Relationship of adiponectin with insulin sensitivity in humans, independent of lipid availability.
OBJECTIVE
To test in humans the hypothesis that part of the association of adiponectin with insulin sensitivity is independent of lipid availability.


METHODS
We studied relationships among plasma adiponectin, insulin sensitivity (by hyperinsulinemic-euglycemic clamp), total adiposity (by DXA), visceral adiposity (VAT; by magnetic resonance imaging), and indices of lipid available to muscle, including circulating and intramyocellular lipid (IMCL; by 1H-magnetic resonance spectroscopy). Our cohort included normal weight to obese men (n = 36).


RESULTS
Plasma adiponectin was directly associated with insulin sensitivity and high-density lipoprotein-cholesterol and inversely with plasma triglycerides but not IMCL. These findings are consistent with adiponectin promoting lipid uptake and subsequent oxidation in muscle and inhibiting TG synthesis in the liver. In multiple regression models that also included visceral and total fat, free fatty acids, TGs, and IMCL, either alone or in combination, adiponectin independently predicted insulin sensitivity, consistent with some of its insulin-sensitizing effects being mediated through mechanisms other than modulation of lipid metabolism. Because VAT directly correlated with total fat and all three indices of local lipid availability, free fatty acids, and IMCL, an efficient regression model of insulin sensitivity (R2 = 0.69, p < 0.0001) contained only VAT (part R2 = 0.12, p < 0.002) and adiponectin (part R2 = 0.41, p < 0.0001) as independent variables.


CONCLUSIONS
Given the broad range of total adiposity and body fat distribution in our cohort, we suggest that insulin sensitivity is robustly associated with adiponectin and VAT.
Diabetes and Obesity Research Program, Garvan Institute of Medical Research, St. Vincent's Hospital, Sydney, Australia. s.furler@garvan.org.au
Stuart M
SM
Furler
Seng Khee
SK
Gan
Ann M
AM
Poynten
Donald J
DJ
Chisholm
Lesley V
LV
Campbell
Adamandia D
AD
Kriketos
D052242:Adiponectin / Q000097:blood*; D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D001823:Body Composition / Q000502:physiology*; D008076:Cholesterol, HDL / Q000097:blood; D015331:Cohort Studies; D015309:Glucose Clamp Technique; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis; D050152:Intra-Abdominal Fat / Q000378:metabolism; D050356:Lipid Metabolism / Q000502:physiology*; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D018482:Muscle, Skeletal / Q000737:chemistry / Q000378:metabolism; D009765:Obesity / Q000378:metabolism*; D014280:Triglycerides / Q000097:blood
D052242:Adiponectin; D008076:Cholesterol, HDL; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D014280:Triglycerides