Corticotropin Releasing Hormone deficiency is associated with changes in nutrient utilization and protection from development of obesity

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 685-694-Mechanisms of Obesity
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-693
Sevasti Karaliota*, Styliani Ourailidou, Panagiotis Tsakanikas, Alexia Polissidis, Fani Vlahou and Katia/Catherine P Karalis
Biomedical Research Foundation of the Academy of Athens, Athens, Greece
The adaptive response to stressors, or “stress response”, is a process innate to all mammals, imperative for the maintenance of homeostasis. Corticotropin Releasing Hormone or Factor (CRH/CRF) is the main mediator of the activation of the hypothalamic-pituitary-adrenal (HPA) axis, necessary for orchestrating the “stress response”. CRH and its receptors are expressed in a variety of tissues and emerging experimental evidence suggests the critical role of the system in the tissue-specific adaptive responses to various challenges. Despite the intimate link between the adaptive response to stressors and energy balance, the exact role of CRH/CRF in the maintenance of energy homeostasis remains elusive. We have previously reported reduced adiposity, body weight gain and improved insulin sensitivity in Crh-null (Crh-/-) mice compared to their wild-type (WT) littermates, in the experimental paradigm of high-fat diet – induced obesity (HFDIO). This particular phenotype was not rescued by short-term glucocorticoid replacement. To further elucidate the basis for this phenotype of the Crh-/- mice, we assessed their metabolic activity while on normal diet (ND) or HFD using CLAMS metabolic cages. We found significant decreases in the respiratory exchange ratio of the Crh-/- mice as compared to WT mice, indicating more efficient lipid versus carbohydrate utilization. In agreement with the above, we identified increased UCP1 expression and associated phenotypic characteristics of brown, or most likely beige, adipose tissue within the white adipose tissue of the Crh-/- mice. The above findings indicate a novel role of CRH in metabolism and support previous, primarily clinical, observations highlighting the central role of the “stress response” in the regulation of energy homeostasis. Although the inability of the Crh-/-mice to mount an efficient adaptive response may be protective against the development of adiposity following hypercaloric diets, it is still possible their impaired ability to store energy to be detrimental when rapid mobilization of energy is required. Our findings contribute to the on-going effort for the understanding of the regulation of energy homeostasis in particular in states of high stress and, hopefully, the development of new, therapeutic interventions.


Nothing to Disclose: SK, SO, PT, AP, FV, KPK

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