Leukotriene-B4 modulates macrophage metabolism and fat loss in type 1 diabetic mice

Ramalho, Theresa; Ramalingam, Latha; Filgueiras, Luciano Ribeiro; Festuccia, William T.; Jancar, Sônia; Moustaid‐Moussa, Naima

doi:10.1002/jlb.ma1218-477rr

Cited by 11 publications

(6 citation statements)

References 36 publications

(81 reference statements)

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“…LTB4 increased in type 1 diabetes and mediated the systemic inflammation and macrophage reprogramming. LTB4/LTB4 receptor (BLT1) can induce fat loss and increased macrophage lipid uptake (57). LTB4 is metabolized into 20-hydroxy-leukotriene B4 and 20-carboxyl-leukotriene B4 in leukocytes and hepatocytes.…”

Section: Discussionmentioning

confidence: 99%

Sacubitril/Valsartan contributes to improving the diabetic kidney disease and regulating the gut microbiota in mice

et al. 2022

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BackgroundDiabetic kidney disease (DKD), as a serious microvascular complication of diabetes, has limted treatment options. It is reported that the Sacubitril/Valsartan (Sac/Val) can improve kidney function, and the disordered gut microbiota and part of its metabolites are related to the development of DKD. Therefore, we aim to explore whether the effect of Sac/Val on DKD is associated with the gut microbiota and related plasma metabolic profiles.MethodsMale C57BL/6J mice were randomly divided into 3 groups: Con group (n = 5), DKD group (n = 6), and Sac/Val group (n = 6) . Sac/Val group was treated with Sac/Val solution. The intervention was given once every 2 days for 6 weeks. We measured the blood glucose and urine protein level of mice at different times. We then collected samples at the end of experiment for the 16s rRNA gene sequencing analysis and the untargeted plasma metabonomic analysis.ResultsWe found that the plasma creatinine concentration of DKD-group mice was significantly higher than that of Con-group mice, whereas it was reduced after the Sac/Val treatment. Compared with DKD mice, Sac/Val treatment could decrease the expression of indicators related to EndMT and renal fibrosis like vimentin, collagen IV and fibronectin in kidney. According to the criteria of LDA ≥ 2.5 and p<0.05, LefSe analysis of gut microbiota identified 13 biomarkers in Con group, and 33 biomarkers in DKD group, mainly including Prevotella, Escherichia_Shigella and Christensenellaceae_R_7_group, etc. For the Sac/Val group, there were 21 biomarkers, such as Bacteroides, Rikenellaceae_RC9_gut_group, Parabacteroides, Lactobacillus, etc. Plasma metabolomics analysis identified a total of 648 metabolites, and 167 important differential metabolites were screened among groups. KEGG pathway of tryptophan metabolism: M and bile secretion: OS had the highest significance of enrichment.ConclusionsSac/Val improves the renal function of DKD mice by inhibiting renal fibrosis. This drug can also regulate gut microbiota in DKD mice.

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Section: Discussionmentioning

confidence: 99%

Sacubitril/Valsartan contributes to improving the diabetic kidney disease and regulating the gut microbiota in mice

et al. 2022

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“…PGE2 initiated the transcription of genes that regulate the malate‐aspartate shuttle, including Got1. Another PUFA, Leukotriene‐B4 (LTB4) has also recently been linked to regulating macrophage metabolism [ 93 ]. Type 1 diabetic mice have increased levels of circulating LTB4.…”

Section: Role Of Exogenous Fatty Acids On Myeloid Cell Functionmentioning

confidence: 99%

Fa(c)t checking: How fatty acids shape metabolism and function of macrophages and dendritic cells

Almeida

Everts

2021

Eur J Immunol

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In recent years there have been major advances in our understanding of the role of free fatty acids (FAs) and their metabolism in shaping the functional properties of macrophages and DCs. This review presents the most recent insights into how cell intrinsic FA metabolism controls DC and macrophage function, as well as the current evidence of the importance of various exogenous FAs (such as polyunsaturated FAs and their oxidation products—prostaglandins, leukotrienes, and proresolving lipid mediators) in affecting DC and macrophage biology, by modulating their metabolic properties. Finally, we explore whether targeted modulation of FA metabolism of myeloid cells to steer their function could hold promise in therapeutic settings.

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“…20,21 Recent research showed that macrophages with enhanced glycolysis could develop into pro-inflammatory phenotype more easily in mice with hyperglycemia. 22 Therefore, whether CD226 molecules affects the glycolysis of macrophages has become a key point in our study.…”

Section: Introductionmentioning

confidence: 99%

CD226 deficiency attenuates cardiac early pathological remodeling and dysfunction via decreasing inflammatory macrophage proportion and macrophage glycolysis in STZ‐induced diabetic mice

et al. 2023

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Diabetic cardiomyopathy (DCM) is one of the main complications in type I diabetic patients. Activated macrophage is critical for directing the process of inflammation during the development of DCM. The present study focused on the roles of CD226 on macrophage function during the DCM progression. It has been found that the number of cardiac macrophages in the hearts of streptozocin (STZ)‐induced diabetes mice was significantly increased compared with that in non‐diabetes mice, and the expression level of CD226 on cardiac macrophages in STZ‐induced diabetes mice was higher than that in non‐diabetes mice. CD226 deficiency attenuated the diabetes‐induced cardiac dysfunction and decreased the proportion of CD86+F4/80+ macrophages in the diabetic hearts. Notably, adoptive transfer of Cd226−/−‐ bone marrow derived macrophages (BMDMs) alleviated diabetes‐induced cardiac dysfunction, which may be due to the attenuated migration capacity of Cd226−/−‐BMDM under high glucose stimulation. Furthermore, CD226 deficiency decreased the macrophage glycolysis accompanying by the downregulated hexokinase 2 (HK2) and lactate dehydrogenase A (LDH‐A) expression. Taken together, these findings revealed the pathogenic roles of CD226 played in the process of DCM and provided a basis for the treatment of DCM.

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Leukotriene-B4 modulates macrophage metabolism and fat loss in type 1 diabetic mice

Cited by 11 publications

References 36 publications

Sacubitril/Valsartan contributes to improving the diabetic kidney disease and regulating the gut microbiota in mice

Sacubitril/Valsartan contributes to improving the diabetic kidney disease and regulating the gut microbiota in mice

Fa(c)t checking: How fatty acids shape metabolism and function of macrophages and dendritic cells

CD226 deficiency attenuates cardiac early pathological remodeling and dysfunction via decreasing inflammatory macrophage proportion and macrophage glycolysis in STZ‐induced diabetic mice

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