bims-aditis Biomed News
on Adipose tissue, inflammation, immunometabolism
Issue of 2021‒10‒31
fourteen papers selected by
Matthew C. Sinton, University of Glasgow
  1. Adipogenic progenitors in different organs: Pathophysiological implications.
  2. Adaptive immune cells shape obesity-associated type 2 diabetes mellitus and less prominent comorbidities.
  3. A Novel Peroxisome Proliferator-Activated Receptor Gamma Ligand Improves Insulin Sensitivity and Promotes Browning of White Adipose Tissue in Obese Mice.
  4. NNMT is induced dynamically during beige adipogenesis in adipose tissues depot-specific manner.
  5. Glycogen metabolism links glucose homeostasis to thermogenesis in adipocytes.
  6. IL-17A reprograms intestinal epithelial cells to facilitate HIV-1 replication and outgrowth in CD4+ T cells.
  7. Asparagine reinforces mTORC1 signaling to boost thermogenesis and glycolysis in adipose tissues.
  8. Effects of dietary macronutrients and body composition on glucose homeostasis in mice.
  9. Alterations of DNA methylation during adipogenesis differentiation of mesenchymal stem cells isolated from adipose tissue of patients with obesity is associated with type 2 diabetes.
  10. Characterization of Adaptive-like γδ T Cells in Ugandan Infants during Primary Cytomegalovirus Infection.
  11. Association between IL-17A, IL-17F and IL-17RA gene polymorphisms and susceptibility to psoriasis and psoriatic arthritis: a meta-analysis.
  12. Histone H4 lysine 16 acetylation controls central carbon metabolism and diet-induced obesity in mice.
  13. γδT Cells Are Required for CD8+ T Cell Response to Vaccinia Viral Infection.
  14. Identification of adipocytes as target cells for Leishmania infantum parasites.
  1. Rev Endocr Metab Disord. 2021 Oct 29.
    Adipogenic progenitors in different organs: Pathophysiological implications.
    Francesca Favaretto, Silvia Bettini, Luca Busetto, Gabriella Milan, Roberto Vettor.
      In physiological conditions, the adipose organ resides in well-defined areas, where it acts providing an energy supply and as an endocrine organ involved in the control of whole-body energy metabolism. Adipose tissue adipokines connect the body's nutritional status to the regulation of energy balance. When it surrounds organs, it provides also for mechanical protection. Adipose tissue has a complex and heterogenous cellular composition that includes adipocytes, adipose tissue-derived stromal and stem cells (ASCs) which are mesenchymal stromal cells, and endothelial and immune cells, which signal to each other and to other tissues to maintain homeostasis. In obesity and in other nutrition related diseases, as well as in age-related diseases, biological and functional changes of adipose tissue give rise to several complications. Obesity triggers alterations of ASCs, impairing adipose tissue remodeling and adipose tissue function, which induces low-grade systemic inflammation, progressive insulin resistance and other metabolic disorders. Adipose tissue grows by hyperplasia recruiting new ASCs and by hypertrophy, up to its expandability limit. To overcome this limitation and to store the excess of nutrients, adipose tissue develops ectopically, involving organs such as muscle, bone marrow and the heart. The origin of ectopic adipose organ is not clearly elucidated, and a possible explanation lies in the stimulation of the adipogenic differentiation of mesenchymal precursor cells which normally differentiate toward a lineage specific for the organ in which they reside. The chronic exposition of these newly-formed adipose depots to the pathological environment, will confer to them all the phenotypic characteristics of a dysfunctional adipose tissue, perpetuating the organ alterations. Visceral fat, but also ectopic fat, either in the liver, muscle or heart, can increase the risk of developing insulin resistance, type 2 diabetes, and cardiovascular diseases. Being able to prevent and to target dysfunctional adipose tissue will avoid the progression towards the complications of obesity and other nutrition-related diseases. The aim of this review is to summarize some of the knowledge regarding the presence of adipose tissue in particular tissues (where it is not usually present), describing the composition of its adipogenic precursors, and the interactions responsible for the development of organ pathologies.
