R. Fabris et al., Preferential channeling of energy fuels toward fat rather than muscle during high free fatty acid availability in rats, DIABETES, 50(3), 2001, pp. 601-608
The preferential channeling of different fuels to fat and changes in the tr
anscription profile of adipose tissue and skeletal muscle are poorly unders
tood processes involved in the pathogenesis of obesity and insulin resistan
ce. Carbohydrate and lipid metabolism may play relevant roles in this conte
xt. Freely moving lean Zucker rats received 3- and 24-h infusions of Intral
ipid (Pharmacia and Upjohn, Milan, Italy) plus heparin, or saline plus hepa
rin, to evaluate how an increase in free fatty acids (nonesterified fatty a
cid [NEFA]) modulates fat tissue and skeletal muscle gene expression and th
us influences fuel partitioning. Glucose uptake was determined in various t
issues at the end of the infusion period by means of the 2-deoxy-[1-H-3]-D-
glucose technique after a euglycemic-hyperinsulinemic clamp: high NEFA leve
ls markedly decreased insulin-mediated glucose uptake in red fiber-type mus
cles but enhanced glucose utilization in visceral fat. Using reverse transc
riptase-polymerase chain reaction and Northern blotting analyses, the mRNA
expression of fatty acid translocase (FAT)/CD36, GLUT4, tumor necrosis fact
or (TNF)-alpha, peroxisome proliferator-activated receptor ((PPAR)-gamma, l
eptin, uncoupling protein (UCP)-2, and UCP-3 was investigated in different
fat depots and skeletal muscles before and after the study infusions. GLUT4
mRNA levels significantly decreased (by similar to 25%) in red fiber-type
muscle (soleus) and increased (by similar to 45%)in visceral adipose tissue
. Furthermore, there were marked increases in FAT/CD36, TNF-alpha, PPAR-gam
ma, leptin, UCP2, and UCP3 mRNA levels in the visceral fat and muscle of th
e treated animals in comparison with those measured in the saline-treated a
nimals. These data suggest that the in vivo gene expression of FAT/CD36, GL
UT4, TNF-alpha, PPAR-gamma, leptin, UCP2, and UCP3 in visceral fat and red
fiber-type muscle are differently regulated by circulating lipids and that
selective insulin resistance seems to favor, at least in part, a prevention
of fat accumulation in tissues not primarily destined for fat storage, thu
s contributing to increased adiposity and the development of a prediabetic
syndrome.