title: Angiopoietin-like protein 4 improves glucose tolerance and insulin resistance but induces liver steatosis in high-fat-diet mice.
abstract: Angiopoietin-like protein 4 (Angptl4) is a secreted protein predominantly expressed in liver and adipose tissues, and has been identified as an adipokine. Angptl4 is the target gene of peroxisome proliferator‑activated receptors, which are widely used as lipid‑lowering and anti‑diabetic drugs, and previous studies have demonstrated that Angptl4 is able to directly stimulate adipocyte lipolysis. The current study focused on how Angptl4 was involved in regulating lipid and glucose metabolism in high‑fat‑diet (HFD) C57 mice. In the present study, mice were divided into three groups, with standard chow mice as a normal control, adenovirus (adv)‑injected HFD mice as a model control and adv‑Angptl4‑injected HFD mice as the Angptl4+ group. Firstly, compared with the normal control group, mice in the model control group gained more body weight with severe liver steatosis and increased serum levels of triglyceride, total cholesterol, free fatty acids, alanine aminotransferase and aspartate aminotransferase. In the Angptl4+ group, Angptl4 reduced the weight growth rate, aggravated hepatic steatosis and further increased all the aforementioned serum indexes. Secondly, compared with the normal control, the model control group had a reduced glucose tolerance and developed insulin resistance. Angptl4 expression and the phosphorylation levels of several insulin signaling pathway‑associated genes, insulin receptor substrate 1, protein kinase B, janus kinase 2, signal transducer and activator of transcription 3 were downregulated in the liver samples. Adv‑Angptl4 injection was observed to improve glucose tolerance and insulin resistance. The genes measured were identified to be upregulated close to normal levels. All the results suggested that Angptl4 served an important role in lipid and glucose metabolism in HFD‑induced obese mice, and this may have a great significance for treatment of hyperlipidemia, diabetes, metabolic syndrome and other diseases.
authors: Department of Endocrinology, Dahua Hospital of Xuhui District, Shanghai 200237, P.R. China.
authors: Yi
authors: Y
authors: Wang
authors: Department of General Surgery, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, P.R. China.
authors: Li-Ming
authors: LM
authors: Liu
authors: Department of Endocrinology, Sixth People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200025, P.R. China.
authors: Li
authors: L
authors: Wei
authors: Department of Endocrinology, Dahua Hospital of Xuhui District, Shanghai 200237, P.R. China.
authors: Wei-Wei
authors: WW
authors: Ye
authors: Department of Endocrinology, Dahua Hospital of Xuhui District, Shanghai 200237, P.R. China.
authors: Xiang-Ying
authors: XY
authors: Meng
authors: Department of Endocrinology, Dahua Hospital of Xuhui District, Shanghai 200237, P.R. China.
authors: Feng
authors: F
authors: Chen
authors: Department of Endocrinology, Dahua Hospital of Xuhui District, Shanghai 200237, P.R. China.
authors: Qian
authors: Q
authors: Xiao
authors: Department of Endocrinology, Dahua Hospital of Xuhui District, Shanghai 200237, P.R. China.
authors: Jian-Yang
authors: JY
authors: Chen
authors: Department of Endocrinology, Dahua Hospital of Xuhui District, Shanghai 200237, P.R. China.
authors: Yong
authors: Y
authors: Zhou
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002784:Cholesterol / Q000097:blood; D059305:Diet, High-Fat / Q000009:adverse effects*; D005227:Fatty Acids / Q000097:blood; D005234:Fatty Liver / Q000097:blood / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction; D014280:Triglycerides / Q000097:blood; D015854:Up-Regulation
chemical_list: D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins; C407088:Angptl4 protein, mouse; D005227:Fatty Acids; D007328:Insulin; D014280:Triglycerides; D002784:Cholesterol; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005947:Glucose