Insulin resistance and obesity in adolescents may lead to increased abdominal fibrogenesis, impairing the capacity of the abdominal subcutaneous adipose tissue (SAT) to store lipids, which may cause fat accumulation in the visceral adipose tissue (VAT) depot and in other organs such as the liver.


  • Abdominal fibrogenesis, but not adipose tissue expandability, is known to increase in adults with obesity and reduce insulin sensitivity; however, little is known about fibrogenesis in adolescents with obesity.
  • In this study, researchers investigated if lipid dynamics, fibrogenesis, and abdominal and gluteal adipocyte turnover show dysregulation to a greater extent in insulin-resistant adolescents with obesity than in insulin-sensitive adolescents with obesity.
  • They recruited 14 individuals between 12 and 20 years with a body mass index over 30 from the Yale Pediatric Obesity Clinic, of whom seven participants were classified as insulin resistant.
  • Deuterated water methodologies were used to study the indices of adipocyte turnover, lipid dynamics, and fibrogenesis in abdominal and gluteal fat deposits.
  • A 3-hour oral glucose tolerance test and multisection MRI scan of the abdominal region were used to assess the indices of glucose metabolism, abdominal fat distribution patterns, and liver fat content.


  • The abdominal and gluteal SAT turnover rate of lipid components (triglyceride production and breakdown as well as de novo lipogenesis contribution) was similar in insulin-resistant and insulin-sensitive adolescents with obesity.
  • The insoluble collagen (type I, subunit α 2) level was higher in the abdominal adipose tissue of insulin-resistant adolescents than in insulin-sensitive adolescents (difference in fractional synthesis rate, 0.611; P < .001), indicating increased abdominal fibrogenesis.
  • Abdominal insoluble collagen I α 2 was associated with higher fasting plasma insulin levels (correlation [r], 0.579; P = .015), a higher visceral to total adipose tissue ratio (r, 0.643; P = .007), and a lower whole-body insulin sensitivity index (r, −0.540; P = .023).
  • There was no evidence of increased collagen production in the gluteal adipose tissue, and as a result, fibrogenesis was observed.


“The increased formation of insoluble collagen observed in insulin-resistant compared with insulin-sensitive individuals contributes to lipid spillover from SAT to VAT and, in turn, serves as a critically important mechanism involved in the complex sequelae of obesity-related metabolic and liver disease pathology,” the authors wrote.


This study, led by Aaron L. Slusher, Department of Pediatrics, Yale School of Medicine, New Haven, Connecticut, was published online in Obesity.


The researchers did not measure hepatic collagen synthesis rates. The analysis was performed on a small study population. The authors were also unable to assess potential sex differences.


The study was funded by the Foundation for the National Institutes of Health and Clara Guthrie Patterson Trust Mentored Research Award. The authors declared no conflicts of interest.

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