Metabolic Context Regulates Distinct Hypothalamic Transcriptional Responses to Antiaging Interventions
AuthorsStranahan, Alexis M.
Becker, Kevin G.
WoodIII, William H.
MetadataShow full item record
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.
CitationInt J Endocrinol. 2012 Aug 27; 2012:732975
- Hypothalamic Angptl4/Fiaf is a novel regulator of food intake and body weight.
- Authors: Kim HK, Youn BS, Shin MS, Namkoong C, Park KH, Baik JH, Kim JB, Park JY, Lee KU, Kim YB, Kim MS
- Issue date: 2010 Nov
- Perturbation of hypothalamic microRNA expression patterns in male rats after metabolic distress: impact of obesity and conditions of negative energy balance.
- Authors: Sangiao-Alvarellos S, Pena-Bello L, Manfredi-Lozano M, Tena-Sempere M, Cordido F
- Issue date: 2014 May
- Altered hypothalamic function in diet-induced obesity.
- Authors: Velloso LA, Schwartz MW
- Issue date: 2011 Dec
- Defective hypothalamic autophagy directs the central pathogenesis of obesity via the IkappaB kinase beta (IKKbeta)/NF-kappaB pathway.
- Authors: Meng Q, Cai D
- Issue date: 2011 Sep 16
- A talk between fat tissue, gut, pancreas and brain to control body weight.
- Authors: Wilson JL, Enriori PJ
- Issue date: 2015 Dec 15