Adiposopathy

Adiposopathy (or sick fat) is defined as pathologic adipocyte and adipose tissue anatomic & functional disturbances, promoted by positive caloric balance, in genetically and environmentally susceptible individuals. The ensuing pathogenic endocrine and immune responses may directly promote cardiovascular disease, and may also cause or worsen among the most common metabolic disease encountered in developed countries. Because many of these metabolic diseases are major cardiovascular disease risk factors (e.g., type 2 diabetes mellitus, hypertension, and dyslipidemia), adiposopathy also indirectly increases CVD risk, and is an important contributor to the metabolic syndrome.Americans, let's face it: We've been a spoiled country for a long time. Adiposopathy (or sick fat) is defined as pathologic adipocyte and adipose tissue anatomic & functional disturbances, promoted by positive caloric balance, in genetically and environmentally susceptible individuals. The ensuing pathogenic endocrine and immune responses may directly promote cardiovascular disease, and may also cause or worsen among the most common metabolic disease encountered in developed countries. Because many of these metabolic diseases are major cardiovascular disease risk factors (e.g., type 2 diabetes mellitus, hypertension, and dyslipidemia), adiposopathy also indirectly increases CVD risk, and is an important contributor to the metabolic syndrome. Most medical organizations recognize obesity as a disease. According to the Obesity Medicine Association Obesity Algorithm: 'Obesity is defined as a chronic, relapsing, multi-factorial, neurobehavioral disease, wherein an increase in body fat promotes adipose tissue dysfunction and abnormal fat mass physical forces, resulting in adverse metabolic, biomechanical, and psychosocial health consequences.' Consistent with this functional definition, patients with the disease of obesity can generally be categorized into patients with 'fat mass disease' and 'sick fat disease.' 'Fat mass disease' represents pathologies related to abnormal physical forces, such as stress on weight-bearing joints, immobility, tissue compression, and tissue friction. 'Sick fat disease' (adiposopathy) results from deranged endocrine and immune responses that contribute to the onset or worsening of elevated blood pressure, blood glucose, blood lipids, and other metabolic diseases. Clinically, a patient is diagnosed as having adiposopathy if an increase in body fat is the most likely cause of the onset or worsening of characteristic metabolic abnormalities. In some respects, the diagnosis of adiposopathy is a diagnosis of exclusion. Type 2 diabetes mellitus has a number of potential causes largely unrelated to excess body fat, such as hemochromatosis, chronic pancreatitis, hypercortisolism, excessive growth hormone, genetic syndromes of insulin resistance, and decreased pancreatic beta cell function due to genetic syndromes or surgical excision. High blood pressure can be due to pheochromocytoma, primary hyperaldosteronism, hypercortisolism, hyperthyroidism, renal artery stenosis, various kidney diseases, and familial or genetic syndromes. Dyslipidemia can be due to hypothyroidism, poorly controlled diabetes mellitus, certain types of liver or kidney disease, and genetic dyslipidemias. However, in the absence of other secondary causes, and in the presence of new onset or worsening of adiposopathic metabolic diseases with an increase in body fat, then by applying the principles of Ockham's Razor (pluralitas non est ponenda sine necessitate), wherein among competing theories with similar predictions, the simpler one is better, then adiposopathy is the simplest explanation why increased body fat leads to metabolic diseases. Diseased fat tissue surrounding various organs can cause illness, such as fat surrounding the heart, muscle, vessels, eyes, and bone. Some have suggested that diseased fat tissue surrounding the heart and vessels can contribute to inflammation and plaque rupture. Although not as well recognized, even the so-called 'protective' subcutaneous fat tissue has the potential to be 'sick' and contribute to metabolic disease. A prime example would be subcutaneous fat tissue found in the abdominal region. Accumulation of fat tissue in this region may have hormonal and immune activity, and thus the potential to cause metabolic disease, between that of visceral fat tissue and other areas of subcutaneous fat tissue. However, other subcutaneous fat tissues also might contribute to metabolic disease, if the fat cells become too enlarged and 'sick.' Admittedly, subcutaneous fat cells typically are larger, and capable of storing more fat when needed. However, subcutaneous fat tissue represents the largest proportion of fat tissue in the body, and is the major source of leptin. One potentially unfavorable effect of leptin is to increase blood pressure, as observed in animals. In humans, the observation of leptin-induced hypertension is not as yet conclusive. But to the extent that leptin may increase blood pressure, then the increase in leptin with subcutaneous fat cells (particularly when they become enlarged) could hardly be characterized as 'protective'. Other potentially detrimental effects of enlarged subcutaneous fat tissue relate to free fatty acids. During fasting, the body can obtain energy through the release of free fatty acids from the triglycerides in fat cells. The fatty acids thus become available for release into the blood. If too high a concentration of certain fatty acids accumulates in the blood because of sick fat tissue, and the body is unable to recruit more healthy fat cells, then existing healthy fat cells become engorged (and thus also sick). The result is that blood fatty acid concentrations increase to levels toxic to tissues such as liver, muscle, and pancreas, and lead to a range of pathological metabolic conditions. There are grounds for suspicion that sick abdominal fat tissue may produce factors that cause subcutaneous fat tissue to also become 'sick' and further contribute to metabolic diseases.