Faculty Collaboration Database

Vanillic acid mitigates hyperinsulinemia induced ER stress mediated altered calcium homeostasis, MAMs distortion and surplus lipogenesis in HepG2 cells. Chem Biol Interact 2023 Apr 25;375:110365

Date

02/11/2023

Pubmed ID

36764371

DOI

10.1016/j.cbi.2023.110365

Scopus ID

2-s2.0-85149894533 (requires institutional sign-in at Scopus site)   14 Citations

Abstract

Hyperinsulinemia (HI) induced insulin resistance (IR) and associated pathologies are the burning and unsolvable issues in diabetes treatment. The cellular, molecular and biochemical events associated with HI are not yet elucidated. Similarly, no focused research on designing therapeutic strategies with natural products for attenuation of HI are seen in literature. Keeping this in mind we planned the present study to evaluate the alterations occurring at ER/Ca²⁺ homeostasis/mitochondria associated endoplasmic reticulum membranes (MAMs) in HepG2 cells during HI and to evaluate the possible beneficial effect of vanillic acid (VA) to mitigate the complications. An in vitro model of HI was established by treating HepG2 cells with human insulin (1 μM) for 24 h. Then, ER stress, Ca²⁺ homeostasis, MAMs, IR and hepatic lipogenesis were studied at protein level. Various proteins critical to ER, Ca²⁺ homeostasis and MAMs such as p-IRE-1α, ATF6, p-PERK, p-eIF2α, CHOP, XBP1, p-CAMKII, InsP3R, SERCA, JNK, GRP78, VDAC, Cyp D, GRP75, MFN2, PTEN and mTORC were studied and found altered significantly causing ER stress, defect in Ca²⁺ movements and distortion of MAMs. The decreased expression of IRS2 and an unaltered expression of IRS1 confirmed the development of selective insulin resistance in hepatocytes during HI and this was the crucial factor for the progression of the hepatic lipid accumulation. We found simultaneous treatment of VA is beneficial up to a certain extent to protect HepG2 cells from the adverse effect of HI via its antioxidant, antilipogenic, mitochondrial and ER protection properties.

Author List

Mohan S, Nair A, Poornima MS, Raghu KG

Author

Anupama Nair Postdoctoral Researcher 3 in the Obstetrics and Gynecology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Calcium
Endoplasmic Reticulum Stress
Hep G2 Cells
Homeostasis
Humans
Insulin Resistance
Lipogenesis
Vanillic Acid