Berberine attenuates the abnormal ectopic lipid deposition in skeletal muscle

Free Radic Biol Med. 2020 Nov 1;159:66-75. doi: 10.1016/j.freeradbiomed.2020.07.028. Epub 2020 Jul 31.

Abstract

Background: Lipid deposition in non-adipose tissue is associated with a propensity to obesity. Skeletal muscle mitochondrial dysfunction, evidenced by incomplete beta oxidation may contribute to ectopic lipid deposition during high fat diet-induced obesity. Berberine (BBR) has been proved to possess the properties of improving metabolic disorders in patients with obesity or type 2 diabetes mellitus. However, the precise mechanism remains obscure.

Methods: Mice were treated with berberine and metabolic profile were analyzed. Mitochondrial number and function were detected after berberine treatment in vitro and in vivo. The role of Adenosine 5'-monophosphate-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) was verified after RNA interference or adenovirus infection.

Results: In the current study, we investigated the influence of berberine on the lipid deposition of skeletal muscle and found that berberine could increase the mitochondrial number and function both in vivo and in vitro. Furthermore, berberine promoted the expression of PGC-1α, the crucial transcriptional coactivator related to mitochondrial biogenesis and function, through AMPK pathway. Berberine reduced the basal oxygen consumption rates (OCR) but increased the maximal OCR in C2C12 myocytes, which indicated that berberine could increase the potential function of mitochondria.

Conclusion: Our results proved that berberine can protect the lean body mass from excessive lipid accumulation, by promoting the mitochondrial biogenesis and improving fatty acid oxidation in an AMPK/PGC-1α dependent manner.

Keywords: AMPK; Berberine; Lipid deposition; PGC-1α; Skeletal muscle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Berberine* / pharmacology
  • Diabetes Mellitus, Type 2*
  • Humans
  • Lipids
  • Mice
  • Mitochondria, Muscle / metabolism
  • Muscle, Skeletal / metabolism
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / genetics
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Lipids
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Transcription Factors
  • Berberine