Zymosan-induced inflammation stimulates neo-adipogenesis

Abstract

Objective: To investigate the potential of inflammation to induce new adipose tissue formation in the in vivo environment. Methods and results: Using an established model of in vivo adipogenesis, a silicone chamber containing a Matrigel and fibroblast growth factor 2 (1 mg/ml) matrix was implanted into each groin of an adult male C57Bl6 mouse and vascularized with the inferior epigastric vessels. Sterile inflammation was induced in one of the two chambers by suspending Zymosan-A (ZA) (200-0.02 mg/ml) in the matrix at implantation. Adipose tissue formation was assessed at 6, 8, 12 and 24 weeks. ZA induced significant adipogenesis in an inverse dose-dependent manner (Po0.001). At 6 weeks adipose tissue formation was greatest with the lowest concentrations of ZA and least with the highest. Adipogenesis occurred both locally in the chamber containing ZA and in the ZA-free chamber in the contralateral groin of the same animal. ZA induced a systemic inflammatory response characterized by elevated serum tumour necrosis factor-a levels at early time points. Aminoguanidine (40 mg/ml) inhibited the adipogenic response to ZA-induced inflammation. Adipose tissue formed in response to ZA remained stable for 24 weeks, even when exposed to the normal tissue environment.Conclusions: These results demonstrate that inflammation can drive neo-adipogenesis in vivo. This suggests the existence of a positive feedback mechanism in obesity, whereby the state of chronic, low-grade inflammation, characteristic of the condition, may promote further adipogenesis. The mobilization and recruitment of a circulating population of adipose precursor cells is likely to be implicated in this mechanism.

Macrophages Play a Key Role in Angiogenesis and Adipogenesis in a Mouse Tissue Engineering Model

“…Interestingly, in this study, we saw that the chambers in the contralateral groin, containing Matrigel but not Zymosan, showed similar tissue growth, including vascularization and development, as the chambers containing Zymosan at all study endpoints (results not shown). This confirms that the response to Zymosan is most likely a systemic inflammatory response as demonstrated by the previous study by Thomas et al 10 and, therefore, influencing both chambers in the same animal. The contralateral chambers in this study could, therefore, not be considered a true control without Zymosan, and results are not shown.…”

“…We recently demonstrated that adding Zymosan, a sterile inflammogen, to a Matrigel matrix in this closed model improves angiogenesis and adipogenesis, strongly suggesting that inflammatory cells/mediators are involved in these processes. 10 This study aims at characterizing the specific role that macrophages play in vascularized adipose tissue development. There are many arguments for a role of macrophages in blood vessel formation.…”

Polycaprolactone nanofibrous mesh reduces foreign body reaction and induces adipose flap expansion in tissue engineering chamber

“…Inflammation and angiogenesis are closely interrelated, [55][56][57] and adipose angiogenesis is a key mediator in recruiting adipose precursor cells as well as the subsequent adipogenesis. 58,59 However, there was a reduced inflammatory level and larger final volume of adipose tissue in the PCL group compared with the control group in our study.…”

Case key about pseudolipomas pathogenesis

“…Our hypothesis was introduced by Campiglio and Signorini: inflammatory background and chemokine network induced by the repairing process can cause the quiescent adipocytes or stem cells to proliferate excessively, finally forming the patient's PTL (6). There are many works that evaluated the association between adypogenesis and inflammation (15), in complex situations such as obesity or in laboratory experience with the use of highly flogogenic polysaccharides (16)(17)(18). This association was verified diminishing the concentrations of TNF alpha and IL6; the adipogenetic stimulation was dramatically suppressed (19)(20)(21).…”