Journal
INTERNATIONAL JOURNAL OF OBESITY
Volume 34, Issue 6, Pages 970-979Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ijo.2009.291
Keywords
acetaminophen; high-fat diet; mice; olanzapine; oxidative stress; tetrahydroindenoindole
Categories
Funding
- NIEHS Center for Environmental Genetics [P30 ES06096]
- NARSAD
- University of Cincinnati Medical College
- NIEHS [T32 ES117051, T32 ES016646]
- NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [T32ES016646, P30ES006096] Funding Source: NIH RePORTER
Ask authors/readers for more resources
Objective: In mice and in humans, treatment with the second-generation antipsychotic drug olanzapine (OLZ) produces excessive weight gain, adiposity and secondary metabolic complications, including loss of glucose and insulin homeostasis. In mice consuming a high-fat (HF) diet, a similar phenotype develops, which is inhibited by the analgesic acetaminophen (APAP) and by the antioxidant tetrahydroindenoindole (THII). Therefore, we examined the ability of APAP and THII to prevent metabolic changes in mice receiving OLZ. Design and Measurement: C57BL/6J mice received either a normal diet or a HF diet, and were administered daily dosages of OLZ (3 mg kg(-1) body weight), alone or with APAP (30 mg kg(-1) body weight) or THII (4.5 mg kg(-1) body weight), for 10 weeks. Parameters of body composition and metabolism, including glucose and insulin homeostasis and oxidative stress, were examined. Results: OLZ treatment doubled the HF diet-induced increases in body weight and percent body fat. These increases were partially prevented by both APAP and THII, although food consumption was constant in all groups. The THII protection was associated with an increase in whole body and mitochondrial respiration. OLZ also exacerbated, and both APAP and THII prevented, HF diet-induced loss of glucose tolerance and insulin resistance. As increased body fat promotes insulin resistance by a pathway involving oxidative stress, we evaluated production of reactive oxygen and lipid peroxidation in white adipose tissue (WAT). HF diet caused an increase in lipid peroxidation, NADPH-dependent O(2) uptake and H(2)O(2) production, which were further exacerbated by OLZ. APAP, THII and the NADPH oxidase inhibitor, diphenyleneiodonium chloride, each abolished oxidative stress in WAT. Conclusions: We conclude that both APAP and THII intervene in the development of obesity and metabolic complications associated with OLZ treatment. International Journal of Obesity (2010) 34, 970-979; doi:10.1038/ijo.2009.291; published online 12 January 2010
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available