    Keywords:  Adipose tissue; Adipose tissue-derived stromal and stem cells (ASCs); Adiposopathy; Intermuscular adipose tissue (IMAT); Mesenchymal stromal cells (MSCs); Obesity; Signaling
    DOI:  https://doi.org/10.1007/s11154-021-09686-6
  2. Nat Rev Endocrinol. 2021 Oct 26.
    Adaptive immune cells shape obesity-associated type 2 diabetes mellitus and less prominent comorbidities.
    Sara SantaCruz-Calvo, Leena Bharath, Gabriella Pugh, Lucia SantaCruz-Calvo, Raji Rajesh Lenin, Jenny Lutshumba, Rui Liu, Adam D Bachstetter, Beibei Zhu, Barbara S Nikolajczyk.
      Obesity and type 2 diabetes mellitus (T2DM) are increasing in prevalence owing to decreases in physical activity levels and a shift to diets that include addictive and/or high-calorie foods. These changes are associated with the adoption of modern lifestyles and the presence of an obesogenic environment, which have resulted in alterations to metabolism, adaptive immunity and endocrine regulation. The size and quality of adipose tissue depots in obesity, including the adipose tissue immune compartment, are critical determinants of overall health. In obesity, chronic low-grade inflammation can occur in adipose tissue that can progress to systemic inflammation; this inflammation contributes to the development of insulin resistance, T2DM and other comorbidities. An improved understanding of adaptive immune cell dysregulation that occurs during obesity and its associated metabolic comorbidities, with an appreciation of sex differences, will be critical for repurposing or developing immunomodulatory therapies to treat obesity and/or T2DM-associated inflammation. This Review critically discusses how activation and metabolic reprogramming of lymphocytes, that is, T cells and B cells, triggers the onset, development and progression of obesity and T2DM. We also consider the role of immunity in under-appreciated comorbidities of obesity and/or T2DM, such as oral cavity inflammation, neuroinflammation in Alzheimer disease and gut microbiome dysbiosis. Finally, we discuss previous clinical trials of anti-inflammatory medications in T2DM and consider the path forward.
    DOI:  https://doi.org/10.1038/s41574-021-00575-1
  3. Mol Metab. 2021 Oct 25. pii: S2212-8778(21)00210-6. [Epub ahead of print] 101363
    A Novel Peroxisome Proliferator-Activated Receptor Gamma Ligand Improves Insulin Sensitivity and Promotes Browning of White Adipose Tissue in Obese Mice.
    Dan Wu, Venkateswararao Eeda, Ram Babu Undi, Shivani Mann, Michael Stout, Hui-Ying Lim, Weidong Wang.
      OBJECTIVE: Nuclear receptor Peroxisome Proliferator-Activated Receptor γ (PPARγ) is a promising target for the treatment of type 2 diabetes. The antidiabetic drug thiazolidinediones (TZDs) are potent insulin sensitizers as full agonists of PPARγ but cause unwanted side effects. Recent discoveries have shown that TZDs improve insulin sensitivity by blocking PPARγ phosphorylation at S273 which decouples the full agonism-associated side effects. PPARγ ligands that act through the blockage of PPARγ phosphorylation but lack the full agonist activity would be expected to improve insulin sensitivity without TZD-associated side effects. However, chemicals that carry such traits and bind to PPARγ with high-affinity are lacking. Moreover, TZDs are known to promote white-to-brown adipocyte conversion and energy expenditure and appear to require their full agonism on PPARγ for this activity. It is unknown whether a partial or non-TZD agonist of PPARγ is capable of promoting browning effect. In this study, we developed a novel non-TZD partial agonist of PPARγ and investigated its function on insulin sensitivity and white-to-brown conversion and energy expenditure in diet-induced obese mice.METHODS: A novel indole-based chemical WO95E was designed via medicinal chemistry and tested for PPARγ binding and activity and for the effect on PPARγ phosphorylation. Diet-induced obese mice were administered with WO95E for 4 weeks. Insulin sensitivity, glucose tolerance, body weight, fat tissue weight, adipocyte size, morphology, energy expenditure, and expression levels of genes involved in PPARγ activity, thermogenesis/browning, and TZD-related side effects were evaluated.
    RESULTS: WO95E binds to PPARγ with high affinity and acts as a PPARγ partial agonist. WO95E inhibits PPARγ phosphorylation and regulates PPARγ phosphorylation-dependent genes. WO95E ameliorates insulin resistance and glucose tolerance in mice of diet-induced obesity, with minimal TZD use-associated side effects. We also found that WO95E promotes white-to-brown adipocyte conversion and energy expenditure and hence protects against diet-induced obesity. WO95E decreases the size of adipocytes and suppresses adipose tissue inflammation. WO95E also suppresses obesity-associated liver steatosis.
    CONCLUSION: WO95E improves insulin sensitivity and glucose homeostasis and promotes browning and energy expenditure by acting as a novel PPARγ phosphorylation inhibitor/partial agonist. Our findings suggest the potential of this compound or its derivative for the therapeutic treatment of insulin resistance and obesity.
    Keywords:  Insulin resistance; Obesity; PPARγ; PPARγ agonist; Type 2 diabetes; White-to-brown conversion
    DOI:  https://doi.org/10.1016/j.molmet.2021.101363
  4. J Physiol Biochem. 2021 Oct 26.
    NNMT is induced dynamically during beige adipogenesis in adipose tissues depot-specific manner.
    Ru Jia, Xiaojing Wei, Jianan Jiang, Zhao Yang, Jiaqi Huang, Jing Liu, Jianqun Yan, Xiao Luo.
      Nicotinamide N-methyltransferase (NNMT) is a novel regulator, shown recently to regulate adipose tissue energy expenditure partly through changing NAD + content, which is essential for mitochondrial. We determine whether NNMT plays important role in energy metabolism during the beige adipogenesis in vivo and in vitro. Male C57BL/6 mice at 8 weeks old were exposed to 4 ℃ for 1, 2, 3, 4, and 5 days, respectively. Interscapular brown adipose tissue (iBAT), inguinal subcutaneous WAT (sWAT), and epididymal WAT (eWAT) were harvested for gene and protein expression analysis and the correlation analysis. In addition, cultured primary mice brown adipocyte (BA) and white adipocyte (WA) treated with or without β3-adrenoceptor agonist (CL316, 243) were also harvested for these analyses. A combination of NNMT and its related genetic (Nmnat1, Nampt, Cyp2e1, Nrk1, Cd38) and proteic analyses and also the NAD + levels demonstrated the dynamical and depot-specific remodeling of NAD metabolism in different adipose tissues in response to cold exposure. While upon CL316, 243 treatment, gene expression of Nnmt, Nampt, Cyp2e1, and Nrk1 was all significantly decreased in WA but not in BA. The increased NAD + amount in BA and WA during the beige adipogenesis was observed. Besides, it is demonstrated that the expression of NNMT both in sWAT and WA showed significant negative correlation with browning markers UCP-1 and PGC-1α at protein levels. Above all, NNMT was induced in WAT during the 'cold remodeling' phase and correlated negatively with the process of browning in sWAT and WA, indicating the specific role of NNMT in the regulation of energy homeostasis during the process of beige adipogenesis.
    Keywords:  Adipose tissue; Beige cells; NAD + metabolism; NNMT; Obesity
    DOI:  https://doi.org/10.1007/s13105-021-00851-8
  5. Nature. 2021 Oct 27.
    Glycogen metabolism links glucose homeostasis to thermogenesis in adipocytes.
    Omer Keinan, Joseph M Valentine, Haopeng Xiao, Sushil K Mahata, Shannon M Reilly, Mohammad Abu-Odeh, Julia H Deluca, Benyamin Dadpey, Leslie Cho, Austin Pan, Ruth T Yu, Yang Dai, Christopher Liddle, Michael Downes, Ronald M Evans, Aldons J Lusis, Markku Laakso, Edward T Chouchani, Mikael Ryde'n, Alan R Saltiel.
      Adipocytes increase energy expenditure in response to prolonged sympathetic activation via persistent expression of uncoupling protein 1 (UCP1)1,2. Here we report that the regulation of glycogen metabolism by catecholamines is critical for UCP1 expression. Chronic β-adrenergic activation leads to increased glycogen accumulation in adipocytes expressing UCP1. Adipocyte-specific deletion of a scaffolding protein, protein targeting to glycogen (PTG), reduces glycogen levels in beige adipocytes, attenuating UCP1 expression and responsiveness to cold or β-adrenergic receptor-stimulated weight loss in obese mice. Unexpectedly, we observed that glycogen synthesis and degradation are increased in response to catecholamines, and that glycogen turnover is required to produce reactive oxygen species leading to the activation of p38 MAPK, which drives UCP1 expression. Thus, glycogen has a key regulatory role in adipocytes, linking glucose metabolism to thermogenesis.
    DOI:  https://doi.org/10.1038/s41586-021-04019-8
  6. iScience. 2021 Nov 19. 24(11): 103225
    IL-17A reprograms intestinal epithelial cells to facilitate HIV-1 replication and outgrowth in CD4+ T cells.
    Tomas Raul Wiche Salinas, Annie Gosselin, Laurence Raymond Marchand, Etiene Moreira Gabriel, Olivier Tastet, Jean-Philippe Goulet, Yuwei Zhang, Dragos Vlad, Hanane Touil, Jean-Pierre Routy, Mariana G Bego, Mohamed El-Far, Nicolas Chomont, Alan L Landay, Éric A Cohen, Cécile Tremblay, Petronela Ancuta.
      The crosstalk between intestinal epithelial cells (IECs) and Th17-polarized CD4+ T cells is critical for mucosal homeostasis, with HIV-1 causing significant alterations in people living with HIV (PLWH) despite antiretroviral therapy (ART). In a model of IEC and T cell co-cultures, we investigated the effects of IL-17A, the Th17 hallmark cytokine, on IEC ability to promote de novo HIV infection and viral reservoir reactivation. Our results demonstrate that IL-17A acts in synergy with TNF to boost IEC production of CCL20, a Th17-attractant chemokine, and promote HIV trans-infection of CD4+ T cells and viral outgrowth from reservoir cells of ART-treated PLWH. Importantly, the Illumina RNA-sequencing revealed an IL-17A-mediated pro-inflammatory and pro-viral molecular signature, including a decreased expression of type I interferon (IFN-I)-induced HIV restriction factors. These findings point to the deleterious features of IL-17A and raise awareness for caution when designing therapies aimed at restoring the paucity of mucosal Th17 cells in ART-treated PLWH.
    Keywords:  Immune response; Immunology; Virology
    DOI:  https://doi.org/10.1016/j.isci.2021.103225
  7. EMBO J. 2021 Oct 27. e108069
    Asparagine reinforces mTORC1 signaling to boost thermogenesis and glycolysis in adipose tissues.
    Yingjiang Xu, Ting Shi, Xuan Cui, Linyu Yan, Qi Wang, Xiaoyan Xu, Qingwen Zhao, Xiaoxuan Xu, Qi-Qun Tang, Huiru Tang, Dongning Pan.
      Brown and beige fat are specialized for energy expenditure by dissipating energy from glucose and fatty acid oxidation as heat. While glucose and fatty acid metabolism have been extensively studied in thermogenic adipose tissues, the involvement of amino acids in regulating adaptive thermogenesis remains little studied. Here, we report that asparagine supplementation in brown and beige adipocytes drastically upregulated the thermogenic transcriptional program and lipogenic gene expression, so that asparagine-fed mice showed better cold tolerance. In mice with diet-induced obesity, the asparagine-fed group was more responsive to β3-adrenergic receptor agonists, manifesting in blunted body weight gain and improved glucose tolerance. Metabolomics and 13 C-glucose flux analysis revealed that asparagine supplement spurred glycolysis to fuel thermogenesis and lipogenesis in adipocytes. Mechanistically, asparagine stimulated the mTORC1 pathway, which promoted expression of thermogenic genes and key enzymes in glycolysis. These findings show that asparagine bioavailability affects glycolytic and thermogenic activities in adipose tissues, providing a possible nutritional strategy for improving systemic energy homeostasis.
    Keywords:  asparagine; brown adipocytes; glycolysis; mTORC1; thermogenesis
    DOI:  https://doi.org/10.15252/embj.2021108069
  8. Natl Sci Rev. 2021 Jan;8(1): nwaa177
    Effects of dietary macronutrients and body composition on glucose homeostasis in mice.
