title: Obesity and cardiovascular disease: role of adipose tissue, inflammation, and the renin-angiotensin-aldosterone system.
abstract: Obesity is a leading contributor to morbidity and mortality worldwide. Chronic overnutrition and lack of physical activity result in excess deposition of adipose tissue and insulin resistance, which plays a key role in the pathophysiology of type 2 diabetes mellitus (DM2) and associated cardiovascular disease (CVD). Dysfunctional adipose tissue in obese individuals is characterized by chronic low-grade inflammation that spreads to several tissues as well as systemically and is able to impact the cardiovascular system, resulting in both functional and anatomical abnormalities. Inflammation is characterized by abnormalities in both innate and adaptive immunity including adipose tissue infiltration by CD4+ T lymphocytes, pro-inflammatory (M1) macrophages, and increased production of adipokines. The renin-angiotensin-aldosterone system (RAAS) is inappropriately activated in adipose tissue and contributes to originating and perpetuating inflammation and excessive oxidative stress by increasing production of reactive oxygen species (ROS). In turn, ROS and pro-inflammatory adipokines cause resistance to the metabolic actions of insulin in several tissues including cardiovascular and adipose tissue. Insulin resistance in cardiovascular tissues is characterized by impaired vascular reactivity and abnormal cardiac contractility as well as hypertrophy, fibrosis, and remodeling, which ultimately result in CVD. In this context, weight loss through caloric restriction, regular physical activity, and surgery as well as pharmacologic RAAS blockade all play a key role in reducing obesity-related cardiovascular morbidity and mortality.
authors.affiliation: Burns, Diabetes and Cardiovascular Center, University of Missouri, Harry S. Truman Memorial Veterans' Hospital, Columbia, MO, USA.
authors.forename: Guido
authors.initials: G
authors.lastname: Lastra
authors.forename: James R
authors.initials: JR
authors.lastname: Sowers
mesh_terms: D000273:Adipose Tissue / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D002318:Cardiovascular Diseases / Q000150:complications* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation / Q000150:complications* / Q000276:immunology / Q000378:metabolism; D007333:Insulin Resistance; D009765:Obesity / Q000150:complications* / Q000276:immunology / Q000378:metabolism; D018384:Oxidative Stress; D012084:Renin-Angiotensin System