Proopiomelanocortin mRNA In Arcuate Nucleus Research Articles

Disengaging insulin from corticosterone: roles of each on energy intake and disposition

Corticosterone and insulin play complex roles in the amount and composition of calories ingested, and the utilization and deposition of this energy. Understanding the interplay of these two hormones is complicated because increasing concentrations of corticosterone dose-dependently increase circulating insulin levels. We addressed individual contributions of each hormone by controlling, at steady-state levels, corticosterone (by adrenalectomy and exogenous replacement) and insulin (by streptozotocin-induced destruction of pancreatic beta-cells and exogenous replacement) across a spectrum of concentrations in rats, creating 8 hormonal combinations. For 5 days after surgery, all rats received chow. At day 5, they were subdivided into those that continued to receive chow and those that had a choice between chow, lard, and 32% sucrose for a further 5 days. During the choice/chow period, total calories ingested were stimulated by corticosterone and choice diet, and subject to a corticosterone-insulin interaction. Sucrose, but not lard, intake was stimulated by insulin. Body weight was increased by insulin, decreased by high corticosterone, and unaffected by diet. White adipose tissue depot weights were stimulated by insulin, corticosterone, and diet. Plasma triglycerides, free fatty acids, total ketone bodies, glucose, and glycerol were all significantly increased by corticosterone and the choice diet but inhibited by insulin. In contrast, plasma leptin was only increased by insulin and diet, plasma glucagon and liver glycogen was only affected by insulin and liver triglycerides, and arcuate nucleus proopiomelanocortin mRNA was only influenced by diet. Collectively, these data show that corticosterone and insulin determine the intake, form, and compartmentalization of energy both independently and interactively.

Acute ethanol decreases NPY mRNA but not POMC mRNA in the arcuate nucleus

The acute effects of ethanol and acetaldehyde on neuropeptide mRNA expression in the arcuate nucleus (ARC) was assessed. Acetaldehyde was increased in blood following ethanol with cyanamide (a potent inhibitor of aldehyde dehydrogenase) administration. Acetaldehyde is a toxin which can cause a variety of adverse effects following ethanol ingestion in some Oriental people with a genetic lower activity of aldehyde dehydrogenase. Neuropeptide Y (NPY) mRNA levels in ARC were significantly decreased in response to ethanol in the presence or absence of cyanamide compared to control. In contrast, proopiomelanocortin mRNA in ARC was not changed. These novel findings suggest that ethanol suppresses NPY gene expression in ARC and may play a role in ethanol-induced changes in neuronal function.

ARC POMC mRNA and PVN α-MSH are lower in obese relative to lean Zucker rats

Effects of obesity on gene expression for opioid peptides and neuropeptide-Y (NPY) in the arcuate nucleus (ARC), and on opioid peptides and α-melanocyte stimulating hormone (α-MSH) in the paraventricular nucleus (PVN) were examined in obese Zucker rats (18 weeks old). Obese Zucker rats are insulin-resistant, diabetic and hyperleptinemic as indicated by high serum glucose, insulin and leptin levels. ARC proOpiomelanocortin (POMC) mRNA levels were significantly lower in the obese relative to lean Zucker rats and ARC proNeuropeptide Y (proNPY) mRNA levels were higher ( P<0.05). There were no differences in proDynorphin and proEnkephalin mRNA levels in the ARC ( P>0.05). Obese Zucker rats had lower α-MSH and dynorphin A 1–17 peptide levels in the paraventricular nucleus (PVN) ( P<0.05), but did not have lower PVN β-endorphin peptide levels ( P>0.05). The decrease in POMC in the ARC and decrease in α-MSH in the PVN seen in the obese Zucker rat in the present study suggest that reduced activity of the melanocortin system in the ARC to PVN pathway may contribute to the related hyperphagia. Reduced activity of the melanocortin system in the ARC to PVN pathway may be due to a disturbance of leptin signaling coupling to POMC.

Decreased Type 2 Corticotropin-Releasing Hormone Receptor mRNA Expression in the Ventromedial Hypothalamus during Repeated Immobilization Stress

Chronic or repeated stress results in reduction of food intake and body weight in rats. Stress-induced anorexia has been attributed to increased corticotropin-releasing hormone (CRH) function in the central nervous system. To explore possible roles of other neuropeptides and peripheral hormones involved in food intake and energy utilization during continuing stress, we examined the impact of repeated immobilization stress on expression of mRNAs coding for CRH, neuropeptide Y (NPY), galanin and pro-opiomelanocortin (POMC) mRNAs in such hypothalamic nuclei as the paraventricular nucleus (PVN), arcuate nucleus (ARC) and dorsomedial hypothalamus (DMH), as well as plasma insulin and leptin concentrations. Changes in type 2 CRH receptor (CRHR-2) mRNA in the ventromedial hypothalamus (VMH), a possible target of anorectic CRH effect, were also examined. Rats were immobilized for 2 h daily for 6 days and sacrificed 24 h after the last immobilization. Immobilized rats had lower food intake and body weight and higher levels of PVN CRH mRNA than controls. Repeated immobiliza tion also lowered plasma insulin and leptin concentrations and VMH CRHR-2 mRNA levels. These results provide additional evidence linking VMH CRHR-2 mRNA levels to plasma leptin concentration. ARC NPY and DMH galanin mRNAs increased following repeated immobilization, while ARC POMC mRNA decreased. DMH NPY mRNA and ARC galanin mRNA were unaltered by immobilization. Since NPY and galanin are considered orexigenic, while the POMC-melanocortin-4 receptor system is apparently anorexigenic, the changes in neuropeptide mRNAs and VMH CRHR-2 mRNA may play counterregulatory roles against anorectic CRH effects.

