THE EFFECTS OF TESTOSTERONE AND HIGH-FAT DIET ON NEUROINFLAMMATION

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 142-166-Hypothalamus-Pituitary Development & Biology
Basic/Clinical
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-165
Anusha Jayaraman*1, Daniella Lent2 and Christian J Pike3
1USC, Los Angeles, CA, 2USC, 3Univ of Southern California, Los Angeles, CA
Inflammatory pathways contribute to the pathogenesis of several diseases, including type 2 diabetes mellitus (T2D). Inflammation is regulated by many factors. For example, testosterone can attenuate inflammation in part by decreasing the expression of pro-inflammatory cytokines such as TNFalpha and IL-1beta. On the other hand, high-fat diet is associated with activation of pro-inflammatory pathways. High-fat diet also induces obesity, promotes T2D, and is associated with decreased testosterone levels. We hypothesize that interactions between low testosterone and high-fat diet-induced metabolic changes both independently and cooperatively regulate inflammatory pathways and accelerate the development of T2D related pathology. In this study, we investigate the effects of experimental manipulation of testosterone levels combined with high-fat diet on neuroinflammation and development of T2D. In particular, we determine the effects of low testosterone levels in the presence and absence of a high-fat diet on (i) expression of pro-inflammatory pathways (ii) metabolic indices of T2D, and (iii) levels of reactive astrocytes and activated microglia. Our preliminary results suggest that low testosterone levels and high-fat diet significantly elevate blood glucose levels, reduce insulin sensitivity, and increase expression levels of TNFalpha, IL-1beta, and IL-6 while decreasing the expression levels of IL-4 transcript. In addition, we show that neurons exhibit reduced survival and poorer neurite outgrowth when co-cultured with glial cultures generated from high-fat fed animals in comparison to glial cultures from animals maintained on a normal diet. We also see changes in the inflammatory pathways in the peripheral nervous system due to manipulated testosterone levels and high-fat diet. These results demonstrate neuroinflammatory effects of high-fat diet, a relationship that is affected by testosterone levels. Together, our findings suggest that low testosterone and obesity are interactive regulators of neuroinflammation that may increase risk of downstream disorders such as T2D and Alzheimer’s disease.

Nothing to Disclose: AJ, DL, CJP

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm