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Corticotropin-Releasing Hormone Decreases Feeding, Oxygen Consumption and Activity of Genetically Obese (ob/ob) and Lean Mice^1,2,

Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824-1224

Acute effects of intracerebroventricularly administered corticotropin-releasing hormone (CRH) on deprivation-induced food intake, whole-body oxygen consumption, brown adipose tissue metabolism, and several locomotive behaviors were examined in 6- to 7-wk-old female genetically obese (ob/ob) and lean mice. Corticotropin-releasing hormone depressed food intake in a dose-dependent manner, with a tendency for greater suppression of intake in intact ob/ob mice than in lean mice. Adrenalectomy abolished this tendency for CRH to be more potent in ob/ob mice than in lean mice. Corticotropin-releasing hormone also lowered the oxygen consumption of ob/ob and lean mice, without affecting brown adipose tissue metabolism as assessed by measurement of GDP binding to brown adipose tissue mitochondria. Grooming activity was lowered in CRH-injected mice. The CRH-induced lowering of oxygen consumption and grooming activity in mice contrasts with CRH-induced elevations of oxygen consumption and grooming in rats, suggesting species-specific responses to this peptide. Because effects of CRH were similar in adrenalectomized ob/ob and lean mice, it is unlikely that obesity-producing abnormalities in ob/ob mice are related to abnormal CRH action mechanisms. However, potential abnormalities in CRH synthesis and/or release cannot be excluded.

KEY WORDS: • genetically obese (ob/ob) mice • corticotropin-releasing hormone • food intake • locomotor activity • whole-body oxygen consumption

¹ Supported by NIH grant DK-15847, USDA National Needs Graduate Fellowship grant 89-38420-4398, and the Michigan Agricultural Experiment Station.

² The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact.

³ To whom correspondence should be addressed.

Manuscript received 6 July 1993. Revision accepted 3 November 1993.

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