ADIPOSE-SPECIFIC OVEREXPRESSION OF GLUT-4 IN TRANSGENIC MICE ALTERS LIPOPROTEIN-LIPASE ACTIVITY

Transgenic mice overexpressing GLUT-4 selectively in adipose tissue us ing the aP2 promoter/enhancer develop obesity, enhanced glucose tolera nce, and increased insulin sensitivity. The current study was designed to determine whether altering glucose transport affects lipoprotein l ipase (LPL) activity. Female transgenic mice (10-12 mo old) have incre ased parametrial fat pad weight, adipocyte size, total body lipid and fasting plasma triglycerides, fatty acids, and glycerol compared with non-transgenics. Stimulation of LPL activity by feeding is blunted in parametrial and perirenal fat from 15- to 22-fold in nontransgenic mic e to three- to sevenfold in transgenics. LPL activity in the fed state in transgenic mice is reduced 60-75% in fat. In heart and skeletal mu scle of transgenic mice, LPL activity in the fasted state is 55-65% lo wer than in nontransgenics and feeding induces an unexpected rise in L PL activity. Muscle LPL activity is strongly and inversely correlated with glucose transport in adipocytes (r = -0.942, P < 0.005), which is increased 15- to 27-fold in the basal state and 4.5- to 6.9- fold in the insulin-stimulated state in transgenics. Whereas stimulation of ad ipose LPL may be blunted by lower plasma insulin levels in transgenics , fasting muscle LPL may be suppressed by elevated plasma lipids. Thus altering the partitioning of glucose between adipose tissue and muscl e alters a critical step for the partitioning of lipoprotein fatty aci ds between these tissues.