tailieunhanh - Báo cáo khoa học: Ablation of Sax2 gene expression prevents diet-induced obesity

Regulation of energy homeostasis is mainly mediated by factors in the hypothalamus and the brainstem. Understanding these regulatory mecha-nisms is of great clinical relevance in the treatment of obesity and related diseases. | 1FEBS Journal Ablation of Sax2 gene expression prevents diet-induced obesity Ruth Simon1 2 Stefan Britsch2 and Andrew Bergemann1 1 Department of Pathology Mount Sinai Schoolof Medicine New York NY USA 2 Institute for Molecular and Cellular Anatomy University of Ulm Germany Keywords brainstem diet-induced obesity energy homeostasis food uptake neural circuitry Correspondence R. Simon Institute for Molecular and Cellular Anatomy University of Ulm Albert-Einstein-Allee 11 D-89081 Ulm Germany Fax 49 731 500 23102 Tel 49 731 500 23225 E-mail These authors contributed equally to this work Received 19 July 2010 revised 5 November 2010 accepted 11 November 2010 doi Regulation of energy homeostasis is mainly mediated by factors in the hypothalamus and the brainstem. Understanding these regulatory mechanisms is of great clinical relevance in the treatment of obesity and related diseases. The homeobox gene Sax2 is expressed predominantly in the brainstem in the vicinity of serotonergic neurons and in the ventral neural tube starting during early development. Previously we have shown that the loss of function of the Sax2 gene in mouse causes growth retardation starting at birth and a high rate of postnatal lethality as well as a dramatic metabolic phenotype. To further define the role of Sax2 in energy homeostasis age-matched adult wild-type Sax2 heterozygous and null mutant animals were exposed to a high-fat diet. Although food uptake among the different groups was comparable Sax2 null mutants fed a high-fat diet exhibited a significantly lower weight gain compared to control animals. Unlike their counterparts Sax2 null mutants did not develop insulin resistance and exhibited significantly lower leptin levels under both standard chow and high-fat diet conditions. Furthermore neuropeptide Y an important regulator of energy homeostasis was significantly decreased in the forebrain of Sax2 null mutants on a high-fat diet. .