title: Fetuin-A downregulates adiponectin through Wnt-PPARγ pathway in lipid induced inflamed adipocyte.
abstract: Adiponectin secreted from adipocytes is an anti-diabetic and anti-atherogenic adipokine. Adiponectin level is known to fall significantly in obesity induced type 2 diabetes which worsen insulin sensitivity because of aberrant lipid management. However, underlying mechanism of adiponectin decrease in obese diabetic condition is yet unclear. We report here that lowering of plasma adiponectin coincided with the higher Fetuin A (FetA) level in high fat diet (HFD) induced obese diabetic mice. Knock down of FetA gene (FetAKD) elevated adiponectin level markedly in HFD mice, while reinforcement of FetA into FetAKDHFD mice reduced its level again. These results indicate FetA's involvement in the lowering of adiponectin level in obesity induced diabetic mice. Our findings to understand how FetA could affect adiponectin decrease demonstrated that FetA could enhance Wnt3a expression in the adipocyte of HFD mice. FetA addition to 3T3L1 adipocyte incubation elevated Wnt3a expression in a dose dependent manner. Overexpression of Wnt3a by FetA inhibited PPARγ and adiponectin. FetA failed to reduce PPARγ and adiponectin in Wnt3a gene knocked down 3T3L1` adipocytes. All these suggest that FetA mediate its inhibitory effect on adiponectin through Wnt3a-PPARγ pathway. Inhibition of adiponectin expression through FetA and Wnt3a significantly compromised with the activation of AMPK and its downstream signalling molecules which adversely affected lipid management causing loss of insulin sensitivity. Downregulation of adiponectin in inflamed adipocyte by FetA through the mediation of Wnt3a and PPARγ is a new report.
authors.affiliation: Department of Zoology, School of Life Science, Visva-Bharati (A Central University), Santiniketan 731235, West Bengal, India.
authors.forename: Soumik
authors.initials: S
authors.lastname: Agarwal
authors.affiliation: Department of Zoology, School of Life Science, Visva-Bharati (A Central University), Santiniketan 731235, West Bengal, India.
authors.forename: Mrittika
authors.initials: M
authors.lastname: Chattopadhyay
authors.affiliation: Department of Zoology, School of Life Science, Visva-Bharati (A Central University), Santiniketan 731235, West Bengal, India.
authors.forename: Sandip
authors.initials: S
authors.lastname: Mukherjee
authors.affiliation: Department of Molecular Biology and Biotechnology, Tezpur University, Tezpur, 784028, Napaam, Sonitpur, Assam, India.
authors.forename: Suman
authors.initials: S
authors.lastname: Dasgupta
authors.affiliation: Department of Endocrinology & Metabolism, Institute of Postgraduate Medical Education and Research/SSKM Hospital, Kolkata 700020, West Bengal, India.
authors.forename: Satinath
authors.initials: S
authors.lastname: Mukhopadhyay
authors.affiliation: Department of Zoology, School of Life Science, Visva-Bharati (A Central University), Santiniketan 731235, West Bengal, India. Electronic address: bhattacharyasa@gmail.com.
authors.forename: Samir
authors.initials: S
authors.lastname: Bhattacharya
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000276:immunology*; D052242:Adiponectin / Q000276:immunology*; D000818:Animals; D002478:Cells, Cultured; D007249:Inflammation / Q000276:immunology; D007333:Insulin Resistance; D008055:Lipids / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009765:Obesity / Q000276:immunology*; D047495:PPAR gamma / Q000276:immunology*; D015398:Signal Transduction; D051153:Wnt Proteins / Q000276:immunology*; D060749:alpha-2-HS-Glycoprotein / Q000276:immunology*
chemical_list: D052242:Adiponectin; D008055:Lipids; D047495:PPAR gamma; D051153:Wnt Proteins; D060749:alpha-2-HS-Glycoprotein
keywords: Adipocyte; Adiponectin; Fetuin-A; Insulin resistance; PPARγ; Wnt3a