“Sick Fat,” Metabolic Disease, and Atherosclerosis

Comparison of cholesterol levels among humans and animals. Atherosclerotic coronary heart disease (CHD) is rare among hunter-gatherers; CHD is the most common cause of mortality in adult Americans. 1 mg/dL = 0.02586 mmol/L. (Adapted with permission from J Am Coll Cardiol.¹⁰)

Relation of body mass index (BMI) to prevalence of metabolic diseases, which are major atherosclerotic coronary heart disease risk factors. The BMI intervals do not represent equal quintiles; rather, they represent established obesity diagnostic and treatment cutoff points.²⁶ The chart data are derived from the National Health and Nutritional Examination Surveys (NHANES), 1999 to 2002, and are based on the following definitions: (1) diabetes mellitus = diagnosed and previously undiagnosed type 1 or type 2 diabetes mellitus; (2) hypertension = administration of antihypertensive medication or systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg; and (3) dyslipidemia = any of the following: total cholesterol ≥240 mg/dL, triglycerides ≥200 mg/dL, low-density lipoprotein cholesterol ≥160 mg/dL, or high-density lipoprotein cholesterol <40 mg/dL. (Adapted with permission from Int J Clin Pract.²⁶ Copyright 2007 Wiley Blackwell.)

Body mass index (BMI) distribution among patients with metabolic diseases. In general, metabolic disease definitions are based on measurements whose abnormalities significantly increase the risk for adverse clinical outcomes. The fact that these metabolic diseases often have a unified underlying pathophysiologic process may help to explain why the distributions of BMI for diabetes mellitus, hypertension, and dyslipidemia are generally similar. (Adapted with permission from Int J Clin Pract.²⁶ Copyright 2007 Wiley Blackwell.)

Adipocyte size and body fat distribution influence whether increased fat weight gain results in “sick” versus “healthy” adipose tissue. (Reprinted with permission from Expert Rev Cardiovasc Ther.⁴⁹ Copyright 2006 Future Drugs Ltd.)

Relation between adiposopathy and major atherosclerotic coronary heart disease risk factors leading to atherosclerosis. FFA = free fatty acid; HDL = high-density lipoprotein; LDL = low-density lipoprotein. (Reprinted with permission from Future Lipidology.⁹ Copyright 2006 Future Drugs Ltd.)

Navigating the consequences of adipocyte hypertrophy and visceral adiposity. Fat cell enlargement and accumulation of adipose tissue in the visceral area often result in pathogenic adipose tissue metabolic and immune responses, including the net release of free fatty acids, which may be lipotoxic to peripheral organs. The potential of pathogenic adipose tissue to cause metabolic disease is largely dependent on cross-talk and interactions with, as well as responses of, other body tissues.

Relation between pathogenic adipose tissue and the characteristic lipid pattern described by the metabolic syndrome: hypertriglyceridemia, low high-density lipoprotein (HDL) cholesterol levels, and small, dense low-density lipoprotein (LDL) particles. CETP = cholesterol ester transfer protein; FFA = free fatty acid; TG = triglyceride; VLDL = very-low-density lipoprotein. (Reprinted with permission from Future Lipidology.⁹ Copyright 2006 Future Drugs Ltd.)