Adipose-tissue and intestinal inflammation - visceral obesity and creeping fat

Abstract

Obesity has become one of the main threats to health worldwide and therefore gained increasing clinical and economic significance as well as scientific attention. General adipose-tissue accumulation in obesity is associated with systemically increased pro-inflammatory mediators and humoral and cellular changes within this compartment. These adipose-tissue changes and their systemic consequences led to the concept of obesity as a chronic inflammatory state. A pathognomonic feature of Crohn's disease (CD) is creeping fat (CF), a locally restricted hyperplasia of the mesenteric fat adjacent to the inflamed segments of the intestine. The precise role of this adipose-tissue and its mediators remains controversial, and ongoing work will have to define whether this compartment is protecting from or contributing to disease activity. This review aims to outline specific cellular changes within the adipose-tissue, occurring in either obesity or CF. Hence the potential impact of adipocytes and resident immune cells from the innate and adaptive immune system will be discussed for both diseases. The second part focuses on the impact of generalized adipose-tissue accumulation in obesity, respectively on the locally restricted form in CD, on intestinal inflammation and on the closely related integrity of the mucosal barrier.

Keywords: Crohn’s disease; adipose-tissue; adipose-tissue inflammation; intestinal inflammation; obesity.

Figure 1

Adipose tissue morphology and expression profile- differences in obesity and CD. (A) Obesity is defined by a general enlargement of adipose tissue. Especially, the visceral fat-tissue undergoes drastic humoral and cellular changes in obese compared to lean individuals. In Crohn’s disease (CD), adipose tissue accumulation is localized around the inflamed intestinal segments. The interplay between adipose tissue and immune cells during inflammation within the tissue is the subject of ongoing research. Given the differences between adipose tissue in CD and obesity, obese CD patients’ adipose tissue might have varying impact on the intestinal inflammation depending on its localization and reason of development. The different adipose tissue morphology and composition between obesity and creeping fat is illustrated in (B). Adipocytes in obesity are hypertrophic and up-regulate pro-inflammatory mediators. Additionally, the immune-cell compartment within the tissue changes to deprived modulatory/anti-inflammatory cells and increased pro-inflammatory immune cells. Creeping fat is characterized by small hyperplastic adipocytes, with enhanced expression of pro- as well as anti-inflammatory mediators and genes. This is also mirrored in a more balanced increase of different immune cells within the tissue.