    Sumei Hu, Jacques Togo, Lu Wang, Yingga Wu, Dengbao Yang, Yanchao Xu, Li Li, Baoguo Li, Min Li, Jianbo Li, Guanlin Wang, Xueying Zhang, Chaoqun Niu, Mohsen Mazidi, Alex Douglas, John R Speakman.
      As a major health issue, obesity is linked with elevated risk of type 2 diabetes. However, whether disrupted glucose homeostasis is due to altered body composition alone, or whether dietary macronutrients play an additional role, independent of their impact on body composition, remains unclear. We investigated the associations between macronutrients, body composition, blood hormones and glucose homeostasis. We fed C57BL/6N mice 29 different diets with variable macronutrients for 12 weeks. After 10 weeks, intraperitoneal glucose tolerance tests were performed. Generalized linear models were generated to evaluate the impacts of macronutrients, body composition and blood hormones on glucose homeostasis. The area under the glucose curve (AUC) was strongly associated with body fat mass, but not dietary macronutrients. AUC was significantly associated with fasting insulin levels. Six genes from transcriptomic analysis of epididymal white adipose tissue and subcutaneous white adipose tissue were significantly associated with AUC. These genes may encode secreted proteins that play important previously unanticipated roles in glucose homeostasis.
    Keywords:  body fat mass; dietary macronutrients; fasting blood glucose; glucose tolerance; mice
    DOI:  https://doi.org/10.1093/nsr/nwaa177
  9. Adipocyte. 2021 Dec;10(1): 493-504
    Alterations of DNA methylation during adipogenesis differentiation of mesenchymal stem cells isolated from adipose tissue of patients with obesity is associated with type 2 diabetes.
    Elaheh Mirzaeicheshmeh, Carlos Zerrweck, Federico Centeno-Cruz, Paulina Baca-Peynado, Angélica Martinez-Hernandez, Humberto García-Ortiz, Cecilia Contreras-Cubas, María Guadalupe Salas-Martínez, Yolanda Saldaña-Alvarez, Elvia C Mendoza-Caamal, Francisco Barajas-Olmos, Lorena Orozco.
      Adipogenesis regulation is crucial for mature adipocyte function. In obesity, a major driver of type 2 diabetes (T2D), this process is disrupted and remains poorly characterized. Here we identified altered DNA methylation profiles in diabetic obese patients, during three adipocytes differentiation stages. We isolated mesenchymal cells from visceral adipose tissue of obese patients with and without T2D to analyse DNA methylation profiles at 0, 3, and 18 days of ex vivo differentiation and documented their impact on gene expression. Methylation and gene expression were analysed with EPIC and Clarion S arrays, respectively. Patients with T2D had epigenetic alterations in all the analysed stages, and these were mainly observed in genes important in adipogenesis, insulin resistance, cell death programming, and immune effector processes. Importantly, at 3 days, we found six-fold more methylated CpG alterations than in the other stages. This is the first study to document epigenetic markers that persist through all three adipogenesis stages and their impact on gene expression, which could be a cellular metabolic memory involved in T2D. Our data provided evidence that, throughout the adipogenesis process, alterations occur in methylation that might impact mature adipocyte function, cause tissue malfunction, and potentially, lead to the development of T2D.
    Keywords:  Adipogenesis; DNA methylation; obesity; type 2 diabetes
    DOI:  https://doi.org/10.1080/21623945.2021.1978157
  10. Viruses. 2021 Oct 03. pii: 1987. [Epub ahead of print]13(10):
    Characterization of Adaptive-like γδ T Cells in Ugandan Infants during Primary Cytomegalovirus Infection.
    Jessica Tuengel, Sanya Ranchal, Alexandra Maslova, Gurpreet Aulakh, Maria Papadopoulou, Sibyl Drissler, Bing Cai, Cetare Mohsenzadeh-Green, Hugo Soudeyns, Sara Mostafavi, Peter van den Elzen, David Vermijlen, Laura Cook, Soren Gantt.
