High-fat diet-induced hypertension and autonomic imbalance are associated with an upregulation of CART in the dorsomedial hypothalamus of mice.
We evaluated herein whether diet-induced obesity alters sympathovagal balance, blood pressure, and neuropeptides levels at the hypothalamus and brainstem 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.
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
Laiali J
LJ
Chaar
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
Aline
A
Coelho
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
Natalia M
NM
Silva
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
William L
WL
Festuccia
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil antunes@icb.usp.br.
Vagner R
VR
Antunes
D000818:Animals; D001342:Autonomic Nervous System Diseases / Q000209:etiology / Q000378:metabolism*; D001794:Blood Pressure / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D059305:Diet, High-Fat / Q000009:adverse effects*; D004302:Dorsomedial Hypothalamic Nucleus / Q000378:metabolism*; D006973:Hypertension / Q000209:etiology / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D020738:Leptin / Q000097:blood; D008297:Male; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009765:Obesity / Q000209:etiology / Q000378:metabolism*; D052243:Resistin / Q000097:blood; D015854:Up-Regulation; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
D007328:Insulin; D015850:Interleukin-6; D020738:Leptin; D009419:Nerve Tissue Proteins; D052243:Resistin; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
Cocaine‐ and amphetamine‐regulated transcript; dorsomedial hypothalamus; hypertension; obesity; sucrose; sympathetic nervous system