title: The multimerization and secretion of adiponectin are regulated by TNF-alpha.
abstract: Obesity is often associated with insulin resistance, mild systemic inflammation, and decreased blood adiponectin. However, some adipokines are increased in the adipose tissue of obese individuals, and whether these adipokines are directly related to the reductions in serum adiponectin levels in an autocrine or paracrine manner remains unknown. This study indicates that the tumor necrosis factor alpha (TNF-α) suppresses the multimerization and secretion of adiponectin both in vitro and in vivo. Additionally, TNF-α remarkably suppressed the expression of the ER-resident chaperone proteins ERO1-La, DsbA-L, and ERp44. Overexpression of the transcription factor PPARγ antagonized the suppressive effect of TNF-α on ERO1-La and DsbA-L expressions. Further study revealed that PPARγ enhanced the transcription of ERO1-La and DsbA-L by directly binding to the PPRE element of ERO1-La and DsbA-L promoters. TNF-α treatment decreased this binding activity. Furthermore, TNF-α treatment enhanced the interaction between adiponectin and ERp44. In this study, we show that TNF-α impairs adiponectin multimerization and consequently decreases adiponectin secretion by altering disulfide bond modification in the endoplasmic reticulum. Altered adiponectin multimerization could explain declined adiponectin levels and altered distribution of adiponectin complexes in the plasma of obese insulin-resistant individuals.
authors.affiliation: Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, 430070, Hubei, People's Republic of China.
authors.forename: Yiduo
authors.initials: Y
authors.lastname: He
authors.affiliation: Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, 430070, Hubei, People's Republic of China.
authors.forename: Linfang
authors.initials: L
authors.lastname: Lu
authors.affiliation: Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, 430070, Hubei, People's Republic of China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Wei
authors.affiliation: Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, 430070, Hubei, People's Republic of China.
authors.forename: Dan
authors.initials: D
authors.lastname: Jin
authors.affiliation: Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, 430070, Hubei, People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Qian
authors.affiliation: Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, 430070, Hubei, People's Republic of China.
authors.forename: An
authors.initials: A
authors.lastname: Yu
authors.affiliation: Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, 430070, Hubei, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Sun
authors.affiliation: Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, 430070, Hubei, People's Republic of China.
authors.forename: Jiesheng
authors.initials: J
authors.lastname: Cui
authors.affiliation: Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, 430070, Hubei, People's Republic of China. yangzq@mail.hzau.edu.cn.
authors.forename: Zaiqing
authors.initials: Z
authors.lastname: Yang
mesh_terms: D052242:Adiponectin / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004032:Diet; D059305:Diet, High-Fat / Q000009:adverse effects; D004220:Disulfides / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018832:Molecular Chaperones / Q000378:metabolism; D009765:Obesity / Q000503:physiopathology; D047495:PPAR gamma / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
chemical_list: D052242:Adiponectin; D004220:Disulfides; D018832:Molecular Chaperones; D047495:PPAR gamma; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha
keywords: Adiponectin; Multimerization; Obesity; PPARγ; Secretion