Characteristics of mesenteric adipose tissue attached to different intestinal segments and their roles in immune regulation.

ABSTRACT

Mesenteric adipose tissue (MAT) plays a critical role in the intestinal physiological ecosystems. Small and large intestines have evidently intrinsic and distinct characteristics. However, whether there exist any mesenteric differences adjacent to the small and large intestines (SMAT and LMAT) has not been properly characterized. We studied the important facets of these differences, such as morphology, gene expression, cell components, and immune regulation of MATs, to characterize the mesenteric differences. The SMAT and LMAT of mice were used for comparison of tissue morphology. Paired mesenteric samples were analyzed by RNA-seq to clarify gene expression profiles. MAT partial excision models were constructed to illustrate the immune regulation roles of MATs, and 16S-seq was applied to detect the subsequent effect on microbiota. Our data show that different segments of mesenteries have different morphological structures. SMAT not only has smaller adipocytes but also contains more fat-associated lymphoid clusters than LMAT. The gene expression profile is also discrepant between these two MATs in mice. B-cell markers were abundantly expressed in SMAT, whereas development-related genes were highly expressed in LMAT. Adipose-derived stem cells of LMAT exhibited higher adipogenic potential and lower proliferation rates than those of SMAT. In addition, SMAT and LMAT play different roles in immune regulation and subsequently affect microbiota components. Finally, our data clarified the described differences between SMAT and LMAT in humans. There were significant differences in cell morphology, gene expression profiles, cell components, biological characteristics, and immune and microbiota regulation roles between regional MATs.NEW & NOTEWORTHY Our results change the paradigm of how we regard MAT as a contiguous and homogeneous tissue to an intensely heterogeneous tissue. Appreciation of the differences between regional MATs will guide future research to investigate the specialized roles of different MATs in intestinal health and disease.