bims-adipim 2023-04-23 papers

bims-adipim

Biomed News

on Adipose immunity and immunometabolism

Issue of 2023–04–23
nine papers selected by
Matthew C. Sinton, University of Glasgow

Thermogenic Phenotyping in Mice.
HSV-2 triggers upregulation of MALAT1 in CD4+ T cells and promotes HIV latency reversal.
Isolation and Mass Spectrometry-Based Profiling of Major Lipids in Brown Adipose Tissue.
Emergence of division of labor in tissues through cell interactions and spatial cues.
Adipokines in glucose and lipid metabolism.
Isolation and Characterization of Brown Adipose Tissue T Cells.
Subcutaneous Transplantation of White Adipose Tissue.
Interaction Between Adipocytes and B Lymphocytes in Human Metabolic Diseases.
The proliferation of human mucosal-associated invariant T cells requires a MYC-SLC7A5-glycolysis metabolic axis.

Methods Mol Biol. 2023 ;2662 117-124

Thermogenic Phenotyping in Mice.

Donghua Hu, Irfan J Lodhi.

  Thermogenesis mediated by brown adipose tissue (BAT) and brown-like fat plays an important role in regulating metabolic homeostasis in mammals. Accurate measurement of metabolic responses to brown fat activation, including heat generation and increased energy expenditure is essential for characterizing thermogenic phenotypes in preclinical studies. Here, we describe two methods for assessing thermogenic phenotypes in mice under non-basal states. First, we describe a protocol for measuring body temperature in cold-treated mice using implantable temperature transponders, which allow for continuous monitoring of body temperature. Second, we describe a method for using indirect calorimetry to measure β3-adrenergic agonist-stimulated changes in oxygen consumption, a proxy for thermogenic fat activation.

Keywords:  Body temperature; Energy expenditure; Indirect calorimetry; Metabolic cages; Oxygen consumption; Thermogenesis

DOI:  https://doi.org/10.1007/978-1-0716-3167-6_10
J Clin Invest. 2023 Apr 20. pii: e164317. [Epub ahead of print]

HSV-2 triggers upregulation of MALAT1 in CD4+ T cells and promotes HIV latency reversal.

Carl A Pierce, Lip Nam Loh, Holly R Steach, Natalia Cheshenko, Paula Preston-Hurlburt, Fengrui Zhang, Stephanie Stransky, Leah Kravets, Simone Sidoli, William M Philbrick, Michel N Nassar, Smita Krishnaswamy, Kevan C Herold, Betsy C Herold.

  HSV-2 coinfection is associated with increased HIV-1 viral loads and expanded tissue reservoirs, but the mechanisms are not well-defined. HSV-2 recurrences result in an influx of activated CD4+ T cells to sites of viral replication and an increase in activated CD4+ T cells in peripheral blood. We hypothesized that HSV-2 induces changes in these cells that facilitate HIV-1 reactivation and replication and tested this hypothesis in human CD4+ T cells and 2D10 cells, a model of HIV-1 latency. HSV-2 promoted latency reversal in HSV-2 infected and bystander 2D10 cells. Bulk and single-cell RNA sequencing studies of activated primary human CD4+ T cells identified decreased expression of HIV-1 restriction factors and increased expression of transcripts including MALAT1 that could drive HIV replication in both the HSV-2-infected and bystander cells. Transfection of 2D10 cells with VP16, an HSV-2 protein that regulates transcription, significantly upregulated MALAT1 expression, decreased trimethylation of lysine 27 on histone H3 protein, and triggered HIV latency reversal. Knockout of MALAT1 from 2D10 cells abrogated the response to VP16 and reduced the response to HSV-2 infection. These results demonstrate that HSV-2 contributes to HIV-1 reactivation through diverse mechanisms including upregulation of MALAT1 to release epigenetic silencing.

Keywords:  AIDS/HIV; T cells; Transcription; Virology

DOI:  https://doi.org/10.1172/JCI164317
Methods Mol Biol. 2023 ;2662 219-239

Isolation and Mass Spectrometry-Based Profiling of Major Lipids in Brown Adipose Tissue.

Dongliang Lu, Hideji Fujiwara, Irfan J Lodhi, Fong-Fu Hsu.

