48Biochemical mechanisms of the anti-obesity effect of a triterpenoid-enriched extract of Cynomorium songaricum in mice with high-fat-diet-induced obesity

Phytomedicine. 2020 Jul 15:73:153038. doi: 10.1016/j.phymed.2019.153038. Epub 2019 Jul 20.

Abstract

Background: HCY2, a triterpenoid-enriched extract of Cynomorii Herba, has been shown to reduce body weight and adiposity and attenuate manifestations of the associated metabolic syndrome in high-fat-diet (HFD)-fed mice.

Purpose: The current study aimed to investigate the biochemical mechanism underlying the anti-obesity effect produced by HCY2.

Study design: An HCY2-containing extract was examined for its effects on the regulation of adenosine monophosphate-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor gamma co-activator-1 (PGC1) pathways and the protein expression related to mitochondrial uncoupling and biogenesis in skeletal muscle using an HFD-induced obese mouse model.

Methods: The obese mouse model was produced by providing HFD (60% kcal from fat) ad libitum. The effects and signaling mechanisms of HCY2 were examined using analytical procedures which included enzyme-linked immunosorbent assay kits, Western blot analysis, and the use of a Clark-type oxygen electrode.

Results: The current study revealed that the weight reduction produced by HCY2 is associated with the activation of the AMPK signaling pathway, with resultant increases in mitochondrial biogenesis and expression of uncoupling protein 3 in skeletal muscle in vivo. The use of a recoupler, ketocholestanol, delineated the precise role of mitochondrial uncoupling in the anti-obesity effect afforded by HCY2 in obese mice.

Conclusion: Our experimental findings offer a promising prospect for the use of HCY2 in the management of obesity through the regulation of AMPK/PGC1 pathways.

Keywords: AMPK; Cynomorium songarium; Mitochondrial biogenesis; Mitochondrial uncoupling; Obesity.

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Animals
  • Anti-Obesity Agents / chemistry
  • Anti-Obesity Agents / pharmacology*
  • Body Weight / drug effects
  • Cynomorium / chemistry*
  • Diet, High-Fat / adverse effects
  • Male
  • Mice, Inbred ICR
  • Mitochondria, Muscle / drug effects
  • Mitochondria, Muscle / metabolism
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism
  • Obesity / drug therapy*
  • Obesity / etiology*
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / metabolism
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology
  • Signal Transduction / drug effects
  • Triterpenes / pharmacology
  • Weight Loss / drug effects

Substances

  • Anti-Obesity Agents
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Plant Extracts
  • Ppargc1a protein, mouse
  • Triterpenes
  • AMP-Activated Protein Kinases