bims-adipim 2023-10-29 papers

Issue of 2023–10–29
three papers selected by
Matthew C. Sinton, University of Glasgow

Biology (Basel). 2023 Sep 27. pii: 1289. [Epub ahead of print]12(10):

White Adipose Tissue Heterogeneity in the Single-Cell Era: From Mice and Humans to Cattle.

Hunter Ford, Qianglin Liu, Xing Fu, Clarissa Strieder-Barboza.

Adipose tissue is a major modulator of metabolic function by regulating energy storage and by acting as an endocrine organ through the secretion of adipokines. With the advantage of next-generation sequencing-based single-cell technologies, adipose tissue has been studied at single-cell resolution, thus providing unbiased insight into its molecular composition. Recent single-cell RNA sequencing studies in human and mouse models have dissected the transcriptional cellular heterogeneity of subcutaneous (SAT), visceral (VAT), and intramuscular (IMAT) white adipose tissue depots and revealed unique populations of adipose tissue progenitor cells, mature adipocytes, immune cell, vascular cells, and mesothelial cells that play direct roles on adipose tissue function and the development of metabolic disorders. In livestock species, especially in bovine, significant gaps of knowledge remain in elucidating the roles of adipose tissue cell types and depots on driving the pathogenesis of metabolic disorders and the distinct fat deposition in VAT, SAT, and IMAT in meat animals. This review summarizes the current knowledge on the transcriptional and functional cellular diversity of white adipose tissue revealed by single-cell approaches and highlights the depot-specific function of adipose tissue in different mammalian species, with a particular focus on recent findings and future implications in cattle.

Keywords: adipose; cattle; livestock; sequencing; single-cell; transcriptional diversity

DOI: https://doi.org/10.3390/biology12101289

Nat Rev Endocrinol. 2023 Oct 23.

Macrophage and T cell networks in adipose tissue.

Ramiah D Jacks, Carey N Lumeng.

The signals and structure of the tissues in which leukocytes reside critically mould leukocyte function and development and have challenged our fundamental understanding of how to define and categorize tissue-resident immune cells. One specialized tissue niche that has a powerful effect on immune cell function is adipose tissue. The field of adipose tissue leukocyte biology has expanded dramatically and has revealed how tissue niches can shape immune cell function and reshape them in a setting of metabolic stress, such as obesity. Most notably, adipose tissue macrophages and T cells are under intense investigation due to their contributions to adipose tissue in the lean and obese states. Both adipose tissue macrophages and T cells have features associated with the metabolic function of adipose tissue that are distinct from features of macrophages and T cells that are classically characterized in other tissues. This Review provides state-of-the-art understanding of adipose tissue macrophages and T cells and discusses how their unique niche can help us to better understand diversity in leukocyte responses.

DOI: https://doi.org/10.1038/s41574-023-00908-2

Sci Signal. 2023 Oct 24. 16(808): eabo6555

Human IL-17A protein production is controlled through a PIP5K1α-dependent translational checkpoint.

Shankar K Revu, Wenjuan Yang, Dhivyaa Rajasundaram, Alexander Brady, Saikat Majumder, Sarah L Gaffen, William Hawse, Zongqi Xia, Mandy J McGeachy.

The cytokine interleukin-17 (IL-17) is secreted by T helper 17 (TH17) cells and is beneficial for microbial control; however, it also causes inflammation and pathological tissue remodeling in autoimmunity. Hence, TH17 cell differentiation and IL-17 production must be tightly regulated, but, to date, this has been defined only in terms of transcriptional control. Phosphatidylinositols are second messengers produced during T cell activation that transduce signals from the T cell receptor (TCR) and costimulatory receptors at the plasma membrane. Here, we found that phosphatidylinositol 4,5-bisphosphate (PIP2) was enriched in the nuclei of human TH17 cells, which depended on the kinase PIP5K1α, and that inhibition of PIP5K1α impaired IL-17A production. In contrast, nuclear PIP2 enrichment was not observed in TH1 or TH2 cells, and these cells did not require PIP5K1α for cytokine production. In T cells from people with multiple sclerosis, IL-17 production elicited by myelin basic protein was blocked by PIP5K1α inhibition. IL-17 protein was affected without altering either the abundance or stability of IL17A mRNA in TH17 cells. Instead, analysis of PIP5K1α-associating proteins revealed that PIP5K1α interacted with ARS2, a nuclear cap-binding complex scaffold protein, to facilitate its binding to IL17A mRNA and subsequent IL-17A protein production. These findings highlight a transcription-independent, translation-dependent mechanism for regulating IL-17A protein production that might be relevant to other cytokines.

DOI: https://doi.org/10.1126/scisignal.abo6555