bims-aditis 2022-01-16 papers

bims-aditis

Biomed News

on Adipose tissue, inflammation, immunometabolism

Issue of 2022–01–16
ten papers selected by
Matthew C. Sinton, University of Glasgow

Adipokines: inflammation and the pleiotropic role of white adipose tissue.
Lipid Transport in Brown Adipocyte Thermogenesis.
Calcitonin gene-related peptide upregulates IL-17A and IL-22 in γδ-T cells through the paracrine effect of langerhans cells on LC/γδ-T co-culture model.
Variable roles of interleukin-17F in different cancers.
TNFα Mediates Inflammation-Induced Effects on PPARG Splicing in Adipose Tissue and Mesenchymal Precursor Cells.
Metabolic adaptation of lymphocytes in immunity and disease.
Adipocyte Biology from the Perspective of In Vivo Research: Review of Key Transcription Factors.
Intertwining roles of circadian and metabolic regulation of the innate immune response.
Emerging role of γδ T cells in protozoan infection and their potential clinical application.
The role of lipid metabolism in shaping the expansion and the function of regulatory T cells.

Br J Nutr. 2022 Jan 28. 127(2): 161-164

Adipokines: inflammation and the pleiotropic role of white adipose tissue.

Paul Trayhurn.

  I had been working on the endocrine and signalling role of white adipose tissue (WAT) since 1994 following the identification of the ob (Lep) gene(1), this after some 15 years investigating the physiological role of brown adipose tissue. The ob gene, a mutation in which it is responsible for the profound obesity of ob/ob (Lepob/Lepob) mice, is expressed primarily in white adipocytes and encodes the pleiotropic hormone leptin. The discovery of this adipocyte hormone had wide-ranging implications, including that white fat has multiple functions that far transcend the traditional picture of a simple lipid storage organ.

Keywords:  Adipokine; Adipose tissue; Hypoxia; Inflammation; Leptin; Obesity; Oxygen; White fat

DOI:  https://doi.org/10.1017/S0007114521003962
Front Physiol. 2021 ;12 787535

Lipid Transport in Brown Adipocyte Thermogenesis.

Gina Wade, Ayren McGahee, James M Ntambi, Judith Simcox.

  Non-shivering thermogenesis is an energy demanding process that primarily occurs in brown and beige adipose tissue. Beyond regulating body temperature, these thermogenic adipocytes regulate systemic glucose and lipid homeostasis. Historically, research on thermogenic adipocytes has focused on glycolytic metabolism due to the discovery of active brown adipose tissue in adult humans through glucose uptake imaging. The importance of lipids in non-shivering thermogenesis has more recently been appreciated. Uptake of circulating lipids into thermogenic adipocytes is necessary for body temperature regulation and whole-body lipid homeostasis. A wide array of circulating lipids contribute to thermogenic potential including free fatty acids, triglycerides, and acylcarnitines. This review will summarize the mechanisms and regulation of lipid uptake into brown adipose tissue including protein-mediated uptake, lipoprotein lipase activity, endocytosis, vesicle packaging, and lipid chaperones. We will also address existing gaps in knowledge for cold induced lipid uptake into thermogenic adipose tissue.

Keywords:  CD36; brown adipose tissue (BAT); fatty acid; fatty acid binding protein (FABP); fatty acid transport protein (FATP); lipoprotein; thermogenesis; triglycerides (TGs)

DOI:  https://doi.org/10.3389/fphys.2021.787535
J Neuroimmunol. 2021 Dec 21. pii: S0165-5728(21)00319-2. [Epub ahead of print]364 577792

Calcitonin gene-related peptide upregulates IL-17A and IL-22 in γδ-T cells through the paracrine effect of langerhans cells on LC/γδ-T co-culture model.

Fen Peng, Siqi Zhao, Xuan Zhang, Siyu Long, Yanling He.

