bims-aditis 2021-11-07 papers

Issue of 2021–11–07
five papers selected by
Matthew C. Sinton, University of Glasgow

Nat Rev Immunol. 2021 Nov 05.

Immune and non-immune functions of adipose tissue leukocytes.

Adipose tissue is a complex dynamic organ with whole-body immunometabolic influence. Much of the work into understanding the role of immune cells in adipose tissue has been in the context of obesity. These investigations have also uncovered a range of typical (immune) and non-typical functions exerted by adipose tissue leukocytes. Here we provide an overview of the adipose tissue immune system, including its role as an immune reservoir in the whole-body response to infection and as a site of parasitic and viral infections. We also describe the functional roles of specialized immunological structures found within adipose tissue. However, our main focus is on the recently discovered 'non-immune' functions of adipose tissue immune cells, which include the regulation of adipocyte homeostasis, as well as responses to changing nutrient status and body temperature. In doing so, we outline the therapeutic potential of the adipose tissue immune system in health and disease.

DOI: https://doi.org/10.1038/s41577-021-00635-7

Endocrinology. 2021 Oct 28. pii: bqab224. [Epub ahead of print]

Crosstalk between adipose and lymphatics in health and disease.

Gregory P Westcott, Evan D Rosen.

Adipose tissue, once thought to be an inert receptacle for energy storage, is now recognized as a complex tissue with multiple resident cell populations which actively collaborate in response to diverse local and systemic metabolic, thermal, and inflammatory signals. A key participant in adipose tissue homeostasis that has only recently captured broad scientific attention is the lymphatic vasculature. The lymphatic system's role in lipid trafficking and mediating inflammation makes it a natural partner in the regulation of adipose tissue, and evidence supporting a bidirectional relationship between lymphatics and adipose tissue has accumulated in recent years. Obesity is now understood to impair lymphatic function, while altered lymphatic function results in aberrant adipose tissue deposition, though the molecular mechanisms governing these phenomena have yet to be fully elucidated. We will review our current understanding of the relationship between adipose tissue and the lymphatic system here, focusing on known mechanisms of lymphatic-adipose cross-talk.

Keywords: Obesity; adipose tissue; lipedema; lymphatic endothelium; lymphedema

DOI: https://doi.org/10.1210/endocr/bqab224

Redox Biol. 2021 Oct 19. pii: S2213-2317(21)00331-1. [Epub ahead of print]48 102171

Metformin reduces macrophage HIF1α-dependent proinflammatory signaling to restore brown adipocyte function in vitro.

Nuria Pescador, Vera Francisco, Patricia Vázquez, Eva María Esquinas, Cristina González-Páramos, M Pilar Valdecantos, Irma García-Martínez, Andrés A Urrutia, Laura Ruiz, Carmen Escalona-Garrido, Marc Foretz, Benoit Viollet, Miguel Ángel Fernández-Moreno, Alfonso L Calle-Pascual, María Jesús Obregón, Julián Aragonés, Ángela M Valverde.

Therapeutic potential of metformin in obese/diabetic patients has been associated to its ability to combat insulin resistance. However, it remains largely unknown the signaling pathways involved and whether some cell types are particularly relevant for its beneficial effects. M1-activation of macrophages by bacterial lipopolysaccharide (LPS) promotes a paracrine activation of hypoxia-inducible factor-1α (HIF1α) in brown adipocytes which reduces insulin signaling and glucose uptake, as well as β-adrenergic sensitivity. Addition of metformin to M1-polarized macrophages blunted these signs of brown adipocyte dysfunction. At the molecular level, metformin inhibits an inflammatory program executed by HIF1α in macrophages by inducing its degradation through the inhibition of mitochondrial complex I activity, thereby reducing oxygen consumption in a reactive oxygen species (ROS)-independent manner. In obese mice, metformin reduced inflammatory features in brown adipose tissue (BAT) such as macrophage infiltration, proinflammatory signaling and gene expression, and restored the response to cold exposure. In conclusion, the impact of metformin on macrophages by suppressing a HIF1α-dependent proinflammatory program is likely responsible for a secondary beneficial effect on insulin-mediated glucose uptake and β-adrenergic responses in brown adipocytes.

Keywords: Brown adipose tissue; Hypoxia-inducible factor-1α; Inflammation; Insulin resistance; Metformin; Obesity

DOI: https://doi.org/10.1016/j.redox.2021.102171

J Vasc Res. 2021 Nov 04. 1-7

Quantification of Lipid Area within Thermogenic Mouse Perivascular Adipose Tissue Using Standardized Image Analysis in FIJI.

Benjamin W Tero, Bethany Fortier, Ashley N Soucy, Ginger Paquette, Lucy Liaw.

Quantification of adipocyte size and number is routinely performed for white adipose tissues using existing image analysis software. However, thermogenic adipose tissue has multilocular adipocytes, making it difficult to distinguish adipocyte cell borders and to analyze lipid proportion using existing methods. We developed a simple, standardized method to quantify lipid content of mouse thermogenic adipose tissue. This method, using FIJI analysis of hematoxylin/eosin stained sections, was highly objective and highly reproducible, with ∼99% inter-rater reliability. The method was compared to direct lipid staining of adipose tissue, with comparable results. We used our method to analyze perivascular adipose tissue (PVAT) from C57BL/6 mice on a normal chow diet, compared to calorie restriction or a high fat diet, where lipid storage phenotypes are known. Results indicate that lipid content can be estimated within mouse PVAT in a quantitative and reproducible manner, and shows correlation with previously studied molecular and physiological measures.

Keywords: FIJI; Image analysis; Lipid quantification; Perivascular adipose tissue; Thermogenic adipose tissue

DOI: https://doi.org/10.1159/000517178