Visceral adipose tissue mesenchymal stromal cells in the intersection of immunology and metabolism.

Visceral adipose tissue (VAT) is now recognized as an endocrine organ that plays a key role in organismal homeostasis by integrating metabolic and immunological aspects. In healthy individuals, this fat depot participates in the storage and release of lipids as per physiological demand, while maintaining a local anti-inflammatory environment. In this regard, recent findings highlight the pivotal role of distinct subtypes of mesenchymal stromal cells (mSCs) as orchestrators of metabolic homeostasis by engendering adipocytes to sustain adequate lipid storage as well as immune regulators via cross-talk with specialized tissue-resident immunocytes, especially regulatory T cells (Tregs) and group 2 innate lymphoid cells (ILC2s) to prevent the development of local inflammation. In addition, these stromal-immunocyte interactions are influenced by a number of physiological conditions such as aging and sex hormones. Perturbation of VAT equilibrium occurring during obesity appreciably alters the distribution and phenotype of mSCs, immunocytes, and other cell types, thereby promoting the development of chronic, low-grade inflammation locally and systemically. These alterations impair metabolic signaling and substantially contribute to the onset of disease, including type 2 diabetes. The present mini-review discusses the latest advances in this area, with an emphasis on the newly uncovered heterogeneity of mSCs, how they communicate with Tregs and ILC2s under different physio-pathological circumstances and future challenges to face.