Raspberry ketone induces brown-like adipocyte formation through suppression of autophagy in adipocytes and adipose tissue

J Nutr Biochem. 2018 Jun;56:116-125. doi: 10.1016/j.jnutbio.2018.01.017. Epub 2018 Feb 13.

Abstract

Promoting white adipose tissue (WAT) to acquire brown-like characteristics is a promising approach for obesity treatment. Although raspberry ketone (RK) has been reported to possess antiobesity activity, its effects on the formation of brown-like adipocytes remain unclear. Therefore, we investigated the effects and underlying mechanism of RK on WAT browning in 3T3-L1 adipocytes and rats with ovariectomy (Ovx)-induced obesity. RK (100 μM) significantly induced browning of 3T3-L1 cells by increasing mitochondrial biogenesis and the expression of browning-specific proteins (PR domain containing 16, PRDM16; peroxisome proliferator-activated receptor gamma coactivator 1-alpha, PGC-1α; uncoupling protein-1, UCP-1) and lipolytic enzymes (hormone-sensitive lipase and adipose triglyceride lipase). RK significantly reduced the expression of the autophagy-related protein Atg12 and increased the expression of p62 and heme oxygenase 1 (HO-1). Additionally, these effects of RK were reversed by the HO-1 inhibitor SnPP (20 μM). In addition, RK (160 mg/kg, gavage, for 8 weeks) significantly reduced body weight gain (Ovx+RK, 191.8 ± 4.6 g vs. Ovx, 223.6 ± 5.9; P < .05), food intake, the amount of inguinal adipose tissue (Ovx+RK, 9.05 ± 1.1 g vs Ovx, 12.9 ± 0.92 g; P < .05) and the size of white adipocytes in Ovx rats. Moreover, compared to expression in the Ovx group, the levels of browning-specific proteins were significantly higher and the levels of autophagy-related proteins were significantly lower in the Ovx+RK group. Therefore, this study elucidated the mechanism associated with RK-induced WAT browning and thus provides evidence to support the clinical use of RK for obesity treatment.

Keywords: 3T3-L1 Adipocyte; Beige adipocyte; Obesity; Ovariectomy; Raspberry ketone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / cytology*
  • Adipose Tissue, Brown / cytology*
  • Animals
  • Autophagy / drug effects*
  • Autophagy-Related Protein 12 / metabolism
  • Body Weight
  • Butanones / pharmacology*
  • Cell Survival
  • Female
  • Heme Oxygenase (Decyclizing) / metabolism
  • Heme Oxygenase-1 / metabolism
  • Lipid Metabolism
  • Membrane Proteins / metabolism
  • Mice
  • Mitochondria / metabolism
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / metabolism
  • Positive Regulatory Domain I-Binding Factor 1 / metabolism
  • Rats
  • Rats, Wistar
  • Transcription Factors / metabolism
  • Uncoupling Protein 1 / metabolism

Substances

  • Atg12 protein, mouse
  • Autophagy-Related Protein 12
  • Butanones
  • Membrane Proteins
  • PRDM16 protein, rat
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Ppargc1a protein, mouse
  • Ppargc1a protein, rat
  • Prdm1 protein, mouse
  • Transcription Factors
  • Ucp1 protein, mouse
  • Ucp1 protein, rat
  • Uncoupling Protein 1
  • raspberry ketone
  • Heme Oxygenase (Decyclizing)
  • Heme Oxygenase-1
  • Hmox1 protein, mouse
  • Hmox1 protein, rat
  • Positive Regulatory Domain I-Binding Factor 1