14-3-3ζ overexpression improves tolerance to acute and chronic cold exposure in male mice
Adaptive thermogenesis is a mechanism of heat production primarily mediated by brown fat. In some instances, cold exposure or adrenergic stimuli can convert white adipocytes into brown-like or beige adipocytes during a process termed “beiging”. Both beige and brown adipocytes express higher levels of uncoupling protein 1 (UCP1) and can release energy in the form of heat following lipid oxidation. The activation of these thermogenic adipocytes increases energy expenditure to reduce body weight in rodents, and it has been postulated to be a promising therapy for the treatment of obesity and diabetes. We previously identified an essential role of the molecular scaffold, 14-3-3ζ, in adipogenesis, but its roles in other adipocyte processes is uncertain. An early identified function of 14-3-3 was its ability to regulate the enzymatic activity of tyrosine hydroxylase, which is indispensable in the production of norepinephrine for thermogenesis. Thus, our study aims to investigate whether 14-3-3ζ influences the development and function of beige and brown adipocytes. We report here that one allele deletion of the gene of 14-3-3ζ did not affect acute cold tolerance. On the other hand, transgenic overexpression of 14-3-3ζ in male mice (TAP) improves cold tolerance due to enhanced beiging with a remarkable increase in Ucp1 mRNA and protein in inguinal white adipose tissue (iWAT). Interestingly, beiging is increased in the TAP mice without any changes in sensitivity to beta-adrenergic stimuli, sympathetic innervation, or norepinephrine content being detected between WT and TAP mice. TAP mice also displayed significantly lower thermal conductance decreasing heat loss during the chronic cold challenge. Collectively, our results point to a novel role of 14-3-3ζ in beiging and increases our understanding of how adaptive thermogenesis is regulated.
14-3-3ζ Beiging Browning Adaptive thermogenesis Brown adipocytes Beige adipocytes 14-3-3 proteins