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Increased Adipose Tissue Fibrogenesis, Not Impaired Expandability, Is Associated With Nonalcoholic Fatty Liver Disease
Author(s) -
Beals Joseph W.,
Smith Gordon I.,
Shankaran Mahalakshmi,
Fuchs Anja,
Schweitzer George G.,
Yoshino Jun,
Field Tyler,
Matthews Marcy,
Nyangau Edna,
Morozov Darya,
Mittendorfer Bettina,
Hellerstein Marc K.,
Klein Samuel
Publication year - 2021
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.31822
Subject(s) - lipogenesis , medicine , endocrinology , nonalcoholic fatty liver disease , adipose tissue , insulin resistance , triglyceride , steatosis , fibrosis , fatty liver , lipid metabolism , obesity , chemistry , disease , cholesterol
Background and Aims It is proposed that impaired expansion of subcutaneous adipose tissue (SAT) and an increase in adipose tissue (AT) fibrosis causes ectopic lipid accumulation, insulin resistance (IR), and metabolically unhealthy obesity. We therefore evaluated whether a decrease in SAT expandability, assessed by measuring SAT lipogenesis (triglyceride [TG] production), and an increase in SAT fibrogenesis (collagen production) are associated with NAFLD and IR in persons with obesity. Approach and Results In vivo abdominal SAT lipogenesis and fibrogenesis, 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 TG (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 TG synthesis rates were greater ( P < 0.05) in both the Ob‐NL (65.9 ± 4.6 g/wk) and Ob‐NAFLD groups (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). Composite expression of collagen genes was inversely correlated with both hepatic and whole‐body insulin sensitivity ( P < 0.001). Conclusions AT expandability is not impaired in persons with obesity and NAFLD. However, SAT fibrogenesis is greater in persons 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.