Division of Pediatric Endocrinology, Department of Pediatrics, Yale University School of Medicine, New Haven, CT.
Department of Nutritional Sciences and Toxicology, University of California at Berkeley, Berkeley, CA.
Diabetes. 2019 Jun;68(6):1168-1177. doi: 10.2337/db18-1162. Epub 2019 Apr 1.
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.
腹部脂肪分布模式（例如，高内脏脂肪组织[VAT]/[VAT+皮下脂肪组织（SAT）]比与肥胖无关）在青少年时期就会带来很高的胰岛素抵抗和 2 型糖尿病风险。最近对肥胖青少年队列的纵向随访发现，高比值（高 VAT/[VAT+SAT]）是随着时间推移发生脂肪肝和代谢损伤的主要决定因素，而这些影响在女孩中比男孩中更为明显。为了揭示与不良 VAT/（VAT+SAT）表型相关的潜在代谢改变，我们使用 HO 标记法测量了体重稳定的肥胖青少年女孩的腹部皮下和臀部/股部脂肪组织（SAT）中脂肪的周转率。这些女孩的肥胖程度相似，但 VAT/（VAT+SAT）比值不同，具有不良（高 VAT/[VAT+SAT]）表型的女孩体内甘油三酯（TG）周转率（代表稳定状态下的脂肪分解和合成）更高，而在腹部和臀部脂肪组织中从头合成脂肪并无显著差异。此外，与具有有利表型的肥胖女孩相比，成熟脂肪细胞的周转率更高，而在这两个部位的基质血管细胞增殖没有差异。更高的 TG 周转率与更高的肝内脂肪储存显著相关。这些发现与这样一种假设相矛盾，即储存 TG 的能力受损或新成熟脂肪细胞的增殖可能是这种情况下异位脂肪分布的潜在机制。总之，这些结果表明，腹部和臀部 SAT 中 TG（脂肪分解）和成熟脂肪细胞的周转率增加可能导致代谢损伤和脂肪肝的发展，即使在疾病的早期阶段也是如此。
