Adiposopathy (or sick fat) refers to the dysfunction of fat cells. This dysfunction may contribute to many of the adverse metabolic conditions associated with obesity and metabolic syndrome.
Diagnosis
Currently, no accepted diagnostic criteria exist for adiposopathy. Although medical and scientific organizations are increasingly acknowledging the central importance of fat tissue in causing metabolic disease, they have not yet agreed upon how adiposopathy is best diagnosed. Proposed criteria include:
;Major criteria:
*Elevated waist circumference or BMI
*Onset or worsening of high blood sugar with weight gain
*Onset or worsening of high blood pressure with weight gain
*Onset or worsening of dyslipidemia with weight gain
;Minor criteria:
*Increase in free fatty acids with weight gain
*Fatty liver with weight gain
*Increase in male hormones in women with weight gain
*Decrease in male hormone in men with weight gain
*Increase in hormones such as leptin and insulin with weight gain
*Increase in immune factors (such as C-Reactive protein, interleukin-6, and tumor necrosis alpha) with weight gain
*Abnormalities in lipoprotein particle size with weight gain
Pathophysiology
Anatomy
Diseased fat tissue surrounding various organs can cause illness, such as fat surrounding the heart, muscle, vessels, eyes, and bone. 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, even other subcutaneous fat tissues might contribute to metabolic disease, if the fat cells become too enlarged and “sick.” Admittedly, subcutaneous fat cells are typically larger, and more capable of storing fat when needed. However, subcutaneous fat tissue represents the large majority of fat tissue in the body, and is the major source of leptin, which is a factor produced by fat cells that has a number of functions. Among the potentially unfavorable effect of leptin is that leptin increases blood pressure, most well described in animals. In humans, leptin-induced hypertension is less 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 is in regard to free fatty acids.8 Triglycerides (fats) are the major constituents found and stored in fat cells, and are composed of a glycerol backbone, attached to three carbon chain fatty acids (hence the “tri” in “triglycerides”). During fasting, the body can obtain energy through the release of free fatty acids from the triglycerides in fat cells, which are then released into the blood. If too many certain fatty acids are released into the blood because fat tissue is sick and unable to recruit more fat cells, and existing fat cells become to big (and thus also sick), then the increase in fatty acids are “toxic” to organs such as the liver, muscle, and pancreas, and lead to metabolic disease. 15 Some have suggested that sick abdominal fat tissue may send out factors that cause subcutaneous fat tissue to also become “sick” and further contribute to metabolic diseases.
In summary, although abdominal or visceral fat tissue is best described to contribute to metabolic disease, abdominal fat is by no means the only fat tissue depot that has the potential to become “sick” and capable of contributing to metabolic ill health.
Physiology
Fat tissue is an active body organ involved in many processes critical to human health,8 including: (1) promotion of blood vessel formation (angiogenesis); (2) fat cell recruitment and development adipogenesis; (3) dissolving and reforming the structures around fat tissue (extracellular matrix); (4) generation, storage and release of fat; (5) growth factor production; (6) glucose metabolism; (6) production of factors that affect blood pressure (such as those associated with the renin-angiotensin system); (7) fat and cholesterol metabolism; (8) enzyme production; (9) hormone production; (10) steroid metabolism; (11) blood clotting (hemostasis); (12) element binding; (13) and immune response (described below). When fat cells and fat tissue remain healthy during fat weight gain, patients may avoid metabolic ill health. However, if enlargement of fat cells and fat tissue causes them to become “sick,” then important fat tissue functions are disrupted, and deranged responses contribute to metabolic disease.
When excessive body weight leads to adiposopathy, this represents a hormone or endocrine disease. Additionally, fat cells and fat tissue also produce many different types of immune factors. (1) adipokines with cytokine activity such as leptin, interleukins, and tumor necrosis factor alpha); (2) acute phase proteins / reactants such as C-reactive protein; (3) adipokines of the alternative complement system; (4) chemotactic/chemoattractant adipokines; and prostaglandins (eicosanoids). From an anti-inflammatory standpoint, fat tissue produces various anti-inflammatory factors However, weight loss therapies in overweight patients not only improve, or sometimes normalize various fat tissue factors that may cause or contribute to metabolic disease, but also improve and sometimes “cure” metabolic diseases such as type 2 diabetes mellitus, hypertension, and dyslipidemia.
As a result, many patients treated with these types of drugs increase body fat. Initially, it may seem odd and almost paradoxical to use a drug that increases fat tissue to treat metabolic diseases that are caused by too much fat tissue. However, when explained through the concept adiposopathy, no such paradox exists. Because PPAR gamma agents work by increasing the amount of healthy, functional fat, decreasing the proportion of sick abdominal fat tissue, and decrease “fatty liver.” All of these effects upon fat tissue are effective in treating sick fat and improving metabolic disease. Thus, it is within the framework of “sick” versus “healthy” fat, that the rationale behind the use of these drugs is easier to understand.
