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

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.

Exercise reduced the formation of new adipocytes in the adipose tissue of mice in vivo

“…At a steady state in AT mass, adipocyte turnover represents adipocyte formation and death. Our findings are consistent with recent studies reporting that lower adipocyte formation, or turnover, in humans is observed in conditions of more favorable metabolic health [ 33 , 34 ]- results that are contrary to the AT expandability hypothesis [ 5 , 6 ]. It could be speculated that increased adipogenesis and turnover reflect adipocyte fragility and death, which can lead to recruitment of macrophages, unfavorable remodeling and inflammation [ 35 ].…”

Increased Adipose Tissue Fibrogenesis, Not Impaired Expandability, Is Associated With Nonalcoholic Fatty Liver Disease

“…Statistical analyses were performed by using SPSS (version 25; IBM, Armonk, NY). Based on a previous report that evaluated SAT TG FSR in insulin‐resistant and ‐sensitive persons with obesity, ( 12 ) we estimated that 25 participants in each obese group would be needed to detect a 0.25 %/wk difference in the TG FSR with a two‐sided α value of 0.05 and a power of 0.8.…”

“…Previous studies that evaluated SAT TG synthesis rates did not evaluate intrahepatic TG (IHTG) content or did not stratify study cohorts into those with and without NAFLD. (12)(13)(14) Moreover, directly evaluating SAT collagen production rates in humans remains open for study. The purpose of the present study was to test the hypothesis that SAT TG synthesis (lipogenesis) is lower, whereas the rate of AT collagen synthesis (fibrogenesis) and regulators of fibrogenesis are higher in persons with obesity and NAFLD than in persons with obesity and normal IHTG content.…”

Adipose Tissue Development and Expansion from the Womb to Adolescence: An Overview

“…According to Sethi et al, the degree of toxicity will depend on the extent and duration of positive energy supply, effectiveness of lipid transport and storage mechanisms, and organ oxidative capacity [ 25 ]. In contrast to this “limited adiposity expandability” hypothesis, a recent study demonstrated that greater turnover of triglycerides and mature adipocytes in abdominal and gluteal SAT of adolescents girls with obesity may determine the accumulation of fat in the liver and metabolic dysfunction in this population [ 26 ]. Another hypothesis is that a persistent positive energy balance affects the secretion of adipokines (e.g., leptin, adiponectin, tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6)), with implications for glucose homeostasis and lipid metabolism and flux [ 25 ].…”