Medical College of Wisconsin
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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



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Scopus ID

2-s2.0-84983143153   23 Citations


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


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

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

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