title: Hindbrain leptin and glucagon-like-peptide-1 receptor signaling interact to suppress food intake in an additive manner.
abstract: BACKGROUND
  The physiological control of feeding behavior involves modulation of the intake inhibitory effects of gastrointestinal satiation signaling via endogenous hindbrain leptin receptor (LepR) and glucagon-like-peptide-1 receptor (GLP-1R) activation.
  
  
  RESULTS
  Using a variety of dose-combinations of hindbrain delivered (4th intracerebroventricular; i.c.v.) leptin and the GLP-1R agonist exendin-4, experiments demonstrate that hindbrain LepR and GLP-1R signaling interact to control food intake and body weight in an additive manner. In addition, the maximum intake suppressive response that could be achieved by 4th i.c.v. leptin alone in non-obese rats (∼33%) was shown to be further suppressed when exendin-4 was co-administered. Importantly, it was determined that the interaction between hindbrain LepR signaling and GLP-1R signaling is relevant to endogenous food intake control, as hindbrain GLP-1R blockade by the selective antagonist exendin-(9-39) attenuated the intake inhibitory effects of hindbrain leptin delivery.
  
  
  CONCLUSIONS
  Collectively, the findings reported here show that hindbrain LepR and GLP-1R activation interact in at least an additive manner to control food intake and body weight. As evidence is accumulating that combination pharmacotherapies offer greater sustained food intake and body weight suppression in obese individuals when compared with mono-drug therapies or lifestyle modifications alone, these findings highlight the need for further examination of combined central nervous system GLP-1R and LepR signaling as a potential drug target for obesity treatment.
authors.affiliation: Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an, People's Republic of China.
authors.forename: S
authors.initials: S
authors.lastname: Zhao
authors.forename: S E
authors.initials: SE
authors.lastname: Kanoski
authors.forename: J
authors.initials: J
authors.lastname: Yan
authors.forename: H J
authors.initials: HJ
authors.lastname: Grill
authors.forename: M R
authors.initials: MR
authors.lastname: Hayes
mesh_terms: D000818:Animals; D001835:Body Weight; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D000077270:Exenatide; D005247:Feeding Behavior; D000067757:Glucagon-Like Peptide-1 Receptor; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007276:Injections, Intraventricular; D020738:Leptin / Q000378:metabolism*; D008297:Male; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018027:Receptors, Glucagon / Q000819:agonists*; D012249:Rhombencephalon / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014688:Venoms / Q000494:pharmacology*
chemical_list: C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D007004:Hypoglycemic Agents; D020738:Leptin; D010455:Peptides; D018027:Receptors, Glucagon; D014688:Venoms; D000077270:Exenatide