title: SPARC is over-expressed in adipose tissues of diet-induced obese rats and causes insulin resistance in 3T3-L1 adipocytes.
abstract: Secreted protein acidic and rich in cysteine (SPARC) is a secretory multifunctional matricellular glycoprotein. High circulating levels of SPARC have been reported to be associated with obesity and insulin resistance. The aim of the present study was to investigate whether SPARC induces insulin resistance and mitochondrial dysfunction in adipocytes. Our results showed that feeding high fat diet to rats for 12 weeks significantly increased SPARC expression in adipose tissues at both mRNA and protein levels. Moreover, SPARC overexpression in stably transfected 3T3-L1 cells induced insulin resistance and mitochondrial dysfunction, as evidenced by inhibition of insulin-stimulated glucose transport, lower ATP synthesis and mitochondrial membrane potential, reduced expression of glucose transporter 4 (GLUT4), and increased levels of reactive oxygen species (ROS) in mature adipocytes. Finally, overexpression of SPARC also modulated the expression levels of several inflammatory cytokines, which play important roles in insulin resistance, glucose and lipid metabolism during adipogenesis. In conclusion, our data suggest that SPARC is involved in obesity-induced adipose insulin resistance and may serve as a potential target in the treatment of obesity and obesity-related insulin resistance.
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, People's Republic of China. Electronic address: cmu1hzhaoyuyan@163.com.
authors.forename: Yuyan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Respiratory Medicine, Cardio-Cerebral Vascular Disease Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, People's Republic of China.
authors.forename: Lizhi
authors.initials: L
authors.lastname: Yuan
authors.affiliation: Food and Fermentation Institute, Ningxia Light Industrial Design and Research Institute, Yinchuan, Ningxia 750001, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yi
authors.affiliation: Food and Fermentation Institute, Ningxia Light Industrial Design and Research Institute, Yinchuan, Ningxia 750001, People's Republic of China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhao
authors.affiliation: Food and Fermentation Institute, Ningxia Light Industrial Design and Research Institute, Yinchuan, Ningxia 750001, People's Republic of China.
authors.forename: Qianru
authors.initials: Q
authors.lastname: Yi
authors.affiliation: Food and Fermentation Institute, Ningxia Light Industrial Design and Research Institute, Yinchuan, Ningxia 750001, People's Republic of China.
authors.forename: Tongwu
authors.initials: T
authors.lastname: Yong
mesh_terms: D041721:3T3-L1 Cells; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D004822:Epididymis / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat / Q000378:metabolism*; D008297:Male; D053078:Membrane Potential, Mitochondrial; D051379:Mice; D009765:Obesity / Q000209:etiology / Q000378:metabolism*; D015676:Osteonectin / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D016207:Cytokines; D015676:Osteonectin; D017382:Reactive Oxygen Species; D005947:Glucose
keywords: Inflammation; Insulin resistance; Mitochondrial dysfunction; Obesity; SPARC