Reduced BAT function as a mechanism for obesity in the hypophagic, neuropeptide Y deficient monosodium glutamate-treated rat

Impact of transient correction of increased adrenocortical activity in hypothalamo-damaged, hyperadipose female rats

“…2,3,4,6,7 Also, the changes in hypothalamic neuronal function particularly enhance hypothalamo-pituitary-adrenal (HPA) axis activity. [8][9][10][11][12] It is known that hypophagic, 13 MSG-damaged rats are characterized by increased adiposity and insulin resistance; 14 however, the exact mechanisms whereby these abnormalities develop are not fully understood. These MSG-induced changes in HPA axis activity, a key function for maintaining homeostasis, have been attributed to dysfunctions of several hypothalamic peptidergic and monoaminergic systems [15][16][17] driving pituitary function, and, in turn, modifying adrenal development and function, 11 thus resulting in enhanced corticoadrenal activity.…”

Decreased lipolysis and enhanced glycerol and glucose utilization by adipose tissue prior to development of obesity in monosodium glutamate (MSG) treated-rats

“…Recently, reduced GLUT4 in BAT was found in both 30 and 90 day old MSG-treated rats. 11 The inactivity of BAT results in a de®cit in energy expenditure for thermogen-esis and it is believed to contribute to the high metabolic ef®ciency and obesity of these animals. We have previously shown that MSG-rats had lower carcass protein and higher carcass lipid content than controls.…”

MSG lesions decrease body mass of suckling-age rats by attenuating circadian decreases of energy expenditure

“…With these alterations of two peptide systems contributing importantly to the control of food intake and energy expenditure, mice (29, 37) and rats (22) are more or less hypophagic but ultimately become obese. MSG-induced damage of the ARC as the origin of these peptidergic pathways further implies impairment of the neuronal targets for circulating leptin as a hormone reducing energy stores, and as a consequence, leptin sensitivity is diminished (4), whereas plasma leptin levels are distinctly increased in postnatally MSG-treated, adult-age-obese rodents (11,22).Because adult-age obesity develops without overt hyperphagia in postnatally MSG-treated mice and rats, reduced energy expenditure is assumed to be fueling the massive increases of fat depots. Adult neonatally MSG-treated mice show a lower core temperature (T c ) during the dark period and beginning of the light period than control mice (8,37,41).…”

“…Postnatal MSG treatment produces central nervous (CNS) neurotoxic cell destruction, with the arcuate nucleus (ARC) as the most sensitive structure (35). With MSG doses sufficient to induce adult-age obesity but low enough to avoid extensive destruction such as retinal lesioning and tail automutilation (3,22,29), the CNS damage is seen in the ventromedial hypothalamus (VMH) and especially the ARC, two brain regions involved in the control of food intake. ARC damage is associated with impaired secretion of the releasing hormones for growth hormone (GHRH) and luteinizing hormone (LHRH) (2, 32), and the resulting changes in adenohypophysial growth hormone (GH) and gonadotropin secretion would explain retarded lean body mass growth and aberrations of gonadal development (19,36).…”

“…With these alterations of two peptide systems contributing importantly to the control of food intake and energy expenditure, mice (29,37) and rats (22) are more or less hypophagic but ultimately become obese. MSG-induced damage of the ARC as the origin of these peptidergic pathways further implies impairment of the neuronal targets for circulating leptin as a hormone reducing energy stores, and as a consequence, leptin sensitivity is diminished (4), whereas plasma leptin levels are distinctly increased in postnatally MSG-treated, adult-age-obese rodents (11,22).…”