Lipophagy mediated carbohydrate-induced changes of lipid metabolism via oxidative stress, endoplasmic reticulum (ER) stress and ChREBP/PPARγ pathways

Cellular and Molecular Life Sciences : CMLS
Tao ZhaoZhi Luo

Abstract

High-carbohydrate diets (HCD) can induce the occurrence of nonalcoholic fatty liver disease (NAFLD), characterized by dramatic accumulation of hepatic lipid droplets (LDs). However, the potential molecular mechanisms are still largely unknown. In this study, we investigated the role of autophagy in the process of HCD-induced changes of hepatic lipid metabolism, and to examine the process of underlying mechanisms during these molecular contexts. We found that HCD significantly increased hepatic lipid accumulation and activated autophagy. Using primary hepatocytes, we found that HG increased lipid accumulation and stimulated the release of NEFA by autophagy-mediated lipophagy, and that lipophagy significantly alleviated high glucose (HG)-induced lipid accumulation. Oxidative and endoplasmic reticulum (ER) stress pathways played crucial regulatory roles in HG-induced lipophagy activation and HG-induced changes of lipid metabolism. Further investigation found that HG-activated lipophagy and HG-induced changes of lipid metabolism were via enhancing carbohydrate response element-binding protein (ChREBP) DNA binding capacity at PPARγ promoter region, which in turn induced transcriptional activation of the key genes related to lipogene...Continue Reading

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Citations

Feb 28, 2020·International Journal of Molecular Sciences·Suzan Attia MawedJie Mei
Feb 20, 2021·Journal of Trace Elements in Medicine and Biology : Organ of the Society for Minerals and Trace Elements (GMS)·Kun WuZhi Luo
Oct 24, 2020·Clinica Chimica Acta; International Journal of Clinical Chemistry·Qing LiuHong-Feng Gu
Apr 9, 2021·Frontiers in Cellular and Infection Microbiology·Prashanta SilwalEun-Kyeong Jo
Dec 23, 2021·Animal Science Journal = Nihon Chikusan Gakkaihō·Xiao LinLong Liu

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Methods Mentioned

BETA
transmission electron microscopy
Protein Assay
PCR
Assay
electrophoresis
MDA
flow cytometry
confocal microscopy

Software Mentioned

FlowJo
Pro Plus
geNorm
Image J
SPSS
Image

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