title: Midkine, a potential link between obesity and insulin resistance.
abstract: Obesity is associated with increased production of inflammatory mediators in adipose tissue, which contributes to chronic inflammation and insulin resistance. Midkine (MK) is a heparin-binding growth factor with potent proinflammatory activities. We aimed to test whether MK is associated with obesity and has a role in insulin resistance. It was found that MK was expressed in adipocytes and regulated by inflammatory modulators (TNF-α and rosiglitazone). In addition, a significant increase in MK levels was observed in adipose tissue of obese ob/ob mice as well as in serum of overweight/obese subjects when compared with their respective controls. In vitro studies further revealed that MK impaired insulin signaling in 3T3-L1 adipocytes, as indicated by reduced phosphorylation of Akt and IRS-1 and decreased translocation of glucose transporter 4 (GLUT4) to the plasma membrane in response to insulin stimulation. Moreover, MK activated the STAT3-suppressor of cytokine signaling 3 (SOCS3) pathway in adipocytes. Thus, MK is a novel adipocyte-secreted factor associated with obesity and inhibition of insulin signaling in adipocytes. It may provide a potential link between obesity and insulin resistance.
authors: Department of Endocrinology, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai, China ; Department of Endocrinology, Shanghai Songjiang Center Hospital, Shanghai, China.
authors: Nengguang
authors: N
authors: Fan
authors: Department of Endocrinology, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors: Haiyan
authors: H
authors: Sun
authors: Department of Endocrinology, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors: Yifei
authors: Y
authors: Wang
authors: Department of Endocrinology, Shanghai Songjiang Center Hospital, Shanghai, China.
authors: Lijuan
authors: L
authors: Zhang
authors: Department of Endocrinology, Shanghai Songjiang Center Hospital, Shanghai, China.
authors: Zhenhua
authors: Z
authors: Xia
authors: Department of Laboratory Medicine, Shanghai Songjiang Center Hospital, Shanghai, China.
authors: Liang
authors: L
authors: Peng
authors: Department of Laboratory Medicine, Shanghai Songjiang Center Hospital, Shanghai, China.
authors: Yanqiang
authors: Y
authors: Hou
authors: Department of Laboratory Medicine, Shanghai Songjiang Center Hospital, Shanghai, China.
authors: Weiqin
authors: W
authors: Shen
authors: Department of Endocrinology, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors: Rui
authors: R
authors: Liu
authors: Department of Endocrinology, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors: Yongde
authors: Y
authors: Peng
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D051379:Mice; D008875:Middle Aged; D000078792:Midkine; D009765:Obesity / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D000077154:Rosiglitazone; D015398:Signal Transduction / Q000187:drug effects; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D016207:Cytokines; D051275:Glucose Transporter Type 4; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C495693:Slc2a4 protein, mouse; D050826:Suppressor of Cytokine Signaling Proteins; D045162:Thiazolidinediones; D014409:Tumor Necrosis Factor-alpha; D000077154:Rosiglitazone; D000078792:Midkine