Our data confirm that both FFM and FM are significant contributors to BMR. When the effect of FM on BMR is removed, any association with leptin concentrations disappears, which suggests that previous links between circulating leptin concentrations and BMR occurred only because of inadequate control for the effects of FM.

The effect of acute exposure to cold on the expression of the ob (obese) gene, which encodes a protein that plays a critical role in the regulation of energy balance and body weight, has been examined in epididymal white adipose tissue of mice. Overnight (18 h) exposure of mice to a temperature of 4 degrees C led to the disappearance of ob mRNA in epididymal white fat, and subsequent studies showed that a cold-induced loss of ob mRNA could occur in as little as 2-4 h of exposure to 4 degrees C. When mice exposed to cold for 18 h were returned to the warm (24 degrees C), there was a rapid stimulation of the expression of the ob gene, the mRNA returning within 2.5 h. Administration of noradrenaline led to a reduction in the level of ob mRNA in mice maintained in the warm, while isoprenaline resulted in the disappearance of the mRNA; these changes in ob mRNA were paralleled by similar changes in lipoprotein lipase mRNA. In contrast to white fat, the level of lipoprotein lipase mRNA in brown adipose tissue was increased by noradrenaline and isoprenaline. It is concluded that there is a cold-induced suppression of ob gene expression in white adipose tissue of mice and that this is mediated primarily by the sympathetic system. The profound effect of cold on ob gene expression indicates that the ob system relates to energy expenditure, as well as to satiety.

Metallothionein (MT) has several putative roles in metal detoxification, in Zn and Cu homeostasis, in scavenging free radicals, and in the acute phase response. Mice of mixed 129͞Ola and C57BL͞6J background with targeted disruption of MT-I and MT-II genes are more sensitive to toxic metals and oxidative stress. We noted that these animals were larger than most strains of mice, and we systematically studied aspects of their physiology and biochemistry relating to energy metabolism. During the first 2 weeks after weaning, the growth rates of MT-null and C57BL͞6J mice were similar, but the transgenic mice became significantly heavier at age 5-6 weeks. At age 14 weeks, the body weight and food intake of MT-null mice was 16 and 30% higher, respectively, compared with C57BL͞6J mice. Most 22-to 39-week-old male MT-null mice were obese, as shown by increased fat accretion, elevated obese (ob) gene expression, and high plasma leptin levels, similar to those recorded in Zucker fatty ( fa͞fa) rats. Seven-week-old MT-null mice also had significantly higher levels of plasma leptin and elevated expression of ob, lipoprotein lipase, and CCAAT enhancer binding protein ␣ genes as compared with age-matched C57BL͞6J mice. These observations indicate that abnormal accretion of body fat and adipocyte maturation is initiated at 5-7 weeks of age, possibly coincident with sexual maturation. Targeted disruption of MT-I and MT-II genes seems to induce moderate obesity, providing a new obese animal model. A link between MT and the regulation of energy balance is implied.

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