Faculty Collaboration Database

Opposing tissue-specific roles of angiotensin in the pathogenesis of obesity, and implications for obesity-related hypertension. Am J Physiol Regul Integr Comp Physiol 2015 Dec 15;309(12):R1463-73

Date

10/23/2015

Pubmed ID

26491099

Pubmed Central ID

PMC4698411

DOI

10.1152/ajpregu.00224.2015

Scopus ID

2-s2.0-84983143153 (requires institutional sign-in at Scopus site)   26 Citations

Abstract

Metabolic disease, specifically obesity, has now become the greatest challenge to improving cardiovascular health. The renin-angiotensin system (RAS) exists as both a circulating hormone system and as a local paracrine signaling mechanism within various tissues including the brain, kidney, and adipose, and this system is strongly implicated in cardiovascular health and disease. Growing evidence also implicates the RAS in the control of energy balance, supporting the concept that the RAS may be mechanistically involved in the pathogenesis of obesity and obesity hypertension. Here, we review the involvement of the RAS in the entire spectrum of whole organism energy balance mechanisms, including behaviors (food ingestion and spontaneous physical activity) and biological processes (digestive efficiency and both aerobic and nonaerobic resting metabolic rates). We hypothesize that opposing, tissue-specific effects of the RAS to modulate these various components of energy balance can explain the apparently paradoxical results reported by energy-balance studies that involve stimulating, versus disrupting, the RAS. We propose a model in which such opposing and tissue-specific effects of the RAS can explain the failure of simple, global RAS blockade to result in weight loss in humans, and hypothesize that obesity-mediated uncoupling of endogenous metabolic rate control mechanisms can explain the phenomenon of obesity-related hypertension.

Author List

Littlejohn NK, Grobe JL

Author

Justin L. Grobe PhD Professor in the Physiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adipose Tissue
Angiotensins
Animals
Anti-Obesity Agents
Antihypertensive Agents
Blood Pressure
Blood-Brain Barrier
Eating
Energy Intake
Energy Metabolism
Feeding Behavior
Health Behavior
Humans
Hypertension
Obesity
Renin-Angiotensin System
Signal Transduction