RESUMEN
AIMS: Previous work has demonstrated that ketogenic diets promote white fat browning; however, the exact mechanisms underlying this phenomenom have yet to be elucidated. Recently, an in vitro study showed that supraphysiological concentrations of ß-hydroxybutyrate (ßHB) had a strong influence on the induction of adipocyte browning. On the other hand, concentrations in the physiological range, achieved through ketogenic diets and prolonged fasting produce values of 1-3â¯mM and 4-7â¯mM, respectively. Herein, we investigated the impact of physiological concentrations of ßHB on metabolism, and the expression of uncoupling protein 1 (UCP1) and other browning markers in adipose tissues. MAIN METHODS: The effects of ßHB on adipocyte browning were investigated in vitro, using primary cultures of isolated visceral and subcutaneous fat cells and cultured 3T3-L1 adipocytes, and in vivo. KEY FINDINGS: It was determined that ßHB failed to induce changes in the oxidative capacity, citrate synthase activity or browning gene expression patterns in isolated adipocytes, and did not exert a permissive effect on ß-adrenergic agonist-induced browning. In addition, 3T3-L1 adipocytes differentiated following ßHB treatment exhibited downregulated Ucp1 expression levels, a result that was recapitulated in the subcutaneous adipose tissue of Wistar rats after ßHB salt treatment. Rats administered ßHB salts also presented reduced brown adipose tissue UCP1 protein expression. SIGNIFICANCE: The mechanisms underlying ketogenic diet-induced browning of adipocytes are not known. The results from the present study indicate that physiological concentrations of ßHB are not responsible for this phenomenon, despite the observed ßHB-mediated downregulation of UCP1 expression.
