title: Nesfatin-1 stimulates fatty-acid oxidation by activating AMP-activated protein kinase in STZ-induced type 2 diabetic mice.
abstract: Nesfatin-1 is an anorexigenic peptide involved in energy homeostasis. Recently, nesfatin-1 was reported to decrease blood glucose level and improve insulin sensitivity in high-fat diet-fed rats. However, little information is known about the influence of nesfatin-1 on lipid metabolism either in physiological or diabetic condition. This study undertook whether nesfatin-1 was involved in the pathophysiology in Streptozotocin-induced type 2 diabetic mice (T2DM), which was induced by a combination of high-calorie diet and two low-doses Streptozotocin. We observed that plasma nesfatin-1 was significantly increased while expression of nesfatin-1 neurons were decreased in hypothalamus in diabetes group compared to only high-calorie diet control group; intravenous injection of nesfatin-1 decreased 0-1h, 0-2h, 0-3h cumulative food intake in T2DM, but 0-24h total food intake had no difference between groups. Body weight and plasma FFA were normalized after nesfatin-1(10 µg/Kg) administration for 6 days. These results suggested that nesfatin-1 improved lipid disorder in T2DM. It was found that blood glucose and insulin resistance coefficient decreased with treatment of nesfatin-1 (both in 1 µg/Kg and 10 µg/Kg doses) in diabetes mice. For further understanding the role of nesfatin-1 on lipid metabolism, we detected p-AMPK and p-ACC of skeletal muscle in T2DM using western blotting. The expression of p-AMPK and p-ACC increased when nesfatin-1 was given with doses 1 µg/Kg but not in doses 10 µg/Kg. Taken together, nesfatin-1 participated in the development of T2DM and stimulated free fatty acid utilization via AMPK-ACC pathway in skeletal muscle in T2DM.
authors.affiliation: Physiology Department of Medical College, Qingdao University, Qingdao, China ; Special Medicine Department of Medical College, Qingdao University, Qingdao, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Dong
authors.affiliation: Class 2, Grade 2009, Medical College, Qingdao University, Qingdao, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Xu
authors.affiliation: Grade 2009, Medical College, Qingdao University, Qingdao, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Xu
authors.affiliation: Grade 2008, Medical College, Qingdao University, Qingdao, China.
authors.forename: Peng-fei
authors.initials: PF
authors.lastname: Wang
authors.affiliation: Grade 2008, Medical College, Qingdao University, Qingdao, China.
authors.forename: Gui-ju
authors.initials: GJ
authors.lastname: Cai
authors.affiliation: Grade 2009, Medical College, Qingdao University, Qingdao, China.
authors.forename: Hai-feng
authors.initials: HF
authors.lastname: Song
authors.affiliation: Grade 2009, Medical College, Qingdao University, Qingdao, China.
authors.forename: Chang-chen
authors.initials: CC
authors.lastname: Wang
authors.affiliation: Grade 2010, Medical College, Qingdao University, Qingdao, China.
authors.forename: Zhao-tong
authors.initials: ZT
authors.lastname: Dong
authors.affiliation: Grade 2010, Medical College, Qingdao University, Qingdao, China.
authors.forename: Yan-jiao
authors.initials: YJ
authors.lastname: Ju
authors.affiliation: Physiology Department of Medical College, Qingdao University, Qingdao, China.
authors.forename: Zheng-yao
authors.initials: ZY
authors.lastname: Jiang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000209:etiology / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000209:etiology / Q000378:metabolism*; D059305:Diet, High-Fat / Q000009:adverse effects; D004789:Enzyme Activation; D005230:Fatty Acids, Nonesterified / Q000097:blood / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D000080866:Nucleobindins; D010084:Oxidation-Reduction; D010766:Phosphorylation; D013311:Streptozocin / Q000633:toxicity
chemical_list: D001786:Blood Glucose; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D009419:Nerve Tissue Proteins; C000630651:Nucb1 protein, mouse; C000630652:Nucb1 protein, rat; D000080866:Nucleobindins; D013311:Streptozocin; D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase