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Blunted hypothalamic neuropeptide gene expression in response to fasting, but preservation of feeding responses to AgRP in aging male Brown Norway rats.
Am J Physiol Regul Integr Comp Physiol. 2004 Jul; 287(1):R138-46.AJ

Abstract

Aging mammals lose the ability to maintain energy balance, exhibiting decreased appetite (anorexia) and impaired ability to maintain body weight. To determine the contribution of hypothalamic neuropeptides, two experiments were performed in male Brown Norway rats. To assess the hypothalamic neuropeptide response to food deprivation, young (Y; 4 mo old), middle-aged (M; 13 mo), and old (O; 25 mo) rats were either ad libitum fed or fasted for 72 h (n = 10/group) and killed. Hypothalamic levels of agouti-related peptide (AgRP), proopiomelanocortin (POMC), and cocaine-amphetamine-regulated transcript (CART) mRNA were assessed by in situ hybridization. With aging, arcuate AgRP gene expression decreased and CART mRNA increased, but POMC mRNA did not change. Fasting-induced changes in gene expression of all neuropeptides studied were attenuated with aging. To test the food intake response to appetite-stimulating neuropeptides, Y, M, O, and very old (VO; 33 mo) rats (n = 4-8/group) received one intracerebroventricular injection of each of three treatments: 0.1 nmol AgRP, 2.34 nmol NPY, and saline control. AgRP increased food intake of all groups by 10-20%, compared with saline, and this effect persisted up to 7 days after injection. VO animals were more sensitive to the effects of AgRP than younger animals. In contrast, NPY increased food intake more in Y than in older animals and its effects did not last >24 h. We conclude that the mechanisms by which arcuate nucleus neurons influence appetite are differentially affected by age and speculate that the melanocortin system may be a useful target for treatment of the anorexia of aging.

Authors+Show Affiliations

VA Puget Sound Health Care System (S-182-GRECC 1660 South Columbian Way, Seattle, WA 98108-1597, USA. twh@u.washington.eduNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15001433

Citation

Wolden-Hanson, Tami, et al. "Blunted Hypothalamic Neuropeptide Gene Expression in Response to Fasting, but Preservation of Feeding Responses to AgRP in Aging Male Brown Norway Rats." American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, vol. 287, no. 1, 2004, pp. R138-46.
Wolden-Hanson T, Marck BT, Matsumoto AM. Blunted hypothalamic neuropeptide gene expression in response to fasting, but preservation of feeding responses to AgRP in aging male Brown Norway rats. Am J Physiol Regul Integr Comp Physiol. 2004;287(1):R138-46.
Wolden-Hanson, T., Marck, B. T., & Matsumoto, A. M. (2004). Blunted hypothalamic neuropeptide gene expression in response to fasting, but preservation of feeding responses to AgRP in aging male Brown Norway rats. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, 287(1), R138-46.
Wolden-Hanson T, Marck BT, Matsumoto AM. Blunted Hypothalamic Neuropeptide Gene Expression in Response to Fasting, but Preservation of Feeding Responses to AgRP in Aging Male Brown Norway Rats. Am J Physiol Regul Integr Comp Physiol. 2004;287(1):R138-46. PubMed PMID: 15001433.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Blunted hypothalamic neuropeptide gene expression in response to fasting, but preservation of feeding responses to AgRP in aging male Brown Norway rats. AU - Wolden-Hanson,Tami, AU - Marck,Brett T, AU - Matsumoto,Alvin M, Y1 - 2004/03/04/ PY - 2004/3/6/pubmed PY - 2004/7/14/medline PY - 2004/3/6/entrez SP - R138 EP - 46 JF - American journal of physiology. Regulatory, integrative and comparative physiology JO - Am. J. Physiol. Regul. Integr. Comp. Physiol. VL - 287 IS - 1 N2 - Aging mammals lose the ability to maintain energy balance, exhibiting decreased appetite (anorexia) and impaired ability to maintain body weight. To determine the contribution of hypothalamic neuropeptides, two experiments were performed in male Brown Norway rats. To assess the hypothalamic neuropeptide response to food deprivation, young (Y; 4 mo old), middle-aged (M; 13 mo), and old (O; 25 mo) rats were either ad libitum fed or fasted for 72 h (n = 10/group) and killed. Hypothalamic levels of agouti-related peptide (AgRP), proopiomelanocortin (POMC), and cocaine-amphetamine-regulated transcript (CART) mRNA were assessed by in situ hybridization. With aging, arcuate AgRP gene expression decreased and CART mRNA increased, but POMC mRNA did not change. Fasting-induced changes in gene expression of all neuropeptides studied were attenuated with aging. To test the food intake response to appetite-stimulating neuropeptides, Y, M, O, and very old (VO; 33 mo) rats (n = 4-8/group) received one intracerebroventricular injection of each of three treatments: 0.1 nmol AgRP, 2.34 nmol NPY, and saline control. AgRP increased food intake of all groups by 10-20%, compared with saline, and this effect persisted up to 7 days after injection. VO animals were more sensitive to the effects of AgRP than younger animals. In contrast, NPY increased food intake more in Y than in older animals and its effects did not last >24 h. We conclude that the mechanisms by which arcuate nucleus neurons influence appetite are differentially affected by age and speculate that the melanocortin system may be a useful target for treatment of the anorexia of aging. SN - 0363-6119 UR - https://www.unboundmedicine.com/medline/citation/15001433/Blunted_hypothalamic_neuropeptide_gene_expression_in_response_to_fasting_but_preservation_of_feeding_responses_to_AgRP_in_aging_male_Brown_Norway_rats_ L2 - http://www.physiology.org/doi/full/10.1152/ajpregu.00465.2003?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -