The hypothalamus and especially the arcuate nucleus of hypothalamus (ARC) are considered to be the main sites of energy homeostasis and food intake regulation. Besides peripheral peptide hormones the hypothalamic acyl-CoA pool size, key enzymes and regulators of acyl-CoA metabolism are associated with food intake (Lam et al Nat Neurosci 2005). Elevated free fatty acids are converted into acyl-CoAs and bound to storage proteins like acyl-CoA binding protein (ACBP). Both acyl CoAs and ACBP have emerged as important regulators of various intracellular functions.

Materials and Methods: 

A rat line overexpressing ACBP was created by standard methods. Tissues were collected from fed and fasted rats. Total RNA and protein was isolated and used to measure differences in either gene expression or protein levels by quantitative realtime rtPCR or Western blotting. Our results demonstrate that ACBP overexpression surprisingly did not influence food intake or animal weight. Brains from transgenic animals had a significant increase in the C20:4 (54%) in the fed state and a decrease in C20:0 levels (40%) in the fasted stage. Fed transgenic rats had a significant reduction of hypothalamic fatty acid synthase (FAS) (28%) and peroxisome proliferator-activated receptors (PPAR) d (43%) mRNA levels, while carnitine palmitoyltransferase 1c (CPT-1) mRNA levels were increased (22%). There were no changes in hypothalamic mRNA levels of SREBP-1 or protein levels of AMP-activated protein kinase (AMPK) a, an important intracellular energy sensor. The changes observed in hypothalamic gene expression in our rats are a reaction to the ACBP overexpression possibly preventing more drastic changes in food intake control and maintaining energy homeostasis. Supported in part by the Finnish Academy and the Federal Ministry of Education and Research.