Independent influences of central fat and skeletal muscle lipids on insulin sensitivity.
OBJECTIVE
Insulin resistance is closely associated with two disparate aspects of lipid storage: the intracellular lipid content of skeletal muscle and the magnitude of central adipose beds. Our aim was to determine their relative contribution to impaired insulin action.


METHODS
Eighteen older (56 to 75 years of age) men were studied before elective knee surgery. Insulin sensitivity (M/Delta I) was determined by hyperinsulinemic-euglycemic clamp. Central abdominal fat (CF) was assessed by DXA. Skeletal muscle was excised at surgery and assayed for content of metabolically active long-chain acyl-CoA esters (LCAC).


RESULTS
Significant inverse relationships were observed between LCAC and M/Delta I (R(2) = 0.34, p = 0.01) and between CF and M/Delta I (R(2) = 0.38, p = 0.006), but not between CF and LCAC (R(2) = 0.0005, p = 0.93). In a multiple regression model (R(2) = 0.71, p < 0.0001), both CF (p = 0.0006) and LCAC (p = 0.0009) were independent statistical predictors of M/Delta I. Leptin levels correlated inversely with M/Delta I (R(2) = 0.60, p = 0.0002) and positively with central (R(2) = 0.41, p = 0.006) and total body fat (R(2) = 0.63, p = 0.0001).


CONCLUSIONS
The mechanisms by which altered lipid metabolism in skeletal muscle influences insulin action may not be related directly to those linking central fat and insulin sensitivity. In particular, it is unlikely that muscle accumulation of lipids directly derived from labile central fat depots is a principal contributor to peripheral insulin resistance. Instead, our results imply that circulating factors, other than nonesterified fatty acids or triglyceride, mediate between central fat depots and skeletal muscle tissue. Leptin was not exclusively associated with central fat, but other factors, secreted specifically from central fat cells, could modulate muscle insulin sensitivity.
Furler
S M
SM
Diabetes and Metabolism Research Program, Garvan Institute of Medical Research, St. Vincent's Hospital, Sydney NSW, Australia.
Poynten
A M
AM
Kriketos
A D
AD
Lowy
A J
AJ
Ellis
B A
BA
Maclean
E L
EL
Courtenay
B G
BG
Kraegen
E W
EW
Campbell
L V
LV
Chisholm
D J
DJ
D015502:Absorptiometry, Photon; D000214:Acyl Coenzyme A / Q000378:metabolism*; D000273:Adipose Tissue / Q000033:anatomy & histology / Q000378:metabolism; D000368:Aged; D001823:Body Composition; D004952:Esters; D015309:Glucose Clamp Technique; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D007333:Insulin Resistance; D050356:Lipid Metabolism; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism
D000214:Acyl Coenzyme A; D004952:Esters; D007328:Insulin; D014280:Triglycerides