  Intense mental stimulation and stress often directly induce or exacerbate psoriasis. On the contrary, patients with nerve injury and nervous system dysfunction have psoriasis remission. The nervous system plays an important role in the inflammatory process of psoriasis, and neuropeptides are considered as local mediators of disease maintenance. To examine the molecular mechanism involved in this, first we analyzed calcitonin gene-related peptide (CGRP)-treated langerhans Cells and γδ-T cells separately. CGRP induced IL-23 mRNA and protein expression via PDK1-Rsk signaling pathway. However, CGRP had no effect on secretion of IL-17A and IL-22 in γδ-T cells. Then we treated LCs/γδ-T cells Co-culture Model with CGRP. CGRP upregulated IL-17A and IL-22 expression in co-culture model through the paracrine effect of LCs. IL-17A and IL-22 are key cytokines of psoriasis. These findings provide a potential mechanism by which nerve factors affect the development of psoriasis.

Keywords:  IL-17A; IL-22; Nerve-immunological mechanism; Peptide; Psoriasis

DOI:  https://doi.org/10.1016/j.jneuroim.2021.577792
BMC Cancer. 2022 Jan 11. 22(1): 54

Variable roles of interleukin-17F in different cancers.

Tiina Mikkola, Rabeia Almahmoudi, Tuula Salo, Ahmed Al-Samadi.

   BACKGROUND: Interleukin (IL)-17 family is a group of six cytokines that plays a central role in inflammatory processes and participates in cancer progression. Interleukin-17A has been shown to have mainly a protumorigenic role, but the other members of the IL-17 family, including IL-17F, have received less attention.
METHODS: We applied systematic review guidelines to study the role of IL-17F, protein and mRNA expression, polymorphisms, and functions, in cancer. We carried out a systematic search in PubMed, Ovid Medline, Scopus, and Cochrane libraries, yielding 79 articles that met the inclusion criteria.
RESULTS: The findings indicated that IL-17F has both anti- and protumorigenic roles, which depend on cancer type and the molecular form and location of IL-17F. As an example, the presence of IL-17F protein in tumor tissue and patient serum has a protective role in oral and pancreatic cancers, whereas it is protumorigenic in prostate and bladder cancers. These effects are proposed to be based on multiple mechanisms, such as inhibition of angiogenesis, vasculogenic mimicry and cancer cell proliferation, migration and invasion, and aggravating the inflammatory process. No solid evidence emerged for the correlation between IL-17F polymorphisms and cancer incidence or patients' prognosis.
CONCLUSION: IL-17F is a multifaceted cytokine. There is a clear demand for more well-designed studies of IL-17F to elucidate its molecular mechanisms in different types of cancer. The studies presented in this article examined a variety of different designs, study populations and primary/secondary outcomes, which unfortunately reduces the value of direct interstudy comparisons.

Keywords:  IL-17F; Lymphocytes; Polymorphism; Prognostic; Systematic review; cancer

DOI:  https://doi.org/10.1186/s12885-021-08969-0
Cells. 2021 Dec 24. pii: 42. [Epub ahead of print]11(1):

TNFα Mediates Inflammation-Induced Effects on PPARG Splicing in Adipose Tissue and Mesenchymal Precursor Cells.

Simona Cataldi, Marianna Aprile, Daniela Melillo, Inès Mucel, Sophie Giorgetti-Peraldi, Mireille Cormont, Paola Italiani, Matthias Blüher, Jean-François Tanti, Alfredo Ciccodicola, Valerio Costa.

