Neuropeptide Y in hypothalamic paraventricular nucleus: a center coordinating energy metabolism

Abstract

Intracerebroventricular injection of neuropeptide Y (NPY) has two effects on energy metabolism in addition to increased feeding: decreased brown fat thermogenesis and increased white fat lipoprotein lipase (LPL) enzymatic activity. We hypothesized that the paraventricular nucleus (PVN) of the hypothalamus is the controlling neural site for these responses. We further hypothesized that NPY stimulation at PVN would reduce gene expression for the critical brown fat thermogenic protein, uncoupling protein (UCP), and increase gene expression for the key white fat storage enzyme, LPL. In the first experiment, three groups of rats received injections every 6 h for 24 h (5 injections total) into the PVN:1) NPY (1 micrograms/1 microliters injection) and ad libitum food; 2) NPY (1 micrograms/1 microliters injection) and food restricted to control intake; 3) saline injection (1 microliter) and ad libitum food. Both NPY-treated groups showed significant reductions (P < 0.05) in brown fat UCP mRNA levels and marked stimulation of LPL mRNA levels relative to controls. In the second experiment, four groups of seven rats had NPY injected into the PVN:0 (vehicle control); 0.1 microgram; 0.5 microgram; and 1 microgram. Injections were made every 6 h for 24 h. There was a dose-related reduction in UCP mRNA produced by the NPY treatment. NPY treatment increased LPL mRNA, but a smooth dosing effect was not evident. The observation that NPY in the PVN can coordinate more than one component of energy metabolism is significant when considered with many reports of responsiveness of NPY activity in the arcuate nucleus-PVN neural circuit to perturbations of energy balance such as fasting and feeding, diabetes, and genetic obesity.(ABSTRACT TRUNCATED AT 250 WORDS)

The impact of the leucine 7 to proline 7 polymorphism of the neuropeptide Y gene on postprandial lipemia and on the response of serum total and lipoprotein lipids to a reduced fat diet

“…It has been suggested that centrally administered NPY increases the expression of LPL mRNA and enhances LPL activity in white adipose tissue thus favoring lipid storage (Billington et al, 1991(Billington et al, , 1994. In the present study, the heparin-releasable LPL activity did not differ among the genotype groups.…”

“…However, disturbed liver uptake or catabolism of LDL could also play a role. NPY has been suggested to regulate LPL activity in adipose tissue of experimental animals (Billington et al, 1991(Billington et al, , 1994. This Table 2 Energy intake, proportion of energy nutrients, and the intake of dietary cholesterol and fiber during the run-in period and the reduced fat diet period, mean AE s.e.m.…”

“…Based on studies in animal models of obesity and type 2 diabetes, it has been suggested that hyperphagia, reduced energy expenditure and obesity in these animal models may be explained by the hypothalamic resistance of insulin inhibition of NPY neurons (Frankish et al, 1995). NPY also seems to favor energy storage through increased lipoprotein lipase (LPL) activity in white adipose tissue (Billington et al, 1991(Billington et al, , 1994. Regarding dietary factors, long term feeding of high-fat diets has been shown to decrease NPY levels in hypothalamus in rats .…”

The Neuroanatomical Axis for Control of Energy Balance

“…But the data are clear with respect to CRH and the melanocortin system, and the conclusions are likely to extend to other feeding-relevant neuropeptides. Indeed, there is evidence for such distributed action for two other peptides, CART and NPY, implicated in the mediation of leptin's effects on energy balance (e.g., 11,22,94,191,195). The multiplicity of sites from which a given treatment may trigger the same response has yet to be assimilated into contemporary models for the control of energy balance.…”

Inhibitory effects of central neuropeptide Y on the somatotropic and gonadotropic axes in male rats are independent of adrenal hormones

“…Of all of these peptides however, NPY is one of the few which actually leads to the development of true obesity and insulin resistance when hypothalamic levels remain chronically elevated [3,28,30,33,40,46,47], as has been reported for various rodent genetic obesity syndromes [2,8,35,42]. The obesity syndrome which results from chronically elevated hypothalamic NPY levels in rodents [3,28,30,33,40,46,47] is still present even when NPY--induced hyperphagia is prevented [3,30,46], demonstrating that hyperphagia is not necessary for central NPY to produce its obesity--like effects. NPY in the hypothalamus is also involved in the regulation of several other important physiological processes including growth [4,22,25], reproduction [4,5,25], and fluid balance [13].…”