bims-adipim Biomed News
on Adipose immunity and immunometabolism
Issue of 2023–09–03
eight papers selected by
Matthew C. Sinton, University of Glasgow
  1. γδ T cells control murine skin inflammation and subcutaneous adipose wasting during chronic Trypanosoma brucei infection.
  2. Whole-Mount Imaging of Adipose Tissue Macrophages.
  3. Isolation and Flow Cytometry Analysis of Macrophages from White Adipose Tissue.
  4. Acute activation of adipocyte lipolysis reveals dynamic lipid remodeling of the hepatic lipidome.
  5. The pathogenetic role of Th17 immune response in atopic dermatitis.
  6. Adipocytes reprogram cancer cell metabolism by diverting glucose towards glycerol-3-phosphate thereby promoting metastasis.
  7. Adipokines in atherosclerosis: unraveling complex roles.
  8. Intracellular ATP delivery to in vitro expanded mouse CD27- γδ T cells.
  1. Nat Commun. 2023 Aug 29. 14(1): 5279
    γδ T cells control murine skin inflammation and subcutaneous adipose wasting during chronic Trypanosoma brucei infection.
    Juan F Quintana, Matthew C Sinton, Praveena Chandrasegaran, Agatha Nabilla Lestari, Rhiannon Heslop, Bachar Cheaib, John Ogunsola, Dieudonne Mumba Ngoyi, Nono-Raymond Kuispond Swar, Anneli Cooper, Neil A Mabbott, Seth B Coffelt, Annette MacLeod.
      African trypanosomes colonise the skin to ensure parasite transmission. However, how the skin responds to trypanosome infection remains unresolved. Here, we investigate the local immune response of the skin in a murine model of infection using spatial and single cell transcriptomics. We detect expansion of dermal IL-17A-producing Vγ6+ cells during infection, which occurs in the subcutaneous adipose tissue. In silico cell-cell communication analysis suggests that subcutaneous interstitial preadipocytes trigger T cell activation via Cd40 and Tnfsf18 signalling, amongst others. In vivo, we observe that female mice deficient for IL-17A-producing Vγ6+ cells show extensive inflammation and limit subcutaneous adipose tissue wasting, independently of parasite burden. Based on these observations, we propose that subcutaneous adipocytes and Vγ6+ cells act in concert to limit skin inflammation and adipose tissue wasting. These studies provide new insights into the role of γδ T cell and subcutaneous adipocytes as homeostatic regulators of skin immunity during chronic infection.
    DOI:  https://doi.org/10.1038/s41467-023-40962-y
  2. Methods Mol Biol. 2024 ;2713 307-322
    Whole-Mount Imaging of Adipose Tissue Macrophages.
    Lydia Sorokin, Luis Henrique Corrêa.
      The adipose tissue comprises highly heterogeneous macrophage populations, which play critical roles in the regulation of adipose tissue function and dysfunction during health and disease. Whole-amount staining is a powerful technique for macrophage characterization within the 3D environment of the adipose tissue, enabling the visualization of different macrophage populations and their interaction with other cells within their in vivo niche. Due to the high-fat content and softness, freezing and sectioning of adipose tissue is difficult, and distortion of tissue morphology typically occurs, especially in the case of white adipose tissue. We describe here a whole-mount staining alternative for adipose tissue imaging that preserves all structures and allows high-resolution image acquisition. We address in a step-by-step manner how to perform immunofluorescence staining of different fat pads and how to optimally visualize cellular and acellular (extracellular matrix) constituents of the adipose tissue and its vasculature, as well as resident and infiltrating macrophage populations.
    Keywords:  Adipose tissue; Adipose tissue macrophages; Brown adipose tissue; Confocal microscopy; Immunofluorescence staining; White adipose tissue; Whole-mount imaging
    DOI:  https://doi.org/10.1007/978-1-0716-3437-0_21
  3. Methods Mol Biol. 2024 ;2713 149-158
    Isolation and Flow Cytometry Analysis of Macrophages from White Adipose Tissue.
    Dalila Juliana Silva Ribeiro, Seniz Yüksel, Andreas Dolf, Dagmar Wachten.
      Macrophages are one of the prominent leukocyte populations in white adipose tissue (WAT) and play an important role during WAT homeostasis and remodeling. Macrophage function in WAT is determined by ontogeny and the local tissue environment. Here, we present a protocol to analyze different macrophage populations from murine WAT using flow cytometry.
