High-fat diet-induced hypertension and autonomic imbalance are associated with an upregulation of CART in the dorsomedial hypothalamus of mice

Author(s)

Chaar, Laiali J. ^[1] ; Coelho, Aline ^[1] ; Silva, Natalia M. ^[1] ; Festuccia, William L. ^[1] ; Antunes, Vagner R. ^[1]

Affiliation

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

• Document type: Journal article
• Source: PHYSIOLOGICAL REPORTS; v. 4, n. 11 JUN 2016.
• Web of Science Citations: 11

Abstract

We evaluated herein whether diet-induced obesity alters sympathovagal balance, blood pressure, and neuropeptides levels at the hypothalamus and brain-stem of mice. Male C57BL6J mice fed with a high-fat (HFD) or a high-fat high-sucrose (HFHSu), or a regular chow diet (C) for 8 weeks were evaluated for metabolic parameters and blood pressure, the latter being performed in conscious freely moving mice. Spectral analysis from the records of systolic blood pressure (SBP) and cardiac pulse intervals (PI) was performed to analyse the autonomic balance in the cardiovascular system. HFD-fed mice developed two distinct hemodynamic phenotypes: hypertensive mice (HFD-H) with high systolic and diastolic BP levels and hypertension-resistant mice (HFD-R) whose BP levels were similar to C group. Spectral analysis of SBP and PI variabilities indicate that the low-frequency (LF)/high-frequency (HF) ratio, which is an index of sympathovagal balance, is higher in HFD-H compared to HFD-R. Along with hypertension and higher LF/HF ratio, HFD-H mice presented increased hypothalamic mRNA levels of cocaine-and amphetamine-regulated transcript (CART), and increased CART-positive neurones in the dorsomedial hypothalamus (DMH) by high-fat diet when compared to C group. Despite developing obesity to similar levels than HFD feeding, intake of a HFHSu was not associated with hypertension in mice neither CART levels increase. Collectively, our main findings indicate that high-fat diet induced-hypertension and autonomic imbalance are associated to an upregulation of CART levels in the DMH of mice. (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 Opportunities: Regular Research Grants
• FAPESP's process: 11/13563-8 - Obesogenic diet and inflammatory process in the brainstem and its interaction with the autonomic nervous system and the arterial pressure
• Grantee: Laiali Jurdi El Chaar
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 09/15354-7 - Role of adipose tissue in the development of obesity and associated co-morbidities: investigation of molecular mechanism and search for alternative therapies
• Grantee: William Tadeu Lara Festuccia
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 10/19018-9 - Inter-relationships among insulin resistance, hypothalamic dysfunction, sympathetic hyperactivity and arterial hypertension induced by high fat, high sucrose diet.
• Grantee: Natália Mauadie Silva
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 15/19530-5 - Involvement of the nutrient sensor mTOR in the development of obesity associated chronic metabolic diseases
• Grantee: William Tadeu Lara Festuccia
• Support Opportunities: Research Projects - Thematic Grants