      Gamma-delta (γδ) T cells are unconventional T cells that help control cytomegalovirus (CMV) infection in adults. γδ T cells develop early in gestation, and a fetal public γδ T cell receptor (TCR) clonotype is detected in congenital CMV infections. However, age-dependent γδ T cell responses to primary CMV infection are not well-understood. Flow cytometry and TCR sequencing was used to comprehensively characterize γδ T cell responses to CMV infection in a cohort of 32 infants followed prospectively from birth. Peripheral blood γδ T cell frequencies increased during infancy, and were higher among CMV-infected infants relative to uninfected. Clustering analyses revealed associations between CMV infection and activation marker expression on adaptive-like Vδ1 and Vδ3, but not innate-like Vγ9Vδ2 γδ T cell subsets. Frequencies of NKG2C+CD57+ γδ T cells were temporally associated with the quantity of CMV shed in saliva by infants with primary infection. The public γδ TCR clonotype was only detected in CMV-infected infants <120 days old and at lower frequencies than previously described in fetal infections. Our findings support the notion that CMV infection drives age-dependent expansions of specific γδ T cell populations, and provide insight for novel strategies to prevent CMV transmission and disease.
    Keywords:  CMV; NKG2C; Vγ8; Vγ9negVδ2; Vδ1; Vδ3; cCMV; gamma delta T cell; gammadelta; immune ontogeny
    DOI:  https://doi.org/10.3390/v13101987
  11. Inflamm Res. 2021 Oct 27.
    Association between IL-17A, IL-17F and IL-17RA gene polymorphisms and susceptibility to psoriasis and psoriatic arthritis: a meta-analysis.
    Fridha Viridiana Villalpando-Vargas, Juan José Rivera-Valdés, Anabell Alvarado-Navarro, Selene Guadalupe Huerta-Olvera, José Macías-Barragán, Erika Martínez-López, Omar Graciano-Machuca.
      BACKGROUND: Psoriasis (Ps) is a chronic dermatosis characterized by erythematous-squamous plaques derived from an inflammatory response. The effect of polymorphisms in the genes that encode the members of the IL-17 family and their receptors has been studied to find an association with the susceptibility to Ps. However, the findings have not been conclusive.OBJECTIVES: To describe the association between IL-17A, IL-17F and IL-17RA gene polymorphisms and susceptibility to Ps.
    METHOD: A systematic review was conducted using the PubMed and Scopus databases to identify studies that evaluated the association between IL-17A, IL-17F, and IL-17RA gene polymorphisms and Ps susceptibility. This meta-analysis included reports published until June 2021. Heterogeneity was assessed using Cochran's Q-statistic test and I2 statistics. The associations between polymorphisms and Ps susceptibility were determined by pooled OR with a 95% CI.
    RESULTS: Fifteen studies were included. The frequency of the T allele of the IL-17F rs763780 polymorphism was significantly lower in patients with vulgar Ps (OR = 0.732, p = 0.026). The TT genotype of the IL-17F rs763780 polymorphism was significantly associated with a decreased frequency in individuals with Ps and psoriatic arthritis (PsA) (TT:TC + CC OR = 0.664, p = 0.046). Regarding IL-17RA polymorphisms, the AG genotype of the rs4819554 polymorphism showed a near-significant decrease in psoriasis risk compared to the GG genotype (AG:GG OR = 0.604, p = 0.050). Other polymorphisms in IL-17A, IL-17F and IL-17RA showed no association with Ps.
    CONCLUSIONS: The T allele and TT genotype of the IL-17F rs763780 polymorphism may be associated with a decreased risk of psoriasis. Therefore, the implications of this variant on psoriasis pathogenesis and treatment require further investigation.
    Keywords:  IL-17A; IL-17F; IL-17RA; Psoriasis; Psoriatic arthritis
    DOI:  https://doi.org/10.1007/s00011-021-01514-6
  12. Nat Commun. 2021 Oct 27. 12(1): 6212
    Histone H4 lysine 16 acetylation controls central carbon metabolism and diet-induced obesity in mice.
    Cecilia Pessoa Rodrigues, Aindrila Chatterjee, Meike Wiese, Thomas Stehle, Witold Szymanski, Maria Shvedunova, Asifa Akhtar.
