bims-aditis Biomed News
on Adipose tissue, inflammation, immunometabolism
Issue of 2022–02–06
nine papers selected by
Matthew C. Sinton, University of Glasgow
  1. Mediating TH17 transit.
  2. γδ T Cells Activated in Different Inflammatory Environments Are Functionally Distinct.
  3. Adipose-tissue plasticity in health and disease.
  4. A clearing-free protocol for imaging intact whole adipose tissue innervation in mice.
  5. Assessment of Metabolic Regulation by Estrogen Receptors.
  6. A Straightforward Method for Adipocyte Size and Count Analysis Using Open-source Software QuPath.
  7. Functions and origins of cardiac fat.
  8. Recruitment and activation of type 3 innate lymphoid cells promote antitumor immune responses.
  9. 2-HG modulates glioma macrophages via Trp metabolism.
  1. Nat Immunol. 2022 Feb;23(2): 150
    Mediating TH17 transit.
    Nicholas J Bernard.
      
    DOI:  https://doi.org/10.1038/s41590-022-01134-0
  2. J Immunol. 2022 Jan 31. pii: ji2100967. [Epub ahead of print]
    γδ T Cells Activated in Different Inflammatory Environments Are Functionally Distinct.
    Deming Sun, Nymph Chan, Hui Shao, Willi K Born, Henry J Kaplan.
      γδ T cells are important immunoregulatory cells in experimental autoimmune uveitis (EAU), and the activation status of γδ T cells determines their disease-enhancing or inhibitory effects. Because γδ T cells can be activated via various pathways, we questioned whether the nature of their activation might impact their function. In this study, we show that γδ T cells activated under different inflammatory conditions differ greatly in their functions. Whereas anti-CD3 treatment activated both IFN-γ+ and IL-17+ γδ T cells, cytokines preferentially activated IL-17+ γδ T cells. γδ T cells continued to express high levels of surface CD73 after exposure to inflammatory cytokines, but they downregulated surface CD73 after exposure to dendritic cells. Although both CD73high and CD73low cells have a disease-enhancing effect, the CD73low γδ T cells are less inhibitory. We also show that polarized activation not only applies to αβ T cells and myeloid cells, but also to γδ T cells. After activation under Th17-polarizing conditions, γδ T cells predominantly expressed IL-17 (gdT17), but after activation under Th1 polarizing conditions (gdT1) they mainly expressed IFN-γ. The pro-Th17 activity of γδ T cells was associated with gdT17, but not gdT1. Our results demonstrate that the functional activity of γδ T cells is strikingly modulated by their activation level, as well as the pathway through which they were activated.
    DOI:  https://doi.org/10.4049/jimmunol.2100967
  3. Cell. 2022 Feb 03. pii: S0092-8674(21)01454-9. [Epub ahead of print]185(3): 419-446
    Adipose-tissue plasticity in health and disease.
    Alexander Sakers, Mirian Krystel De Siqueira, Patrick Seale, Claudio J Villanueva.
      Adipose tissue, colloquially known as "fat," is an extraordinarily flexible and heterogeneous organ. While historically viewed as a passive site for energy storage, we now appreciate that adipose tissue regulates many aspects of whole-body physiology, including food intake, maintenance of energy levels, insulin sensitivity, body temperature, and immune responses. A crucial property of adipose tissue is its high degree of plasticity. Physiologic stimuli induce dramatic alterations in adipose-tissue metabolism, structure, and phenotype to meet the needs of the organism. Limitations to this plasticity cause diminished or aberrant responses to physiologic cues and drive the progression of cardiometabolic disease along with other pathological consequences of obesity.
    Keywords:  adipocyte; adipocyte progenitor; adipose tissue; beige fat; brown fat; diabetes; obesity; thermogenesis
    DOI:  https://doi.org/10.1016/j.cell.2021.12.016
  4. STAR Protoc. 2022 Mar 18. 3(1): 101109
    A clearing-free protocol for imaging intact whole adipose tissue innervation in mice.
    Jake W Willows, Magdalena Blaszkiewicz, Kristy L Townsend.
      Here we provide a clearing-free protocol for processing intact, whole mount subcutaneous white adipose tissue (scWAT) for immunofluorescence as an alternative to current clearing-based approaches. We use a combination of Z-depth reduction and autofluorescence quenching techniques to fluorescently label, image, and quantify adipose tissue innervation effectively throughout intact mouse tissues without the need for optical clearing or light sheet microscopy. This protocol has been optimized and validated for adipose neurovascular labeling. For complete details on the use and execution of this protocol, please refer to Willows et al. (2021).
    Keywords:  Metabolism; Microscopy; Model Organisms; Neuroscience
    DOI:  https://doi.org/10.1016/j.xpro.2021.101109
  5. Methods Mol Biol. 2022 ;2418 383-404
    Assessment of Metabolic Regulation by Estrogen Receptors.
    Geetanjali Sharma, Eric R Prossnitz.
