Project Details

Description

Blast-related mild traumatic brain injury (mTBI) is common among Service members and Veterans who served in Iraq and Afghanistan. TBI has many long-term adverse health consequences as summarized in a recent report by the Institute of Medicine. However, it remains unclear if TBI increases the susceptibility to diabetes and other metabolic diseases. Given the tremendous impact that diabetes and metabolic diseases have on the quality of life and morbidity by fueling cardiovascular disease, cancer, impaired cognition, and reducing life expectancy, it is important to establish if mTBI can indeed cause metabolic disease and if so, through which mechanisms.The brain, and in particular the hypothalamus, maintains homeostasis by controlling glucose and lipid metabolism. Within the hypothalamus, insulin signaling controls systemic metabolism mostly through the control of autonomic outflow to metabolically important organs such as liver and adipose tissue. Insulin resistance in the brain is an important aspect of systemic insulin resistance. Experimental induction of insulin resistance selectively in the hypothalamus is sufficient to un-restrain hepatic glucose output and adipose tissue lipolysis. This systemic insulin resistance can lead to diabetes and metabolic diseases such as fatty liver and dyslipidemia. Obesity but also neurodegenerative diseases such as Alzheimer’s are characterized by hypothalamic insulin resistance and impaired glucose and lipid metabolism, illustrating that impaired brain function from a variety of causes can lead to metabolic impairment and increased susceptibility to diabetes.Based on these considerations and strong preliminary data, we hypothesize that mTBI disrupts central nervous system control of metabolism and increases the susceptibility to diabetes. We further hypothesize that there are feed-forward mechanisms induced by TBI that worsen the long-term adverse health consequences of TBI. Our studies in a rat model of blast-induced mTBI will examine with state-of-the-art methods if mTBI impairs glucose and lipid homeostasis and is associated with brain insulin resistance. If successful, these studies will establish that a long-term consequence of mTBI is diabetes and identify strategies to ameliorate metabolic disease.

StatusFinished
Effective start/end date15/07/1814/01/20

Funding

  • Congressionally Directed Medical Research Programs: $279,129.00

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