title: Central adiponectin acutely improves glucose tolerance in male mice.
abstract: Adiponectin, an adipocyte-derived hormone, regulates glucose and lipid metabolism. It is also antiinflammatory. During obesity, adiponectin levels and sensitivity are reduced. Whereas the action of adiponectin in the periphery is well established the neuroendocrine role of adiponectin is largely unknown. To address this we analyzed the expression of adiponectin and the 2 adiponectin receptors (AdipoR1 and AdipoR2) in response to fasting and to diet-induced and genetic obesity. We also investigated the acute impact of adiponectin on central regulation of glucose homeostasis. Adiponectin (1 μg) was injected intracerebroventricularly (ICV), and glucose tolerance tests were performed in dietary and genetic obese mice. Finally, the influence of ICV adiponectin administration on central signaling cascades regulating glucose homeostasis and on markers of hypothalamic inflammation was assessed. Gene expression of adiponectin was down-regulated whereas AdipoR1 was up-regulated in the arcuate nucleus of fasted mice. High-fat (HF) feeding increased AdipoR1 and AdipoR2 gene expression in this region. In mice on a HF diet and in leptin-deficient mice acute ICV adiponectin improved glucose tolerance 60 minutes after injection, whereas normoglycemia in control mice was unaffected. ICV adiponectin increased pAKT, decreased phospho-AMP-activated protein kinase, and did not change phospho-signal transducer and activator of transcription 3 immunoreactivity. In HF-fed mice, ICV adiponectin reversed parameters of hypothalamic inflammation and insulin resistance as determined by the number of phospho-glycogen synthase kinase 3 β(Ser9) and phospho-c-Jun N-terminal kinase (Thr183/Tyr185) immunoreactive cells in the arcuate nucleus and ventromedial hypothalamus. This study demonstrates that the insulin-sensitizing properties of adiponectin are at least partially based on a neuroendocrine mechanism that involves centrally synthesized adiponectin.
authors.affiliation: Department of Animal Physiology (C.E.K., C.L., K.L., J.B., A.B., G.B., A.T.), Faculty of Biology, Philipps University Marburg, D-35043 Marburg, Germany; Metabolic Health Group (L.M.W.), Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen AB21 9SB, United Kingdom; and Centre for Neuroendocrinology and Department of Anatomy and Structural Biology (D.R.G.), University of Otago, Dunedin, New Zealand.
authors.forename: Christiane E
authors.initials: CE
authors.lastname: Koch
authors.forename: Chrishanthi
authors.initials: C
authors.lastname: Lowe
authors.forename: Karen
authors.initials: K
authors.lastname: Legler
authors.forename: Jonas
authors.initials: J
authors.lastname: Benzler
authors.forename: Alisa
authors.initials: A
authors.lastname: Boucsein
authors.forename: Gregor
authors.initials: G
authors.lastname: Böttiger
authors.forename: David R
authors.initials: DR
authors.lastname: Grattan
authors.forename: Lynda M
authors.initials: LM
authors.lastname: Williams
authors.forename: Alexander
authors.initials: A
authors.lastname: Tups
mesh_terms: D052242:Adiponectin / Q000008:administration & dosage / Q000009:adverse effects / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D059305:Diet, High-Fat / Q000009:adverse effects; D018149:Glucose Intolerance / Q000209:etiology / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007276:Injections, Intraventricular; D007333:Insulin Resistance; D020738:Leptin / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009765:Obesity / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D054419:Receptors, Adiponectin / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014697:Ventromedial Hypothalamic Nucleus / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D052242:Adiponectin; C499919:Adipoq protein, mouse; D000894:Anti-Inflammatory Agents, Non-Steroidal; D007004:Hypoglycemic Agents; D020738:Leptin; D009419:Nerve Tissue Proteins; D054419:Receptors, Adiponectin; C475419:adiponectin receptor 1, mouse; C475421:adiponectin receptor 2, mouse