Abnormalities of leptin and ghrelin regulation in obesity-prone juvenile rats.
Rats selectively bred to develop diet-induced obesity (DIO) spontaneously gain more body weight between 5 and 7 wk of age than do those bred to be diet resistant (DR). Here, chow-fed DIO rats ate 9% more and gained 19% more body weight from 5 to 6 wk of age than did DR rats but had comparable leptin and insulin levels. However, 6-wk-old DIO rats had 29% lower plasma ghrelin levels at dark onset but equivalent levels 6 h later compared with DR rats. When subsequently fed a high-energy (HE; 31% fat) diet for 10 days, DIO rats ate 70% more, gained more body and adipose depot weight, had higher leptin and insulin levels, and had 22% lower feed efficiency than DR rats fed HE diet. In DIO rats on HE diet, leptin levels increased significantly at 3 days followed by increased insulin levels at 7 days. These altered DIO leptin and ghrelin responses were associated with 10% lower leptin receptor mRNA expression in the arcuate (ARC), dorsomedial (DMN), and ventromedial hypothalamic nuclei and 13 and 15% lower ghrelin receptor (GHS-R) mRNA expression in the ARC and DMN than in the DR rats. These data suggest that increased ghrelin signaling is not a proximate cause of DIO, whereas reduced leptin sensitivity might play a causal role.
Levin
Barry E
BE
Neurology Service, Department of Veterans Affairs Medical Center, 127C VA Medical Center, 385 Tremont Ave., E. Orange, NJ 07018-1095, USA. levin@umdnj.edu
Dunn-Meynell
Ambrose A
AA
Ricci
Matt R
MR
Cummings
David E
DE
D000273:Adipose Tissue / Q000033:anatomy & histology; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000737:chemistry; D001835:Body Weight; D004032:Diet; D004041:Dietary Fats / Q000008:administration & dosage; D004302:Dorsomedial Hypothalamic Nucleus / Q000737:chemistry; D004435:Eating; D002149:Energy Intake; D054439:Ghrelin; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood*; D008297:Male; D009765:Obesity / Q000097:blood / Q000209:etiology* / Q000235:genetics; D009929:Organ Size; D036361:Peptide Hormones / Q000097:blood*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000235:genetics; D054440:Receptors, Ghrelin; D054411:Receptors, Leptin; D015398:Signal Transduction; D014697:Ventromedial Hypothalamic Nucleus / Q000737:chemistry
D004041:Dietary Fats; D054439:Ghrelin; D007328:Insulin; D020738:Leptin; D036361:Peptide Hormones; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D054440:Receptors, Ghrelin; D054411:Receptors, Leptin