Autophagy Ablation in Adipocytes Induces Insulin Resistance and Reveals Roles for Lipid Peroxide and Nrf2 Signaling in Adipose-Liver Crosstalk

Jinjin Cai; Karla M Pires; Maroua Ferhat; Bhagirath Chaurasia; Márcio A Buffolo; Rana Smalling; Ashot Sargsyan; Donald L Atkinson; Scott A Summers; Timothy E Graham; Sihem Boudina

doi:10.1016/j.celrep.2018.10.040

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Autophagy Ablation in Adipocytes Induces Insulin Resistance and Reveals Roles for Lipid Peroxide and Nrf2 Signaling in Adipose-Liver Crosstalk

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Autophagy Ablation in Adipocytes Induces Insulin Resistance and Reveals Roles for Lipid Peroxide and Nrf2 Signaling in Adipose-Liver Crosstalk

Jinjin Cai, Karla M Pires, Maroua Ferhat, Bhagirath Chaurasia, Márcio A Buffolo, Rana Smalling, Ashot Sargsyan, Donald L Atkinson, Scott A Summers, Timothy E Graham, …

Cell reports (Cambridge), Vol.25(7), pp.1708-1717.e5

11/13/2018

DOI: 10.1016/j.celrep.2018.10.040

PMCID: PMC6802939

PMID: 30428342

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Abstract

Autophagy is a homeostatic cellular process involved in the degradation of long-lived or damaged cellular components. The role of autophagy in adipogenesis is well recognized, but its role in mature adipocyte function is largely unknown. We show that the autophagy proteins Atg3 and Atg16L1 are required for proper mitochondrial function in mature adipocytes. In contrast to previous studies, we found that post-developmental ablation of autophagy causes peripheral insulin resistance independently of diet or adiposity. Finally, lack of adipocyte autophagy reveals cross talk between fat and liver, mediated by lipid peroxide-induced Nrf2 signaling. Our data reveal a role for autophagy in preventing lipid peroxide formation and its transfer in insulin-sensitive peripheral tissues.

Adipocytes - cytology

Adipocytes - metabolism

Adipose Tissue - metabolism

Adipose Tissue, Brown - metabolism

Adipose Tissue, Brown - pathology

Adipose Tissue, White - metabolism

Adipose Tissue, White - pathology

Adiposity

Animals

Autophagy

Autophagy-Related Proteins - metabolism

Body Composition

Body Weight

Humans

Inflammation - pathology

Insulin Resistance

Kelch-Like ECH-Associated Protein 1 - metabolism

Lipid Peroxides - metabolism

Lipoproteins, HDL - metabolism

Liver - metabolism

Mice, Knockout

Mitochondria - metabolism

NF-E2-Related Factor 2 - metabolism

Signal Transduction

Ubiquitin-Conjugating Enzymes - metabolism

Details

Title: Subtitle: Autophagy Ablation in Adipocytes Induces Insulin Resistance and Reveals Roles for Lipid Peroxide and Nrf2 Signaling in Adipose-Liver Crosstalk
Creators: Jinjin Cai - University of Utah
Karla M Pires - University of Utah
Maroua Ferhat - University of Utah
Bhagirath Chaurasia - University of Utah
Márcio A Buffolo - University of Utah
Rana Smalling - University of Utah
Ashot Sargsyan - University of Utah
Donald L Atkinson - University of Utah
Scott A Summers - University of Utah
Timothy E Graham - University of Utah
Sihem Boudina - University of Utah
Resource Type: Journal article
Publication Details: Cell reports (Cambridge), Vol.25(7), pp.1708-1717.e5
DOI: 10.1016/j.celrep.2018.10.040
PMID: 30428342
PMCID: PMC6802939
NLM abbreviation: Cell Rep
ISSN: 2211-1247
eISSN: 2211-1247
Grant note: R01 DK100826 / NIDDK NIH HHS R01 DK099110 / NIDDK NIH HHS R01 DK098646 / NIDDK NIH HHS
Language: English
Date published: 11/13/2018
Academic Unit: Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Internal Medicine
Record Identifier: 9984360157602771

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