Differential regulation of expression of genes encoding uncoupling proteins 2 and 3 in brown adipose tissue during lactation in mice

Thermogenic activity in brown adipose tissue (BAT) decreases during lactati on; the down-regulation of the gene encoding uncoupling protein 1 (UCP1) is involved in this process. Our studies show that UCP2 mRNA expression does not change during the breeding cycle in mice. In contrast, UCP3 mRNA is dow n-regulated in lactation but it recovers after weaning, in parallel with UC P1 mRNA. This leads to a decrease in the content of UCP3 in BAT mitochondri a during lactation. Lowering the energy-sparing necessities of lactating da ms by decreasing litter size or feeding with a high-fat diet prevented the down-regulation of UCP1 mRNA and UCP3 mRNA, In most cases this resulted in a less marked decrease in UCP1 and UCP3 protein in BAT mitochondria owing t o lactation. Fasting for 24 h caused a different response in UCP1 and UCP3 mRNA expression: it decreased UCP1 mRNA levels but had no effect on UCP3 mR NA abundance in virgin mice; it even increased UCP3 mRNA expression in lact ating dams, These changes did not lead to modifications in UCP1 or UCP3 pro tein abundance. Whereas acute treatment with peroxisome-proliferator-activa ted receptor (PPAR)alpha and PPAR gamma agonists increased UCP1 mRNA levels only in lactating dams, UCP3 mRNA expression was induced by both kinds of PPAR activator in lactating dams and by PPAR alpha agonists in virgin mice. It is concluded that modifications of UCP2 mRNA levels are not part of the physiological adaptations taking place in BAT during lactation. In contras t, the downregulation of UCP3 mRNA expression and mitochondrial UCP3 conten t is consistent with a role for the gene encoding UCP3 in the decrease in m etabolic fuel oxidation and thermogenesis in BAT during lactation.