Physiological concentrations of β-hydroxybutyrate do not promote adipocyte browning.

Abstract:

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 β-hydroxybutyrate (βHB) 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 1-3 mM and 4-7 mM, respectively. Herein, we investigated the impact of physiological concentrations of βHB on metabolism, and the expression of uncoupling protein 1 (UCP1) and other browning markers in adipose tissues. MAIN METHODS:The effects of βHB 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 βHB 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 β-adrenergic agonist-induced browning. In addition, 3T3-L1 adipocytes differentiated following βHB treatment exhibited downregulated Ucp1 expression levels, a result that was recapitulated in the subcutaneous adipose tissue of Wistar rats after βHB salt treatment. Rats administered βHB 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 βHB are not responsible for this phenomenon, despite the observed βHB-mediated downregulation of UCP1 expression.

journal_name

Life Sci

journal_title

Life sciences

authors

de Oliveira Caminhotto R,Andreotti S,Komino ACM,de Fatima Silva F,Sertié RAL,Christoffolete MA,Reis GB,Lima FB

doi

10.1016/j.lfs.2019.116683

subject

Has Abstract

pub_date

2019-09-01 00:00:00

pages

116683

eissn

0024-3205

issn

1879-0631

pii

S0024-3205(19)30609-5

journal_volume

232

pub_type

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