I just came across the following article, and haven't quite digested the whole thing just yet. Still, it is interesting so I thought I would share it here. This post will be about the most curious topic in this paper, but I hope to revisit this in a series of future blog posts (hence the "I" in the title).
Near as I can tell, the lead author, Harold Bays, is the doctor who coined the term "adiposopathy" or "sick fat".
Adiposopathy is pathologic adipose tissue dysfunction that may be initiated and/or exacerbated by fat accumulation (adiposity) in genetically susceptible patients [1••]. Adipocytes are metabolically active and adipose tissue is an important endocrine organ (Table 1) [2••]. Abnormalities of adipocyte factors contribute to dysmetabolism (Fig. 1), and adiposopathy [1••,3•] promotes some of the most common metabolic diseases encountered in clinical practice, including type 2 diabetes mellitus (T2DM), hypertension, and dyslipidemia.
This is a summary paper focusing on the fact that it is dysfunction of the adipose tissue rather than the amount of adipose tissue that is responsible for Metabolic Syndrome. Thus explaining your "metabolically obese thin people" and "metabolically normal obese people", etc. The focus, as the title implies, is MetS treatments that target the fat cell dysfunction rather than simply the person's fat mass.
Sick fat appears to be related to adipocyte hypertrophy -- an enlarged fat cell:
It has been known since the 1970s that adipocyte hypertrophy increases the lipid/protein ratio of the adipocyte (through a relative consistency in protein content coupled with increased fat content) [13], decreases the responsiveness of adipose tissue to insulin [14], and increases the risk of metabolic diseases such as T2DM [15] and dyslipidemia, even if adipocyte hypertrophy is found in only slightly overweight individuals [16]. In fact, adipocyte hypertrophy is more closely linked to metabolic abnormalities, such as insulin resistance, than is an increase in total body fat [17].
An increase in fat cell size represents a failure of adipose tissue to adequately proliferate and differentiate [18] (as found with obesity and T2DM [19]) and, therefore, a failure to inadequately accommodate a further increase in energy influx [20]. Adipocyte hypertrophy may indicate a resistance or inability to store triglycerides beyond some maximal amount [21].
(This is consistent with the
Critical Visceral Fat Theory I blogged on previously.)
For this post, I want to focus on the discussion of one of the pharmaceutical treatments: PPAR-gamma agonists. (Here's a
LINK to general information on these drugs --
thiazolidinediones or “glitazones.” -- Actos and Avandia). I'm not promoting pharmaceutical therapy, and Avandia has seen a lot of negative press of late, but nonetheless I find the mechanism of action of these drugs to be interesting.
These compounds appear to "cure" sick fat by stimulating the proliferation of new, small, young adipocytes and/or promote the death (apoptosis) of dysfunctional hypertrophied large fat cells. Since SCAT has a greater ability to differentiate, and VAT cells are more metabolically active, this seems to have differential effects on the two types of adipose tissue. These drugs tend to cause fat mass gain in SCAT, and loss in VAT, but appear to be most effective in the patients who are fatter to begin with and who gain more fat. Yes, you read that right.
From an adipose tissue metabolism standpoint, PPARγ agents have been shown to reduce free fatty acids [23••,91], increase adiponectin [92–94], and reduce leptin [93] (although not consistently so [95]), with unconfirmed effects upon resistin [95,96], IL-6 [97], and tumor necrosis factor-α [95,97]. Thus, it appears that many of the favorable effects of PPARγ agents upon glucose metabolism and adipocyte function may be most related to improvements in free fatty acid metabolism
I've seen diabetics list these meds in their treatment regimes and yet be on weight loss regimes. In some ways this seems counter productive. One way to try to cure sick fat is to try to reverse the dysfunction by emptying out the cells. Another, it appears, would be to replace sick adipocytes with healthy ones. While weight gain may be the last thing a person wants, I know I probably would resist it were I diabetic, it is interesting to consider.
