Muir and colleagues challenge the view of adipose tissue fibrosis as a contributing factor to type 2 diabetes in human obesity in a paper in the current issue of Obesity. In line with previous observations, they found that adipocyte hypertrophy is more tightly associated with diabetes even when normalized for overall obesity. However in contrast to other studies, they report that diabetic individuals display reduced extracellular matrix (ECM) deposition in their subcutaneous and visceral adipose tissues as judged by Sirius red stain and collagen immunohistochemistry (staining intensity was normalized to tissue area). Furthermore, the adipocytes were smaller in fibrotic areas. There was also an inverse correlation between HbA1c levels and visceral adipose tissue expression of fibrosis genes (such as LOX and Col 6A1) as well as between HbA1c levels and preadipocyte frequency in visceral adipose tissue. Based on these observations, these authors propose that adipose fibrosis is an adaptive feature that preserves adipocyte functionality by restricting hypertrophy (ref to Muir et al). These results stand in sharp contrast to many other studies, eg a recently published study by Gugliemi and colleagues reports that omental adipose tissue fibrosis in obese subjects is positively correlated with insulin resistance as judged by glucose clamps (1). The notion of a negative impact of adipose tissue fibrosis on local and systemic parameters is also supported by multiple animal studies that suggest that adipose tissue fibrosis contributes to obesity-related metabolic complications (2, 3, 4, 5, 6).

These discrepancies raise a number of questions: How do we define adipose tissue fibrosis? Does increased deposition of ECM in adipose tissue always imply fibrosis? Is there a causal relationship between ECM deposition and adipocyte hypertrophy or hyperplasia? Are there adipose depot differences? Is a large adipocyte necessarily a dysfunctional adipocyte? These are key questions, and the answers (or lack thereof) highlight the complexity of the adipose tissue response to this (patho) physiological change.