Recently Zhang et al. cloned a gene that is expressed only in adipose tissue of the mouse. The obese phenotype of the ob/ob mouse is linked to a mutation in the obese gene that results in expression of a truncated inactive protein. Human and rat homologues for this gene are known. Previous experiments predict such a hormone to have a hypothalamic target. Hypothalamic neuropeptide Y stimulates food intake, decreases thermogenesis, and increases plasma insulin and corticosterone levels making it a potential target. Here we express the obese protein in Escherichia coli and find that it suppresses food intake and decreases body weight dramatically when administered to normal and ob/ob mice but not db/db (diabetic) mice, which are thought to lack the appropriate receptor. High-affinity binding was detected in the rat hypothalamus. One mechanism by which this protein regulated food intake and metabolism was inhibition of neuropeptide-Y synthesis and release.

TINSLEY, FRANK C., GERSH Z. TAICHER, AND MARK L. HEIMAN. Evaluation of a quantitative magnetic resonance method for mouse whole body composition analysis. Obes Res. 2004;12:150 -160. Objective: To evaluate applicability, precision, and accuracy of a new quantitative magnetic resonance (QMR) analysis for whole body composition of conscious live mice. Research Methods and Procedures: Repeated measures of body composition were made by QMR, DXA, and classic chemical analysis of carcass using live and dead mice with different body compositions. Caloric lean and dense diets were used to produce changes in body composition. In addition, different strains of mice representing widely diverse populations were analyzed. Results: Precision was found to be better for QMR than for DXA. The coefficient of variation for fat ranged from 0.34% to 0.71% compared with 3.06% to 12.60% for DXA. Changes in body composition in response to dietary manipulation were easily detected using QMR. An increase in fat mass of 0.6 gram after 1 week (p Ͻ 0.01) was demonstrated in the absence of hyperphagia or a change in mean body weight. Discussion: QMR and DXA detected similar fat content, but the improved precision afforded by QMR compared with DXA and chemical analysis allowed detection of a significant difference in body fat after 7 days of consuming a diet rich in fat even though average body weight did not significantly change. QMR provides a very precise, accurate, fast, and easy-to-use method for determining fat and lean tissue of mice without the need for anesthesia. Its ability to detect differences with great precision should be of value when characterizing phenotype and studying regulation of body composition brought about by pharmacological and dietary interventions in energy homeostasis.

in bone tissue there is a strong correlation between hydrogen NMR signal and bone-mineral density as measured by X-ray. QMR provides a very precise, accurate, fast, and easy to use method for determining fat and lean mass of mice without the need for anesthesia. Its ability to detect differences and monitor changes in body composition in mice with great precision should be of great value in characterizing phenotypes and studying drugs affecting obesity.

Vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP) are two closely related peptides that bind two homologous G protein-coupled receptors, VIP/PACAP receptor 1 (VPAC1R) and VIP/PACAP receptor II (VPAC2R), with equally high affinity. Recent reports suggest that VPAC2R plays a role in circadian rhythm and T cell functions. To further elucidate the functional activities of VPAC2R, we generated VPAC2R-deficient mice by deleting exons VIII-X of the VPAC2R gene. The VPAC2R-deficient mice showed retarded growth and had reduced serum IGF-I levels compared with gender-matched, wild-type siblings. The mutant mice appeared healthy and fertile at a young adult age. However, older male mutant mice exhibited diffuse seminiferous tubular degeneration with hypospermia and reduced fertility rate. The mutant mice appeared to have an increase in insulin sensitivity. VPAC2R-deficient mice had increased lean mass and decreased fat mass with reduced serum leptin levels. Indirect calorimetry experiments showed that the respiratory quotient values immediately following the transition into the dark cycle were significantly higher in male knockout mice for about 4 h. Additionally, male and female VPAC2R-deficient mice presented an increased basal metabolic rate (23% and 10%, respectively) compared with their wild-type siblings. Our results suggest that VPAC2R plays an important role in growth, basal energy expenditure, and male reproductive functions.