Corticotropin-releasing hormone decreases feeding, oxygen consumption and activity of genetically obese (ob/ob) and lean mice.

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.