The effect of moxonidine on feeding and body fat in obese Zucker rats: role of hypothalamic NPY neurones

Abstract

1 The antihypertensive agent moxonidine, an imidazoline I i -receptor agonist, also induces hypophagia and lowers body weight in the obese spontaneously hypertensive rat, but the central mediation of this action and the neuronal pathways that moxonidine may interact with are not known. We studied whether moxonidine has anti-obesity e ects in the genetically-obese and insulinresistant fa/fa Zucker rat, and whether these are mediated through inhibition of the hypothalamic neuropeptide Y (NPY) neurones. 2 Lean and obese Zucker rats were given moxonidine (3 mg kg 71 day 71 ) or saline by gavage for 21 days. 3 Moxonidine decreased food intake throughout by 20% in obese rats (P50.001) and by 8% in lean rats (P50.001), and reduced weight gain that ®nal body weight was 15% lower in obese (P50.001) and 7% lower in lean (P50.01) rats than their untreated controls. Plasma insulin and leptin levels were decreased in moxonidine-treated obese rats (P50.01 and P50.05), but unchanged in treated lean rats. Uncoupling protein-1 gene expression in brown adipose tissue was stimulated by 40 ± 50% (P40.05) in both obese and lean animals given moxonidine. Obese animals given moxonidine showed a 37% reduction in hypothalamic NPY mRNA levels (P=0.01), together with signi®cantly increased NPY concentrations in the paraventricular nucleus (P50.05), but no changes in the arcuate nucleus or other nuclei; this is consistent with reduced NPY synthesis in the arcuate nucleus and blocked release of NPY in the paraventricular nucleus. In lean animals, moxonidine did not a ect NPY levels or NPY mRNA. 4 The hypophagic, thermogenic and anti-obesity e ects of moxonidine in obese Zucker rats may be partly due to inhibition of the NPY neurones, whose inappropriate overactivity may underlie obesity in this model.

Cystathionine-γ lyase-derived hydrogen sulfide mediates the cardiovascular protective effects of moxonidine in diabetic rats

“…The suppressed gain in BW was exacerbated by pharmacological interventions that improved (moxonidine) or worsened (DL-propargylglycine) glycemic control (Table 1), which rules out the dependence of glycemic control on gain in BW in our model system. The moxonidine-evoked reduction in BW gain agrees with findings in obese spontaneously hypertensive rats (SHR) (Bing et al, 1999). Here, we present the first evidence for a favorable moxonidine effect on glycemic control in a diabetic rat model (Fig.…”

Decrease of Obesity by Allantoin via Imidazoline I1-Receptor Activation in High Fat Diet-Fed Mice

“…The activation of I 1 R has been reported to improve hypertension and hyperlipidemia [16]. Additionally, I 1 R activation was shown to attenuate hyperphagia in STZ-induced diabetic mice by lowering the hypothalamic NPY level [17], similar to the mechanism observed in Zucker rats [32]. Previous studies demonstrated that appetite was reduced by an increase in blood pressure [33, 34].…”

Involvement of Supraspinal Imidazoline Receptors and Descending Monoaminergic Pathways in Tizanidine-Induced Inhibition of Rat Spinal Reflexes

“…Although their physiological functions are not fully determined, it has been demonstrated that I 1 receptors, found predominantly in the brain stem (5), play a role in the regulation of arterial blood pressure (6) and food intake (7). It is known that I 2 receptors mediate antinociceptive effects (29) and that some populations of I 2 receptors are located intracellularly in the outer membrane of the mitochondrion and inhibit monoamine oxidase activity (30).…”