title: Coinjection of CCK and leptin reduces food intake via increased CART/TRH and reduced AMPK phosphorylation in the hypothalamus.
abstract: CCK and leptin are anorectic hormones produced in the small intestine and white adipose tissue, respectively. Investigating how these hormones act together as an integrated anorectic signal is important for elucidating the mechanisms by which energy balance is maintained. We found here that coadministration of subthreshold CCK and leptin, which individually have no effect on feeding, dramatically reduced food intake in rats. Phosphorylation of AMP-activated protein kinase (AMPK) in the hypothalamus significantly decreased after coinjection of CCK and leptin. In addition, coadministration of these hormones significantly increased mRNA levels of anorectic cocaine- and amphetamine-regulated transcript (CART) and thyrotropin-releasing hormone (TRH) in the hypothalamus. The interactive effect of CCK and leptin on food intake was abolished by intracerebroventricular preadministration of the AMPK activator AICAR or anti-CART/anti-TRH antibodies. These findings indicate that coinjection of CCK and leptin reduces food intake via reduced AMPK phosphorylation and increased CART/TRH in the hypothalamus. Furthermore, by using midbrain-transected rats, we investigated the role of the neural pathway from the hindbrain to the hypothalamus in the interaction of CCK and leptin to reduce food intake. Food intake reduction induced by coinjection of CCK and leptin was blocked in midbrain-transected rats. Therefore, the neural pathway from hindbrain to hypothalamus plays an important role in transmitting the anorectic signals provided by coinjection of CCK and leptin. Our findings give further insight into the mechanisms of feeding and energy balance.
authors.affiliation: Frontier Science Research Center, University of Miyazaki, Miyazaki, Japan.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Akieda-Asai
authors.affiliation: Frontier Science Research Center, University of Miyazaki, Miyazaki, Japan.
authors.forename: Paul-Emile
authors.initials: PE
authors.lastname: Poleni
authors.affiliation: Frontier Science Research Center, University of Miyazaki, Miyazaki, Japan dateyuka@med.miyazaki-u.ac.jp.
authors.forename: Yukari
authors.initials: Y
authors.lastname: Date
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000096:biosynthesis*; D054369:Agouti-Related Protein / Q000096:biosynthesis; D000818:Animals; D015153:Blotting, Western; D002766:Cholecystokinin / Q000494:pharmacology*; D004435:Eating / Q000187:drug effects*; D007031:Hypothalamus / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D007276:Injections, Intraventricular; D020738:Leptin / Q000494:pharmacology*; D008297:Male; D008636:Mesencephalon / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D009478:Neuropeptide Y / Q000096:biosynthesis; D010766:Phosphorylation; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000096:biosynthesis; D013973:Thyrotropin-Releasing Hormone / Q000096:biosynthesis*; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
chemical_list: C515197:AGRP protein, rat; D054369:Agouti-Related Protein; D020738:Leptin; D009419:Nerve Tissue Proteins; D009478:Neuropeptide Y; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein; D013973:Thyrotropin-Releasing Hormone; D002766:Cholecystokinin; D055372:AMP-Activated Protein Kinases
keywords: cholecystokinin; food intake; leptin; midbrain transection