Chen J, Leong PK, Leung HY, Chan WM, Wong HS, Ko KM
 School of Life and Health Science, The Chinese University of Hong Kong, Shenzhen
 Division of Life Science, The Hong Kong University of Science & Technology, Clear Water Bay, Hong Kong
 Buck Institute for Research on Aging, Novato, USA
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.