Physiological role of cytokines in the regulation of mammalian metabolism

Baat, Axel de; Trinh, Beckey; Ellingsgaard, Helga; Donath, Marc Y.

doi:10.1016/j.it.2023.06.002

Cited by 23 publications

(5 citation statements)

References 127 publications

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“…Next, we examined the production of inflammatory cytokines. Consistent with impaired type 2 immunity, levels of the inflammatory cytokines TNF, IL-1β and IL-6, which have previously been shown to drive adipose tissue inflammation (de Baat et al, 2023; Hotamisligil, 2017), were significantly increased in the adipose tissue of ILC2 ΔACC1 mice ( Figure 3H ). Thus, expression of ACC1 is essential for the maintenance and function of VAT ILC2 to prevent perturbance of adipose tissue immune homeostasis and inflammation.…”

Section: Resultssupporting

confidence: 74%

Anabolic lipid metabolism regulates adipose type 2 innate lymphoid cell differentiation to maintain metabolic health

Theodorou,

Yu,

Nikolka

et al. 2024

Preprint

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Group 2 innate lymphoid cells (ILC2) residing in the adipose tissue play an important role in maintaining the metabolic health and energy balance of the organisms. In obesity ILC2 numbers are reduced and their function is impaired, leading to the progression of metabolic inflammation. However, which events impact on ILC2 biology in the adipose tissue in obesity remains unresolved. Here, we find that high fat diet (HFD)-induced obesity in mice results in the metabolic reprogramming of adipose ILC2, impairing mitochondrial function and the expression of the enzyme Acetyl-CoA carboxylase 1 (ACC1). Investigating a possible connection between ACC1 and obesity-induced changes in ILC2, we show that fatty acids directly reduce the expression of ACC1, while pharmacological inhibition of ACC1 diminishes mitochondrial function and ILC2 metabolism. Furthermore, deletion of ACC1 in ILC2 phenocopies the overall reduction and functional impairment of ILC2 observed in obesity, which ultimately leads to increased triglycerides in circulation, adipose tissue hypertrophy and inflammation, even in the absence of HFD. Through single-cell RNA sequencing analysis we uncover that HFD-feeding or deletion of ACC1 results in the accumulation of undifferentiated ILC2 and ILC progenitors in the adipose tissue, suggesting that ACC1 may primarily regulate the maturation of ILC2. Together, these results reveal that obesity could predominately impair adipose ILC2 differentiation and activation by impacting on the expression of ACC1, rather than inducing cell death through lipid overload and lipotoxicity.

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Section: Resultssupporting

confidence: 74%

Anabolic lipid metabolism regulates adipose type 2 innate lymphoid cell differentiation to maintain metabolic health

Theodorou,

Yu,

Nikolka

et al. 2024

Preprint

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“…The results indicated that treatment with PPAPH+L induced the upregulation of HMOX1, [ 30 ] SAT1, [ 31 ] and ASCL4, validating that the ROS generated by PPAPH+L disturbed the REDOX and lipid balance in cells, resulting in cell ferroptosis. Additionally, PPAPH+L also elicited genetic alterations involving TNFRSF1B (TNFR2), TRAF1, IL‐6, [ 32 ] CXCL2, [ 33 ] CSF1, connected to the TNF signaling pathway, and NF‐κB signaling pathway, which could promote immune activation and immunogenic cell death (ICD). Genes related to cell apoptosis and cellular senescence, such as CAPN2, GADD45A, GADD45B, CTSL, EIF4EBP1 (4E‐BP1), [ 34 ] SERPINE1, and CDKN1A [ 35 ] were also upregulated after PPAPH+L treatment.…”

Section: Resultsmentioning

confidence: 99%

A Multifunctional Bimetallic Nanoplatform for Synergic Local Hyperthermia and Chemotherapy Targeting HER2‐Positive Breast Cancer

