Effect of leptin replacement on intrahepatic and intramyocellular lipid content in patients with generalized lipodystrophy.
OBJECTIVE
To investigate whether leptin-induced improvements in glycemic control, hyperlipidemia, and insulin sensitivity in hypoleptinemic patients with generalized lipodystrophies are accompanied by reduction in intrahepatic and intramyocellular lipid (IMCL) accumulation.


METHODS
We examined the effects 8-10 months of subcutaneous leptin replacement therapy on insulin sensitivity, IMCL, and intrahepatic lipid content in two patients with acquired generalized lipodystrophy and one patient with congenital generalized lipodystrophy. All patients had extreme lack of body fat, low plasma leptin levels, and elevated serum triglycerides, but only two had diabetes. Insulin sensitivity was measured by a high-dose (0.2 IU/kg) insulin tolerance test, as well as by hyperinsulinemic-euglycemic glucose clamp studies in two patients. IMCL and intrahepatic lipid content were measured by (1)H magnetic resonance spectroscopy. All measurements were obtained before and during 2-10 months of leptin therapy.


RESULTS
Glycemic control and lipoprotein levels markedly improved with leptin therapy in the two diabetic patients, and a slight improvement in lipoprotein levels was seen in the nondiabetic patients. Insulin stimulated glucose uptake during 60-120 min of the euglycemic clamp studies, and the rate of glucose disappearance during the insulin tolerance test nearly doubled with leptin therapy. As compared with the baseline period, after 8-10 months of leptin therapy, the mean intrahepatic lipid content was reduced by approximately 80% and the IMCL content was reduced by approximately 42%.


CONCLUSIONS
Reduction in IMCL and intrahepatic lipid content may partly explain leptin-induced improvement in insulin sensitivity in patients with generalized lipodystrophy.
Simha
Vinaya
V
Division of Nutrition and Metabolic Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9052, USA.
Szczepaniak
Lidia S
LS
Wagner
Anthony J
AJ
DePaoli
Alex M
AM
Garg
Abhimanyu
A
D000293:Adolescent; D000328:Adult; D001786:Blood Glucose; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D020738:Leptin / Q000008:administration & dosage* / Q000097:blood; D050356:Lipid Metabolism; D008060:Lipodystrophy / Q000188:drug therapy* / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D016896:Treatment Outcome
D001786:Blood Glucose; D020738:Leptin