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    Metabolic Context Regulates Distinct Hypothalamic Transcriptional Responses to Antiaging Interventions

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    Authors
    Stranahan, Alexis M.
    Martin, Bronwen
    Chadwick, Wayne
    Park, Sung-Soo
    Wang, Liyun
    Becker, Kevin G.
    WoodIII, William H.
    Zhang, Yongqing
    Maudsley, Stuart
    Issue Date
    2012-08-27
    URI
    http://hdl.handle.net/10675.2/821
    
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    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
    ae974a485f413a2113503eed53cd6c53
    10.1155/2012/732975
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