title: Ghrelin receptor regulates appetite and satiety during aging in mice by regulating meal frequency and portion size but not total food intake.
abstract: Aging is often associated with overweight and obesity. There exists a long-standing debate about whether meal pattern also contributes to the development of obesity. The orexigenic hormone ghrelin regulates appetite and satiety by activating its receptor, growth hormone secretagogue receptor (GHS-R). In mice, circulating ghrelin concentrations and brain GHS-R expression were shown to increase with aging. To assess whether GHS-R regulates feeding pattern during aging, we studied meal patterns for the following cohorts of male mice fed a normal unpurified diet: 1) 3-4 mo, young wild-type (WT) mice; 2) 3-4 mo, young Ghsr-null (Ghsr(-/-)) mice; 3) 12-14 mo, middle-aged WT (WT-M) mice; 4) 12-14 mo, middle-aged Ghsr(-/-) (Ghsr(-/-)-M) mice; 5) 24-26 mo, old WT (WT-O) mice; and 6) 24-26 mo, old Ghsr(-/-) (Ghsr(-/-)-O) mice. Although the total daily food intake of Ghsr(-/-) mice was similar to that of WT controls, Ghsr(-/-)-M and Ghsr(-/-)-O mice had 9% (P = 0.07) and 16% (P < 0.05) less body weight compared with WT-M and WT-O mice, respectively, primarily due to reduced fat mass (P < 0.05, WT-M vs. Ghsr(-/-)-M and WT-O vs. Ghsr(-/-)-O). Intriguingly, Ghsr(-/-)-M mice ate larger meals (on average, Ghsr(-/-)-M mice ate 0.117 g/meal and WT-M mice ate 0.080 g/meal; P < 0.01) and took a longer time to eat (Ghsr(-/-)-M, 196.0 s and WT-M, 128.9 s; P < 0.01), but ate less frequently (Ghsr(-/-)-M, 31.0 times/d and WT-M, 42.3 times/d; P < 0.05) than WT-M controls. In addition, we found that expression of hypothalamic orexigenic peptides, neuropeptide Y (NPY) and agouti-related peptide (AgRP), was relatively lower in aged WT mice (P = 0.09 for NPY and P = 0.06 for AgRP), but anorexic peptide pro-opiomelanocortin (POMC) expression remained unchanged between the WT age groups. Interestingly, old Ghsr(-/-) mice had greater hypothalamic NPY expression (102% higher; P < 0.05) and AgRP expression (P = 0.07) but significantly lower POMC expression (P < 0.05) when compared with age-matched WT-O controls. Thus, our results indicate that GHS-R plays an important role in the regulation of meal pattern and that GHS-R ablation may modulate feeding behavior through the regulation of hypothalamic neuropeptides. Our results collectively suggest that ghrelin receptor antagonism may have a beneficial effect on metabolism during aging.
authors.affiliation: USDA/Agricultural Research Service Children's Nutrition Research Center, Department of Pediatrics, and State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China;
authors.forename: Ligen
authors.initials: L
authors.lastname: Lin
authors.affiliation: USDA/Agricultural Research Service Children's Nutrition Research Center, Department of Pediatrics, and.
authors.forename: Alli M
authors.initials: AM
authors.lastname: Nuotio-Antar
authors.affiliation: USDA/Agricultural Research Service Children's Nutrition Research Center, Department of Pediatrics, and Division of Endocrinology, Department of Internal Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China;
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Ma
authors.affiliation: Department of Pharmacology, University of Texas Health Science Center, San Antonio, TX; and Metabolic Syndrome Research Center, Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
authors.affiliation: USDA/Agricultural Research Service Children's Nutrition Research Center, Department of Pediatrics, and.
authors.forename: Marta L
authors.initials: ML
authors.lastname: Fiorotto
authors.affiliation: USDA/Agricultural Research Service Children's Nutrition Research Center, Department of Pediatrics, and Huffington Center on Aging and Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX; yuxiangs@bcm.edu.
authors.forename: Yuxiang
authors.initials: Y
authors.lastname: Sun
mesh_terms: D000273:Adipose Tissue; D000367:Age Factors; D000375:Aging; D000818:Animals; D001069:Appetite Regulation; D001835:Body Weight; D004435:Eating; D002149:Energy Intake; D005247:Feeding Behavior; D054439:Ghrelin / Q000378:metabolism*; D007031:Hypothalamus; D008297:Male; D062407:Meals; D051379:Mice; D008815:Mice, Inbred Strains; D009479:Neuropeptides / Q000378:metabolism; D064787:Portion Size; D054440:Receptors, Ghrelin / Q000378:metabolism*; D012527:Satiation; D012528:Satiety Response
chemical_list: D054439:Ghrelin; D009479:Neuropeptides; D054440:Receptors, Ghrelin