  Low-grade chronic inflammation and reduced differentiation capacity are hallmarks of hypertrophic adipose tissue (AT) and key contributors of insulin resistance. We identified PPARGΔ5 as a dominant-negative splicing isoform overexpressed in the AT of obese/diabetic patients able to impair adipocyte differentiation and PPARγ activity in hypertrophic adipocytes. Herein, we investigate the impact of macrophage-secreted pro-inflammatory factors on PPARG splicing, focusing on PPARGΔ5. We report that the epididymal AT of LPS-treated mice displays increased PpargΔ5/cPparg ratio and reduced expression of Pparg-regulated genes. Interestingly, pro-inflammatory factors secreted from murine and human pro-inflammatory macrophages enhance the PPARGΔ5/cPPARG ratio in exposed adipogenic precursors. TNFα is identified herein as factor able to alter PPARG splicing-increasing PPARGΔ5/cPPARG ratio-through PI3K/Akt signaling and SRp40 splicing factor. In line with in vitro data, TNFA expression is higher in the SAT of obese (vs. lean) patients and positively correlates with PPARGΔ5 levels. In conclusion, our results indicate that inflammatory factors secreted by metabolically-activated macrophages are potent stimuli that modulate the expression and splicing of PPARG. The resulting imbalance between canonical and dominant negative isoforms may crucially contribute to impair PPARγ activity in hypertrophic AT, exacerbating the defective adipogenic capacity of precursor cells.

Keywords:  PPARG splicing; TNFα; adipocyte precursors; dominant negative isoform; hypertrophic obesity; inflammation

DOI:  https://doi.org/10.3390/cells11010042
Immunity. 2022 Jan 11. pii: S1074-7613(21)00548-3. [Epub ahead of print]55(1): 14-30

Metabolic adaptation of lymphocytes in immunity and disease.

Nicole M Chapman, Hongbo Chi.

Adaptive immune responses mediated by T cells and B cells are crucial for protective immunity against pathogens and tumors. Differentiation and function of immune cells require dynamic reprogramming of cellular metabolism. Metabolic inputs, pathways, and enzymes display remarkable flexibility and heterogeneity, especially in vivo. How metabolic plasticity and adaptation dictate functional specialization of immune cells is fundamental to our understanding and therapeutic modulation of the immune system. Extensive progress has been made in characterizing the effects of metabolic networks on immune cell fate and function in discrete microenvironments or immunological contexts. In this review, we summarize how rewiring of cellular metabolism determines the outcome of adaptive immunity in vivo, with a focus on how metabolites, nutrients, and driver genes in immunometabolism instruct cellular programming and immune responses during infection, inflammation, and cancer in mice and humans. Understanding context-dependent metabolic remodeling will manifest legitimate opportunities for therapeutic intervention of human disease.

DOI: https://doi.org/10.1016/j.immuni.2021.12.012
Int J Mol Sci. 2021 Dec 28. pii: 322. [Epub ahead of print]23(1):

Adipocyte Biology from the Perspective of In Vivo Research: Review of Key Transcription Factors.

Maria N Evseeva, Maria S Balashova, Konstantin Y Kulebyakin, Yury P Rubtsov.

  Obesity and type 2 diabetes are both significant contributors to the contemporary pandemic of non-communicable diseases. Both disorders are interconnected and associated with the disruption of normal homeostasis in adipose tissue. Consequently, exploring adipose tissue differentiation and homeostasis is important for the treatment and prevention of metabolic disorders. The aim of this work is to review the consecutive steps in the postnatal development of adipocytes, with a special emphasis on in vivo studies. We gave particular attention to well-known transcription factors that had been thoroughly described in vitro, and showed that the in vivo research of adipogenic differentiation can lead to surprising findings.

Keywords:  CEBP/α; CEBP/β; CEBP/δ; CREB; PPARγ; adipogenesis; knockout; obesity; transcription factor

DOI:  https://doi.org/10.3390/ijms23010322
Semin Immunopathol. 2022 Jan 12.

Intertwining roles of circadian and metabolic regulation of the innate immune response.

Shannon L Cox, James R O'Siorain, Lauren E Fagan, Annie M Curtis, Richard G Carroll.

  It has emerged that an interconnected relationship exists between metabolism, circadian rhythms, and the immune system. The relationship between metabolism and circadian rhythms is not that surprising given the necessity to align rhythms of feeding/fasting with activity/rest. Recently, our understanding of the importance of metabolic pathways in terms of immune function, termed immunometabolism, has grown exponentially. It is now appreciated that the time of day during which the innate immune system is challenged strongly conditions the subsequent response. Recent observations have found that many individual components that make up the circadian clock also control aspects of metabolism in innate immune cells to modulate inflammation. This circadian/metabolic axis may be a key factor driving rhythmicity of immune function and circadian disruption is associated with a range of chronic inflammatory diseases such as atherosclerosis, obesity, and diabetes. The field of "circadian immunometabolism" seeks to reveal undiscovered circadian controlled metabolic pathways that in turn regulate immune responses. The innate immune system has been intricately linked to chronic inflammatory diseases, and within the immune system, individual cell types carry out unique roles in inflammation. Therefore, circadian immunometabolism effects are unique to each innate immune cell.

