Monocarboxylate transporter 1 deficiency impacts CD8+ T lymphocytes proliferation and recruitment to adipose tissue during obesity

Macchi, Chiara; Moregola, A.; Greco, Maria Francesca; Svecla, M.; Bonacina, Fabrizia; Dhup, Suveera; Dadhich, Rajesh Kumar; Audano, Matteo; Sonveaux, Pierre; Mauro, Claudio; Mitro, Nico; Ruscica, Massimiliano; Norata, Giuseppe Danilo

doi:10.1016/j.isci.2022.104435

Cited by 18 publications

(21 citation statements)

References 49 publications

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“…Specifically, VSMC PCSK9 -EVs led to a drop in the oxidative phosphorylation and a rise in glycolytic activity in THP-1 monocytes. Cells involved in the pro-inflammatory response must rapidly provide energy to fuel inflammation, which is essentially accomplished by glycolysis and high lactate production [ 67 , 68 ].…”

Section: Discussionmentioning

confidence: 99%

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PCSK9 Confers Inflammatory Properties to Extracellular Vesicles Released by Vascular Smooth Muscle Cells

Greco

Rizzuto

Zara

et al. 2022

IJMS

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Vascular smooth muscle cells (VSMCs) are key participants in both early- and late-stage atherosclerosis and influence neighbouring cells possibly by means of bioactive molecules, some of which are packed into extracellular vesicles (EVs). Proprotein convertase subtilisin/kexin type 9 (PCSK9) is expressed and secreted by VSMCs. This study aimed to unravel the role of PCSK9 on VSMCs-derived EVs in terms of content and functionality. EVs were isolated from human VSMCs overexpressing human PCSK9 (VSMCPCSK9-EVs) and tested on endothelial cells, monocytes, macrophages and in a model of zebrafish embryos. Compared to EVs released from wild-type VSMCs, VSMCPCSK9-EVs caused a rise in the expression of adhesion molecules in endothelial cells and of pro-inflammatory cytokines in monocytes. These acquired an increased migratory capacity, a reduced oxidative phosphorylation and secreted proteins involved in immune response and immune effector processes. Concerning macrophages, VSMCPCSK9-EVs enhanced inflammatory milieu and uptake of oxidized low-density lipoproteins, whereas the migratory capacity was reduced. When injected into zebrafish embryos, VSMCPCSK9-EVs favoured the recruitment of macrophages toward the site of injection. The results of the present study provide evidence that PCSK9 plays an inflammatory role by means of EVs, at least by those derived from smooth muscle cells of vascular origin.

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Section: Discussionmentioning

confidence: 99%

“…To further shed light on THP-1 glycolysis, the Seahorse XF Glycolytic Rate Assay was used. Rates at basal level as well as after injections of Rotenone plus antimycin A (1 μM) and 2-deoxy-D-glucose (50 mM) were recorded [ 68 ].…”

Section: Methodsmentioning

confidence: 99%

PCSK9 Confers Inflammatory Properties to Extracellular Vesicles Released by Vascular Smooth Muscle Cells

Greco

Rizzuto

Zara

et al. 2022

IJMS

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“…Colon specimens were collected after sacrifice from each mouse and total RNA was extracted according to spin column (Qiagen, Milan, Italy). Tissue samples were homogenized by using TissueLyser II (QIAGEN, Milan, Italy) in ice cold commercial lysis buffer (RNeasy Micro Kit, Qiagen) supplemented with RNase-free DNase I (RNase-Free DNase Set, Qiagen) ( 44 , 45 ). Reverse transcription-polymerase first-strand cDNA synthesis was performed by using maxima 1strand cDNA synthesis kit (Thermo, Life Technologies, Waltham, MA, USA).…”

Section: Methodsmentioning

confidence: 99%

Lentilactobacillus kefiri SGL 13 and Andrographis paniculata alleviate dextran sulfate sodium induced colitis in mice

Manna¹,

Rizzi²,

Bafile³

et al. 2023

Front. Nutr.

