AdipoR1 mediates the anorexigenic and insulin/leptin-like actions of adiponectin in the hypothalamus.
Adiponectin exerts an insulin-sensitizing effect, improving insulin action in peripheral tissues and restraining insulin resistance. Here, we explore the hypothesis that adiponectin can reproduce some of the actions of insulin/leptin in the hypothalamus. The presence of AdipoR1 and AdipoR2 was mapped to the arcuate and lateral hypothalamic nuclei. Icv adiponectin reduced food intake, which was accompanied by activation/engagement of IRS1/2, ERK, Akt, FOXO1, JAK2 and STAT3. All these actions were dependent on AdipoR1, since inhibition of this receptor, and not of AdipoR2, completely reversed the effects described above. Thus, adiponectin acts in the hypothalamus, activating elements of the canonical insulin and leptin signaling pathways and promoting reduction of food intake.
Coope
Andressa
A
Department of Internal Medicine, State University of Campinas, Brazil.
Milanski
Marciane
M
Araújo
Eliana P
EP
Tambascia
Marcos
M
Saad
Mário J A
MJ
Geloneze
Bruno
B
Velloso
Lício A
LA
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D052242:Adiponectin / Q000494:pharmacology* / Q000502:physiology; D000818:Animals; D000855:Anorexia / Q000139:chemically induced* / Q000378:metabolism; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D004435:Eating / Q000187:drug effects*; D051858:Forkhead Transcription Factors / Q000378:metabolism; D007026:Hypothalamic Area, Lateral / Q000187:drug effects* / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology / Q000502:physiology; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D053614:Janus Kinase 2 / Q000378:metabolism; D020738:Leptin / Q000494:pharmacology / Q000502:physiology; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D016372:RNA, Antisense / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D054419:Receptors, Adiponectin / Q000235:genetics / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000071161:Forkhead Box Protein O1
D048868:Adaptor Proteins, Signal Transducing; D052242:Adiponectin; D002352:Carrier Proteins; D051858:Forkhead Transcription Factors; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; D053614:Janus Kinase 2; D020738:Leptin; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D051057:Proto-Oncogene Proteins c-akt; D016372:RNA, Antisense; D054419:Receptors, Adiponectin; D050796:STAT3 Transcription Factor; C515694:Appl1 protein, rat; C526296:Irs1 protein, rat; C526299:Irs2 protein, rat; C494088:Stat3 protein, rat; C504339:adiponectin receptor 1, rat; C506573:adiponectin receptor 2, rat; C074639:Foxo1 protein, rat; D000071161:Forkhead Box Protein O1; C507927:Jak2 protein, rat