Isoquercetin regulates SREBP-1C via AMPK pathway in skeletal muscle to exert antihyperlipidemic and anti-inflammatory effects in STZ induced diabetic rats
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Diabetes mellitus (DM) is a cluster of metabolic diseases that exhibits high blood glucose levels accompanied by hyperlipidemia and inflammation. DM is the primary risk factor contributes majorly to cardiovascular disease (CVD) mediated morbidity and mortality. The incidence of dyslipidemia seems to attribute considerably to the initiation of CVDs. The beneficial action of isoquercetin on hyperlipidemia and related signaling pathways are not documented yet, hence we decide to carry out this study. The experimental rats were divided into five groups: Group 1, control rats; group 2, isoquercetin control (40 mg/kg b.w); group 3, diabetic rats (STZ-40 mg/kg b.w); group 4, diabetic + isoquercetin (40 mg/kg b.w); and group 5, diabetic + glibenclamide (600 µg/kg b.w). The animals were sacrificed at the end of the experimental duration of 45 days. Results of our analysis reveal that isoquercetin have a major impact on the tissue lipid profile, isoquercetin strongly regulates the expression of various lipid-metabolizing enzymes, C-reactive protein, expression of various inflammatory genes, SREBP-1C genes and proteins and AMP-activated protein kinase-α (AMPK) signaling pathway genes and proteins. Results recommend that isoquercetin can be effective in mitigating the consequences of hyperlipidemia and DM.
KeywordsStreptozotocin Hyperlipidemia HMG-Co-A AMPK-α SREBP-1C
AMP-activated protein kinase-α
Fatty acid synthase
- HMG Co-A
3-Hydroxy 3-methyl glutaryl coenzyme A
Lecithin cholesterol acyltransferase
Sterol regulatory element-binding protein-1
Type 2 diabetes mellitus
Authors thank Ms. Yinhua Liu in Zhuhai Campus of Zunyi Medical University for her technical assistance on the use of the animal facility.
BX and SSMC designed, written and proofread the manuscript, MJ designed, carried out the experiments, written and proofread the manuscript, TZ helped in feeding the animals and dissection, ZW helped in carrying out few molecular studies.
The work was jointly supported by two grants R201714 and R201914 from Beijing Normal University-Hong Kong Baptist University United International College, Zhuhai, Guangdong, China.
Compliance with ethical standards
Conflict of interest
Authors declare no conflict of interest.
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