Nrf2 deletion from adipocytes, but not hepatocytes, potentiates systemic metabolic dysfunction after long-term high-fat diet-induced obesity in mice

American Journal of Physiology. Endocrinology and Metabolism
Dionysios V ChartoumpekisThomas W Kensler

Abstract

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a canonical regulator of cytoprotective gene expression, but evidence of its cross talk with other pathways, including metabolic ones, is ever increasing. Pharmacologic or systemic genetic activation of the Nrf2 pathway partially protects from obesity in mice and ameliorates fasting hyperglycemia in mice and humans. However, systemic Nrf2 deletion also protects from diet-induced obesity and insulin resistance in mice. To further investigate the effect of the disruption of Nrf2 on obesity in a tissue-specific manner, we focused on adipocytes and hepatocytes with targeted deletion of Nrf2. To this end, mice with cell-specific deletion of Nrf2 in adipocytes (ANKO) or hepatocytes (HeNKO) were fed a high-fat diet (HFD) for 6 mo and showed similar increases in body weight and body fat content. ANKO mice showed a partially deteriorated glucose tolerance, higher fasting glucose levels, and higher levels of cholesterol and nonesterified fatty acids compared with their Control counterparts. The HeNKO mice, though, had lower insulin levels and trended toward improved insulin sensitivity without having any difference in liver triglyceride accumulation. This study compared for the first ...Continue Reading

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Citations

Jun 8, 2018·The Journal of Endocrinology·Clara LefrancAurelie Nguyen Dinh Cat
Apr 5, 2020·Biomolecules·Concepción Santiago-FernándezLourdes Garrido-Sánchez
Sep 26, 2020·International Journal of Molecular Sciences·Shiri LiHirohito Ichii
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Feb 14, 2021·Redox Biology·Bato KoracAleksandra Jankovic
Dec 18, 2020·International Journal of Molecular Sciences·David E Stec, Terry D Hinds
Mar 29, 2021·Redox Biology·David Ross, David Siegel

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Methods Mentioned

BETA
genotyping
PCRs
enzyme-linked immunosorbent assay
ELISA
PCR
electrophoresis
dissection

Software Mentioned

geNorm
GraphPad Prism
PrimerBank

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