Lenhard J, Spencer D, Croom D, Weiel J; Conference on Retroviruses and Opportunistic Infections.

7th Conf Retrovir Oppor Infect Jan 30 Feb 2 2000 Conf Retrovir Oppor Infect 7th 2000 San Franc Calif. 2000 Jan 30-Feb 2; 7: 83 (abstract no. 41).

Glaxo Wellcome Inc., Res. Triangle Park, NC.

Objective: Previously, it has been suggested that efavirenz (EFV) may alter lipid levels in humans. While the effect of PIs on fat metabolism in mice has been reported, the effect of EFV in rodents has not been described. Thus, the effect of EFV on lipid metabolism in mice was investigated. Methods: AKR/J mice were fed a low fat diet and treated for two weeks with 50 mg/kg/d EFV or placebo. The effects on gene expression, liver weight, serum lipids, alkaline phosphatase, and beta-hydroxybutyric acid were measured. Results: EFV treated mice had greater serum levels of triglycerides (29% or 42 mg/dL, P=0.011), free fatty acids (26% or 0.23 mEq/L, P=0.0006), alkaline phosphatase (26% or 24 U/L, P=0.001), and total cholesterol (11% or 8 mg/dL, 0.007) than control mice. Moreover, in epididymal fat of EFV treated mice the ratio of fatty acid synthase (FAS) to tumor necrosis factor (TNF-alpha) increased by >2 fold relative to control mice. Similarly, liver weight was 22% greater in EFV treated mice than control mice (P=0.0004). However, serum levels of beta-hydroxybutyric acid (ketone bodies), glucose, glycerol, HDL cholesterol and expression of HMG CoA synthase in liver (an enzyme controlling ketone and cholesterol biosynthesis) remained unchanged in mice treated with EFV (P>0.05). Conclusion: In contrast to the reported effects of PIs (e.g., amprenavir) in AKR/J mice fed a low fat diet, EFV treatment results in elevation of serum lipid levels. These effects may be due to altered production of proteins in fat (e.g., FAS and TNF-alpha) or liver that regulate lipid metabolism. EFV does not affect ketogenesis or HMG CoA synthase expression, suggesting EFV may not cause hyperlipidemia by altering mitochondrial function.

Publication Types:

• Meeting Abstracts

Keywords:

• Adipose Tissue
• Animals
• Body Weight
• Cholesterol
• Cholesterol, HDL
• Fatty Acid Synthetase Complex
• Fatty Liver
• Hepatomegaly
• Humans
• Hydroxymethylglutaryl-CoA Synthase
• Hyperlipidemias
• Lipids
• Liver
• Mice
• Mice, Inbred C57BL
• Mice, Obese
• Muridae
• Obesity
• Oxazines
• Triglycerides
• efavirenz

Other ID:

• GWAIDS0005423

UI: 102242920

From Meeting Abstracts