Identification of candidate genes for a factor regulating energy balance in humans.
Weigle D.S. | Wilson B.E.
The identification of specific genes associated with the development of obesity in humans is hindered both by the polygenic nature of this disorder and by the impact of environmental factors on body weight. To develop a panel of candidate genes for linkage studies of obese kindreds, we hypothesized that adipocytes normally secrete one or more peptides mediating satiety or increased thermogenesis under conditions of excessive fat storage. Defective production or action of such peptides would be followed by expansion of the adipose mass until a signal sufficient to restore energy balance was achieved. A subtractive cloning strategy was developed to identify cDNA for genes expressed at a higher level by adipocytes from primates made obese by gastrostomy overfeeding, as opposed to ad libitum-fed primates. The cDNA for any transcriptionally regulated adipocyte gene products that normally function to limit body weight gain should be among those cloned selectively from the adipose tissue of overfed animals. One of the cloned cDNA species hybridizes to a novel 5 kb mRNA, which is present in both rodent and human adipose tissue and in rodent and primate brain. cDNA probes for the overfeeding-induced 5 kb mRNA, as well as other cDNA species cloned in this manner, may now be used in nonparametric sib-pair linkage studies to detect any association with the obese phenotype in humans.
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