  Brown adipose tissue (BAT) is an important regulator of metabolic homeostasis through its role in adaptive thermogenesis and control of whole-body glucose metabolism. Lipids play multiple roles in BAT functions, including serving as a fuel source for thermogenesis, mediating inter-organelle cross talk, and acting as BAT-derived signaling molecules that influence systemic energy metabolism. Profiling of various lipids in BAT under distinct metabolic states could provide new insights into their roles in the biology of the thermogenic fat. In this chapter, we describe a step-by-step workflow starting from sample preparations to mass spectrometry-based analysis of fatty acids and phospholipids in BAT.

Keywords:  Brown adipose tissue; Folch method; Free fatty acid; Mass spectrometry; Phospholipid; Solid phase extraction; Sphingolipid

DOI:  https://doi.org/10.1007/978-1-0716-3167-6_20
Cell Rep. 2023 Apr 20. pii: S2211-1247(23)00423-0. [Epub ahead of print]42(5): 112412

Emergence of division of labor in tissues through cell interactions and spatial cues.

Miri Adler, Noa Moriel, Aleksandrina Goeva, Inbal Avraham-Davidi, Simon Mages, Taylor S Adams, Naftali Kaminski, Evan Z Macosko, Aviv Regev, Ruslan Medzhitov, Mor Nitzan.

  Most cell types in multicellular organisms can perform multiple functions. However, not all functions can be optimally performed simultaneously by the same cells. Functions incompatible at the level of individual cells can be performed at the cell population level, where cells divide labor and specialize in different functions. Division of labor can arise due to instruction by tissue environment or through self-organization. Here, we develop a computational framework to investigate the contribution of these mechanisms to division of labor within a cell-type population. By optimizing collective cellular task performance under trade-offs, we find that distinguishable expression patterns can emerge from cell-cell interactions versus instructive signals. We propose a method to construct ligand-receptor networks between specialist cells and use it to infer division-of-labor mechanisms from single-cell RNA sequencing (RNA-seq) and spatial transcriptomics data of stromal, epithelial, and immune cells. Our framework can be used to characterize the complexity of cell interactions within tissues.

Keywords:  CP: Developmental biology; Pareto optimality; division of labor; enterocytes; fibroblasts; lateral inhibition; macrophages; morphogens; self-organization

DOI:  https://doi.org/10.1016/j.celrep.2023.112412
Adipocyte. 2023 Dec;12(1): 2202976

Adipokines in glucose and lipid metabolism.

Xueqing Wang, Siwen Zhang, Zhuo Li.

  Adipokines are proteins secreted by adipose tissue to regulate glucolipid metabolism and play vital roles in our body. Different adipokines have more than one endocrine function and be divided into several different categories according to their functions, including adipokines involved in glucolipid metabolism, the inflammatory response, insulin action, activation of brown adipose tissue (BAT) and appetite regulation. Multiple adipokines interact with each other to regulate metabolic processes. Based on the recent progress of adipokine research, this article discusses the role and mechanism of various adipokines in glucolipid metabolism, which may provide new ideas for understanding the pathogenesis and improving the treatment of various metabolic diseases.

Keywords:  Insulin resistance; adiponectin; appetite; inflammation; leptin

DOI:  https://doi.org/10.1080/21623945.2023.2202976
Methods Mol Biol. 2023 ;2662 203-208

Isolation and Characterization of Brown Adipose Tissue T Cells.

Ling-Ran Kong, Cheng-Chao Ruan.

  Brown adipose tissue (BAT) is a specialized fat depot that can dissipate energy through uncoupled respiration and thermogenesis. Various immune cells such as macrophages, eosinophils, type 2 innate lymphoid cells, and T lymphocytes were recently found to have an unexpected involvement in controlling the thermogenic activity of brown adipose tissue. Here, we describe a protocol for isolation and characterization of T cells from brown adipose tissue.

Keywords:  Brown adipose tissue; Enzyme digestion; Flow cytometry; T cells

DOI:  https://doi.org/10.1007/978-1-0716-3167-6_18
Methods Mol Biol. 2023 ;2662 183-192

Subcutaneous Transplantation of White Adipose Tissue.

