Limits...
Effect of leptin infusion on insulin sensitivity and lipid metabolism in diet-induced lipodystrophy model mice.

Nagao K, Inoue N, Ujino Y, Higa K, Shirouchi B, Wang YM, Yanagita T - Lipids Health Dis (2008)

Bottom Line: Lipodystrophies are rare acquired and genetic disorders characterized by the complete or partial absence of body fat with a line of metabolic disorders.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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Applied Biochemistry and Food Science, Saga University, Saga 840-8502, Japan. knagao@cc.saga-u.ac.jp

ABSTRACT

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.

Conclusion: 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.

Show MeSH

Related in: MedlinePlus

Scheme showing possible mechanisms of CLA-induced lipodystrophy.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2278145&req=5

Figure 1: Scheme showing possible mechanisms of CLA-induced lipodystrophy.

Mentions: To understand the pathophysiology of lipodystrophy and evaluate the efficacy and safety of clinical treatments, several transgenic mouse models that mimic the features of lipodystrophy, such as aP2-SREBP-1c mouse [11-13] and A-ZIP/F1 mouse [14-16], have been established. Additionally, it has been reported that feeding of conjugated linoleic acid (CLA), a group of positional and geometric isomers of linoleic acid, with a low-fat diet also induces lipodystrophy, characterized by an increase in hepatic lipid content concomitant with a decrease in body fat mass in mice [17,18]. It has been suggested that lipodystrophy may occur in mice because they are too sensitive to the CLA-induced reduction in body fat [19,20]. We previously reported that short-term feeding of CLA decreased weights of adipose tissues and hepatic lipid levels without inducing adverse effects in mice [21]. Tsuboyama-Kasaoka, Miyazaki, Kasaoka, and Ezaki [22] also reported that increasing the amount of fat in a CLA-supplemented diet substantially reduces the lipodystrophy effect. These results indicate that dietary CLA induces fatty liver and hyperinsulinemia through the drastic reduction of adipocytokine levels due to a paucity of adipose tissue, but not through the direct induction of hepatic lipid synthesis and insulin resistance (Figure 1). Because the pathogenesis of these metabolic abnormalities in CLA-fed mice is similar to that in human lipodystrophy, we expect the use of CLA-fed mice as a diet-induced lipodystrophy model.


Effect of leptin infusion on insulin sensitivity and lipid metabolism in diet-induced lipodystrophy model mice.

Nagao K, Inoue N, Ujino Y, Higa K, Shirouchi B, Wang YM, Yanagita T - Lipids Health Dis (2008)

Scheme showing possible mechanisms of CLA-induced lipodystrophy.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2278145&req=5

Figure 1: Scheme showing possible mechanisms of CLA-induced lipodystrophy.
Mentions: To understand the pathophysiology of lipodystrophy and evaluate the efficacy and safety of clinical treatments, several transgenic mouse models that mimic the features of lipodystrophy, such as aP2-SREBP-1c mouse [11-13] and A-ZIP/F1 mouse [14-16], have been established. Additionally, it has been reported that feeding of conjugated linoleic acid (CLA), a group of positional and geometric isomers of linoleic acid, with a low-fat diet also induces lipodystrophy, characterized by an increase in hepatic lipid content concomitant with a decrease in body fat mass in mice [17,18]. It has been suggested that lipodystrophy may occur in mice because they are too sensitive to the CLA-induced reduction in body fat [19,20]. We previously reported that short-term feeding of CLA decreased weights of adipose tissues and hepatic lipid levels without inducing adverse effects in mice [21]. Tsuboyama-Kasaoka, Miyazaki, Kasaoka, and Ezaki [22] also reported that increasing the amount of fat in a CLA-supplemented diet substantially reduces the lipodystrophy effect. These results indicate that dietary CLA induces fatty liver and hyperinsulinemia through the drastic reduction of adipocytokine levels due to a paucity of adipose tissue, but not through the direct induction of hepatic lipid synthesis and insulin resistance (Figure 1). Because the pathogenesis of these metabolic abnormalities in CLA-fed mice is similar to that in human lipodystrophy, we expect the use of CLA-fed mice as a diet-induced lipodystrophy model.

Bottom Line: Lipodystrophies are rare acquired and genetic disorders characterized by the complete or partial absence of body fat with a line of metabolic disorders.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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Applied Biochemistry and Food Science, Saga University, Saga 840-8502, Japan. knagao@cc.saga-u.ac.jp

ABSTRACT

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.

Conclusion: 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.

Show MeSH
Related in: MedlinePlus