STZ-induced diabetes decreases and insulin normalizes POMC mRNA in arcuate nucleus and pituitary in rats.

Effects of streptozotocin (STZ)-induced diabetes and insulin on opioid peptide gene expression were examined in rats. In experiment 1, three groups were administered STZ (75 mg/kg ip single injection). Two groups were killed at either 2 or 4 wk. In the third group, insulin treatment (7.0 IU/kg x 1 day for 3 wk) was initiated 1 wk after STZ injection. STZ induced hyperphagia and reduced weight gain. Insulin decreased food intake and increased body weight relative to diabetes. Proopiomelanocortin (POMC) mRNA in arcuate nucleus (Arc) and pituitary decreased in diabetes and normalized after insulin treatment. Prodynorphin (proDyn) mRNA increased in diabetes and normalized in the pituitary after insulin but not in the Arc. Diabetes did not alter proenkephalin (proEnk) expression in the Arc or pituitary, nor dynorphin A1-17 or beta-endorphin in paraventricular nucleus (PVN). alpha-Melanocyte-stimulating hormone (alpha-MSH) peptide levels were decreased in the PVN and normalized following insulin treatment. Diabetes increased Arc neuropeptide Y mRNA, and insulin suppressed this increase. In experiment 2, insulin (2.5 IU/kg sc) daily for 1 wk in normal rats increased Arc POMC mRNA, but not proDyn and proEnk mRNA. These results suggest that Arc POMC expression and PVN alpha-MSH peptide levels decrease in diabetes. Also, insulin may influence Arc and pituitary POMC activity in neurons that regulate energy metabolism.

Gonadal Steroid Hormone Regulation of Proopiomelanocortin Gene Expression in Arcuate Neurons That Innervate the Medial Preoptic Area of the Rat

The density of beta-endorphin (beta-endo)-like immunoreactive (IR) fibers in the medial preoptic area (MPOA) has been shown to vary across the estrous cycle and is gonadal steroid hormone-dependent. These beta-endo-containing fibers are presumably projections of proopiomelanocortin (POMC) neurons which are located in the arcuate nucleus (ARC). POMC mRNA level varies across the estrous cycle in the ARC and its expression is differentially altered by gonadal steroid hormones. However, it is unclear how gonadal steroids regulate POMC gene expression in ARC neurons that innervate the MPOA. Therefore, combined fluorogold (FG) retrograde neuronal labeling and in situ hybridization histochemistry were used to investigate the effects of gonadal steroid hormone treatment on POMC gene expression in ARC neurons supplying the MPOA of ovariectomized (OVX) female rats. POMC-expressing cells were located in the ARC and median eminence (ME), wherein such neurons were significantly larger than unlabeled cells that surround them. A relatively greater number of ARC POMC neurons were observed to innervate the medial portion of the medial preoptic nucleus (MPN) than the lateral portion of the MPN. Estradiol (E2) and progesterone (P) treatment before FG injection did not affect the number of FG and POMC double-labeled neurons in the ARC, which suggests that hormone treatment did not alter the number of POMC-expressing neurons projecting to the MPN. In OVX animals, ARC POMC mRNA labeling was relatively low, and increased significantly in neurons of the most rostral ARC region 48 h after E2 treatment. P administration enhanced and prolonged the effect of E2 in this group of ARC neurons. E2P treatment significantly increased POMC mRNA expression beginning 13 h after P injection in all but the most caudal ARC POMC neurons. Thereafter, E2P treatment gradually increased POMC mRNA expression for at least 1 additional day. Gonadal steroid hormone treatment apparently affects POMC mRNA expression uniformly in neurons of the same ARC subdivision without regard to their efferent targets. Diurnal variation of POMC mRNA expression is present only in the most rostral ARC region, which contains a population of E2-sensitive POMC neurons. The results suggest that the relatively greater beta-endo-like IR fiber density in the medial MPN is due to a greater number of POMC neurons innervating this region. The pattern of innervation of the MPN by POMC neurons is unaffected by gonadal steroid hormone treatment, which appears to induce POMC expression in ARC neurons, and eventually to stimulate the synthesis and transport of beta-endo in POMC neuronal axons which project to the MPOA.(ABSTRACT TRUNCATED AT 400 WORDS)