    Keywords:  Flow cytometry; Macrophages; White adipose tissue
    DOI:  https://doi.org/10.1007/978-1-0716-3437-0_10
  4. J Lipid Res. 2023 Aug 26. pii: S0022-2275(23)00107-4. [Epub ahead of print] 100434
    Acute activation of adipocyte lipolysis reveals dynamic lipid remodeling of the hepatic lipidome.
    Sicheng Zhang, Kevin J Williams, Amandine Verlande-Ferrero, Alvin P Chan, Gino B Su, Erin E Kershaw, James E Cox, John Alan Maschek, Suzanne N Shapira, Heather R Christofk, Thomas Q de Aguiar Vallim, Selma Masri, Claudio J Villanueva.
      Adipose tissue is the site of long-term energy storage. During the fasting state, exercise, and cold exposure, the white adipose tissue mobilizes energy for peripheral tissues through lipolysis. The mobilization of lipids from white adipose tissue to the liver can lead to excess triglyceride accumulation and fatty liver disease. Although the white adipose tissue is known to release free fatty acids, a comprehensive analysis of lipids mobilized from white adipocytes in vivo has not been completed. In these studies, we provide a comprehensive quantitative analysis of the adipocyte secreted lipidome and show that there is inter-organ crosstalk with liver. Our analysis identifies multiple lipid classes released by adipocytes in response to activation of lipolysis. Time-dependent analysis of the serum lipidome, showed that free fatty acids increase within 30 minutes of β3-adrenergic receptor activation, and subsequently decrease, followed by a rise in serum triglycerides, liver triglycerides, and several ceramide species. The triglyceride composition of liver is enriched for linoleic acid despite higher concentrations of palmitate in the blood. To further validate that these findings were a specific consequence of lipolysis, we generated mice with conditional deletion of ATGL exclusively in adipocytes. This loss of in vivo adipocyte lipolysis prevented the rise in serum free fatty acids and hepatic triglycerides. Furthermore, conditioned media from adipocytes promotes lipid remodeling in hepatocytes with concomitant changes in genes/pathways mediating lipid utilization. Together these data highlight critical role of adipocyte lipolysis in inter-organ crosstalk between adipocytes and liver.
    Keywords:  Adipocytes; Adipose tissue triglyceride lipase; Ceramides; Fasting; Lipase; Lipid droplets; Lipidomics; Lipids; Liver; Triglycerides
    DOI:  https://doi.org/10.1016/j.jlr.2023.100434
  5. Curr Opin Allergy Clin Immunol. 2023 10 01. 23(5): 446-453
    The pathogenetic role of Th17 immune response in atopic dermatitis.
    Eden David, Tali Czarnowicki.
       PURPOSE OF REVIEW: As we continue to unravel the pathophysiology and immune mechanisms underlying atopic dermatitis (AD), the emergence of targeted treatments has provided new options for management. Although there are available therapies targeting various immune pathways in AD, the precise pathogenic role of interleukin (IL)-17 in AD pathogenesis remains unclear. The objective of this review is to examine the existing data pertaining to the role of IL-17 in AD and shed light on the potential of targeting this pathway as a therapeutic approach in AD treatment.
    RECENT FINDINGS: IL-17 has a dual role of pro-inflammatory and immune protective function, making it an important player in several autoimmune and inflammatory conditions. The extent of IL-17 axis involvement in AD pathogenesis is still debatable. Emerging data show that Th17-related cytokines/chemokines are elevated in skin and sera samples of AD patients, with some articles reporting correlations with disease severity. Particularly increased Th17 signature in specific AD patient subsets, such as Asian-origin or pediatric patients, suggests that certain patients' disease presentations are more predominantly influenced by Th17, and, thus, they may benefit more from Th17 therapeutic targeting approaches. Lack of clinical efficacy with anti-Th17 biologics in AD patients, underscores the need to better elucidate the role of Th17 in AD pathogenesis, along with its utility in therapy.
    SUMMARY: The well established role of IL-17 in autoimmune disorders hints for its possible participation in AD disease pathogenesis. Subsequent investigations are needed to assess whether the targeting of specific IL-17 isoforms, homodimers, or heterodimers in specific subpopulations of AD can modify treatment outcomes.
    DOI:  https://doi.org/10.1097/ACI.0000000000000926
  6. Nat Metab. 2023 Aug 31.
    Adipocytes reprogram cancer cell metabolism by diverting glucose towards glycerol-3-phosphate thereby promoting metastasis.