History
It has been known since the 1970’s that when fat cells become too big, they may become bloated and dysfunctional, or “sick.” It has also been known since the 1940’s that if fat gain occurs in the belly or abdominal (visceral) region, that this is another example of sick fat that promotes metabolic diseases. Finally, if fat growth exceeds its blood vessel supply, then the lack of oxygen delivery by the blood may also result in pathologic responses from fat tissue. In summary, it has been known for decades that adverse changes in fat cell and fat tissue anatomy result in sick fat which causes metabolic disease.
More recently, an additional event that has prompted the concept and term of “adiposopathy” is the evolving recognition of the profound hormone and immune importance of fat tissue. In the past, fat cells and fat tissue were considered by many as being inert, or hormonally and immunologically inactive. However, this has been proven incorrect, and it is now generally accepted that fat tissue is an active hormone,
Yet another historical event that moved medical science towards recognizing fat tissue as an underlying cause of metabolic disease has been the problematic issues that have arisen with the “metabolic syndrome.” The metabolic syndrome is a commonly used medical term to describe atherosclerotic coronary heart disease risk factors that tend to cluster together. Over the years, there have been at least 15 other similar terms used to generally describe the same clustering. According to one common definition, a patient is said to have “metabolic syndrome” if he or she has 3 or more the 5 following criteria: (1) abdominal obesity, (2) elevated triglycerides, (3) reduced high density lipoprotein cholesterol levels, (4) high blood pressure, and (5) high blood sugar. However, different scientific and medical organizations have different definitions for the “metabolic syndrome.” Also, the term “metabolic syndrome” does not describe, nor is it intended to describe a unifying cause of any disease. Since “metabolic syndrome” is not a disease, regulatory agencies (such as the Food and Drug Administration) do not approve drugs to treat metabolic syndrome, as a specific indicated use. Finally, the “metabolic syndrome” may be no better at predicting atherosclerotic coronary heart disease than an assessment of its individual components. As such, major scientific and medical organizations have questioned the usefulness of the metabolic syndrome, sometimes in open conflict with other major scientific and medical organizations.
Society and culture
The scientific and medical organizations are not alone in grappling with if and/or when too much body fat is actually a “disease.” Many patients and clinicians have the same uncertainties. This is reflected by the attitude of many of the public as well. Many are often resistant to the idea that gaining too much fat is a disease, for a number of reasons. One illustrative example in pop culture would be the “song” entitled: " Underwear Goes Inside the Pants " performed by Lazyboy in the album Lazyboy TV (2004). An excerpt of the publicly disclosed lyrics includes:
Given all the problems with medical terms such as overweight, obesity, and metabolic syndrome in describing when excessive body fat is a disease, adiposopathy has emerged as a term that reflects the fact that adipose (fat) tissue is no less capable of being diseased as any other body organ. The addition of the suffix “pathy” to an organ is not only accepted, but an historic universal identifier as to when a body tissue is diseased. This is in recognition that the use of weight loss therapies and drugs in overweight patients must not only improve the weight of patients, but must also improve the health of patients. Unfortunately, not everyone understands the central role that sick fat plays in the development of metabolic disease. This is partly because in the past, most of the attention of what causes metabolic disease was given to other body organs. In the past, the importance of fat tissue was often ignored, even as the obesity epidemic was contributing to the epidemic of metabolic diseases such as type 2 diabetes mellitus, hypertension, and dyslipidemia.
This has placed many clinical scientists at odds with basic researchers, clinicians and patients. The animal data supporting adiposopathy as a contributing cause to metabolic disease is overwhelming. Clinicians and patients well know through “real life” experiences that gaining body fat often causes patients to develop or worsen high blood sugar (diabetes mellitus), high blood pressure (hypertension), and dyslipidemia (abnormal cholesterol or fats in the blood). In fact, clinicians often recommend, and patients often expect that weight reduction efforts will improve, if not cure these metabolic diseases. However, many clinical scientists and even medical organizations continue to resist what is obvious to others, and that is that fat cells and fat tissue are hormonally and immunologically active. Many refuse to acknowledge the scientific and clinical evidence that too much body fat can cause or worsen metabolic disease, if the fat becomes sick.
In order to give greater recognition to the “adipocentric” (fat tissue as a central cause) paradigm of metabolic disease, a “Adiposopathy Working Group” was assembled to develop a consensus regarding whether adipospathy was truly an endocrine disease. In 2008, this group of experts in both the scientific and clinical field of Endocrinology reported their opinions in the International Journal of Clinical Practice.
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