Glucocorticoids, the Etiology of Obesity and the Metabolic Syndrome

Dallman, Mary F.; Akana, Susan F.; Pecoraro, Norman C.; Warne, James P.; Fleur, Susanne E. la; Foster, Michelle T.

doi:10.2174/156720507780362236

Cited by 46 publications

(43 citation statements)

References 61 publications

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“…Both cortisol and IGF-I are important components of glucose metabolism regulation (Dallman et al, 2007; Figure 1 Observed associations between plasma cortisol concentrations measured before and after ACTH injection (a; white dots, females and black dots, males), and between plasma cortisol concentration and CBG binding activity in females (b) and males (c; black dots, before and white dots, after ACTH injection). All axes in log scale.…”

Section: Discussionmentioning

confidence: 99%

The cortisol response to ACTH in pigs, heritability and influence of corticosteroid-binding globulin

Larzul

Terenina

Foury

et al. 2015

Animal

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In the search for biological basis of robustness, this study aimed (i) at the determination of the heritability of the cortisol response to ACTH in juvenile pigs, using restricted maximum likelihood methodology applied to a multiple trait animal model, and (ii) at the study of the relationships between basal and stimulated cortisol levels with corticosteroid-binding globulin (CBG), IGF-I and haptoglobin, all important players in glucose metabolism and production traits. At 6 weeks of age, 298 intact male and female piglets from 30 litters (30 dams and 30 boars) were injected with 250 µg ACTH(1-24) (Synacthen). Blood was taken before ACTH injection to measure basal levels of cortisol, glucose, CBG, IGF-I and haptoglobin, and 60 min later to measure stimulated cortisol levels and glucose. Cortisol increased 2.8-fold after ACTH injection, with a high correlation between basal and stimulated levels (phenotypic correlation, r p = 0.539; genetic correlation, r g = 0.938). Post-ACTH cortisol levels were highly heritable ( h 2 = 0.684) and could therefore be used for genetic selection of animals with a more reactive hypothalamic-pituitary-adrenocortical axis. CBG binding capacity correlated with cortisol levels measured in basal conditions in males only. No correlation was found between CBG binding capacity and post-ACTH cortisol levels. Basal IGF-I concentration was positively correlated with BW at birth and weaning, and showed a high correlation with CBG binding capacity with a strong sexual dimorphism, the correlation being much higher in males than in females. Basal haptoglobin concentrations were negatively correlated with CBG binding capacity and IGF-I concentrations. Complex relationships were also found between circulating glucose levels and these different variables that have been shown to be related to glucose resistance in humans. These data are therefore valuable for the genetic selection of animals to explore the consequences on production and robustness traits, but also point at pigs as a relevant model to explore the underlying mechanisms of the metabolic syndrome including the contribution of genetic factors.

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Section: Discussionmentioning

confidence: 99%

The cortisol response to ACTH in pigs, heritability and influence of corticosteroid-binding globulin

Larzul

Terenina

Foury

et al. 2015

Animal

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“…obesity (Dallman et al 2007). Nevertheless, patients with Cushing syndrome submitted to adrenalectomy also showed a reduction of obesity (Chow et al 2008).…”

Section: Figurementioning

confidence: 98%

HPA axis and vagus nervous function are involved in impaired insulin secretion of MSG-obese rats

Miranda

Torrezan

Oliveira

et al. 2016

Journal of Endocrinology

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Neuroendocrine dysfunctions such as the hyperactivity of the vagus nerve and hypothalamus–pituitary–adrenal (HPA) axis greatly contribute to obesity and hyperinsulinemia; however, little is known about these dysfunctions in the pancreatic β-cells of obese individuals. We used a hypothalamic-obesity model obtained by neonatal treatment with monosodiuml-glutamate (MSG) to induce obesity. To assess the role of the HPA axis and vagal tonus in the genesis of hypercorticosteronemia and hyperinsulinemia in an adult MSG-obese rat model, bilateral adrenalectomy (ADX) and subdiaphragmatic vagotomy (VAG) alone or combined surgeries (ADX–VAG) were performed. To study glucose-induced insulin secretion (GIIS) and the cholinergic insulinotropic process, pancreatic islets were incubated with different glucose concentrations with or without oxotremorine-M, a selective agonist of the M3muscarinic acetylcholine receptor (M3AChR) subtype. Protein expression of M3AChR in pancreatic islets, corticosteronemia, and vagus nerve activity was also evaluated. Surgeries reduced 80% of the body weight gain. Fasting glucose and insulin were reduced both by ADX and ADX–VAG, whereas VAG was only associated with hyperglycemia. The serum insulin post-glucose stimulation was lower in all animals that underwent an operation. Vagal activity was decreased by 50% in ADX rats. In the highest glucose concentration, both surgeries reduced GIIS by 50%, whereas ADX-VAG decreased by 70%. Additionally, M3AChR activity was recovered by the individual surgeries. M3AChR protein expression was reduced by ADX. Both the adrenal gland and vagus nerve contribute to the hyperinsulinemia in the MSG model, although adrenal is more crucial as it appears to modulate parasympathetic activity and M3AChR expression in obesity.

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“…In obesity and metabolic syndrome, excessive plasma glucocorticoid level is considered a factor that leads to diabetes (Kyrou et al 2006, Dallman et al 2007). Cushing's syndrome with elevated plasma glucocorticoid level and treatment with therapeutic doses of glucocorticoid often cause impaired glucose tolerance and type 2 diabetes.…”

Section: Introductionmentioning

confidence: 99%

Sub-chronic stimulation of glucocorticoid receptor impairs and mineralocorticoid receptor protects cytosolic Ca2+ responses to glucose in pancreatic β-cells

Koizumi

Yada

2008

Journal of Endocrinology

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The development of diabetes associated with stress, obesity, and metabolic syndrome involves elevated plasma glucocorticoid levels. It has been shown that short-term (!1 day) exposure to glucocorticoids reduces insulin secretion from pancreatic islets by affecting several steps of glucose signaling in b-cells. However, longer term direct effects of glucocorticoids on b-cells remain to be established. In this study, single b-cells isolated from rat islets were treated with glucocorticoids, mineralocorticoids, and their receptor agonists/antagonists for 3 days in culture, followed by assessment of the b-cell responsiveness to glucose by measuring cytosolic Ca

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Glucocorticoids, the Etiology of Obesity and the Metabolic Syndrome

Cited by 46 publications

References 61 publications

The cortisol response to ACTH in pigs, heritability and influence of corticosteroid-binding globulin

The cortisol response to ACTH in pigs, heritability and influence of corticosteroid-binding globulin

HPA axis and vagus nervous function are involved in impaired insulin secretion of MSG-obese rats

Sub-chronic stimulation of glucocorticoid receptor impairs and mineralocorticoid receptor protects cytosolic Ca2+ responses to glucose in pancreatic β-cells

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