The Immunometabolic Roles of Various Fatty Acids in Macrophages and Lymphocytes

Neto, José Cesar Rosa; Calder, Philip C.; Curi, Rui; Newsholme, Philip; Sethi, J.; Silveira, Loreana Sanches

doi:10.3390/ijms22168460

Cited by 19 publications

(8 citation statements)

References 124 publications

(172 reference statements)

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“…Thus, Dangardt et al demonstrated that n -3 MUFA supplementation increases serum levels and decreases TNFα, IL-6, and IL-1β levels in the PBMCs of subjects with obesity [ 114 ]. In line with this, Zhao et al revealed that the treatment of people with obesity with n -3 MUFAs, such as linolenic acid, decreases free plasma FAs, IL-6, and TNFα levels and increase PPARγ expression in mononuclear cells (PBMCs) [ 11 , 115 ]. Furthermore, oleic acid (OA) is an n -9 MUFA, recognized as a versatile nutraceutical and effective biomolecule, with potent antioxidant capacity because it can directly regulate both the synthesis and the activity of antioxidants enzymes [ 158 ].…”

Section: Resultsmentioning

confidence: 96%

“…This implies an active characteristic metabolic state: while M1 macrophages primarily use glucose consumption and lactate excretion, M2 macrophages use OXPHOS, FAO, and mitochondrial respiration [ 69 ]. Thus, Rosa et al proposed that FAO induces M2 [ 11 , 70 ]. Moreover, the repolarization of M2 to M1 after infection conditions with the consequent metabolic reprogramming leads to an impaired TCA cycle in M1 and succinate accumulation [ 30 ].…”

Section: Resultsmentioning

confidence: 99%

“…This change of state, which includes phenotypical and functional modifications from the resting state to the activated and effector state from these immune cells, supposes an increase in their energy requirements that affect their intracellular metabolism [ 10 ]. This implies deep changes in different metabolic pathways, such as glycolysis, the tricarboxylic acid (TCA) or Krebs cycle, the pentose phosphate pathway (PPP), fatty acid (FA) oxidation (FAO), fatty acid synthesis (FAS), amino acid metabolism, and oxidative phosphorylation (OXPHOS) [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

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Nutraceuticals as Potential Therapeutic Modulators in Immunometabolism

et al. 2023

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Nutraceuticals act as cellular and functional modulators, contributing to the homeostasis of physiological processes. In an inflammatory microenvironment, these functional foods can interact with the immune system by modulating or balancing the exacerbated proinflammatory response. In this process, immune cells, such as antigen-presenting cells (APCs), identify danger signals and, after interacting with T lymphocytes, induce a specific effector response. Moreover, this conditions their change of state with phenotypical and functional modifications from the resting state to the activated and effector state, supposing an increase in their energy requirements that affect their intracellular metabolism, with each immune cell showing a unique metabolic signature. Thus, nutraceuticals, such as polyphenols, vitamins, fatty acids, and sulforaphane, represent an active option to use therapeutically for health or the prevention of different pathologies, including obesity, metabolic syndrome, and diabetes. To regulate the inflammation associated with these pathologies, intervention in metabolic pathways through the modulation of metabolic energy with nutraceuticals is an attractive strategy that allows inducing important changes in cellular properties. Thus, we provide an overview of the link between metabolism, immune function, and nutraceuticals in chronic inflammatory processes associated with obesity and diabetes, paying particular attention to nutritional effects on APC and T cell immunometabolism, as well as the mechanisms required in the change in energetic pathways involved after their activation.

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Section: Resultsmentioning

confidence: 96%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Nutraceuticals as Potential Therapeutic Modulators in Immunometabolism

et al. 2023

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“…M2 macrophages are involved in the resolution, activated during the repair phase of functional activity of tissue injury, through OXPHOS and FAO as the main functional pathways ( 28 ). There is also evidence that FAO induces M2 phenotypic transformation, although whether this process is sufficient for M2 polarization has not been fully elucidated ( 29 ), inhibiting fatty acid transporter proteins promotes their M1 phenotype ( 30 ). Therefore, we are not yet able to determine the causal relationship between reprogramming of FAO energy utilization and M2 polarization behavior.…”

Section: Differences In Metabolic Reprogramming Macrophagesmentioning

confidence: 99%

Macrophage Polarization, Metabolic Reprogramming, and Inflammatory Effects in Ischemic Heart Disease

Sun

Deng

et al. 2022

Front. Immunol.

