The long-term objective of this fellowship to elucidate molecular, biochemical, and physiological mechanism(s) coupling the sensing of (macro-) nutrients within the hypothalamus to the regulation of liver glucose metabolism. Here we tested the hypothesis that the metabolism of lactate within the mediobasal hypothalamus is a pivotal (required) step in the central sensing of carbohydrates, which in turn induces robust changes in liver glucose fluxes. First, we enhance the hypothalamic availability and metabolism of lactate and pyruvate by increasing levels of either glucose or lactate (Aim 1). Since the entry of lactate-derived carbons in the TCA cycle requires its conversion to pyruvate (catalyzed by the enzyme lactate dehydrogenase) we wish to examine whether this biochemical step is indeed required for the sensing of both lactate and glucose within the hypothalamus (AIM 2). Next we investigate whether activation of hypothalamic KATP channels is required for the effects of central glucose and lactate (Aim 3). Lastly, we wish to explore the physiological impact of these observations by negating the hypothalamic sensing mechanism during physiological elevations in the circulating lactate levels (Aim 4). ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32DK072876-01
Application #
6999607
Study Section
Special Emphasis Panel (ZRG1-F06 (20))
Program Officer
Hyde, James F
Project Start
2005-07-01
Project End
2007-06-30
Budget Start
2005-07-01
Budget End
2006-06-30
Support Year
1
Fiscal Year
2005
Total Cost
$43,976
Indirect Cost
Name
Albert Einstein College of Medicine
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
110521739
City
Bronx
State
NY
Country
United States
Zip Code
10461
Lam, Tony K T (2007) Brain Glucose Metabolism Controls Hepatic Glucose and Lipid Production. Cellscience 3:63-69
Muse, Evan D; Lam, Tony K T; Scherer, Philipp E et al. (2007) Hypothalamic resistin induces hepatic insulin resistance. J Clin Invest 117:1670-8
Lam, Tony K T; Gutierrez-Juarez, Roger; Pocai, Alessandro et al. (2007) Brain glucose metabolism controls the hepatic secretion of triglyceride-rich lipoproteins. Nat Med 13:171-80