Correlation between lipid and glycogen contents in liver and insulin resistance in high-fat-fed rats treated with the lipoprotein lipase activator NO-1886.

Abstract

Insulin resistance results in accumulation of triglyceride content and reduction of glycogen content in skeletal muscle. However, very few studies have measured lipid content and glycogen content in liver associated with insulin resistance. We studied the relationship between liver lipid content, liver glycogen, and insulin resistance in high-fat-fed rats, which are animal models of insulin resistance. High-fat-fed rats were hyperlipidemic, hyperglycemic, and hyperinsulinemic. Furthermore, the glucose infusion rates (GIR) were lower (normal rats, 10.35 +/- 1.66; high-fat-fed rats, 4.86 +/- 0.93 mg/kg/min; P <.01) and the triglyceride and cholesterol contents in liver were higher in the high-fat-fed rats than in normal rats. On the other hand, the glycogen content in liver was lower than in normal rats. There was an inverse relationship between liver triglyceride content and liver glycogen content. When the lipoprotein lipase (LPL) activator NO-1886 was administered to the high-fat-fed rats at a daily dose of 50 mg/kg body weight for 10 weeks, GIR (9.87 +/- 3.76 mg/kg/min, P <.05 v high-fat-fed control group) improved, causing an improvement of the hyperlipidemia, hyperglycemia, and hyperinsulinemia. Furthermore, NO-1886 decreased triglyceride and cholesterol concentrations and increased glycogen content in liver of the high-fat-fed rats. In this study, we found that insulin resistance caused fatty liver and reduced glycogen content in liver. Administration of the LPL activator NO-1886 improved the insulin resistance, resulting in an improvement in the relationship between triglyceride and glycogen content in liver of high-fat-fed rats.

• Authors: Masataka Kusunoki, Kazuhiko Tsutsumi, Tsutomu Hara, Hitoshi Ogawa, Takao Nakamura, Tetsuro Miyata, Fumihiko Sakakibara, Yoshitaka Fukuzawa, Takashi Suga, Shinichi Kakumu, Yutaka Nakaya
• Journal: Metabolism: clinical and experimental (Metabolism) Vol. 51 Issue 6 Pg. 792-5 (Jun 2002) ISSN: 0026-0495 [Print] United States
• PMID: 12037738 (Publication Type: Journal Article)
• Copyright: Copyright 2002, Elsevier Science (USA). All rights reserved.

Chemical References

• Benzamides
• Blood Glucose
• Dietary Fats
• Hypolipidemic Agents
• Insulin
• Lipids
• Organophosphorus Compounds
• Triglycerides
• 4-diethoxyphosphorylmethyl-N-(4-bromo-2-cyanophenyl)benzamide
• Glycogen
• Cholesterol
• Lipoprotein Lipase

Topics

• Animals
• Benzamides (pharmacology)
• Blood Glucose
• Body Weight (drug effects)
• Cholesterol (metabolism)
• Dietary Fats (pharmacology)
• Enzyme Activation (drug effects)
• Glucose Clamp Technique
• Glycogen (metabolism)
• Hypolipidemic Agents (pharmacology)
• Insulin (blood)
• Insulin Resistance (physiology)
• Lipid Metabolism
• Lipids (blood)
• Lipoprotein Lipase (metabolism)
• Liver (drug effects, metabolism)
• Male
• Organophosphorus Compounds (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Triglycerides (metabolism)