Brown adipose tissue (BAT) is a metabolically active tissue in mammals that burns calories and releases the energy as heat. For this reason, BAT is very important for the energy homeostasis and temperature regulation of small or hibernating mammals and human infants. Recent studies have suggested that the protein responsible for dissipating stored energy as heat in BAT, called uncoupling protein 1 (UCP1), is involved in the control of body weight. Unfortunately, nearly all BAT in humans disappears by adulthood, ruling out the possibility that UCP1 might play a role in adult weight loss. However, the discovery of uncoupling proteins in tissues other than BAT has sparked new interest in their role as potential factors in obesity. Specifically, evidence suggests that UCP3, an uncoupling protein found in skeletal muscle, may also have an impact on body weight regulation. In the present study, Rodriguez and co-workers provide evidence of differences between male and female rats in the regulation of UCP3 expression in response to obesity, overfeeding and fasting.

Male and female rats were free to feed on one of two different types of diet. The high-fat `cafeteria' diet consisted of cookies with liver pate,sobrassads (a Majorcan cured sausage), candies, fresh bacon, biscuits,chocolate, salted peanuts, cheese, ensai mada (a Majorcan pastry) and milk containing 20% sucrose. By contrast, the control diet consisted of standard rat chow that had significantly higher levels of protein and carbohydrates and a lower level of fat compared with the cafeteria diet.

In both sexes, the energy intake of cafeteria rats was threefold greater that that of control rats, despite the same basic energy requirements. While both male and female rats fed cafeteria diets showed an increase in body mass compared with control rats, females gained substantially more weight than males, accounted for in part by a slight but sustained higher energy intake per gram.

After chronic overindulgence on the cafeteria diet, mRNA expression of UCP3 was increased in both male and female rats. However, this upregulation was more evident in males. Interestingly, fasting also induced UCP3 expression and was again more pronounced in males than in females. In addition, the males with the highest UCP3 mRNA levels tended to be the most obese, but Rodríguez did not find this correlation in females.

It appears that UCP3 expression is increased under conditions of enhanced fat utilization by muscle, either through fasting or through the consumption of high-fat diets. This suggests that UCP3 may be involved in the handling of fats as a fuel substrate in muscle, and, in the case of dietary over-indulgence, the induction of UCP3 could function to limit the bodyweight gain.

The authors point out that the reduced ability of female rats to induce muscle UCP3 could contribute to the higher capacity that females have to save fat stores in times of dietary excess, which could be an advantage for certain gender-specific biological functions such as pregnancy. This study not only supports a role for UCP3 in body weight regulation but also emphasizes that gender-specific strategies should be considered in future studies on obesity.

Rodríguez, A. M., Roca, P., Bonet, M. L., Picó,C., Oliver, P. and Palou, A. (
). Positive correlation of skeletal muscle UCP3 mRNA levels with overweight in male, but not in female,rats.
Am. J. Physiol. Regul. Intergr. Comp. Physiol.
(published online, 15 May 2003) 10.1152/ajpregu.00698.202