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Berberine alleviates lipid metabolism disorders via inhibition of mitochondrial complex I in gut and liver
- Source :
- International Journal of Biological Sciences. 17:1693-1707
- Publication Year :
- 2021
- Publisher :
- Ivyspring International Publisher, 2021.
-
Abstract
- This study is to investigate the relationship between berberine (BBR) and mitochondrial complex I in lipid metabolism. BBR reversed high-fat diet-induced obesity, hepatic steatosis, hyperlipidemia and insulin resistance in mice. Fatty acid consumption, β-oxidation and lipogenesis were attenuated in liver after BBR treatment which may be through reduction in SCD1, FABP1, CD36 and CPT1A. BBR promoted fecal lipid excretion, which may result from the reduction in intestinal CD36 and SCD1. Moreover, BBR inhibited mitochondrial complex I-dependent oxygen consumption and ATP synthesis of liver and gut, but no impact on activities of complex II, III and IV. BBR ameliorated mitochondrial swelling, facilitated mitochondrial fusion, and reduced mtDNA and citrate synthase activity. BBR decreased the abundance and diversity of gut microbiome. However, no change in metabolism of recipient mice was observed after fecal microbiota transplantation from BBR treated mice. In primary hepatocytes, BBR and AMPK activator A769662 normalized oleic acid-induced lipid deposition. Although both the agents activated AMPK, BBR decreased oxygen consumption whereas A769662 increased it. Collectively, these findings indicated that BBR repressed complex I in gut and liver and consequently inhibited lipid metabolism which led to alleviation of obesity and fatty liver. This process was independent of intestinal bacteria.
- Subjects :
- Male
Mitochondrial Diseases
Lipid Metabolism Disorder
Berberine
Lipid Metabolism Disorders
Pharmacology
Applied Microbiology and Biotechnology
Mice
Mice, Inbred AKR
03 medical and health sciences
Microscopy, Electron, Transmission
medicine
Animals
Citrate synthase
Molecular Biology
Ecology, Evolution, Behavior and Systematics
030304 developmental biology
0303 health sciences
Electron Transport Complex I
biology
Chemistry
Fatty liver
AMPK
Lipid metabolism
Cell Biology
Lipid Metabolism
medicine.disease
Intestines
Disease Models, Animal
Liver
mitochondrial fusion
Lipogenesis
biology.protein
Steatosis
Oxidation-Reduction
Developmental Biology
Subjects
Details
- ISSN :
- 14492288
- Volume :
- 17
- Database :
- OpenAIRE
- Journal :
- International Journal of Biological Sciences
- Accession number :
- edsair.doi.dedup.....31e9f98b16cf891771b3701e5319433f