Expression of Genes for Appetite-Regulating Peptides in the Hypothalamus of Genetically Selected Lean and Fat Sheep

Abstract

Background/Aims: The aim was to determine whether genetic selection of sheep for body composition could be accounted for by changes in the level of expression of genes for appetite-regulating peptides in the hypothalamus. We examined gene expression in the hypothalamus of genetically lean, normal and fat ewes (n = 5/group). Methods: Plasma growth hormone (GH) and metabolic indicators were measured and gene expression in brains was quantified by in situ hybridization. Results: Body weight and voluntary food intake (VFI) were similar between groups, but lean and fat animals respectively had low and high indices of adiposity. GH levels were higher in lean and fat animals than in controls. In the arcuate nucleus (ARC), neuropeptide Y (NPY) expression/cell was higher in the lean animals than in normal animals, but overall NPY expression was similar in fat and normal animals. Pro-opiomelanocortin (POMC) and leptin receptor (ObRb) expression in the ARC was similar across groups. Orexin (ORX) and melanin-concentrating hormone (MCH) expression was inversely correlated to adiposity, being higher in lean and lower in fat animals. Conclusion: Expression of genes for orexigenic neuropeptides is altered in a consistent way. Energy expenditure is reduced by MCH but increased by ORX, so increased expression of the latter may cause increased energy expenditure in the lean animals and vice versa in the fat animals.

Selected hormonal and neurotransmitter mechanisms regulating feed intake in sheep

“…ORX gene expression was enhanced in short-day photoperiod when appetite is typically lower (Archer et al, 2002b). Similarly, following sheep throughout periods of seasonal appetite changes again demonstrated a negative correlation of ORX to adiposity (Anukulkitch et al, 2010). Related is the demonstration that 100% of ORX neurons express the leptin receptor, suggesting a means of communicating nutritional status to the appetite centers of the hypothalamus to integrate appetite signals (Iqbal et al, 2001c).…”

“…However, ORX gene expression was negatively associated with adiposity in sheep selected for fatness or lean body condition (Anukulkitch et al, 2010). ORX gene expression was enhanced in short-day photoperiod when appetite is typically lower (Archer et al, 2002b).…”

Innate Obesity, Revealed by Selection Markers, Confers Significant Imprint of Hypothalamic Genes Controlling Energy Expenditure

“…This is not surprising given that the plasma leptin concentration is not increased in the obese genotype compared to normal body weight controls [55] . Furthermore, expression of ObRb in the ARC is similar in obese and lean animals [55] .…”

“…This model was originally developed with selection based on back-fat thickness in a population of approximately 3,000 animals. Lean and fat animals were chosen and then selectively bred for 10-15 generations, creating the genetically lean and obese lines [53,55,56] . A series of studies consistently show that the lean and fat lines have similar body weights, despite large differences in adiposity; genetically fat sheep accumulate significant amounts of adipose tissue within the abdominal/visceral compartment [55,57] .…”

“…Lean and fat animals were chosen and then selectively bred for 10-15 generations, creating the genetically lean and obese lines [53,55,56] . A series of studies consistently show that the lean and fat lines have similar body weights, despite large differences in adiposity; genetically fat sheep accumulate significant amounts of adipose tissue within the abdominal/visceral compartment [55,57] . The inherent differences in adiposity are not due to differences in food intake, as genetically lean and fat sheep eat similar amounts [55,58] , but the key physiological determinant of the 2 differing phenotypes is adaptive thermogenesis [58] .…”