Research Article Details
| Article ID: | A03453 |
| PMID: | 33994854 |
| Source: | Int J Biol Sci |
| Title: | Berberine alleviates lipid metabolism disorders via inhibition of mitochondrial complex I in gut and liver. |
| 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. |
| DOI: | 10.7150/ijbs.54604 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S01 | Improve insulin resistance | insulin sensitizer; insulin resistance; glucose tolerance | Biguanide: increases 5-AMP activated protein kinase signaling; SGLT-2 inhibitor; Thiazalidinedione: selective PPAR-γ agonists; GLP-1 agonist | Metformin; Empagliflozin; Canagliflozin; Rosiglitazone; Pioglitazone; Liraglutide | Details |
| S02 | Enhance lipid metabolism | triglyceride-lowering; lipid tolerance; lipid metabolism | 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitor; Decreases intestinal cholesterol absorption; FXR agonist; ACC inhibitor; FAS inhibitor; DGAT2 inhibitor; SCD-1 inhibitor | Atorvastatin; Ezetimibe; Obeticholic Acid; GS-9674; GS-0976; TVB-2640; IONIS-DGAT2rx; Aramchol; | Details |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name | |
|---|---|---|---|---|---|---|---|
| T01 | 5'-AMP-activated protein kinase subunit beta-1 | PRKAB1 | activator | Kinase | Q9Y478 | AAKB1_HUMAN | Details |
| T10 | Caspase-1 | CASP1 | inhibitor | Enzyme | P29466 | CASP1_HUMAN | Details |
| T22 | Stearoyl-CoA desaturase | SCD | inhibitor | Enzyme | O00767 | SCD_HUMAN | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I13 | 3146 | Lipid metabolism disorder | An inherited metabolic disorder that involves the creation and degradation of lipids. http://en.wikipedia.org/wiki/Lipid_metabolism | disease of metabolism/ inherited metabolic disorder | Details |
| I05 | 9352 | Type 2 diabetes mellitus | A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 | disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus | Details |
| I14 | 9970 | Obesity | An overnutrition that is characterized by excess body fat, traditionally defined as an elevated ratio of weight to height (specifically 30 kilograms per meter squared), has_material_basis_in a multifactorial etiology related to excess nutrition intake, decreased caloric utilization, and genetic susceptibility, and possibly medications and certain disorders of metabolism, endocrine function, and mental illness. https://en.wikipedia.org/wiki/Obesity | disease of metabolism/acquired metabolic disease/ nutrition disease/overnutrition | Details |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D587 | Fecal microbiota transplantation | Miscellany | -- | -- | -- | Under investigation | Details |
| D080 | Citrulline | Chemical drug | DB00155 | -- | -- | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |
| D029 | Berberine | Chemical drug | DB04115 | AMPK activator | Improve insulin resistance | Under clinical trials | Details |