Central action of CART induces neuronal activation in the paraventricular and dorsomedial hypothalamus of diet-induced obese and lean mice

Author(s)

Romeu, Deborah de Paula ^[1] ; Ribeiro, Luciene Maria ^[1] ; Antunes, Vagner Roberto ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, 1524 Prof Lineu Prestes Ave, BR-05508900 Sao Paulo - Brazil

• Document type: Journal article
• Source: Neuroscience Letters; v. 686, p. 175-180, NOV 1 2018.
• Web of Science Citations: 1

Abstract

The cocaine- and amphetamine-regulated transcript (CART) is a peptide commonly studied in the feeding behavior, but it exerts an important role in the autonomic and cardiovascular control as well. It is known that exogenous administration of CART in the central nervous system can elicit increase in blood pressure of both conscious and anesthetized rodents, but little is known whether these central effects might differ between lean and obese animals. We have recently shown that diet-induced obese mice that developed hypertension presented an upregulation of CART levels in the dorsomedial nucleus of hypothalamus, while obese normotensive ones had not. Herein we investigate whether the central action of CART could activate differently the hypothalamic nuclei of diet-induced obese mice compared to the lean counterparts by using Fos protein expression, C57BL/6 mice were randomly assigned to two cohorts, one fed with a high-fat diet for 8 weeks (obese), and the other fed with regular rodent chow (lean). Both groups received an ICV injection of CART at the dose of 400 mu M, 1 mM or vehicle. Subsequently, the brains were processed for Fos protein immunohistochemical in order to identify hypothalamic neuronal activation. Significantly greater numbers of Fos-positive neurons were observed in the PVN and DMH of obese mice that received CART 1 mM, when compared to the lean control. These results indicate that the central action of CART induces neuronal activation in the hypothalamic nuclei of obese and lean mice, and this could be relevant to the different autonomic and cardiovascular adjustments that an organism exposed to different diet and metabolic condition. (AU)

• FAPESP's process: 13/06206-0 - Gene expression changes of neuropeptides and proinflammatory factors of the hypothalamus and brainstem nucleus involved with cardiovascular regulation in diet-induced obesity animals
• Grantee: Vagner Roberto Antunes
• Support type: Regular Research Grants
• FAPESP's process: 16/21991-3 - Salt-induced hypertension: role of purinergic signaling in the neuronal cells at the hypothalamus level, and its correlation with the autonomic nervous system and blood pressure control
• Grantee: Vagner Roberto Antunes
• Support type: Regular Research Grants
• FAPESP's process: 15/07944-0 - Evaluation of central effect of CART on cardiovascular parameters of diet-induced obesity mice
• Grantee: Deborah de Paula Romeu
• Support type: Scholarships in Brazil - Scientific Initiation