N-Procalcitonin: Central Effects on Feeding and Energy Homeostasis in Rats

Abstract

Procalcitonin (PCT), the precursor of calcitonin (CT), is a 116-amino-acid peptide, but PCT itself has no known activity. However, although the C cells of the thyroid gland are the dominant source of circulating CT, PCT and its free bioactive amino-terminal fragment (N-PCT) have been localized in adipocytes and neuroendocrine cells as well as in some hypothalamic regions of primary importance in the regulation of feeding and energy balance. These findings together with the coelaboration of N-PCT and CT, and N-PCT's sequence conservation during evolution, suggest that N-PCT has a critical, and as yet undefined, physiological function. We demonstrate here that intracerebroventricular administration of N-PCT significantly decreased food intake and body weight gain for at least 48 h in conscious, freely moving, and unstressed rats fed ad libitum. These effects were accompanied by a transitory increase in body temperature and a decrease in locomotor activity. Moreover, after intracerebroventricular N-PCT administration, Fos protein, a marker of neuronal activation, was found in regions of primary importance in the integration of hormonal signals for energy homeostasis and feeding. In contrast, ip administration of N-PCT did not elicit any anorectic or catabolic effects. Furthermore, PCT was found in key feeding areas such as the arcuate nucleus of free-feeding rats, and its level was significantly reduced after fasting. These results suggest that N-PCT can function as an endogenous ligand for the CT receptor and may act as a catabolic signaling molecule in the central regulation of feeding behavior and energy homeostasis.

Serum PCT and its Relation to Body Weight Gain in Pulmonary Tuberculosis

“…One very recent study attributes an anorectic effect to amino-PCT (N-PCT), the biologically active fragment of PCT. It has been shown that administration of N-PCT to free-feeding, freely moving unstressed rats significantly reduced food intake in a dose-dependent manner and decreased body weight gain [11]. In the present study, body weight gain during intensive phase tended more towards the desirable gain of 5 % in the study group with a lower increase in serum PCT than in the group with a higher increase in the prohormone.…”

“…However, although in group 1b serum PCT increased and in group 2a the prohormone decreased at the end of intensive phase, percentage body weight gain in group 1b was better than in group 2a. Tavares et al [11] mention in their study that the anorectic effect of N-PCT was extremely potent at even low doses but comparatively less significant at the highest dose. Their study suggests that the central receptors mediating N-PCTs anorectic effect were already fully activated at lower doses.…”

“…Previous authors have reported that administration of amino-PCT (N-PCT), the biologically active fragment of PCT to free-feeding, freely moving unstressed rats significantly reduced food intake in a dose-dependent manner and decreased body weight gain; hence it has the potential to be an important physiological regulator of energy homeostasis. Further, abundant expression of PCT-like immunoreactivity was detected in free feeding rats in regions of the brain implicated for feeding behavior; whereas PCT expression was significantly reduced in fasted rats [11]. These authors have however expressed their view that further research is necessary to assess N-PCT induction in some well-characterized anorexia-eliciting paradigms.…”

Aminoprocalcitonin-mediated suppression of feeding involves the hypothalamic melanocortin system

“…Moreover, c-Fos expression, a marker of neuronal activity, was observed primarily within the ARC and PVN after icv injection of N-PCT (54, 57). In vitro and in vivo studies suggest that N-PCT, similarly to other neuropeptides of the CT family, like amylin and CT gene-related peptides, can function as a ligand for the 55,57). Together, these findings suggest that the anorectic actions of N-PCT likely occur within the hypothalamus.…”

“…Although CT has been considered as an enigmatic hormone (19), and there is not a true ligand for CT-R, N-PCT has the potential to be an endogenous ligand for central CT-R. Recent evidence indicates that N-PCT can function as a ligand for the CT-R and may act as an anorectic signaling molecule in the CNS (47,54,55).The CT-R has been cloned and characterized in different cell types and species (40). Two CT-R isoforms, CTa and CTb, have been described in the rat brain with an overlapping distribution pattern particularly in hypothalamic nuclei involved in feeding behavior, including the arcuate nucleus (ARC) and the paraventricular nucleus (PVN) (4,23,48).…”