Fatty Liver Links Insulin Resistance and Abdominal Fat

Byron's Comments:

Developing a fatty liver clogs the main organ of metabolism. This increases insulin resistance by depressing adiponectin, with consequent abdominal weight gain. Excessive leptin levels drive this entire process, as leptin too high is the main cause of adiponectin going too low.

Study Title:

Increased fat accumulation in liver may link insulin resistance with subcutaneous abdominal adipocyte enlargement, visceral adiposity, and hypoadiponectinemia in obese individuals

Study Abstract:

Background: Enlargement of adipocytes from subcutaneous abdominal adipose tissue (SAT), increased intrahepatic lipid content (IHL), intramyocellular lipid content (IMCL), and low circulating adiponectin concentrations are associated with insulin resistance.

Objective: Because adiponectin increases fat oxidation in skeletal muscle and liver, and the expression of the adiponectin gene in SAT is inversely associated with adipocyte size, we hypothesized that hypoadiponectinemia links hypertrophic obesity with insulin resistance via increased IMCL and IHL.

Design: Fifty-three obese Pima Indians with a mean (±SD) age of 27 ± 8 y, body fat of 35 ± 5%, and normal glucose regulation (normal fasting and 2-h glucose concentration per WHO 1999 criteria) underwent euglycemic-hyperinsulinemic clamp, biopsies of SAT and vastus lateralis muscle, and magnetic resonance imaging of the abdomen.

Results: Adipocyte diameter (AD) correlated positively with body fat (P

< 0.0001) and IHL (estimated from magnetic resonance imaging intensity of liver; P = 0.047). No association was found between AD and plasma adiponectin or IMCL. Plasma adiponectin negatively correlated with type II IMCL (IIA, P = 0.004; IIX, P = 0.009) or IHL (P = 0.02). In a multivariate analysis, plasma adiponectin, AD, and visceral adipose tissue (VAT) independently predicted IHL. Low insulin-mediated glucose disposal was associated with low plasma adiponectin (P = 0.02) and high IHL (P = 0.0003), SAT (P = 0.02), and VAT (P = 0.04). High IHL was the only predictor of reduced insulin-mediated suppression of hepatic glucose production (P = 0.02) and the only independent predictor of insulin-mediated glucose disposal in a multivariate analysis.

Conclusions: Increased lipid content in the liver may independently link hypoadiponectinemia, hypertrophic obesity, and increased visceral adiposity with peripheral and hepatic insulin resistance.

Study Information:

Juraj Koska, Norbert Stefan, Paska A Permana, Christian Weyer, Mina Sonoda, Clifton Bogardus, Steven R Smith, Denis R Joanisse, Tohru Funahashi, Jonathan Krakoff and Joy C Bunt Increased fat accumulation in liver may link insulin resistance with subcutaneous abdominal adipocyte enlargement, visceral adiposity, and hypoadiponectinemia in obese individuals American Journal of Clinical Nutrition 2008 February Vol. 87, No. 2, 295-302

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