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Increased adipose tissue fibrogenesis, not impaired expandability, is associated with nonalcoholic fatty liver disease |
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Hepatology. 2021 Mar 20. doi: 10.1002/hep.31822. Online ahead of print.
Joseph W Beals 1, Gordon I Smith 1, Mahalakshmi Shankaran 2, Anja Fuchs 3, George G Schweitzer 1, Jun Yoshino 1, Tyler Field 2, Marcy Matthews 2, Edna Nyangau 2, Darya Morozov 4, Bettina Mittendorfer 1, Marc K Hellerstein 2, Samuel Klein 1
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Author information
- 1Center for Human Nutrition and Atkins Center of Excellence in Obesity Medicine, Washington University School of Medicine, St Louis, MO, USA.
- 2University of California Berkeley, Berkeley, CA, USA.
- 3Department of Surgery, Washington University School of Medicine, St Louis, MO, USA.
- 4Department of Radiology, Washington University School of Medicine, St Louis, MO, USA.
Abstract
Background and aims: It is proposed that impaired expansion of subcutaneous adipose tissue (SAT) and an increase in adipose tissue fibrosis causes ectopic lipid accumulation, insulin resistance and metabolically unhealthy obesity. We therefore evaluated whether a decrease in SAT expandability, assessed by measuring SAT lipogenesis (triglyceride production), and an increase in SAT fibrogenesis (collagen production) are associated with NAFLD and insulin resistance in people with obesity.
Approach and results: In vivo abdominal SAT lipogenesis and fibrogenesis, the expression of SAT genes involved in extracellular matrix (ECM) formation, and insulin sensitivity were assessed in three groups of participants stratified by adiposity and intrahepatic triglyceride (IHTG) content: 1) healthy lean with normal IHTG content (Lean-NL; n=12); 2) obese with normal IHTG content and normal glucose tolerance (Ob-NL; n=25); and 3) obese with NAFLD and abnormal glucose metabolism (Ob-NAFLD; n=25). Abdominal SAT triglyceride synthesis rates were greater (P <0.05) in both the Ob-NL (65.9±4.6 g/wk) and Ob-NAFLD (71.1±6.7 g/wk) than the Lean-NL group (16.2±2.8 g/wk) without a difference between the Ob-NL and Ob-NAFLD groups. Abdominal SAT collagen synthesis rate and the composite expression of genes encoding collagens progressively increased from the Lean-NL to the Ob-NL to the Ob-NAFLD groups and were greater in the Ob-NAFLD than the Ob-NL group (P <0.05). The composite expression of collagen genes was inversely correlated with both hepatic and whole-body insulin sensitivity (P <0.001).
Conclusions: Adipose tissue expandability is not impaired in people with obesity and NAFLD. However, SAT fibrogenesis is greater in people with obesity and NAFLD than in those with obesity and normal IHTG content, and is inversely correlated with both hepatic and whole-body insulin sensitivity.
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