OBESITY GENE Introduction Zhang, Proenca, Maf

Zhang, Proenca, Maffel, Barone, Leopold, and Friedman state that obesity is a common nutritional disorder in Western societies. Increased body weight or an excess of body fat relative to lean body mass, is found to be associated with type II diabetes, hypertension, hyperlipidemia and some cancers. Obesity is found to be strongly heritable, however predisposing genes have not been identified. Research regarding obesity dating back to 1783 has implied that food intake versus energy output, is physiologically regulated. Evidence shows that body weight appears to be determined by mechanisms that balance food intake and energy expenditure. The site of this regulation is a subject of nearly one hundred years of debate. Early work has identified a causal gene for a dominantly inherited form of obesity, the yellow agouti mutation (intensity of yellow pigmentation correlates positively with extents of obesity). Of the mouse obesity mutations, the ob (obese) and the db (diabetes) genes are the most intensively studied. The obese or ob gene is a molecule that is found to regulate energy balance in the mouse. The obese mutation (ob) was identified in 1950; it is a single gene mutation that results in obesity and type II diabetes (2, 3, 8).

The ob gene in mice is researched in an effort to further understand physiologic pathways that regulate adiposity and body weight, and to understand the pathogenesis of obesity (8). The gene product of the o

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the possibility that the db gene and the hypothalamus are downstream of the ob gene in the pathway regulating adipose tissue mass; the suggestion that the db locus encodes the ob receptor is also supported. The mouse ob gene product is found to circulate in mouse and human plasma and may regulate adipose tissue (7). The authors report that signals by the fat cell that are responsible for quantitative variations in expression levels of the ob gene are not known. Evidence indicates that fat cell lipid content and/or size is important for determining body weight; adipocytes from db/db mice compared to normal mice, are five times as large. It is possible that fat cells may express low levels of ob RNA that increases in proportion to cell size, or it may be that cell size only correlates with intracellular signals that increase expression of the ob gene in adipocytes. Either way, it is concluded that signal-transduction pathway components regulating synthesis of ob RNA are likely to be important regarding body weight. Future studies regarding molecules regulating ob gene expression and effects of the encoded protein at site of action, will enhance the understanding of body weight regulation (7). OB Protein Halaas, Gajiwala,

Category: Medical - O