Activity of the Hypothalamic Melanocortin System Decreases in Middle-Aged and Increases in Old Rats

Nóra Füredi, Alexandra Mikó, B. Gaszner, Diána Feller, Ildikó Rostás, Judit Tenk, Margit Solymár, M. Balaskó, Erika Pétervári

Research output: Article

1 Citation (Scopus)

Abstract

Appearance of middle-aged obesity and aging anorexia both in humans and rodents suggests a role for regulatory alterations. Hypothalamic melanocortin agonist, α-melanocyte-stimulating hormone (α-MSH) produced in the arcuate nucleus (ARC), reduces body weight via inducing hypermetabolism and anorexia mainly through melanocortin 4 receptors (MC4Rs) in the paraventricular nucleus (PVN). Orexigenic ARC-derived agouti-related protein (AgRP) is an inverse agonist on MC4R in the PVN. Previously, we demonstrated that characteristic age-related shifts in the catabolic effects of α-MSH may contribute both to middle-aged obesity and aging anorexia. Responsiveness to α-MSH decreases in middle-aged rats compared with young adults, whereas in old age it rises again significantly. We hypothesized corresponding age-related dynamics of endogenous melanocortins. Therefore, we quantified mRNA gene expression and peptide or protein level of α-MSH, AgRP, and MC4R in the ARC and PVN of male Wistar rats of five age groups (from young to old). Immunofluorescence and quantitative reverse transcriptase polymerase chain reaction were applied. α-MSH and MC4R immunoreactivities in the ARC and PVN declined in middle-aged and increased together with their expressions in aging rats. AgRP gene expression but not its immunoreactivity increased in aging rats. Our results demonstrate that age-dependent changes of endogenous melanocortins contribute to middle-aged obesity and aging anorexia.

Original languageEnglish
Pages (from-to)438-445
Number of pages8
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Volume73
Issue number4
DOIs
Publication statusPublished - márc. 14 2018

Fingerprint

Melanocortins
Melanocyte-Stimulating Hormones
Receptor, Melanocortin, Type 4
Arcuate Nucleus of Hypothalamus
Agouti-Related Protein
Paraventricular Hypothalamic Nucleus
Anorexia
Obesity
Gene Expression
Reverse Transcriptase Polymerase Chain Reaction
Fluorescent Antibody Technique
Wistar Rats
Young Adult
Rodentia
Age Groups
Body Weight
Messenger RNA
Peptides
Proteins

ASJC Scopus subject areas

  • Ageing
  • Geriatrics and Gerontology

Cite this

Activity of the Hypothalamic Melanocortin System Decreases in Middle-Aged and Increases in Old Rats. / Füredi, Nóra; Mikó, Alexandra; Gaszner, B.; Feller, Diána; Rostás, Ildikó; Tenk, Judit; Solymár, Margit; Balaskó, M.; Pétervári, Erika.

In: Journals of Gerontology - Series A Biological Sciences and Medical Sciences, Vol. 73, No. 4, 14.03.2018, p. 438-445.

Research output: Article

Füredi, Nóra ; Mikó, Alexandra ; Gaszner, B. ; Feller, Diána ; Rostás, Ildikó ; Tenk, Judit ; Solymár, Margit ; Balaskó, M. ; Pétervári, Erika. / Activity of the Hypothalamic Melanocortin System Decreases in Middle-Aged and Increases in Old Rats. In: Journals of Gerontology - Series A Biological Sciences and Medical Sciences. 2018 ; Vol. 73, No. 4. pp. 438-445.
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AU - Füredi, Nóra

AU - Mikó, Alexandra

AU - Gaszner, B.

AU - Feller, Diána

AU - Rostás, Ildikó

AU - Tenk, Judit

AU - Solymár, Margit

AU - Balaskó, M.

AU - Pétervári, Erika

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N2 - Appearance of middle-aged obesity and aging anorexia both in humans and rodents suggests a role for regulatory alterations. Hypothalamic melanocortin agonist, α-melanocyte-stimulating hormone (α-MSH) produced in the arcuate nucleus (ARC), reduces body weight via inducing hypermetabolism and anorexia mainly through melanocortin 4 receptors (MC4Rs) in the paraventricular nucleus (PVN). Orexigenic ARC-derived agouti-related protein (AgRP) is an inverse agonist on MC4R in the PVN. Previously, we demonstrated that characteristic age-related shifts in the catabolic effects of α-MSH may contribute both to middle-aged obesity and aging anorexia. Responsiveness to α-MSH decreases in middle-aged rats compared with young adults, whereas in old age it rises again significantly. We hypothesized corresponding age-related dynamics of endogenous melanocortins. Therefore, we quantified mRNA gene expression and peptide or protein level of α-MSH, AgRP, and MC4R in the ARC and PVN of male Wistar rats of five age groups (from young to old). Immunofluorescence and quantitative reverse transcriptase polymerase chain reaction were applied. α-MSH and MC4R immunoreactivities in the ARC and PVN declined in middle-aged and increased together with their expressions in aging rats. AgRP gene expression but not its immunoreactivity increased in aging rats. Our results demonstrate that age-dependent changes of endogenous melanocortins contribute to middle-aged obesity and aging anorexia.

AB - Appearance of middle-aged obesity and aging anorexia both in humans and rodents suggests a role for regulatory alterations. Hypothalamic melanocortin agonist, α-melanocyte-stimulating hormone (α-MSH) produced in the arcuate nucleus (ARC), reduces body weight via inducing hypermetabolism and anorexia mainly through melanocortin 4 receptors (MC4Rs) in the paraventricular nucleus (PVN). Orexigenic ARC-derived agouti-related protein (AgRP) is an inverse agonist on MC4R in the PVN. Previously, we demonstrated that characteristic age-related shifts in the catabolic effects of α-MSH may contribute both to middle-aged obesity and aging anorexia. Responsiveness to α-MSH decreases in middle-aged rats compared with young adults, whereas in old age it rises again significantly. We hypothesized corresponding age-related dynamics of endogenous melanocortins. Therefore, we quantified mRNA gene expression and peptide or protein level of α-MSH, AgRP, and MC4R in the ARC and PVN of male Wistar rats of five age groups (from young to old). Immunofluorescence and quantitative reverse transcriptase polymerase chain reaction were applied. α-MSH and MC4R immunoreactivities in the ARC and PVN declined in middle-aged and increased together with their expressions in aging rats. AgRP gene expression but not its immunoreactivity increased in aging rats. Our results demonstrate that age-dependent changes of endogenous melanocortins contribute to middle-aged obesity and aging anorexia.

KW - Aging anorexia

KW - Brain aging

KW - Hormones

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KW - Obesity

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