      Estrogens, predominantly 17β-estradiol (E2), are a class of steroid hormones critical for diverse functions in the body both during normal physiology and disease. Primary actions of E2 include reproduction and development of secondary sexual characteristics. In addition, E2 action is involved in the nervous, immune, vascular, muscular, skeletal, and endocrine systems, all of which contribute to multiple aspects of metabolism. The actions of E2 have traditionally been attributed to the classical nuclear estrogen receptors (ERα and ERβ) that largely mediate transcriptional/genomic activities. However, over the last decade, the G protein-coupled estrogen receptor (GPER/GPR30) has become recognized as a mediator of rapid as well as transcriptional actions of E2, employing both in vitro and in vivo approaches. Recent evidence strongly supports the role of GPER in metabolic regulation. Murine genetic knockout (KO) models and pharmacological tools (agonists and antagonists) represent important approaches to understand the mechanisms of E2 action in physiology and disease via GPER. Studies in cells and GPER KO mice have revealed functions for GPER in the regulation of body weight and metabolism. This chapter focuses on methods relevant for the evaluation of metabolic parameters in vivo, ex vivo, and in vitro. We have emphasized glucose homeostasis through the determination of glucose and insulin tolerance, pancreatic islet function, and glucose uptake. In addition, we describe methods of adipocyte isolation, differentiation of preadipocytes, and evaluation of mitochondrial function.
    Keywords:  Adipocyte; Adipose; Estrogen; GPER; Glucose tolerance; Insulin resistance; Insulin sensitivity; Metabolism; Mitochondrial function; Obesity
    DOI:  https://doi.org/10.1007/978-1-0716-1920-9_21
  6. Adipocyte. 2022 Dec;11(1): 99-107
    A Straightforward Method for Adipocyte Size and Count Analysis Using Open-source Software QuPath.
    Ville A Palomäki, Vesa Koivukangas, Sanna Meriläinen, Petri Lehenkari, Tuomo J Karttunen.
      Changes in adipose tissue morphology, depicted by cell morphology alterations such as enlargement of fat cells, always accompany over-weight and obesity. The variables related to cell size have been shown to associate with low-grade inflammation of adipose tissue and common obesity-related comorbidities including metabolic syndrome and type 2 diabetes. Quantifying fat cell morphology from images of histological specimens can be tedious. Here, we present a straightforward method for the task using the free open-source software QuPath with its inbuilt tools only. Measurements of human adipose tissue samples with the described protocol showed an excellent correlation with those obtained with ImageJ software with Adipocyte Tools plugin combined with manual correction of misdetections. Intraclass correlation between the two methods was at good to excellent level. The method described here can be applied to considerably large tissue areas, even whole-slide analysis.
    Keywords:  Adipocyte Tools; Adipocyte size; ImageJ; Qupath; fat cell size; obesity
    DOI:  https://doi.org/10.1080/21623945.2022.2027610
  7. FEBS J. 2022 Feb 03.
    Functions and origins of cardiac fat.
    Zhengkai Lu, Zhen Jiang, Juan Tang, Chao-Po Lin, Hui Zhang.
      Triglyceride droplets can be stored within cardiac adipocytes and cardiomyocytes in the heart. Cardiac adipocytes reside in three distinct regions: pericardial, epicardial, and intramyocardial adipose tissues. In healthy individuals, cardiac adipose tissues modulate cardiovascular functions and energy partitioning, which are thus protective. However, ectopic deposition of cardiac adipose tissues turns them into adverse lipotoxic, prothrombotic, and pro-inflammatory tissues with local and systemic contribution to the development of cardiovascular disorders. Accumulation of triglyceride droplets in cardiomyocytes may lead to lipotoxic injury of cardiomyocytes and contribute to the development of cardiac hypertrophy and dysfunction. Here, we summarize the roles of cardiac adipocytes and myocardial triglyceride droplets under physiological and pathological conditions, and review the cellular sources of cardiac adipocytes in heart development and diseases. Understanding the functions and cellular origins of cardiac fat will provide clues for future studies on pathophysiological processes and the treatment of cardiovascular diseases.
    Keywords:  Cellular origin; cardiac adipocyte; cardiomyocyte; epicardial adipose tissue; intramyocardial adipose tissue
    DOI:  https://doi.org/10.1111/febs.16388
  8. Nat Immunol. 2022 Feb;23(2): 262-274
    Recruitment and activation of type 3 innate lymphoid cells promote antitumor immune responses.
    Mélanie Bruchard, Mannon Geindreau, Anaïs Perrichet, Caroline Truntzer, Elise Ballot, Romain Boidot, Cindy Racoeur, Emilie Barsac, Fanny Chalmin, Christophe Hibos, Thomas Baranek, Christophe Paget, Bernhard Ryffel, Cédric Rébé, Catherine Paul, Frédérique Végran, François Ghiringhelli.
      Tumors poorly infiltrated by T cells are more resistant to immunogenic chemotherapies and checkpoint inhibition than highly infiltrated tumors. Using murine models, we found that CCR6+ type 3 innate lymphoid cells (ILC3s) can trigger an increase in the number of T cells infiltrating a tumor. Shortly after administration of cisplatin chemotherapy, production of the chemokine CCL20 and proinflammatory cytokine IL-1β at the tumor site led to the recruitment and activation of ILC3s. Within the tumor, ILC3 production of the chemokine CXCL10 was responsible for the recruitment of CD4+ and CD8+ T lymphocytes to the tumor. ILC3-dependent infiltration of T cells was essential for antitumor immune responses and increased the efficacy of checkpoint inhibition. Thus, we reveal an essential role of CCL20 and IL-1β, which promote ILC3-dependent antitumor immunity and enhance tumor sensitivity to immunotherapy.
    DOI:  https://doi.org/10.1038/s41590-021-01120-y
  9. Nat Cancer. 2021 Jul;2(7): 677-679
    2-HG modulates glioma macrophages via Trp metabolism.
    Marie Jo Halaby, Tracy L McGaha.
      
    DOI:  https://doi.org/10.1038/s43018-021-00231-7
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