D-mannitol induces a brown fat-like phenotype via a β3-adrenergic receptor-dependent mechanism

Hui Jeon Jeon, Dong Kyu Choi, Jaeheon Choi, Seul Lee, Heejin Lee, Ji Hoon Yu, Sang Hyun Min

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

The presence of brown adipocytes within white adipose tissue is associated with pheno-types that exhibit improved metabolism and proper body weight maintenance. Therefore, a variety of dietary agents that facilitate the browning of white adipocytes have been investigated. In this study, we screened a natural product library comprising 133 compounds with the potential to promote the browning of white adipocytes, and found that D-mannitol induces the browning of 3T3-L1 adipocytes by enhancing the expression of brown fat-specific genes and proteins, and upregulating lipid metabolism markers. D-mannitol also increased the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase 1 (ACC), suggesting a possible role in lipolysis and fat oxidation. Moreover, an increase in the expression of genes associated with D-mannitol-induced browning was strongly correlated with the activation of the β3-adrenergic receptor as well as AMPK, protein kinase A (PKA), and PPARγ coactivator 1α (PGC1α). D-mannitol effectively reduced the body weight of mice fed a high-fat diet, and increased the expression of β1-oxidation and energy expenditure markers, such as Cidea, carnitine palmityl transferase 1 (CPT1), uncoupling protein 1 (UCP1), PGC1α, and acyl-coenzyme A oxidase (ACOX1) in the inguinal white adipose tissue. Our findings suggest that D-mannitol plays a dual regulatory role by inducing the generation of a brown fat-like phenotype and enhancing lipid metabolism. These results indicate that D-mannitol can function as an anti-obesity supplement.

Original languageEnglish
Article number768
JournalCells
Volume10
Issue number4
DOIs
StatePublished - Apr 2021

Keywords

  • Brown adipocyte
  • Browning
  • D-mannitol
  • Obesity
  • β3-adrenergic receptor

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