MCH ACTION AS DEFINED THROUGH GENE KNOCKOUT

$209,314P01FY2000DKNIH

Beth Israel Deaconess Medical Center, Boston MA

Investigators

Linked publications & trials

Paper 36323237 Paper 23804023 Paper 23790727 Paper 22727014 Paper 22590531 Paper 22201680 Paper 22100407 Paper 22000926 Paper 21209093 Paper 21209091 Paper 21048120 Paper 21037584 Paper 21035764 Paper 20876718 Paper 20451522 Paper 20421294 Paper 20374961 Paper 20368432 Paper 20212134 Paper 19826103 Paper 19819947 Paper 19819944 Paper 19738035 Paper 19633655 Paper 19528236 Paper 19447150 Paper 19401456 Paper 19361544 Paper 19359377 Paper 19357287 Paper 19350671 Paper 19160495 Paper 19074037 Paper 19038216 Paper 18829956 Paper 18809470 Paper 18669597 Paper 18577694 Paper 18552842 Paper 18535571 Paper 18382766 Paper 18356844 Paper 18281019 Paper 18162515 Paper 18001293 Paper 17983585 Paper 17983579 Paper 17596444 Paper 17550778 Paper 17488640 Paper 17299079 Paper 17202473 Paper 17185376 Paper 16846858 Paper 16845389 Paper 16823474 Paper 16788162 Paper 16709629 Paper 16687413 Paper 16443777 Paper 16423694 Paper 16322794 Paper 16320257 Paper 16284652 Paper 16054052 Paper 16054045 Paper 15928024 Paper 15690487 Paper 15630408 Paper 15504958 Paper 15207242 Paper 15090642 Paper 14749508 Paper 12933644 Paper 12917494 Paper 12904474 Paper 12897241 Paper 12840062 Paper 12826331 Paper 12797957 Paper 12788909 Paper 12684481 Paper 12612907 Paper 12543978 Paper 12541307 Paper 12368907 Paper 12142539 Paper 12110165 Paper 12093887 Paper 11970898 Paper 11840221 Paper 11812753 Paper 11370008 Paper 11309481 Paper 11241374 Paper 11160162 Paper 11134186 Paper 10953022 Paper 10891488

Abstract

Obesity is a serious medical condition with complex etiology; it is a significant risk factor for a number of illnesses including type II diabetes, coronary artery disease a number of neoplasms including endometrial and colon cancer. Although very common, the causes of obesity are poorly understood and available treatments are not particularly effective. A number of peripheral hormones and neuropeptides have been implicated in the pathogenesis of the impaired energy balance which results in obesity. We discovered that the hypothalamic peptide, melanin concentrating hormone is important in the regulation of energy balance. In addition to a number of physiologic studies we generated a mouse in which the MCH gene was ablated. Homozygous MCH-/- mice have a lean phenotype, with a 25% reduction in total body weight and 50% reduction in total body fat and reduced levels of leptin. Decreased eating during the dark cycle contributes t least in part to the phenotype, however, the reduction in eating is only 15%. Preliminary data indicates that ablation of the MCH gene may also lead to increased oxygen consumption. This study proposes to examine the causes of the lean phenotype in detail and to ascertain the relative contributions of MCH and the two other peptides derived from the MCH gene, N-EI and N- GE. To determine the role of MCH in mediating the orexigenic or appetite inhibiting actions of other neuropeptides (NPY, alphaMSH, GLP-1) the effect of a number of appetite regulating peptides in MCH-/- mice will be assessed. In addition to examine the importance of MCH in mediating obesity in single gene models of rodent obesity MCH-/- mice will be crossbred to leptin deficient (ob/ob) mice and leptin resistance A/gamma (agouti) mice. MCH-/- mice will also be crossbred to mice with ablations in NPY or orexin, other neuropeptides implicated in energy, balance, to determine the effect of multiple gene ablation on energy balance.

View original record on NIH RePORTER →