In the June 21 issue of JACC, Dr. Harold E. Bays argues for establishing “adiposopathy” as a full-fledged disease to provide a coherent understanding of the role of fat tissue in cardiovascular disease, dispel the confusion related to the many-named “metabolic syndrome,” and resolve the obesity paradox. Does he succeed in this task? What would Virchow have to say?
Adiposopathy (or “sick fat”) is defined as pathologic adipose tissue anatomic/functional disturbances promoted by positive caloric balance in genetically and environmentally susceptible individuals that result in adverse endocrine and immune responses that may directly promote CVD, and may cause or worsen metabolic disease.
So we have 1) no clear hallmark beyond ill-defined “anatomic/functional disturbances;” 2) no identifiable cause apart from the “promoting” effect of an unrestrained appetite; 3) the customary contingencies of “genetic and environmental” susceptibilities; and 4) no specific sign or symptom. Koch’s postulates for the modern age!
To be fair, Bays gives an interesting (and possibly correct) pathophysiologic hypothesis based on the recent discovery that fat cells are not necessarily terminally differentiated but may increase in number in response to excess calories. So the gist of Bays’ proposal is that problems arise in obesity if new cells do not increase in number while existing cells hypertrophy “excessively:”
If adipogenesis proceeds unencumbered in peripheral subcutaneous adipose tissue, then adiposity may not cause demonstrable adipose tissue dysfunction or adverse metabolic consequences. Conversely, if adipogenesis is impaired, then the lack of adipocytes to adequately proliferate(or differentiate) may be pathophysiologically analogous to a relative lack of adipocytes, sometimes described as representing an acquired lipodystrophy. The lack of excess energy storage in new fat cells due to inadequate adipogenesis may cause existing fat cells to undergo excessive hypertrophy, causing adipocyte dysfunction and pathogenic adipocyte and adipose tissue endocrine and immune responses.
An interesting idea, but most of the paper is a compendium of experiments from the last 10 years that link fat tissue with metabolic abnormalities, most of it tissue culture and small animal bench work with no clear relevance to homo sapiens, and in many cases no clear connection to Bays’ pathophysiologic proposal for “sick fat.” So the author is forced to mitigate his pronouncements by a liberal use of the conditional, producing sentences like
..while VAT [visceral adipose tissue] is generally considered among the most pathogenic fat depots, if SAT [subcutaneous adipose tissue] fat storage is limited or impaired during positive caloric balance and if SAT net free fatty acid release is increased into the circulation, then this SAT dysfunction may adversely affect nonhepatic organs, resulting in lipotoxicity to muscle (causing insulin resistance) and the pancreas (possibly reducing insulin secretion).
If the liver and muscle are “inflexible” (limited) in their ability to metabolize increased free fatty acid influx,then this may cause “lipotoxic” intraorgan and intracellular accumulation of lipid metabolites (e.g., fatty acyl coenzyme A, diacylglycerol, ceramide), which contributes to insulin resistance. The pancreas and arterial tissues maybe adversely affected as well, possibly causing beta-cell dysfunction and accelerated atherosclerosis, respectively.
I have counted 59 uses of the word “may”, 16 occurrences of “if,” 15 phenomena described as “potential.” But Bays’ conclusion couldn’t be more clear:
Adiposopathy or “sick fat” is a cardiovascular disease.
In the game of exaggerated claims, adiposopathologists are heavy weight champions!
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