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Background  A low-protein diet increases the expression and circulating concentration of FGF21. FGF21 stimulates the browning process of WAT by enhancing the expression of UCP1 coupled with an increase in PGC1α. Interestingly, the consumption of a low-protein diet could stimulate WAT differentiation into beige/brite cells by increasing FGF21 expression and  Ucp1  mRNA abundance. However, whether the stimulus of a low-protein diet on WAT browning can synergistically interact with another browning stimulus, such as cold exposure, remains elusive.    Results  In the present study, rats were fed 6% (low), 20% (adequate), or 50% (high) dietary protein for 10 days and subsequently exposed to 4 °C for 72 h. Body weight, food intake, and energy expenditure were measured, as well as WAT browning and BAT thermogenesis markers and FGF21 circulating levels. The results showed that during cold exposure, the consumption of a high-protein diet reduced UCP1, TBX1,  Cidea ,  Cd137 , and  Prdm16  in WAT when compared with the consumption of a low-protein diet. In contrast, at room temperature, a low-protein diet increased the expression of UCP1,  Cidea , and  Prdm16  associated with an increase in FGF21 expression and circulating levels when compared with a consumption of a high-protein diet. Consequently, the consumption of a low-protein diet increased energy expenditure.    Conclusions  These results indicate that in addition to the environmental temperature, WAT browning is nutritionally modulated by dietary protein, affecting whole-body energy expenditure.    Graphical abstract

Interaction between the amount of dietary protein and the environmental temperature on the expression of browning markers in adipose tissue of rats