Effects of Leptin and Corticosterone on the Expression of Corticotropin-Releasing Hormone, Agouti-Related Protein, and Proopiomelanocortin in the Brain of &lt;i&gt;ob/ob&lt;/i&gt; Mouse

Arvaniti, Konstantinia; Huang, Qingling; Richard, Denis

doi:10.1159/000054639

Cited by 69 publications

(43 citation statements)

References 36 publications

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“…Centrally, SSR125543 increased CRF mRNA levels in the parvocellular division of the PVN of both lean and obese Zucker rats, which likely resulted from an attenuation of the negative feedback regulation of CRF synthesis by corticosterone ( Jingami et al 1985, Young et al 1986, Herman et al 1992, Arvaniti et al 2001. Consistent with the corticosterone results, CRF 1 receptor blockade prevented the fastinginduced increase in c-fos mRNA levels in the PVN of obese rats.…”

Section: Discussionmentioning

confidence: 69%

Effects of the CRF1 receptor antagonist SSR125543 on energy balance and food deprivation-induced neuronal activation in obese Zucker rats

Doyon¹,

Samson²,

Lalonde³

et al. 2007

Journal of Endocrinology

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The corticotropin-releasing factor (CRF) system is involved in numerous physiological and behavioral actions, including the regulation of energy balance. We examined the effects of the CRF 1 receptor antagonist, SSR125543, on energy balance and food deprivation-induced neuronal activation in obese rats. Lean (Fa/?) and obese ( fa/fa) Zucker rats were treated orally with SSR125543 at a daily dose of 30 mg/kg for 21 days. Rats were killed either fed ad libitum or food deprived for 6 h in order to induce a mild stress response in obese rats. SSR125543 reduced plasma corticosterone levels in lean rats, prevented corticosterone response to fasting in obese rats, and increased CRF mRNA levels in the paraventricular hypothalamic nucleus (PVN) of both lean and obese rats, further confirming that the antagonist partially blocked CRF 1 receptors. SSR125543 increased protein gain in obese rats. Whole carcass analyses showed reduced energy and fat gains in lean rats. Consistent with reduced fat gain, circulating triglyceride and leptin levels were reduced in SSR125543-treated lean rats. In obese rats, circulating glucose levels and the homeostasis model assessment of insulin resistance index of insulin resistance were reduced by SSR125543 treatment. CRF 1 receptor blockade increased uncoupling protein-1 mRNA levels in interscapular brown adipose tissue of obese rats. The antagonist partly blocked the fasting-induced changes in c-fos mRNA levels in the PVN and arcuate nucleus of obese rats. Overall, these results suggest that although SSR125543 had relatively mild effects on energy balance, CRF 1 receptor blockade attenuated several metabolic effects of short-term fasting and improved plasma variables related to the metabolic syndrome and diabetes.

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Section: Discussionmentioning

confidence: 69%

Effects of the CRF1 receptor antagonist SSR125543 on energy balance and food deprivation-induced neuronal activation in obese Zucker rats

Doyon¹,

Samson²,

Lalonde³

et al. 2007

Journal of Endocrinology

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“…A stimulatory effect of leptin on CRH expression was observed in the paraventicular nucleus (PVN) of rats 2-6 h after either intracerebroventricular (icv) or intraperitoneal administration of the peptide, consistent with its anorexigenic action [31,32] . However, leptin infusion for 7 days was found to downregulate CRH expression in the mouse PVN and to prevent the compensatory rise of CRH in adrenalectomized mice [33] . A shorter period of subcutaneous leptin infusion did not have any effect on CRH expression in either mice or rats [30] .…”

Section: Leptin and The Hpa Axismentioning

confidence: 88%

Adipokines and Cardiovascular Risk in Cushing’s Syndrome

et al. 2011

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Cushing’s syndrome (CS) is associated with increased cardiovascular morbidity and mortality. Recent evidence also suggests that increased cardiovascular risk may persist even after long-term remission of CS. Increased central obesity, a typical feature of CS, is associated with altered production of adipokines, which contributes to the pathogenesis of several metabolic and cardiovascular complications observed in this condition. In vitro and in vivo studies have shown a relationship between cortisol and adipokines in several experimental settings. In patients with either active or ‘cured’ CS, an increase in leptin and resistin levels as well as the release of pro-inflammatory cytokines, such as tumor necrosis factor-α and interleukin-6, may be associated with increased cardiovascular risk. For other adipokines, including adiponectin, results are inconclusive. Studies are needed to further elucidate the interactions between clinical and subclinical increases in cortisol production and altered adipokine release in CS.

