Increased Adipose Tissue Fibrogenesis, Not Impaired Expandability, Is Associated With Nonalcoholic Fatty Liver Disease
Joseph W. Beals
Center for Human Nutrition and Atkins Center of Excellence in Obesity Medicine, Washington University School of Medicine, St. Louis, MO
Search for more papers by this authorGordon I. Smith
Center for Human Nutrition and Atkins Center of Excellence in Obesity Medicine, Washington University School of Medicine, St. Louis, MO
Search for more papers by this authorMahalakshmi Shankaran
University of California Berkeley, Berkeley, CA
Search for more papers by this authorAnja Fuchs
Department of Surgery, Washington University School of Medicine, St. Louis, MO
Search for more papers by this authorGeorge G. Schweitzer
Center for Human Nutrition and Atkins Center of Excellence in Obesity Medicine, Washington University School of Medicine, St. Louis, MO
Search for more papers by this authorJun Yoshino
Center for Human Nutrition and Atkins Center of Excellence in Obesity Medicine, Washington University School of Medicine, St. Louis, MO
Search for more papers by this authorDarya Morozov
Department of Radiology, Washington University School of Medicine, St. Louis, MO
Search for more papers by this authorBettina Mittendorfer
Center for Human Nutrition and Atkins Center of Excellence in Obesity Medicine, Washington University School of Medicine, St. Louis, MO
Search for more papers by this authorMarc K. Hellerstein
University of California Berkeley, Berkeley, CA
Search for more papers by this authorCorresponding Author
Samuel Klein
Center for Human Nutrition and Atkins Center of Excellence in Obesity Medicine, Washington University School of Medicine, St. Louis, MO
ADDRESS CORRESPONDENCE AND REPRINT REQUESTS TO:
Samuel Klein, M.D.
Center for Human Nutrition, Washington University School of Medicine
660 South Euclid Avenue
Campus Box 8031
St. Louis, MO 63110
E-mail: [email protected]
Tel.: +1-314-362-8708
Search for more papers by this authorJoseph W. Beals
Center for Human Nutrition and Atkins Center of Excellence in Obesity Medicine, Washington University School of Medicine, St. Louis, MO
Search for more papers by this authorGordon I. Smith
Center for Human Nutrition and Atkins Center of Excellence in Obesity Medicine, Washington University School of Medicine, St. Louis, MO
Search for more papers by this authorMahalakshmi Shankaran
University of California Berkeley, Berkeley, CA
Search for more papers by this authorAnja Fuchs
Department of Surgery, Washington University School of Medicine, St. Louis, MO
Search for more papers by this authorGeorge G. Schweitzer
Center for Human Nutrition and Atkins Center of Excellence in Obesity Medicine, Washington University School of Medicine, St. Louis, MO
Search for more papers by this authorJun Yoshino
Center for Human Nutrition and Atkins Center of Excellence in Obesity Medicine, Washington University School of Medicine, St. Louis, MO
Search for more papers by this authorDarya Morozov
Department of Radiology, Washington University School of Medicine, St. Louis, MO
Search for more papers by this authorBettina Mittendorfer
Center for Human Nutrition and Atkins Center of Excellence in Obesity Medicine, Washington University School of Medicine, St. Louis, MO
Search for more papers by this authorMarc K. Hellerstein
University of California Berkeley, Berkeley, CA
Search for more papers by this authorCorresponding Author
Samuel Klein
Center for Human Nutrition and Atkins Center of Excellence in Obesity Medicine, Washington University School of Medicine, St. Louis, MO
ADDRESS CORRESPONDENCE AND REPRINT REQUESTS TO:
Samuel Klein, M.D.
Center for Human Nutrition, Washington University School of Medicine
660 South Euclid Avenue
Campus Box 8031
St. Louis, MO 63110
E-mail: [email protected]
Tel.: +1-314-362-8708
Search for more papers by this authorAbstract
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.
Supporting Information
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| hep31822-sup-0001-FigS1-S4.pdfPDF document, 650.3 KB | Fig S1-S4 |
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Author names in bold designate shared co-first authorship.
