Chronic C75 treatment of diet-induced obese mice increases fat oxidation and reduces food intake to reduce adipose mass

Jagan N. Thupari, Eun Kyoung Kim, Timothy H. Moran, Gabriele V. Ronnett, Francis P. Kuhajda

Research output: Contribution to journalArticlepeer-review

Abstract

Obesity and its attendant disorders, such as type 2 diabetes, are global health problems. We previously reported that C75, an inhibitor of fatty acid synthase (FAS) and stimulator of carnitine palmitoyltransferase I (CPT I), caused anorexia and profound weight loss in lean and genetically obese mice. To approximate human obesity, we utilized a chronic C75 treatment model for diet-induced obese (DIO) mice. Chronic C75 treatment decreased food consumption and increased energy expenditure due to increased fatty acid oxidation in both DIO and lean mice. There was a substantial loss of adipose tissue and resolution of hepatic steatosis in C75-treated DIO mice. Analysis of changes in the expression of hypothalamic neuropeptides demonstrated that the reduced food consumption in C75-treated DIO mice was accompanied by an increase in cocaine and amphetamine-related transcript expression but not by changes in neuropeptide Y such as seen with acute C75 treatment of lean mice. Inhibition of FAS and stimulation of CPT I provide a means to achieve stable, sustained weight loss in DIO mice.

Original languageEnglish (US)
Pages (from-to)E97-E104
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume287
Issue number1 50-1
DOIs
StatePublished - Jul 2004

Keywords

  • Carnitine palmitoyltransferase I
  • Fatty acid synthase
  • Neuropeptide Y

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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