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IntroductionInflammatory bowel diseases (IBD) are chronic inflammatory conditions that typically involve diarrhea, abdominal pain, fatigue, and weight loss, with a dramatic impact on patients’ quality of life. Standard medications are often associated with adverse side effects. Thus, alternative treatments such as probiotics are of great interest. The purpose of the present study was to evaluate the effects of oral administration of Lentilactobacillus kefiri (basonym: Lactobacillus kefiri) SGL 13 and Andrographis paniculata, namely, Paniculin 13™, on dextran sodium sulfate (DSS)- treated C57BL/6J mice.MethodsColitis was induced by administering 1.5% DSS in drinking water for 9 days. Forty male mice were divided into four groups, receiving PBS (control), 1.5% DSS, Paniculin 13™ and 1.5% DSS + Paniculin 13™.ResultsThe results showed that body weight loss and Disease Activity Index (DAI) score were improved by Paniculin 13™. Moreover, Paniculin 13™ ameliorated DSS-induced dysbiosis, by modulating the gut microbiota composition. The gene expression of MPO, TNFα and iNOS in colon tissue was reduced and these data matched with the histological results, supporting the efficacy of Paniculin 13™ in reducing the inflammatory response. No adverse effects were associated to Paniculin 13™ administration.DiscussionIn conclusion, Paniculin 13™ could be an effective add-on approach to conventional therapies for IBD.

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“…Metabolomic data were obtained by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), as previously described [ 30 , 31 ], with some modifications described below. We used an API-3500 triple quadrupole mass spectrometer (AB Sciex, Framingham, MA, USA) coupled with an ExionLC™ AC System (AB Sciex).…”

Section: Methodsmentioning

confidence: 99%

Rewiring of Glucose and Lipid Metabolism Induced by G Protein-Coupled Receptor 17 Silencing Enables the Transition of Oligodendrocyte Progenitors to Myelinating Cells

Marangon

Audano

Pedretti

et al. 2022

Cells

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In the mature central nervous system (CNS), oligodendrocytes (OLs) provide support and insulation to axons thanks to the production of a myelin sheath. During their maturation to myelinating cells, OLs require energy and building blocks for lipids, which implies a great investment of energy fuels and molecular sources of carbon. The oligodendroglial G protein-coupled receptor 17 (GPR17) has emerged as a key player in OL maturation; it reaches maximal expression in pre-OLs, but then it has to be internalized to allow terminal maturation. In this study, we aim at elucidating the role of physiological GPR17 downregulation in OL metabolism by applying transcriptomics, metabolomics and lipidomics on differentiating OLs. After GPR17 silencing, we found a significant increase in mature OL markers and alteration of several genes involved in glucose metabolism and lipid biosynthesis. We also observed an increased release of lactate, which is partially responsible for the maturation boost induced by GPR17 downregulation. Concomitantly, GPR17 depletion also changed the kinetics of specific myelin lipid classes. Globally, this study unveils a functional link between GPR17 expression, lactate release and myelin composition, and suggests that innovative interventions targeting GPR17 may help to foster endogenous myelination in demyelinating diseases.

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Monocarboxylate transporter 1 deficiency impacts CD8+ T lymphocytes proliferation and recruitment to adipose tissue during obesity

Cited by 18 publications

References 49 publications

PCSK9 Confers Inflammatory Properties to Extracellular Vesicles Released by Vascular Smooth Muscle Cells

PCSK9 Confers Inflammatory Properties to Extracellular Vesicles Released by Vascular Smooth Muscle Cells

Lentilactobacillus kefiri SGL 13 and Andrographis paniculata alleviate dextran sulfate sodium induced colitis in mice

Rewiring of Glucose and Lipid Metabolism Induced by G Protein-Coupled Receptor 17 Silencing Enables the Transition of Oligodendrocyte Progenitors to Myelinating Cells

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