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Macrophages are highly plastic cells, and the polarization-activating actions that represent their functional focus are closely related to metabolic reprogramming. The metabolic reprogramming of macrophages manifests itself as a bias toward energy utilization, transforming their inflammatory phenotype by changing how they use energy. Metabolic reprogramming effects crosstalk with the biological processes of inflammatory action and are key to the inflammatory function of macrophages. In ischemic heart disease, phenotypic polarization and metabolic shifts in circulating recruitment and tissue-resident macrophages can influence the balance of inflammatory effects in the heart and determine disease regression and prognosis. In this review, we present the intrinsic link between macrophage polarization and metabolic reprogramming, discussing the factors that regulate macrophages in the inflammatory effects of ischemic heart disease. Our aim is to estabilsh reliable regulatory pathways that will allow us to better target the macrophage metabolic reprogramming process and improve the symptoms of ischemic heart disease.

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“…Obesity results from an imbalance between energy intake and expenditure, in which the excess energy is stored as triglyceride in white adipose tissue with both increased fat cell size (hypertrophy) and number (hyperplasia) [18]. Obesity induces a state of chronic, low-grade inflammation in fat that is accompanied by the local secretion of cytokines and chemokines, causing attenuation of insulin action [19][20][21][22][23]. Obesity is closely associated with a number of diseases including type 2 diabetes (T2D), cardiovascular disease, hypertension, dementia, and certain cancers [24,25].…”

Section: Introductionmentioning

confidence: 99%

Adipose Tissue Steroid Receptor RNA Activator 1 (SRA1) Expression Is Associated with Obesity, Insulin Resistance, and Inflammation

Kochumon

Arefanian

Sindhu

et al. 2021

Cells

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Steroid receptor RNA activator 1 (SRA1) is involved in pathophysiological responses of adipose tissue (AT) in obesity. In vitro and animal studies have elucidated its role in meta-inflammation. Since SRA1 AT expression in obesity/type 2 diabetes (T2D) and the relationship with immune-metabolic signatures remains unclear, we assessed AT SRA1 expression and its association with immune–metabolic markers in individuals with obesity/T2D. For this, 55 non-diabetic and 53 T2D individuals classified as normal weight (NW; lean), overweight, and obese were recruited and fasting blood and subcutaneous fat biopsy samples were collected. Plasma metabolic markers were assessed using commercial kits and AT expression of SRA1 and selected immune markers using RT-qPCR. SRA1 expression was significantly higher in non-diabetic obese compared with NW individuals. SRA1 expression associated with BMI, PBF, serum insulin, and HOMA-IR in the total study population and people without diabetes. SRA1 associated with waist circumference in people without diabetes and NW participants, whereas it associated inversely with HbA1c in overweight participants. In most study subgroups AT SRA1 expression associated directly with CXCL9, CXCL10, CXCL11, TNF-α, TGF-β, IL2RA, and IL18, but inversely with CCL19 and CCR2. TGF-β/IL18 independently predicted the SRA1 expression in people without diabetes and in the total study population, while TNF-α/IL-2RA predicted SRA1 only in people with diabetes. TNF-α also predicted SRA1 in both NW and obese people regardless of the diabetes status. In conclusion, AT SRA1 expression is elevated in people with obesity which associates with typical immunometabolic markers of obesity/T2D, implying that SRA1 may have potential as a biomarker of metabolic derangements.

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The Immunometabolic Roles of Various Fatty Acids in Macrophages and Lymphocytes

Cited by 19 publications

References 124 publications

Nutraceuticals as Potential Therapeutic Modulators in Immunometabolism

Nutraceuticals as Potential Therapeutic Modulators in Immunometabolism

Macrophage Polarization, Metabolic Reprogramming, and Inflammatory Effects in Ischemic Heart Disease

Adipose Tissue Steroid Receptor RNA Activator 1 (SRA1) Expression Is Associated with Obesity, Insulin Resistance, and Inflammation

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