Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity

TLDR

Visceral adipose tissue is a key risk factor for obesity‑related metabolic disorders, yet its close correlation with intrahepatic triglyceride content suggests that IHTG may be a superior marker of metabolic disease. The study aimed to determine the independent association of IHTG and VAT with metabolic function in obese subjects. Using stable‑isotope tracer techniques, euglycemic–hyperinsulinemic clamps, VLDL‑TG secretion assays, and tissue biopsies, the authors assessed insulin sensitivity and ectopic triglyceride accumulation in groups matched for VAT or IHTG. Subjects with elevated IHTG exhibited markedly reduced hepatic, adipose, and muscle insulin sensitivity and nearly doubled VLDL‑TG secretion, whereas VAT differences had no effect, indicating that IHTG—not VAT—is a superior marker of obesity‑related metabolic derangements.

Abstract

Visceral adipose tissue (VAT) is an important risk factor for obesity-related metabolic disorders. Therefore, a reduction in VAT has become a key goal in obesity management. However, VAT is correlated with intrahepatic triglyceride (IHTG) content, so it is possible that IHTG, not VAT, is a better marker of metabolic disease. We determined the independent association of IHTG and VAT to metabolic function, by evaluating groups of obese subjects, who differed in IHTG content (high or normal) but matched on VAT volume or differed in VAT volume (high or low) but matched on IHTG content. Stable isotope tracer techniques and the euglycemic–hyperinsulinemic clamp procedure were used to assess insulin sensitivity and very-low-density lipoprotein–triglyceride (VLDL-TG) secretion rate. Tissue biopsies were obtained to evaluate cellular factors involved in ectopic triglyceride accumulation. Hepatic, adipose tissue and muscle insulin sensitivity were 41, 13, and 36% lower ( P < 0.01), whereas VLDL-triglyceride secretion rate was almost double ( P < 0.001), in subjects with higher than normal IHTG content, matched on VAT. No differences in insulin sensitivity or VLDL-TG secretion were observed between subjects with different VAT volumes, matched on IHTG content. Adipose tissue CD36 expression was lower ( P < 0.05), whereas skeletal muscle CD36 expression was higher ( P < 0.05), in subjects with higher than normal IHTG. These data demonstrate that IHTG, not VAT, is a better marker of the metabolic derangements associated with obesity. Furthermore, alterations in tissue fatty acid transport could be involved in the pathogenesis of ectopic triglyceride accumulation by redirecting plasma fatty acid uptake from adipose tissue toward other tissues.