Central adiponectin acutely improves glucose tolerance in male mice

Christiane E Koch, Chrishanthi Lowe, Karen Legler, Jonas Benzler, Alisa Boucsein, Gregor Böttiger, David R Grattan, Lynda M Williams, Alexander Tups

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1806-1816
Number of pages11
Issue number5
Early online date24 Feb 2014
Publication statusPublished - 2014

Bibliographical note

Date of Acecptance: 17/02/2014

Acknowledgments: This study was funded by the German Ministry of Education and Research (Grant 0315087 to A.T.). L.M.W. was funded by Rural and Environment Science and Analytical Services Division.


  • Adiponectin
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal
  • Arcuate Nucleus
  • Diet, High-Fat
  • Glucose Intolerance
  • Hypoglycemic Agents
  • Injections, Intraventricular
  • Insulin Resistance
  • Leptin
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Obese
  • Nerve Tissue Proteins
  • Neurons
  • Obesity
  • Receptors, Adiponectin
  • Signal Transduction
  • Ventromedial Hypothalamic Nucleus


Dive into the research topics of 'Central adiponectin acutely improves glucose tolerance in male mice'. Together they form a unique fingerprint.

Cite this