Adipose specific overexpression of glut4 in transgenic mice alters
lipoprotein lipase activity.
Gnudi, Luigi, Dalan R. Jensen, Effie Tozzo, Robert H. Eckel, and
Barbara B. Kahn.
Harvard Thorndike Research Laboratory and the Department of
Medicine at Harvard Medical School and Beth Israel Hospital, Boston,
MA, 02215, and Division of Endocrinology, Department of Medicine,
University of Colorado Health Sciences Center, Denver, CO, 80262
APStracts 2:0306R, 1995.
Transgenic mice overexpressing GLUT4 selectively in adipose tissue
using the aP2 promoter/enhancer develop obesity, enhanced glucose
tolerance and increased insulin sensitivity. The current study was
designed to determine whether altering glucose transport affects
lipoprotein lipase (LPL) activity. Female transgenic mice have
increased parametrial fat pad weight, adipocyte size, total body
lipid and fasting plasma triglycerides, fatty acids and glycerol
compared to nontransgenics. Stimulation of LPL activity by feeding is
blunted in parametrial and perirenal fat from 15-22-fold in
nontransgenic mice to 3-7-fold in transgenics. LPL activity in the
fed state in transgenic mice is reduced 60-75% in fat. In heart and
skeletal muscle of transgenic mice, LPL activity in the fasted state
is 55-65% lower than in nontransgenics and feeding induces an
unexpected rise in LPL activity. Muscle LPL activity is strongly and
inversely correlated with glucose transport in adipocytes (r=-0.942,
p<0.005) which is increased 15-27-fold in the basal state and
4.5-6.9 fold in the insulin stimulated state in transgenics. Whereas
stimulation of adipose 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 muscle alters a critical step for the
partitioning of lipoprotein fatty acids between these tissues.
Received 4 May 1995; accepted in final form 1 November 1995.
APS Manuscript Number R270-5.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 30 November 95