Differential Effects of Central Leptin, Insulin, or Glucose Administration during Fasting on the Hypothalamic-Pituitary-Thyroid Axis and Feeding-Related Neurons in the Arcuate Nucleus

Abstract

The reductions in circulating levels of leptin, insulin, and glucose with fasting serve as important homeostasis signals to neurons of the hypothalamic arcuate nucleus that synthesize neuropeptide Y (NPY)/agouti-related protein (AGRP) and alpha-MSH/cocaine and amphetamine-regulated transcript. Because the central administration of leptin is capable of preventing the inhibitory effects of fasting on TRH mRNA in hypophysiotropic neurons primarily through effects on the arcuate nucleus, we determined whether the continuous administration of 30 mU/d insulin or 648 microg/d glucose into the cerebrospinal fluid by osmotic minipump might also have similar effects on the hypothalamic-pituitary-thyroid axis. As anticipated, the intracerebroventricular infusion of leptin reduced fasting-induced elevations in NPY and AGRP mRNA and increased proopiomelanocortin and cocaine and amphetamine-regulated transcript mRNA in the arcuate nucleus. In addition, leptin prevented fasting-induced reduction in pro-TRH mRNA levels in the paraventricular nucleus and in circulating thyroid hormone levels. In contrast, whereas insulin increased proopiomelanocortin mRNA and both insulin and glucose reduced NPY mRNA in arcuate nucleus neurons, neither prevented the fasting-induced suppression in hypophysiotropic TRH mRNA or circulating thyroid hormone levels. We conclude that insulin and glucose only partially replicate the central effects of leptin and may not be essential components of the hypothalamic-pituitary-thyroid regulatory system during fasting.

Circulating hormones and hypothalamic energy balance: regulatory gene expression in the Lou/C and Wistar rats

“…In this regard, it is well established that decreased TSH and T4 levels during food deprivation can be reversed following leptin administration. The blunted TSHthyroid axis in this setting is due to decrease synthesis of thyrotrophin-releasing hormone at hypothalamic levels (Fekete et al 2006). Taken together, our findings indicate that Lou/C rats exhibit biochemical features of central hypothyroidism as an adaptative mechanism to decrease energy expenditure in the face of low energy stores.…”

Effect of different glycaemic conditions on gene expression of neuropeptides involved in control of food intake in rainbow trout; interaction with stress

“…No similar studies have been carried out in fish to date. In mammals, the increase in glucose levels during the starved-to-fed transition is not accompanied by changes in CART expression in the hypothalamus (Stolarczyk et al, 2010), although the decrease in glucose levels during the fed-to-fasted transition is accompanied by a decrease in hypothalamic CART mRNA levels (Fekete et al, 2006). This suggests a specificity of the response in rainbow trout compared with that known in mammals, in which changes were observed not only in the hypothalamus but also in the hindbrain and occurred only under hyperglycaemic conditions.…”

The Influence of Intranasal Insulin on Hypothalamic-Pituitary-Thyroid Axis in Normal and Diabetic Rats

“…However, there are no reports that address the influence of centrally administered insulin on thyroid status of rats. One study describes the effect of insulin administered into the brain on the thyroid status of starving rats, but since levels of insulin, leptin, and glucose in these animals were significantly reduced, this could affect the regulation of the activity of TRH-producing hypothalamic neurons without and under the brain insulin action [54]. Importantly, the extent to which the function of the HPT axis and the thyroid status depend on brain insulin level is one of immediate problems for clinical and experimental endocrinology and neurology.…”