title: Hypothalamic Npy mRNA is correlated with increased wheel running and decreased body fat in calorie-restricted rats.
abstract: The neuro-molecular mechanisms that regulate the relationship between physical activity level, energy homeostasis regulation, and body fat are unclear. Thus, we aimed to investigate the relationship between mRNAs in the hypothalamic arcuate nucleus (ARC) related to energy homeostasis, wheel running distance, and body fat in ad lib (AL) and calorie-restricted (CR) growing rats. We hypothesized that changes in select mRNAs (Pomc, Cart, Agrp, Npy, Lepr, Insr, Mc4r, Ampk, Sirt1, Sirt3) in CR would be associated with decreases in body fat percentage and increased wheel running behavior. Male Wistar rats were given access to voluntary running wheels at 4 weeks of age and randomized into AL (n=8) and CR (70% of AL; n=7) groups at 5 weeks of age until study termination at 12 weeks of age. Body composition, serum leptin, insulin, and adiponectin, and ARC mRNA expression in AL and CR rats were assessed and correlated with week-12 running distance to examine potential relationships that may exist. By 12 weeks of age, wheel running was increased ∼3.3-fold (p=0.03) while body fat percentage was ∼2-fold lower in CR compared to AL (p=0.001). Compared to AL, ARC Npy mRNA expression was ∼2-fold greater in CR (p=0.02), while Lepr, Insr, Ampk, and Sirt1 mRNA were additionally increased in CR (p<0.05). Significant correlations existed between ARC Npy mRNA levels versus week-12 wheel running distance (r=0.81, p=0.03), body fat (r=-0.93, p<0.01), and between body fat and wheel running (r=-0.83, p=0.02) in CR, but not in AL. These results reveal possible mechanisms by which fat-brain crosstalk may influence physical activity during energy deficit. These data suggest that below a 'threshold' fat content, body fat may drive activity levels, potentially through hypothalamic Npy action.
authors.affiliation: Department of Biomedical Sciences, University of Missouri, Columbia, MO 65211, USA.
authors.forename: Gregory N
authors.initials: GN
authors.lastname: Ruegsegger
authors.affiliation: Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, MO 65211, USA.
authors.forename: Katherine R
authors.initials: KR
authors.lastname: Speichinger
authors.affiliation: Department of Biomedical Sciences, University of Missouri, Columbia, MO 65211, USA.
authors.forename: Jacob B
authors.initials: JB
authors.lastname: Manier
authors.affiliation: Department of Biomedical Sciences, University of Missouri, Columbia, MO 65211, USA.
authors.forename: Kyle M
authors.initials: KM
authors.lastname: Younger
authors.affiliation: Department of Biomedical Sciences, University of Missouri, Columbia, MO 65211, USA.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Childs
authors.affiliation: Department of Biomedical Sciences, University of Missouri, Columbia, MO 65211, USA; Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, MO 65211, USA; Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO 65211, USA; Dalton Cardiovascular Research Center, University of Missouri, Columbia, MO 65211, USA. Electronic address: boothf@missouri.edu.
authors.forename: Frank W
authors.initials: FW
authors.lastname: Booth
mesh_terms: D000273:Adipose Tissue; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism*; D031204:Caloric Restriction; D004435:Eating; D004734:Energy Metabolism; D008297:Male; D009043:Motor Activity; D009478:Neuropeptide Y / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D011897:Random Allocation; D017208:Rats, Wistar
chemical_list: D009478:Neuropeptide Y; D012333:RNA, Messenger
keywords: Caloric restriction; Hypothalamus; Neuropeotide Y (Npy); Physical activity; Wheel running