PDIA4, a novel ER stress chaperone, modulates adiponectin expression and inflammation in adipose tissue.

Autor:	Su SC; Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan., Chien CY; School of Dentistry, National Defense Medical Center, Taipei, Taiwan., Chen YC; School of Dentistry, National Defense Medical Center, Taipei, Taiwan., Chiang CF; School of Dentistry, National Defense Medical Center, Taipei, Taiwan., Lin FH; School of Public Health, National Defense Medical Center, Taipei, Taiwan., Kuo FC; Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan., Huang CL; Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan., Li PF; Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan., Liu JS; Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan., Lu CH; Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan., Ho LJ; Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan., Hsieh CH; Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan., Hung YJ; Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.; Department and Graduate Institute of Biochemistry, National Defense Medical Center, Taipei, Taiwan., Shieh YS; Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.; School of Dentistry, National Defense Medical Center, Taipei, Taiwan.; Department and Graduate Institute of Biochemistry, National Defense Medical Center, Taipei, Taiwan., Lee CH; Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.; Department and Graduate Institute of Biochemistry, National Defense Medical Center, Taipei, Taiwan.
Jazyk:	angličtina
Zdroj:	BioFactors (Oxford, England) [Biofactors] 2022 Sep; Vol. 48 (5), pp. 1060-1075. Date of Electronic Publication: 2022 Jun 08.
DOI:	10.1002/biof.1872
Abstrakt:	Increasing evidence supporting a causal link between obesity and endoplasmic reticulum (ER) stress in adipose tissue is being reported. Protein disulfide isomerase 4 (PDIA4) is a novel ER chaperone involved in the pancreatic β-cells pathogenesis in diabetes. However, the role of PDIA4 in obesity progression remains poorly understood. To assess the relationship between PDIA4, adiponectin, and metformin, we used the palmitate-induced inflammation in hypertrophic adipocytes and the high-fat diet-induced obesity mouse model. Our results revealed that palmitate-induced hypertrophic adipocytes exhibit obesity-associated conditions such as increased lipid accumulation, inflammation, and reduced glucose uptake. Pharmacological and genetic inhibition of PDIA4 significantly reverses these obesity-associated conditions in adipocytes. PDIA4 mechanistically promotes obesity progression via adiponectin downregulation. Furthermore, metformin modulates PDIA4 and adiponectin expression and improves obesity-associated conditions in both in vitro adipocytes and in vivo mouse models. Serum PDIA4 concentrations are also associated with body mass index, adiponectin, triglycerides, and inflammatory cytokines in humans. This is the first study demonstrating that PDIA4 modulates adipocytes by downregulating adiponectin. Moreover, metformin may serve as a potential therapeutic for preventing obesity via PDIA4-targeting. (© 2022 International Union of Biochemistry and Molecular Biology.)
Databáze:	MEDLINE
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