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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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Abstract

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.

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Abbreviations

ACC:

Acetyl-CoA carboxylase

AMPK-α:

AMP-activated protein kinase-α

DM:

Diabetes mellitus

FAS:

Fatty acid synthase

HDL:

High-density lipoprotein

HMG Co-A:

3-Hydroxy 3-methyl glutaryl coenzyme A

LCAT:

Lecithin cholesterol acyltransferase

LDL:

Low-density lipoprotein

LPL:

Lipoprotein lipase

PL:

Phospholipids

STZ:

Streptozotocin

SREBP-1C:

Sterol regulatory element-binding protein-1

TC:

Total cholesterol

T2DM:

Type 2 diabetes mellitus

TG:

Triglycerides

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Acknowledgements

Authors thank Ms. Yinhua Liu in Zhuhai Campus of Zunyi Medical University for her technical assistance on the use of the animal facility.

Funding

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.

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Authors and Affiliations

  1. Food Science and Technology Program, Beijing Normal University-Hong Kong Baptist University United International College, 2000, Jintong Road, Tangjiawan, Zhuhai, 519087, Guangdong, China

    Muthukumaran Jayachandran, Tongze Zhang, Ziyuan Wu & Baojun Xu

  2. Biomedicine Research and Development Center, Zhuhai Campus of the Zunyi Medical University, Zhuhai, 519041, Guangdong, China

    Yinhua Liu

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  1. Muthukumaran Jayachandran
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  2. Tongze Zhang
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  3. Ziyuan Wu
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Contributions

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.

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Correspondence to Baojun Xu.

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Jayachandran, M., Zhang, T., Wu, Z. et al. Isoquercetin regulates SREBP-1C via AMPK pathway in skeletal muscle to exert antihyperlipidemic and anti-inflammatory effects in STZ induced diabetic rats. Mol Biol Rep 47, 593–602 (2020). https://doi.org/10.1007/s11033-019-05166-y

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