OBESE GENE-EXPRESSION - REDUCTION BY FASTING AND STIMULATION BY INSULIN AND GLUCOSE IN LEAN MICE, AND PERSISTENT ELEVATION IN ACQUIRED (DIET-INDUCED) AND GENETIC (YELLOW AGOUTI) OBESITY

Mutations in the obese (ob) gene lead to obesity, This gene has been r ecently cloned, but the factors regulating its expression have not bee n elucidated, To address the regulation of the ob gene with regard to body weight and nutritional factors, Northern blot analysis was used t o assess ob mRNA in adipose tissue from mice [lean, obese due to diet, or genetically (yellow agouti) obese] under different nutritional con ditions, ob mRNA was elevated in both forms of obesity, compared to le an controls, correlated with elevations in plasma insulin and body wei ght, but not plasma glucose, In lean C57BL/6J mice, but not in mice wi th diet-induced obesity, ob mRNA decreased after a 48-hr fast. Similar ly, in lean C57BL/6J controls, but not in obese yellow mice, i.p, gluc ose injection significantly increased ob mRNA, For up to SO min after glucose injection, ob mRNA in lean mice significantly correlated with plasma glucose, but not with plasma insulin, In a separate study with only lean mice, ob mRNA was inhibited >90% by fasting, and elevated ap proximate to 2-fold 30 min after i.p. injection of either glucose or i nsulin, These results suggest that in lean animals glucose and insulin enhance ob ene expression, In contrast to our results in lean mice, i n obese animals ob mRNA is elevated and relatively insensitive to nutr itional state, possibly due to chronic exposure to elevated plasma ins ulin and/or glucose.