The goal of this thesis project is to determine whether the metabolism of fatty acid within the hypothalamus plays an important role in the regulation of energy and glucose homeostasis in aging. Specifically, I plan to induce bi-directional changes in the hypothalamic expression of two critical enzymes in fatty acid metabolism: malonyl-CoA decarboxylase (MOD) and carnitine palmitoyl transferase 1 (CPT1) and then examine their impact on the metabolic syndrome of aging in rats. I will pursue two experimental aims. 1) Identify the role of malonyl-CoA in the development of the metabolic syndrome of aging. I postulate that decreased cellular levels of malonyl-CoA lead to the progressive loss of lipid (and other nutrient) sensing in the hypothalamus of aging rats 2) Identify the role of LCFA-CoA in the development of the metabolic syndrome of aging. I postulate that decreased cellular levels of LCFA-CoA lead to the progressive loss of lipid (and other nutrient) sensing in the hypothalamus of aging rats. In doing these experiments, I will learn multiple physiologic, pharmacologic, and molecular techniques that will help me grow into an independent scientist while solving an important medical problem.
| Ross, R A; Rossetti, L; Lam, T K T et al. (2010) Differential effects of hypothalamic long-chain fatty acid infusions on suppression of hepatic glucose production. Am J Physiol Endocrinol Metab 299:E633-9 |
| Ross, Rachel; Wang, Penny Y T; Chari, Madhu et al. (2008) Hypothalamic protein kinase C regulates glucose production. Diabetes 57:2061-5 |