      Noncommunicable diseases (NCDs) account for over 70% of deaths world-wide. Previous work has linked NCDs such as type 2 diabetes (T2D) to disruption of chromatin regulators. However, the exact molecular origins of these chronic conditions remain elusive. Here, we identify the H4 lysine 16 acetyltransferase MOF as a critical regulator of central carbon metabolism. High-throughput metabolomics unveil a systemic amino acid and carbohydrate imbalance in Mof deficient mice, manifesting in T2D predisposition. Oral glucose tolerance testing (OGTT) reveals defects in glucose assimilation and insulin secretion in these animals. Furthermore, Mof deficient mice are resistant to diet-induced fat gain due to defects in glucose uptake in adipose tissue. MOF-mediated H4K16ac deposition controls expression of the master regulator of glucose metabolism, Pparg and the entire downstream transcriptional network. Glucose uptake and lipid storage can be reconstituted in MOF-depleted adipocytes in vitro by ectopic Glut4 expression, PPARγ agonist thiazolidinedione (TZD) treatment or SIRT1 inhibition. Hence, chronic imbalance in H4K16ac promotes a destabilisation of metabolism triggering the development of a metabolic disorder, and its maintenance provides an unprecedented regulatory epigenetic mechanism controlling diet-induced obesity.
    DOI:  https://doi.org/10.1038/s41467-021-26277-w
  13. Front Immunol. 2021 ;12 727046
    γδT Cells Are Required for CD8+ T Cell Response to Vaccinia Viral Infection.
    Rui Dai, Xiaopei Huang, Yiping Yang.
      Vaccinia virus (VV) is the most studied member of the poxvirus family, is responsible for the successful elimination of smallpox worldwide, and has been developed as a vaccine vehicle for infectious diseases and cancer immunotherapy. We have previously shown that the unique potency of VV in the activation of CD8+ T cell response is dependent on efficient activation of the innate immune system through Toll-like receptor (TLR)-dependent and -independent pathways. However, it remains incompletely defined what regulate CD8+ T cell response to VV infection. In this study, we showed that γδT cells play an important role in promoting CD8+ T cell response to VV infection. We found that γδT cells can directly present viral antigens in the context of MHC-I for CD8+ T cell activation to VV in vivo, and we further demonstrated that cell-intrinsic MyD88 signaling in γδT cells is required for activation of γδT cells and CD8+ T cells. These results illustrate a critical role for γδT cells in the regulation of adaptive T cell response to viral infection and may shed light on the design of more effective vaccine strategies based on manipulation of γδT cells.
    Keywords:  CD8 T cells; MyD88 pathway; adaptive immunity; innate immunity; vaccinia virus; γδT cells
    DOI:  https://doi.org/10.3389/fimmu.2021.727046
  14. Sci Rep. 2021 Oct 28. 11(1): 21275
    Identification of adipocytes as target cells for Leishmania infantum parasites.
    Aurélie Schwing, Didier F Pisani, Christelle Pomares, Alissa Majoor, Sandra Lacas-Gervais, Jennifer Jager, Emmanuel Lemichez, Pierre Marty, Laurent Boyer, Grégory Michel.
      Leishmania infantum is the causative agent of visceral leishmaniasis transmitted by the bite of female sand flies. According to the WHO, the estimated annual incidence of leishmaniasis is one million new cases, resulting in 30,000 deaths per year. The recommended drugs for treating leishmaniasis include Amphotericin B. But over the course of the years, several cases of relapses have been documented. These relapses cast doubt on the efficiency of actual treatments and raise the question of potential persistence sites. Indeed, Leishmania has the ability to persist in humans for long periods of time and even after successful treatment. Several potential persistence sites have already been identified and named as safe targets. As adipose tissue has been proposed as a sanctuary of persistence for several pathogens, we investigated whether Leishmania infantum could be found in this tissue. We demonstrated both in cell cultures and in vivo that Leishmania infantum was able to infect adipocytes. Altogether our results suggest adipocytes as a 'safe target' for Leishmania infantum parasites.
    DOI:  https://doi.org/10.1038/s41598-021-00443-y
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