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“…Genetic manipulations, such as the introduction of a musclespecific GLUT4 transgene, dramatically improve glucose tolerance although diabetes is not completely corrected [27]. Hormonal manipulations, such as adrenalectomy [28] and treatment with thiazolidinediones [29], can also improve glucose tolerance and insulin sensitivity. Manipulation of the diet, so that all carbohydrates are replaced with protein, also can bring about an improvement in glycaemic control [11].…”

Section: Discussionmentioning

confidence: 99%

Differential beta cell responses to hyperglycaemia and insulin resistance in two novel congenic strains of diabetes (FVB-Lepr db ) and obese (DBA-Lep ob ) mice

Chua¹,

Liu

et al. 2002

Diabetologia

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Aims. Our goal was to identify genetic variants that determine the response to insulin resistance and hyperglycaemia. This report documents the diabetes syndrome of two new congenic strains of mice generated by the transfer of the Lepr db mutation to the FVB/NJ strain and the Lep ob mutation to the DBA/2J strain. Methods. Mice were characterised by measures of blood metabolites and hormones along with challenges with glucose and insulin injections. Histological examinations of the endocrine pancreas and the kidneys were also carried out. Results. Obese mice of the FVB-db congenic strain show long-term hyperglycaemia that is primarily due to severe insulin resistance. The hyperglycaemia in the fed state persists despite escalating secretion of insulin and massive increase of pancreatic beta cells. Obese FVB-db mice show evidence of mesangial matrix expansion, a hallmark of diabetic nephropathy.Leptin-deficient mice of the DBA-ob strain have variable obesity-diabetes. In mice with high insulin (>10 ng/ml), DBA-ob/ob mice maintain their increased adiposity and have a large increase in betacell number. In mice with low insulin (<1 ng/ml) DBA-ob/ob mice have greatly diminished adiposity. These mice have atrophied islets with evidence of increased beta-cell neogenesis from the ductal epithelium. Conclusions. The strain-specific responses suggest the existence of genetic variants that control insulin sensitivity and beta-cell responses in the strains described in this report. These new models of obesity-diabetes should prove useful in dissecting the genetic control of beta-cell responses to hyperglycaemia and insulin resistance. [Diabetologia (2002) [6,7], SHR [8], and LA [9]. In rats, it seems that only obese males are subject to developing severe hyperglycaemia and contraction of beta-cell numbers.The loss of beta cells in these obesity-diabetes models is not mediated by the immune system. Studies have shown that C57BLKS/J db/db (K-db) mice develop their characteristic diabetes phenotype independent of a functional immune system [10]. The response of the beta cell in these obese rodents is subject to dietary influences. When placed on a completely carbohydrate-free diet (CHO-free diet), obese C57BLKS/J db/db mice are able to maintain near-euglycaemia and preserve their pancreatic beta-cell mass [11].While these strain-specific phenotypes have been documented [4], some of the congenic strains have been lost. This report describes the generation and characterisation of several new congenic mouse strains carrying mutations of Lep or Lepr. The FVB congenic strains (FVB-db and FVB-ob) provide a new diabetes phenotype that has not been described previously. Obese FVB mice suffer a prolonged period of hyperglycaemia that produces massive expansion of beta-cell mass. We show data that the early onset of severe insulin resistance probably accounts for the hyperglycaemia of these strains. The islet hyperplasia of obese FVB mice suggests that prolonged hyperglycaemia does not eventually lead to complete betacell atro...

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Effects of Leptin and Corticosterone on the Expression of Corticotropin-Releasing Hormone, Agouti-Related Protein, and Proopiomelanocortin in the Brain of <i>ob/ob</i> Mouse

Cited by 69 publications

References 36 publications

Effects of the CRF1 receptor antagonist SSR125543 on energy balance and food deprivation-induced neuronal activation in obese Zucker rats

Effects of the CRF1 receptor antagonist SSR125543 on energy balance and food deprivation-induced neuronal activation in obese Zucker rats

Adipokines and Cardiovascular Risk in Cushing’s Syndrome

Differential beta cell responses to hyperglycaemia and insulin resistance in two novel congenic strains of diabetes (FVB-Lepr db ) and obese (DBA-Lep ob ) mice

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