Opposing tissue-specific roles of angiotensin in the pathogenesis of obesity, and implications for obesity-related hypertension.
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.
Department of Pharmacology, the Obesity Research and Education Initiative, the Fraternal Order of Eagles' Diabetes Research Center, the François M. Abboud Cardiovascular Research Center, and the Center for Hypertension Research, University of Iowa, Iowa City, Iowa.
Nicole K
NK
Littlejohn
Department of Pharmacology, the Obesity Research and Education Initiative, the Fraternal Order of Eagles' Diabetes Research Center, the François M. Abboud Cardiovascular Research Center, and the Center for Hypertension Research, University of Iowa, Iowa City, Iowa justin-grobe@uiowa.edu.
Justin L
JL
Grobe
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D000809:Angiotensins / Q000378:metabolism*; D000818:Animals; D019440:Anti-Obesity Agents / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001794:Blood Pressure; D001812:Blood-Brain Barrier / Q000378:metabolism / Q000503:physiopathology; D004435:Eating; D002149:Energy Intake; D004734:Energy Metabolism / Q000187:drug effects; D005247:Feeding Behavior; D015438:Health Behavior; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D009765:Obesity / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D012084:Renin-Angiotensin System / Q000187:drug effects; D015398:Signal Transduction
D000809:Angiotensins; D019440:Anti-Obesity Agents; D000959:Antihypertensive Agents
angiotensin; energy; hypertension; metabolism; obesity