Chronic leptin treatment normalizes basal glucose transport in a fiber type-specific manner in high-fat-fed rats.

The aim of this investigation was to determine if a high-fat diet impaired and subsequent leptin administration improved non-insulin-stimulated (basal) glucose transport in rodents. Twenty-four male Sprague Dawley rats were divided into 1 of 2 groups: (1) normal diet (control [CON], n = 8) or (2) high-fat diet (n = 16) and received standard rat chow or a high-fat diet, respectively, for 12 weeks. The high-fat diet animals were then further subdivided into high fat (HF) (n = 8) or high-fat-leptin (HF-LEP) (n = 8) groups. The HF-LEP animals were injected with leptin (10 mg leptin/kg/d), while the CON and HF animals received vehicle over a 12-day treatment period. Following the 12-day treatment period, all animals were subjected to hind limb perfusion to assess rates of basal skeletal muscle 3-O-methyl-D-glucose (3-MG) transport. Compared with the CON group, rates of 3-MG transport were reduced in the soleus (sol) and plantaris (plant) of the HF, but not the HF-LEP animals. Differences in skeletal muscle 3-MG transport could not be accounted for by an altered GLUT1 protein concentration. In contrast, a high-fat diet reduced and chronic leptin treatment normalized the skeletal muscle GLUT4 protein concentration. The results indicate that a high-fat diet reduces and subsequent leptin treatment improves basal skeletal muscle glucose transport in a fiber-type-specific manner, but these changes do not appear to be due to alterations in the GLUT1 protein concentration. Copyright 2002, Elsevier Science (USA). All rights reserved.