Keywords:  Circadian immunometabolism; Circadian rhythms; Inflammation; Innate immunity; Metabolism

DOI:  https://doi.org/10.1007/s00281-021-00905-5
Infect Genet Evol. 2022 Jan 11. pii: S1567-1348(22)00007-7. [Epub ahead of print] 105210

Emerging role of γδ T cells in protozoan infection and their potential clinical application.

Awnish Kumar, Bhawana Singh, Rahul Tiwari, Vishal Kumar Singh, Siddharth Sankar Singh, Shyam Sundar, Rajiv Kumar.

  γδ T cells are thymus derived heterogeneous and unconventional T- lymphocyte expressing TCR γ (V γ9) and TCRδ (Vδ2) chain and play an important role in connecting innate and adaptive armaments of immune response. These cells can recognize wide ranges of antigens even without involvement of major histocompatibility complex and exert their biological functions by cytotoxicity or activating various types of immune cells. In recent past; γδ T cells have emerged as an important player during protozoa infection and rapidly expand after exposure with them. They have also been widely studied in vaccine induced immune response against many bacterial and protozoan infections with improved clinical outcome. In this review, we will discuss the various roles of γδ T cells in immunity against malaria and leishmaniasis, the two important protozoan diseases causing significant mortality and morbidity throughout the world.

Keywords:  Immune response; Leishmaniasis; Malaria; Protozoan; γδ T cells

DOI:  https://doi.org/10.1016/j.meegid.2022.105210
Clin Exp Immunol. 2021 Dec 15. pii: uxab033. [Epub ahead of print]

The role of lipid metabolism in shaping the expansion and the function of regulatory T cells.

Alessandra Pinzon Grimaldos, Simone Bini, Ilenia Pacella, Alessandra Rossi, Alessia Di Costanzo, Ilenia Minicocci, Laura D'Erasmo, Marcello Arca, Silvia Piconese.

  Metabolic inflammation, defined as a chronic low-grade inflammation, is implicated in numerous metabolic diseases. In recent years, the role of regulatory T cells (Tregs) as key controllers of metabolic inflammation has emerged, but our comprehension on how different metabolic pathways influence Treg functions needs a deeper understanding. Here we focus on how circulating and intracellular lipid metabolism, in particular cholesterol metabolism, regulates Treg homeostasis, expansion, and functions. Cholesterol is carried through the bloodstream by circulating lipoproteins (chylomicrons, very low-density lipoproteins, low-density lipoproteins). Tregs are equipped with a wide array of metabolic sensors able to perceive and respond to changes in the lipid environment through the activation of different intracellular pathways thus conferring to these cells a crucial metabolic and functional plasticity. Nevertheless, altered cholesterol transport, as observed in genetic dyslipidemias and atherosclerosis, impairs Treg proliferation and function through defective cellular metabolism. The intracellular pathway devoted to the cholesterol synthesis is the mevalonate pathway and several studies have shown that this pathway is essential for Treg stability and suppressive activity. High cholesterol concentrations in the extracellular environment may induce massive accumulation of cholesterol inside the cell thus impairing nutrients sensors and inhibiting the mevalonate pathway. This review summarizes the current knowledge regarding the role of circulating and cellular cholesterol metabolism in the regulation of Treg metabolism and functions. In particular, we will discuss how different pathological conditions affecting cholesterol transport may affect cellular metabolism in Tregs.

Keywords:  Treg; atherosclerosis; cholesterol; dyslipidemia; lipoproteins

DOI:  https://doi.org/10.1093/cei/uxab033