Energy homeostasis in Prader-Willi syndrome: how clinical research informs studies of animal models of genetic obesity: comment on 'Nutritional phases in Prader-Willi syndrome,' Miller et al., 2011. Am J Med Genet Part A, 155:1040-1049.

摘要

Unusual clinical cases and animal models have been instrumental in understanding the genetics of complex disorders such as obesity. We now know that genetic mutations can cause syndromic childhood obesity, and that the responsible genes encode proteins such as the melanocortin 4 receptor, leptin and its cognate receptor, the neurotrophin BDNF and its receptor, and the hypothalamic transcription factor SIM1 [Michaud et al, 2001; Farooqi et al, 2003, 2007; Gray et al., 2006]. Whether an animal model preceded the discovery of human mutations, or was generated by a targeted mutation, most animal models of syndromic obesity not only recapitulate the human phenotype, but have enabled dissection of the intricate neurological and metabolic circuits that are dysre-gulated in severe obesity [Cowley et al., 2001; Xu et al., 2003; Kublaoui et al., 2006; Friedman, 2009]. Prader-Willi Syndrome (PWS) is a striking exception to this success story.