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


METHODS
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.
Koska
Juraj
J
Obesity and Diabetes Clinical Research Section, NIDDK/NIH/DHHS, Phoenix, AZ 85016, USA.
Stefan
Norbert
N
Permana
Paska A
PA
Weyer
Christian
C
Sonoda
Mina
M
Bogardus
Clifton
C
Smith
Steven R
SR
Joanisse
Denis R
DR
Funahashi
Tohru
T
Krakoff
Jonathan
J
Bunt
Joy C
JC
D017667:Adipocytes / Q000378:metabolism / Q000473:pathology*; D052242:Adiponectin / Q000097:blood*; D000328:Adult; D005234:Fatty Liver / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D007198:Indians, North American; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat / Q000378:metabolism* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D015999:Multivariate Analysis; D009765:Obesity / Q000378:metabolism* / Q000473:pathology; D050507:Subcutaneous Fat, Abdominal / Q000378:metabolism* / Q000473:pathology
D052242:Adiponectin