AJP - Regulatory, Integrative and Comparative Physiology, Vol 264, Issue 6 1224-R1228, Copyright © 1993 by American Physiological Society
Skeletal muscle glucose metabolism in obesity-prone and obesity-resistant rats
M. J. Pagliassotti, K. A. Shahrokhi and J. O. Hill
Department of Molecular Physiology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
Ad libitum access to a high-fat (HF) diet produces a wide range of weight
gain in rats. Rats most susceptible to weight gain on such a diet (obesity
prone; OP) are more insulin resistant after 4-5 wk of diet exposure than
are those most resistant (obesity resistant; OR) to weight gain. To
investigate whether skeletal muscle glucose metabolism contributes to
insulin resistance in this model, insulin-stimulated glucose metabolism was
assessed in the perfused hindquarter of rats exposed to either a low-fat
(LF, n = 6) or HF diet for 5 wk. Delineation of OP (n = 6) and OR (n = 6)
rats was based on body weight gain. OP rats gained 60% more body weight
while eating only 10% more energy than OR rats. Single-pass perfusions were
carried out for 2 h in the presence of glucose, insulin, and
[U-14C]glucose. Insulin-stimulated glucose uptake (mumol.100 g-1.min-1) was
14.2 +/- 0.9 in LF, 11.1 +/- 0.8 in OR, and 6.2 +/- 0.6 in OP. Glucose
oxidation (mumol.100 g-1.min-1) was 1.7 +/- 0.3 and 1.2 +/- 0.3 in LF and
OR, respectively, but was 0.2 +/- 0.1 in OP. Net glycogen synthesis was
significantly reduced in OP compared with OR and LF despite similar
glycogen synthase I activity. Muscle triglyceride concentration was not
significantly different in OR and OP rats. These results demonstrate
significant defects in skeletal muscle glucose uptake and disposal in rats
most susceptible to HF diet-induced obesity. Clearly, the heterogeneous
response to a HF diet involves not only body weight gain but also skeletal
muscle fuel metabolism.
