Diet-induced obesity and low testosterone increase neuroinflammation and impair neural function

Journal of Neuroinflammation

Christian J Pike¹  Daniella Lent-Schochet¹  Anusha Jayaraman¹ 

[1] Davis School of Gerontology, University of Southern California, 3715 McClintock Avenue, Los Angeles 90089, CA, USA

关键词: Testosterone;    Peripheral nervous system;    Neuroinflammation;    Glia;    Diet-induced obesity;    Central nervous system;   

Others  :  1150729
DOI  :  10.1186/s12974-014-0162-y

 received in 2014-03-18, accepted in 2014-08-28,  发布年份 2014

【 摘 要 】

Background

Low testosterone and obesity are independent risk factors for dysfunction of the nervous system including neurodegenerative disorders such as Alzheimer¿s disease (AD). In this study, we investigate the independent and cooperative interactions of testosterone and diet-induced obesity on metabolic, inflammatory, and neural health indices in the central and peripheral nervous systems.

Methods

Male C57B6/J mice were maintained on normal or high-fat diet under varying testosterone conditions for a four-month treatment period, after which metabolic indices were measured and RNA isolated from cerebral cortex and sciatic nerve. Cortices were used to generate mixed glial cultures, upon which embryonic cerebrocortical neurons were co-cultured for assessment of neuron survival and neurite outgrowth. Peripheral nerve damage was determined using paw-withdrawal assay, myelin sheath protein expression levels, and Na⁺,K⁺-ATPase activity levels.

Results

Our results demonstrate that detrimental effects on both metabolic (blood glucose, insulin sensitivity) and proinflammatory (cytokine expression) responses caused by diet-induced obesity are exacerbated by testosterone depletion. Mixed glial cultures generated from obese mice retain elevated cytokine expression, although low testosterone effects do not persist ex vivo. Primary neurons co-cultured with glial cultures generated from high-fat fed animals exhibit reduced survival and poorer neurite outgrowth. In addition, low testosterone and diet-induced obesity combine to increase inflammation and evidence of nerve damage in the peripheral nervous system.

Conclusions

Testosterone and diet-induced obesity independently and cooperatively regulate neuroinflammation in central and peripheral nervous systems, which may contribute to observed impairments in neural health. Together, our findings suggest that low testosterone and obesity are interactive regulators of neuroinflammation that, in combination with adipose-derived inflammatory pathways and other factors, increase the risk of downstream disorders including type 2 diabetes and Alzheimer¿s disease.

【 授权许可】

   
2014 Jayaraman et al.; licensee BioMed Central Ltd.

【 图 表 】

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