Hypothalamic gene expression in long-term fasted rats: relationship with body fat.
Many hypothalamic neuropeptides are involved in the regulation of energy homeostasis and feeding behavior. We have investigated whether and to what extent neuropeptide Y (NPY), agouti-related protein (AGRP), melanin-concentrating hormone (MCH), and prepro-orexin (prepro-OX) as well as pro-opiomelanocortin (POMC) and cocaine and amphetamine-regulated transcript (CART) mRNA levels are affected in rat hypothalamus. An experimental model of long-term fasting rat characterized by three metabolic phases from changes in lipid and protein utilization was used. Except for prepro-OX and compared to fed group, starvation induced an increase in the orexigenic gene expressions that was much more marked in phase 3 (by 2.5-, 8.1-, and 13.5-fold for MCH, AGRP, and NPY, respectively) than in phase 2 (by about 1.5-2.2-fold as an average) of fasting. AGRP and NPY mRNA levels were inversely related to body fat content. Anorexigenic gene expression was only slightly affected at both fasting stages. We conclude that the regulation of NPY and AGRP gene expression is primarily involved during late fasting and could mediate the concomitant enhanced drive for refeeding.
Bertile
Fabrice
F
Centre d'Ecologie et Physiologie Energétiques, UPR 9010 CNRS, associé à l'Université Louis Pasteur, 23 rue Becquerel, FR-67087 Strasbourg Cedex 2, France. Fabrice.Bertile@c-strasbourg.fr
Oudart
Hugues
H
Criscuolo
François
F
Maho
Yvon Le
YL
Raclot
Thierry
T
D000273:Adipose Tissue / Q000033:anatomy & histology; D054369:Agouti-Related Protein; D000818:Animals; D005215:Fasting; D005786:Gene Expression Regulation; D007028:Hypothalamic Hormones / Q000096:biosynthesis / Q000235:genetics; D007031:Hypothalamus / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D007700:Kinetics; D008297:Male; D008543:Melanins / Q000096:biosynthesis / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D009478:Neuropeptide Y / Q000096:biosynthesis / Q000235:genetics; D009479:Neuropeptides / Q000096:biosynthesis / Q000235:genetics; D009584:Nitrogen / Q000652:urine; D000068797:Orexins; D010907:Pituitary Hormones / Q000096:biosynthesis / Q000235:genetics; D011333:Pro-Opiomelanocortin / Q000096:biosynthesis / Q000235:genetics; D014176:Protein Biosynthesis; D011498:Protein Precursors / Q000096:biosynthesis / Q000235:genetics; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015431:Weight Loss; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
C515197:AGRP protein, rat; D054369:Agouti-Related Protein; D007028:Hypothalamic Hormones; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008543:Melanins; D009419:Nerve Tissue Proteins; D009478:Neuropeptide Y; D009479:Neuropeptides; D000068797:Orexins; D010907:Pituitary Hormones; D011498:Protein Precursors; D011506:Proteins; D012333:RNA, Messenger; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein; D011333:Pro-Opiomelanocortin; C019463:melanin-concentrating hormone; D009584:Nitrogen