Effect of leptin infusion on insulin sensitivity and lipid metabolism in diet-induced lipodystrophy model mice.
BACKGROUND
Lipodystrophies are rare acquired and genetic disorders characterized by the complete or partial absence of body fat with a line of metabolic disorders. Previous studies demonstrated that dietary conjugated linoleic acid (CLA) induces hepatic steatosis and hyperinsulinemia through the drastic reduction of adipocytokine levels due to a paucity of adipose tissue in mice and the pathogenesis of these metabolic abnormalities in CLA-fed mice is similar to that in human lipodystrophy. The present study explores the effect of leptin infusion on the pathogenesis of diet-induced lipodystrophy in mice. C57BL/6N mice were assigned to three groups: (1) mice were fed a semisynthetic diet supplemented with 6% corn oil and infused PBS intraperitoneally (normal group), (2) mice were fed a semisynthetic diet supplemented with 4% corn oil plus 2% CLA and infused PBS intraperitoneally (lipodystrophy-control group), and (3) mice were fed a semisynthetic diet supplemented with 4% corn oil plus 2% CLA and infused recombinant murine leptin intraperitoneally (lipodystrophy-leptin group). All mice were fed normal or lipodystrophy model diets for 4 weeks and were infused intrapeneally 0 or 5 mug of leptin per day from third week of the feeding period for 1 week.


RESULTS
The results indicate that leptin infusion can attenuate hepatic steatosis and hyperinsulinemia through the reduction of hepatic triglyceride synthesis and the improvement of insulin sensitivity in diet-induced lipodystrophy model mice.


CONCLUSIONS
We expect the use of this model for clarifying the pathophysiology of lipodystrophy-induced metabolic abnormalities and evaluating the efficacy and safety of drug and dietary treatment.
Nagao
Koji
K
Department of Applied Biochemistry and Food Science, Saga University, Saga 840-8502, Japan. knagao@cc.saga-u.ac.jp
Inoue
Nao
N
Ujino
Yoko
Y
Higa
Kouki
K
Shirouchi
Bungo
B
Wang
Yu-Ming
YM
Yanagita
Teruyoshi
T
D054392:Adipokines / Q000097:blood; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D004032:Diet; D004195:Disease Models, Animal; D007263:Infusions, Parenteral; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D020738:Leptin / Q000008:administration & dosage* / Q000494:pharmacology*; D050356:Lipid Metabolism / Q000187:drug effects*; D008060:Lipodystrophy / Q000097:blood / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D051379:Mice; D008810:Mice, Inbred C57BL; D014280:Triglycerides / Q000378:metabolism
D054392:Adipokines; D007328:Insulin; D020738:Leptin; D014280:Triglycerides; D000410:Alanine Transaminase