The neuronal (pro)renin receptor and astrocyte inflammation in the central regulation of blood pressure and blood glucose in mice fed a high-fat diet

Author:

Worker Caleb J.12,Li Wencheng3,Feng Cheng-yuan4,Souza Lucas A. C.12,Gayban Ariana Julia B.12,Cooper Silvana G.12,Afrin Sanzida12,Romanick Samantha24,Ferguson Bradley S.24,Feng Earley Yumei12ORCID

Affiliation:

1. Department of Pharmacology and Physiology and Cell Biology, University of Nevada, Reno, School of Medicine, Reno, Nevada

2. Center for Molecular and Cellular Signal Transduction in the Cardiovascular System, University of Nevada, Reno, Nevada

3. Department of Pathology, Wake Forest University, Winston-Salem, North Carolina

4. Department of Neurology, Loma Linda University, Loma Linda, California

Abstract

We report here that the neuronal (pro)renin receptor (PRR), a key component of the brain renin-angiotensin system (RAS), plays a critical role in the central regulation of high-fat-diet (HFD)-induced metabolic pathophysiology. The neuronal PRR is known to mediate formation of the majority of angiotensin (ANG) II, a key bioactive peptide of the RAS, in the central nervous system and to regulate blood pressure and cardiovascular function. However, little is known about neuronal PRR function in overnutrition-related metabolic physiology. Here, we show that PRR deletion in neurons reduces blood pressure, neurogenic pressor activity, and fasting blood glucose and improves glucose tolerance without affecting food intake or body weight following a 16-wk HFD. Mechanistically, we found that a HFD increases levels of the PRR ligand (pro)renin in the circulation and hypothalamus and of ANG II in the hypothalamus, indicating activation of the brain RAS. Importantly, PRR deletion in neurons reduced astrogliosis and activation of the astrocytic NF-κB p65 (RelA) in the arcuate nucleus and the ventromedial nucleus of the hypothalamus. Collectively, our findings indicate that the neuronal PRR plays essential roles in overnutrition-related metabolic pathophysiology.

Funder

NIH/NHLBI

NIH/NIGMS

AHA

Publisher

American Physiological Society

Subject

Physiology (medical),Physiology,Endocrinology, Diabetes and Metabolism

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