    Abir Mukherjee, Divya Bezwada, Francesco Greco, Malu Zandbergen, Tong Shen, Chun-Yi Chiang, Medine Tasdemir, Johannes Fahrmann, Dmitry Grapov, Michael R La Frano, Hieu S Vu, Brandon Faubert, John W Newman, Liam A McDonnell, Luigi Nezi, Oliver Fiehn, Ralph J DeBerardinis, Ernst Lengyel.
      In the tumor microenvironment, adipocytes function as an alternate fuel source for cancer cells. However, whether adipocytes influence macromolecular biosynthesis in cancer cells is unknown. Here we systematically characterized the bidirectional interaction between primary human adipocytes and ovarian cancer (OvCa) cells using multi-platform metabolomics, imaging mass spectrometry, isotope tracing and gene expression analysis. We report that, in OvCa cells co-cultured with adipocytes and in metastatic tumors, a part of the glucose from glycolysis is utilized for the biosynthesis of glycerol-3-phosphate (G3P). Normoxic HIF1α protein regulates the altered flow of glucose-derived carbons in cancer cells, resulting in increased glycerophospholipids and triacylglycerol synthesis. The knockdown of HIF1α or G3P acyltransferase 3 (a regulatory enzyme of glycerophospholipid synthesis) reduced metastasis in xenograft models of OvCa. In summary, we show that, in an adipose-rich tumor microenvironment, cancer cells generate G3P as a precursor for critical membrane and signaling components, thereby promoting metastasis. Targeting biosynthetic processes specific to adipose-rich tumor microenvironments might be an effective strategy against metastasis.
    DOI:  https://doi.org/10.1038/s42255-023-00879-8
  7. Front Cardiovasc Med. 2023 ;10 1235953
    Adipokines in atherosclerosis: unraveling complex roles.
    Jiaying Luo, Zhiwei He, Qingwen Li, Mengna Lv, Yuli Cai, Wei Ke, Xuan Niu, Zhaohui Zhang.
      Adipokines are biologically active factors secreted by adipose tissue that act on local and distant tissues through autocrine, paracrine, and endocrine mechanisms. However, adipokines are believed to be involved in an increased risk of atherosclerosis. Classical adipokines include leptin, adiponectin, and ceramide, while newly identified adipokines include visceral adipose tissue-derived serpin, omentin, and asprosin. New evidence suggests that adipokines can play an essential role in atherosclerosis progression and regression. Here, we summarize the complex roles of various adipokines in atherosclerosis lesions. Representative protective adipokines include adiponectin and neuregulin 4; deteriorating adipokines include leptin, resistin, thrombospondin-1, and C1q/tumor necrosis factor-related protein 5; and adipokines with dual protective and deteriorating effects include C1q/tumor necrosis factor-related protein 1 and C1q/tumor necrosis factor-related protein 3; and adipose tissue-derived bioactive materials include sphingosine-1-phosphate, ceramide, and adipose tissue-derived exosomes. However, the role of a newly discovered adipokine, asprosin, in atherosclerosis remains unclear. This article reviews progress in the research on the effects of adipokines in atherosclerosis and how they may be regulated to halt its progression.
    Keywords:  adipokine; atherosclerosis; endothelial cell; macrophage; vascular smooth muscle cell
    DOI:  https://doi.org/10.3389/fcvm.2023.1235953
  8. STAR Protoc. 2023 Aug 25. pii: S2666-1667(23)00499-9. [Epub ahead of print]4(3): 102532
    Intracellular ATP delivery to in vitro expanded mouse CD27- γδ T cells.
    Yunke Wang, Jun Yan.
      Intracellular ATP supports the function of γδT17 cells in mice. Here, we present a protocol for intracellular ATP delivery to in vitro expanded mouse CD27- γδ T cells. We describe steps for pre-coating well plates, preparing lymphocytes, culturing CD27- γδ T cells, and ATP delivery. We then detail functional evaluation of γδ T cells by flow cytometry. Appropriate concentrations of control and ATP vesicles are detailed for intracellular ATP delivery, which can also be applied to other immune cells. For complete details on the use and execution of this protocol, please refer to Wang et al. (2023).1.
    Keywords:  Cell Culture; Cell Isolation; Flow Cytometry/Mass Cytometry; Health Sciences; Immunology; Metabolism
    DOI:  https://doi.org/10.1016/j.xpro.2023.102532
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