Neuroendocrine, Metabolic, and Immune Functions during the Acute Phase Response of Inflammatory Stress in Monosodium <i>L</i>-Glutamate-Damaged, Hyperadipose Male Rat

Abstract

In rats, neonatal treatment with monosodium L-glutamate (MSG) induces several metabolic and neuroendocrine abnormalities, which result in hyperadiposity. No data exist, however, regarding neuroendocrine, immune and metabolic responses to acute endotoxemia in the MSG-damaged rat. We studied the consequences of MSG treatment during the acute phase response of inflammatory stress. Neonatal male rats were treated with MSG or vehicle (controls, CTR) and studied at age 90 days. Pituitary, adrenal, adipo-insular axis, immune, metabolic and gonadal functions were explored before and up to 5 h after single sub-lethal i.p. injection of bacterial lipopolysaccharide (LPS; 150 µg/kg). Our results showed that, during the acute phase response of inflammatory stress in MSG rats: (1) the corticotrope-adrenal, leptin, insulin and triglyceride responses were higher than in CTR rats, (2) pro-inflammatory (TNFα) cytokine response was impaired and anti-inflammatory (IL-10) cytokine response was normal, and (3) changes in peripheral estradiol and testosterone levels after LPS varied as in CTR rats. These data indicate that metabolic and neroendocrine-immune functions are altered in MSG-damaged rats. Our study also suggests that the enhanced corticotrope-corticoadrenal activity in MSG animals could be responsible, at least in part, for the immune and metabolic derangements characterizing hypothalamic obesity.

Prolonged but Not Short Negative Energy Condition Restored Corticoadrenal Leptin Sensitivity in the Hypothalamic Obese Rat

“…Moreover, the area under the curve of circulating glucocorticoid concentrations throughout the whole fasting period was significantly (p < 0.05) higher in MSG (68.18 ± 11.84 µg/dl/5 h) than in normal (30.79 ± 7.05 µg/dl/ 5 h) rats. These observations fully agree with our present in vitro observations and with earlier data from our laboratory [4, 20, 21, 35, 36] and others [8, 9, 11] indicating HPA axis hyperactivity in MSG rats. Moreover, enhanced glucocorticoid levels could also be accounted for by decreased metabolic clearance rate of this hormone in this animal model [9, 10].…”

Chronic Glucocorticoid-Rich Milieu and Liver Dysfunction

“…Indeed, MSG animals are partly refractory to leptin inhibition (leptin resistance) of food intake and body weight gain [15] and, importantly, to the leptin negative control on adrenocortical function [16–18]. Moreover, the adult MSG rat phenotype is also characterized by an enhanced proinflammatory peripheral environment [19]. …”

“…Because of the overall endocrine-metabolic characteristics, namely, hypercorticosteronemia and adipose tissue mass excess, the MSG rat is an excellent experimental model for basic investigation of different dysfunctions representative of the human Cushing's syndrome (hypothalamic obesity) phenotype [13, 14, 16–19]. Interestingly, it has been addressed that correcting their high circulating levels of GC various neuroendocrine and adiposity dysfunctions can be reversed [16, 18], including the hypertrophy of abdominal white adipocytes [14].…”

White Adipose Tissue and Circadian Rhythm Dysfunctions in Obesity: Pathogenesis and Available Therapies

“…In these circumstances, the new adipocytes develop a normal function. On the other hand, in rats with chronic high serum levels of LEP, GC and insulin, their visceral WAT undergoes a marked reduction in the number of compromised APCs, namely white APCs (WAPs), and a significant delay in their capacity to differentiate into mature adipocytes [20] ; consequently, the local WAT pad becomes full of dysfunctional-hypertrophic adipocytes [21] , a situation reverted by normalization of the high endogenous GC milieu [21] . When WAT mass increases by adipocyte hypertrophy, these large-size adipocytes develop a secretory dysfunction characterized by overproduction (synthesis and release) of adipokines that decrease tissue sensitivity to insulin, promote oxidative stress (OS), and display proinflammatory effects (LEP, resistin, tumor necrosis factor-α, plasminogen activator inhibitor type 1, interleukin-1 [IL-1], IL-6); conversely, they release lower amounts of adiponectin (ADIPOQ; an insulin-sensitizing adipokine) [22] .…”