Circulating hormones and hypothalamic energy balance: regulatory gene expression in the Lou/C and Wistar rats.
To ascertain the mechanisms underlying low caloric intake and low body weight in the Lou/C rat, the circulating hormone levels and gene expression of hypothalamic peptides and receptors important in energy balance and the induction of suppressor of cytokine signalling 3 (SOCS3) gene expression in response to leptin challenge were compared with Wistar rats. Plasma leptin levels were lower in the Lou/C rat, as were levels of rat corticosterone, TSH and T4 but not T3. Ghrelin levels were higher in the Lou/C rat. Total leptin receptor (Ob-R) and the long form of the leptin receptor (Ob-Rb) gene expression were lower in the arcuate (ARC) and ventromedial nuclei (VMN) in Lou/C rat. Ghrelin receptor expression in the ARC and VMN was lower in Lou/C than in Wistar rats. However, agouti gene-related peptide (AgRP) and neuropeptide Y (NPY) gene expression were higher in the Lou/C rat. There was no difference in the level of cocaine- and amphetamine-regulated transcript gene expression in the ARC, but both were higher in the paraventricular nuclei of the Lou/C breed. There was no difference in Ob-R gene expression in, or [(125)I]leptin binding to, the choroid plexus. SOCS3 mRNA induction in response to leptin was lower in the Lou/C rat. This study reveals that the comparatively low plasma leptin, TSH and T4 levels, and high ghrelin levels together with high levels of AgRP and NPY gene expression seen in the Lou/C rat are indicative of a strong drive to eat and decreased energy expenditure, which are in direct opposition to the comparatively low body weight and adiposity of this rat strain.
Mitchell
Sharon E
SE
Obesity and Metabolic Health Division, Rowett Research Institute, Aberdeen AB21 9SB, UK.
Nogueiras
Ruben
R
Rance
Kellie
K
Rayner
D Vernon
DV
Wood
Sharon
S
Dieguez
Carlos
C
Williams
Lynda M
LM
D054369:Agouti-Related Protein; D000818:Animals; D001835:Body Weight / Q000235:genetics*; D002831:Choroid Plexus / Q000737:chemistry / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D002149:Energy Intake / Q000235:genetics*; D004734:Energy Metabolism / Q000235:genetics*; D015870:Gene Expression; D005786:Gene Expression Regulation; D054439:Ghrelin; D007028:Hypothalamic Hormones / Q000097:blood* / Q000235:genetics; D017403:In Situ Hybridization / Q000379:methods; D007328:Insulin / Q000097:blood; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D020738:Leptin / Q000097:blood / Q000494:pharmacology; D009478:Neuropeptide Y / Q000235:genetics; D036361:Peptide Hormones / Q000097:blood; D011485:Protein Binding; D011897:Random Allocation; D051381:Rats; D011922:Rats, Mutant Strains; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000378:metabolism; D054411:Receptors, Leptin; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
D054369:Agouti-Related Protein; D054439:Ghrelin; D007028:Hypothalamic Hormones; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D020738:Leptin; D009478:Neuropeptide Y; D036361:Peptide Hormones; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; C491410:Socs3 protein, rat; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014284:Triiodothyronine; D013972:Thyrotropin; D013974:Thyroxine; D003345:Corticosterone