Dataset Information

The role of autophagy in high-fat diet-induced insulin resistance of adipose tissues in mice.

ABSTRACT:

Aims

Studies have observed changes in autophagic flux in the adipose tissue of type 2 diabetes patients with obesity. However, the role of autophagy in obesity-induced insulin resistance is unclear. We propose to confirm the effect of a high-fat diet (HFD) on autophagy and insulin signaling transduction from adipose tissue to clarify whether altered autophagy-mediated HFD induces insulin resistance, and to elucidate the possible mechanisms in autophagy-regulated adipose insulin sensitivity.

Methods

Eight-week-old male C57BL/6 mice were fed with HFD to confirm the effect of HFD on autophagy and insulin signaling transduction from adipose tissue. Differentiated 3T3-L1 adipocytes were treated with 1.2 mM fatty acids (FAs) and 50 nM Bafilomycin A1 to determine the autophagic flux. 2.5 mg/kg body weight dose of Chloroquine (CQ) in PBS was locally injected into mouse epididymal adipose (10 and 24 h) and 40 µM of CQ to 3T3-L1 adipocytes for 24 h to evaluate the role of autophagy in insulin signaling transduction.

Results

The HFD treatment resulted in a significant increase in SQSTM1/p62, Rubicon expression, and C/EBP homologous protein (CHOP) expression, yet the insulin capability to induce Akt (Ser473) and GSK3β (Ser9) phosphorylation were reduced. PHLPP1 and PTEN remain unchanged after CQ injection. In differentiated 3T3-L1 adipocytes treated with CQ, although the amount of phospho-Akt stimulated by insulin in the CQ-treated group was significantly lower, CHOP expressions and cleaved caspase-3 were increased and bafilomycin A1 induced less accumulation of LC3-II protein.

Conclusion

Long-term high-fat diet promotes insulin resistance, late-stage autophagy inhibition, ER stress, and apoptosis in adipose tissue. Autophagy suppression may not affect insulin signaling transduction via phosphatase expression but indirectly causes insulin resistance through ER stress or apoptosis.

SUBMITTER: Budi YP

PROVIDER: S-EPMC9387522 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

The role of autophagy in high-fat diet-induced insulin resistance of adipose tissues in mice.

Budi Yovita Permata YP Li Yi-Hsuan YH Huang Chien C Wang Mu-En ME Lin Yi-Chun YC Jong De-Shien DS Chiu Chih-Hsien CH Jiang Yi-Fan YF

PeerJ 20220815

<h4>Aims</h4>Studies have observed changes in autophagic flux in the adipose tissue of type 2 diabetes patients with obesity. However, the role of autophagy in obesity-induced insulin resistance is unclear. We propose to confirm the effect of a high-fat diet (HFD) on autophagy and insulin signaling transduction from adipose tissue to clarify whether altered autophagy-mediated HFD induces insulin resistance, and to elucidate the possible mechanisms in autophagy-regulated adipose insulin sensitivi ...[more]

PMID: 35990905

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Dataset Information

The role of autophagy in high-fat diet-induced insulin resistance of adipose tissues in mice.

Aims

Methods

Results

Conclusion

Publications

The role of autophagy in high-fat diet-induced insulin resistance of adipose tissues in mice.

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