Zhao,

Chang,

Tong

et al. 2024

Advanced Science

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Anti‐HER2 (human epidermal growth factor receptor 2) therapies significantly increase the overall survival of patients with HER2‐positive breast cancer. Unfortunately, a large fraction of patients may develop primary or acquired resistance. Further, a multidrug combination used to prevent this in the clinic places a significant burden on patients. To address this issue, this work develops a nanotherapeutic platform that incorporates bimetallic gold‐silver hollow nanoshells (AuAg HNSs) with exceptional near‐infrared (NIR) absorption capability, the small‐molecule tyrosine kinase inhibitor pyrotinib (PYR), and Herceptin (HCT). This platform realizes targeted delivery of multiple therapeutic effects, including chemo‐and photothermal activities, oxidative stress, and immune response. In vitro assays reveal that the HCT‐modified nanoparticles exhibit specific recognition ability and effective internalization by cells. The released PYR inhibit cell proliferation by downregulating HER2 and its associated pathways. NIR laser application induces a photothermal effect and tumor cell apoptosis, whereas an intracellular reactive oxygen species burst amplifies oxidative stress and triggers cancer cell ferroptosis. Importantly, this multimodal therapy also promotes the upregulation of genes related to TNF and NF‐κB signaling pathways, enhancing immune activation and immunogenic cell death. In vivo studies confirm a significant reduction in tumor volume after treatment, substantiating the potential effectiveness of these nanocarriers.

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“…Immune activation is also known to provoke endothelial cell activation and coagulation ( 31 ). Finally, given the interactions between, on the one hand, the immune system and microbiota ( 32 ), metabolism ( 33 ), as well as hormones ( 34 ) on the other, T4 loss may provoke dysbiosis, hormonal and metabolic perturbations. Thus, in addition to impairing anti-SARS-CoV-2 immune response and participating in a cytokine storm during the acute phase, programmed T4 cell death could thereafter contribute to sequelae.…”

Section: Discussionmentioning

confidence: 99%

T4 apoptosis in the acute phase of SARS-CoV-2 infection predicts long COVID

Cezar,

Kundura,

André

et al. 2024

Front. Immunol.

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BackgroundAs about 10% of patients with COVID-19 present sequelae, it is important to better understand the physiopathology of so-called long COVID.MethodTo this aim, we recruited 29 patients hospitalized for SARS-CoV-2 infection and, by Luminex®, quantified 19 soluble factors in their plasma and in the supernatant of their peripheral blood mononuclear cells, including inflammatory and anti-inflammatory cytokines and chemokines, Th1/Th2/Th17 cytokines, and endothelium activation markers. We also measured their T4, T8 and NK differentiation, activation, exhaustion and senescence, T cell apoptosis, and monocyte subpopulations by flow cytometry. We compared these markers between participants who developed long COVID or not one year later.ResultsNone of these markers was predictive for sequelae, except programmed T4 cell death. T4 lymphocytes from participants who later presented long COVID were more apoptotic in culture than those of sequelae-free participants at Month 12 (36.9 ± 14.7 vs. 24.2 ± 9.0%, p = 0.016).ConclusionsOur observation raises the hypothesis that T4 cell death during the acute phase of SARS-CoV-2 infection might pave the way for long COVID. Mechanistically, T4 lymphopenia might favor phenomena that could cause sequelae, including SARS-CoV-2 persistence, reactivation of other viruses, autoimmunity and immune dysregulation. In this scenario, inhibiting T cell apoptosis, for instance, by caspase inhibitors, could prevent long COVID.

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Physiological role of cytokines in the regulation of mammalian metabolism

Cited by 23 publications

References 127 publications

Anabolic lipid metabolism regulates adipose type 2 innate lymphoid cell differentiation to maintain metabolic health

Anabolic lipid metabolism regulates adipose type 2 innate lymphoid cell differentiation to maintain metabolic health

A Multifunctional Bimetallic Nanoplatform for Synergic Local Hyperthermia and Chemotherapy Targeting HER2‐Positive Breast Cancer

T4 apoptosis in the acute phase of SARS-CoV-2 infection predicts long COVID

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