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

Abstract

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.

(p-ClPhSe)2Reduces Hepatotoxicity Induced by Monosodium Glutamate by Improving Mitochondrial Function in Rats

“…Then, any alteration in the liver homeostasis could compromise the glucose levels and contribute to development of metabolic diseases [Rolo and Palmeira, ; Bhatti et al, ]. In fact, hyperglycemia is a characteristic symptom of rats treated with MSG [Shen et al, ; Miranda et al, ]. In animal models, subcutaneous neonatal MSG administration induces neuroendocrine obesity through hypothalamic lesion: resulting in fat tissue accumulation, glucose intolerance, hyperinsulinemia, and insulin resistance [Shen et al, ; Miranda et al, ; Quines et al, ].…”

“…In fact, hyperglycemia is a characteristic symptom of rats treated with MSG [Shen et al, ; Miranda et al, ]. In animal models, subcutaneous neonatal MSG administration induces neuroendocrine obesity through hypothalamic lesion: resulting in fat tissue accumulation, glucose intolerance, hyperinsulinemia, and insulin resistance [Shen et al, ; Miranda et al, ; Quines et al, ]. Furthermore, it has been demonstrated that hyperglycemia is associated with systemic insulin resistance and mitochondrial dysfunction in animal models of obesity induced by MSG administration [Shen et al, ; Miranda et al, ].…”

Sex differences in major depression and comorbidity of cardiometabolic disorders: impact of prenatal stress and immune exposures

“…Impaired β-cell function and number have been reported following in utero DEX exposure during the last trimester [210,218,219], yet there are few studies examining sex differences in pancreas development or the effects of DEX on developing β-cells. Moreover, since normal pancreatic β-cell function is dependent upon an appropriate autonomic innervation [220,221] in adulthood and during development [222], the same factors that underlie prenatal stress induced changes in cardiovascular function may similarly be involved in the programming of metabolism.…”

Monosodium l‐glutamate‐obesity onset is associated with disruption of central control of the hypothalamic‐pituitary‐adrenal axis and autonomic nervous system

“…However, central glucocorticoid infusion induces an anabolic process, increasing parasympathetic nervous system activity (PNS) and food ingestion via activation of neuropeptide Y (NPY) expression . Recent evidence suggests that imbalanced ANS output and defects in the HPA axis, leading to high glucocorticoids levels, are linked to obesity and cardiometabolic disease onset …”