Metabolic Context Regulates Distinct Hypothalamic Transcriptional Responses to Antiaging Interventions

Hdl Handle:
http://hdl.handle.net/10675.2/821
Title:
Metabolic Context Regulates Distinct Hypothalamic Transcriptional Responses to Antiaging Interventions
Authors:
Stranahan, Alexis M.; Martin, Bronwen; Chadwick, Wayne; Park, Sung-Soo; Wang, Liyun; Becker, Kevin G. ( 0000-0002-6794-6656 ) ; WoodIII, William H.; Zhang, Yongqing; Maudsley, Stuart
Abstract:
The hypothalamus is an essential relay in the neural circuitry underlying energy metabolism that needs to continually adapt to changes in the energetic environment. The neuroendocrine control of food intake and energy expenditure is associated with, and likely dependent upon, hypothalamic plasticity. Severe disturbances in energy metabolism, such as those that occur in obesity, are therefore likely to be associated with disruption of hypothalamic transcriptomic plasticity. In this paper, we investigated the effects of two well-characterized antiaging interventions, caloric restriction and voluntary wheel running, in two distinct physiological paradigms, that is, diabetic (db/db) and nondiabetic wild-type (C57/Bl/6) animals to investigate the contextual sensitivity of hypothalamic transcriptomic responses. We found that, both quantitatively and qualitatively, caloric restriction and physical exercise were associated with distinct transcriptional signatures that differed significantly between diabetic and non-diabetic mice. This suggests that challenges to metabolic homeostasis regulate distinct hypothalamic gene sets in diabetic and non-diabetic animals. A greater understanding of how genetic background contributes to hypothalamic response mechanisms could pave the way for the development of more nuanced therapeutics for the treatment of metabolic disorders that occur in diverse physiological backgrounds.
Citation:
Int J Endocrinol. 2012 Aug 27; 2012:732975
Issue Date:
27-Aug-2012
URI:
http://hdl.handle.net/10675.2/821
DOI:
10.1155/2012/732975
PubMed ID:
22934110
PubMed Central ID:
PMC3427989
Type:
Article
ISSN:
1687-8345
Appears in Collections:
Department of Physiology: Faculty Research and Presentations

Full metadata record

DC FieldValue Language
dc.contributor.authorStranahan, Alexis M.en_US
dc.contributor.authorMartin, Bronwenen_US
dc.contributor.authorChadwick, Wayneen_US
dc.contributor.authorPark, Sung-Sooen_US
dc.contributor.authorWang, Liyunen_US
dc.contributor.authorBecker, Kevin G.en_US
dc.contributor.authorWoodIII, William H.en_US
dc.contributor.authorZhang, Yongqingen_US
dc.contributor.authorMaudsley, Stuarten_US
dc.date.accessioned2012-10-26T20:35:11Z-
dc.date.available2012-10-26T20:35:11Z-
dc.date.issued2012-08-27en_US
dc.identifier.citationInt J Endocrinol. 2012 Aug 27; 2012:732975en_US
dc.identifier.issn1687-8345en_US
dc.identifier.pmid22934110en_US
dc.identifier.doi10.1155/2012/732975en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/821-
dc.description.abstractThe hypothalamus is an essential relay in the neural circuitry underlying energy metabolism that needs to continually adapt to changes in the energetic environment. The neuroendocrine control of food intake and energy expenditure is associated with, and likely dependent upon, hypothalamic plasticity. Severe disturbances in energy metabolism, such as those that occur in obesity, are therefore likely to be associated with disruption of hypothalamic transcriptomic plasticity. In this paper, we investigated the effects of two well-characterized antiaging interventions, caloric restriction and voluntary wheel running, in two distinct physiological paradigms, that is, diabetic (db/db) and nondiabetic wild-type (C57/Bl/6) animals to investigate the contextual sensitivity of hypothalamic transcriptomic responses. We found that, both quantitatively and qualitatively, caloric restriction and physical exercise were associated with distinct transcriptional signatures that differed significantly between diabetic and non-diabetic mice. This suggests that challenges to metabolic homeostasis regulate distinct hypothalamic gene sets in diabetic and non-diabetic animals. A greater understanding of how genetic background contributes to hypothalamic response mechanisms could pave the way for the development of more nuanced therapeutics for the treatment of metabolic disorders that occur in diverse physiological backgrounds.en_US
dc.rightsCopyright © 2012 Alexis M. Stranahan et al.en_US
dc.subjectResearch Articleen_US
dc.titleMetabolic Context Regulates Distinct Hypothalamic Transcriptional Responses to Antiaging Interventionsen_US
dc.typeArticleen_US
dc.identifier.pmcidPMC3427989en_US
dc.contributor.corporatenameDepartment of Physiology-

Related articles on PubMed

All Items in Scholarly Commons are protected by copyright, with all rights reserved, unless otherwise indicated.