Is Visceral Adiposity the “Enemy Within”?

Abstract

"Has it ever struck you that there's a thin man inside every fat man, just as they say there's a statue inside every block of stone?" George Orwell, Coming Up For Air (1939) R ecently, data from diverse areas of investigation have come together to implicate chronic low-level inflammation as an important pathogenetic factor in atherosclerotic cardiovascular disease (CVD). As recently summarized by Ross, 1 studies in cell biology, animal models, clinical research, and epidemiology have been remarkably consistent in validating the early work of Virchow 2 and others, suggesting that atherosclerotic lesions are essentially an inflammatory response. In clinical research and epidemiology, 2 inflammation blood markers in particular, fibrinogen and C-reactive protein (CRP), have been used. Many studies have confirmed that these markers predict future cardiovascular events independently of more traditional cardiovascular risk factors, such as plasma lipid levels. [3][4][5] Because of this, several investigators have suggested that CRP might prove useful in clinical practice, 6,7 whereas others have favored fibrinogen. 8,9 Although there are important details to work out before either of these markers enters the clinical domain, this interest provides a clear and compelling imperative for understanding how inflammation integrates into both normal physiology and atherothrombotic pathophysiology. See p 961 and 968Focusing on CRP, population-based research efforts have revealed that in general, women have slightly higher values than men, blacks have higher values than whites, and those with clinical CVD have higher values than those without [10][11][12][13] et al, manuscript in preparation). In those without clinical CVD, metabolic variables consistently correlated with CRP include body mass index (BMI), glucose tolerance status/diabetes status, and level of coagulation activation. In addition, depending on the population being studied, other correlates of CRP may include smoking status, plasma lipids (especially HDL cholesterol), hypertension, evidence of chronic infection, and measures of subclinical atherosclerotic disease, such as ankle-brachial blood pressure index (ABI).

Abdominal obesity and carotid artery wall thickness. The Los Angeles Atherosclerosis Study

“…12,27,28 Visceral fat has a higher lipolytic activity than subcutaneous fat, and readily releases high levels of fatty acids and glycerol directly to the liver via the portal vein. This leads to increased production of …”

“…Visceral fat, like adipose tissue in general, also has key roles in the regulation of coagulation, fibrinolysis, and low-level inflammation, and is strongly correlated with C-reactive protein. 12,29 There are several problems in relating epidemiologic studies of abdominal obesity to this conceptual rationale of the atherogenicity of visceral fat. Several different indirect measures of abdominal obesity have been used; most commonly the waist circumference and waist-to-hip ratio, and all of them include both subcutaneous and intraabdominal fat.…”

“…[1][2][3][4][5][6][7] Two unresolved issues are whether central obesity is associated with the primary pathogenesis of atherosclerosis or with factors which precipitate clinical events, and whether the contribution of abdominal obesity is mediated through the pathway of associations with the well-known biological causal factors such as high blood pressure, abnormal lipoprotein levels and glucose intolerance, [8][9][10][11] or if other factors such as inflammation or coagulation are involved. 12 Early cohort-based autopsy studies showed little evidence of association of total body obesity with atherosclerosis, but none of them included measures of central obesity. 13 One international autopsy study showed no association of the thickness of the abdominal panniculus (subcutaneous fat pad) with raised lesions in the coronary arteries or aortas in any of the study population subgroups; 14 however, a recent study of young adults did report a significant association between the thickness of the abdominal panniculus and extent of atherosclerosis in the right coronary artery.…”

Women’s Ischemic Syndrome Evaluation

“…4 These markers are largely independent of lipid effects but are closely related to insulin resistance and adiposity. [5][6][7] Some medications have large, but often inconsistent, effects on these markers. For example, hormone replacement therapy can increase CRP levels 2-to 3-fold, 8 whereas fibrinogen is unaffected by estrogen.…”

Plasma Leptin and Adiposity During Antipsychotic Treatment of Schizophrenia

“…Increased adiposity, especially visceral abdominal adiposity, is associated with insulin resistance, elevated plasma glucose and lipid levels, and a systemic inflammatory state (Montague and O'Rahilly, 2000;Tracy, 2001). All of these conditions may contribute to the elevated cardiovascular mortality associated with obesity.…”