Yu-Sheng Yeh, Mari Iwase, Satoko Kawarasaki, Jungin Kwon, Astrid Rodriguez-Velez, Xiangyu Zhang, Se-Jin Jeong, Tsuyoshi Goto, Babak Razani.

  In the research setting, white adipose tissue (WAT) transplantation, also known as fat transplantation, is often used to understand the physiological function of adipocytes or associated stromal vascular cells such as macrophages in the context of local and systemic metabolism. The mouse is the most common animal model used where WAT from a donor is transferred either to a subcutaneous site of the same organism or to a subcutaneous region of a recipient. Here, we describe in detail the procedure for heterologous fat transplantation, and, given the need for survival surgery, peri- and postoperative care and subsequent histological confirmation of fat grafts will also be discussed.

Keywords:  Adipose tissue; Adipose tissue histology; Fat transplantation; Lipodystrophy; Mouse surgery

DOI:  https://doi.org/10.1007/978-1-0716-3167-6_16
Biochemistry (Mosc). 2023 Feb;88(2): 280-288

Interaction Between Adipocytes and B Lymphocytes in Human Metabolic Diseases.

Ekaterina M Stasevich, Elina A Zheremyan, Dmitriy V Kuprash, Anton M Schwartz.

  Diseases associated with the disorders of carbohydrate and lipid metabolism are widespread in the modern world. Interaction between the cells of adipose tissue - adipocytes - and immune system cells is an essential factor in pathogenesis of such diseases. Long-term increase in the glucose and fatty acid levels leads to adipocyte hypertrophy and increased expression of pro-inflammatory cytokines and adipokines by these cells. As a result, immune cells acquire a pro-inflammatory phenotype, and new leukocytes are recruited. Inflammation of adipose tissue leads to insulin resistance and stimulates formation of atherosclerotic plaques and development of autoimmunity. New studies show that different groups of B lymphocytes play an essential role in regulation of adipose tissue inflammation. Decrease in the number of B-2 lymphocytes suppresses development of a number of metabolic diseases, whereas decreased numbers of the regulatory B lymphocytes and B-1 lymphocytes are associated with more severe pathology. Recent studies showed that adipocytes influence B lymphocyte activity both directly and by altering activity of other immune cells. These findings provide better understanding of the molecular mechanisms of human pathologies associated with impaired carbohydrate and lipid metabolism, such as type 2 diabetes mellitus.

Keywords:  B lymphocytes; B1 lymphocytes; B2 lymphocytes; adipocytes; adipokines; diabetes; regulatory B lymphocytes

DOI:  https://doi.org/10.1134/S0006297923020104
Sci Signal. 2023 Apr 18. 16(781): eabo2709

The proliferation of human mucosal-associated invariant T cells requires a MYC-SLC7A5-glycolysis metabolic axis.

Nidhi Kedia-Mehta, Marta M Pisarska, Christina Rollings, Chloe O'Neill, Conor De Barra, Cathriona Foley, Nicole A W Wood, Neil Wrigley-Kelly, Natacha Veerapen, Gurdyal Besra, Ronan Bergin, Nicholas Jones, Donal O'Shea, Linda V Sinclair, Andrew E Hogan.

Mucosal-associated invariant T (MAIT) cells are an abundant population of innate T cells that recognize bacterial ligands and play a key role in host protection against bacterial and viral pathogens. Upon activation, MAIT cells undergo proliferative expansion and increase their production of effector molecules such as cytokines. In this study, we found that both mRNA and protein abundance of the key metabolism regulator and transcription factor MYC was increased in stimulated MAIT cells. Using quantitative mass spectrometry, we identified the activation of two MYC-controlled metabolic pathways, amino acid transport and glycolysis, both of which were necessary for MAIT cell proliferation. Last, we showed that MAIT cells isolated from people with obesity showed decreased MYC mRNA abundance upon activation, which was associated with defective MAIT cell proliferation and functional responses. Collectively, our data uncover the importance of MYC-regulated metabolism for MAIT cell proliferation and provide additional insight into the molecular basis for the functional defects of MAIT cells in obesity.

DOI: https://doi.org/10.1126/scisignal.abo2709