, compared to 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 triglyceride turnover rates were significantly correlated with higher intrahepatic fat stores. These findings are contrary to the hypothesis that impaired capacity to deposit triglycerides 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 triglycerides (lipolysis) and of mature adipocytes in both abdominal and gluteal subcutaneous adipose tissues may contribute to metabolic impairment and the development of fatty liver, even at this very early stage of disease.