Maresin1 Alleviates Metabolic Dysfunction in Septic Mice: A <sup>1</sup>H NMR-Based Metabolomics Analysis

Yu, Hao; Zheng, Hong; Wang, Ruo-Han; Li, Hui; Yang, Lili; Bhandari, Sneha; Liu, Yongjian; Han, Jun; Smith, Fang Gao; Gao, Hongchang

doi:10.1155/2019/2309175

Cited by 23 publications

(25 citation statements)

References 40 publications

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“…Fibrillar Aβ in plaques has been shown to stimulate microglia to secret pro-inflammatory cytokines, including IL-1, IL-6 and TNF-α (Murphy et al, 1998; Combs et al, 2001). There are reports indicating that MaR1 reduces TNF-α and IL-6 secretion in peripheral inflammation disease models such as septic mouse model (Hao et al, 2019), and human periodontal ligament cell model. In line with previous reports, we found MaR1 could reverse the increased levels of TNF-α and IL-6 induced by Aβ 42 in the central nervous system.…”

Section: Discussionmentioning

confidence: 99%

Maresin 1 Improves Cognitive Decline and Ameliorates Inflammation in a Mouse Model of Alzheimer’s Disease

Yin

Wang

et al. 2019

Front. Cell. Neurosci.

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Alzheimer’s disease (AD) is one of the most common neurodegenerative disease. Accumulating evidences suggest an active role of inflammation in the pathogenesis of AD. Inflammation resolution is an active process that terminates inflammation and facilitates the restoration of inflamed tissue to homeostasis. Resolution of inflammation has been shown to be conducted by a group of specialized pro-resolving lipid mediators (SPMs) including lipoxins, resolvins, protectins, and maresins (MaRs). Recent studies have demonstrated that failure of inflammation resolution can lead to chronic inflammation and, hence, contribute to AD progression. We have previously shown that MaR1 can improve neuronal survival and increase microglial phagocytosis of Aβ. However, the effects of MaR1 on animal models of AD have not been reported. In this study, we aim to investigate the effects of MaR1 on behavioral deficits and pathological changes in a mouse model of AD. Mice received bilateral injections of Aβ42 protein into the hippocampus, followed by administration of MaR1 by intra-cerebroventricular injection. The behavioral changes in the mice were analyzed using Morris water maze. Immunohistochemistry, Fluoro-Jade B (FJB) staining, cytometric beads array (CBA), and western blot analysis were used to demonstrate molecular changes in the mice hippocampus and cortex. Our results showed that MaR1 treatment significantly improved the cognitive decline, attenuated microglia and astrocyte activation. In addition, we found that MaR1 decreased the pro-inflammatory cytokines TNF-α, IL-6, and MCP-1 production induced by Aβ42 and increased the anti-inflammatory cytokines IL-2, IL-10 secretion with or without Aβ42 stimulation. Moreover, western blot results showed that MaR1 up-regulated the levels of proteins related to survival pathway including PI3K/AKT, ERK and down-regulated the levels of proteins associated with inflammation, autophagy, and apoptosis pathways such as p38, mTOR and caspase 3. To conclude, MaR1 improved the cognitive decline, ameliorated pro-inflammatory glia cells activation via improving survival, enhancing autophagy, inhibiting inflammation and apoptosis pathways. In conclusion, this study shows that inflammation resolution may be a potential therapeutic target for AD.

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Section: Discussionmentioning

confidence: 99%

Maresin 1 Improves Cognitive Decline and Ameliorates Inflammation in a Mouse Model of Alzheimer’s Disease

Yin

Wang

et al. 2019

Front. Cell. Neurosci.

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“…Previous study [21] reported that MaR1 could affect metabolic pathway in CLP-induced septic mice. They found that the levels of LDL/VLDL, glucose, isoleucine, and acetone levels were reduced in serum of CLP-induced septic mice.…”

Section: Discussionmentioning

confidence: 93%

“…Previous preclinical studies have reported that mice treated with MaR1 showed altered serum LDL/VLDL levels, and it also exerts potent anti-inflammatory and proresolution activities under both physiologic and disease conditions [9,21,22]. Thus, we assessed lipid-metabolic parameters and inflammatory factors in our subjects.…”

Section: Clinical and Laboratory Characteristics Of Studymentioning

confidence: 99%

Decreased Plasma Maresin 1 Concentration Is Associated with Diabetic Foot Ulcer

Tian

Huang

et al. 2020

Mediators of Inflammation

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Aims. To assess the maresin 1 (MaR1) contents in type 2 diabetic patients with or without diabetic foot ulcer and to analyze the association of MaR1 concentrations with several metabolism-related parameters. Methods. Plasma MaR1 concentrations were analyzed in 96 subjects with normal glucose tolerant (NC, n=43), type 2 diabetes (T2DM, n=40), or diabetic foot ulcer (DFU, n=13). The intravenous glucose tolerance test (IVGTT) and biochemical parameters were measured in all participants. Results. Plasma MaR1 concentrations were significant decreased in type 2 diabetes patient with or without DFU compared with NC (both P<0.001) and were lowest in DFU patients among these 3 groups. (DFU vs. T2DM, P<0.05). Plasma MaR1 concentrations were negatively correlated with BMI, waist circumference (Wc), waist hip ratio (WHR), systolic blood pressure (SBP), diastolic blood pressure (DBP), LDL-c, FPG, 2hPG, HbA1c, and homeostasis model assessment for insulin resistance (HOMA-IR) (all P<0.05) and were positively correlated with HDL-c, acute insulin response (AIR), area under the curve of the first-phase (0-10 min) insulin secretion (AUC), and homeostasis model assessment for beta-cell function (HOMA-β) (all P<0.05). After adjusting for age and sex, Wc, WHR, TG, FPG, 2hPG, HbA1c, HOMA-IR, AIR, AUC, and HOMA-β remain statistically significant (all P<0.05). Conclusions. Plasma MaR1 concentration were decreased in T2DM with or without DFUs and were the lowest in DFU patients. The decreased plasma MaR1 strongly associated with obesity, impaired glucose and lipid metabolism, reduced first-phase of glucose-stimulated insulin secretion, and enhanced insulin resistance.

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“…For autophagy observation with electron microscope, lung tissues were fixed with glutaraldehyde. Resin-embedded lung tissue sections were cut at 50–70 nm thickness, stained with uranyl acetate and lead acetate, and then detected under a transmission electron microscope as previously described ( 24 ).…”

Section: Methodsmentioning

confidence: 99%

MicroRNA-34a Inhibition Alleviates Lung Injury in Cecal Ligation and Puncture Induced Septic Mice

Chen

Ding

et al. 2020

Front. Immunol.

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Sepsis is the leading cause of death in intensive care units. MicroRNA-34a (miR-34a) is involved in sepsis progression, while its underlying mechanisms on sepsis-induced lung injury remain obscure. Oxidative stress, pyroptosis, and inhibition of autophagy can result in organ injury. MiR-34a has been reported to regulate oxidative stress and autophagy via inhibiting silent information regulator T1 (SIRT1) and autophagy gene 4B (ATG4B) signaling. This study aimed at identifying the function of miR-34a in oxidative stress, inflammation, pyroptosis, and autophagy in sepsis-induced lung injury. Male 8-week-old C57BL/6 mice were subjected to cecal ligation and puncture and treated with miR-34a antagomir/agomir. Survival ( n = 10), histopathological changes ( n = 6), and lung wet-to-dry ratio ( n = 6) were recorded and assayed. Other detection ( n = 6) was performed to investigate the level of oxidative stress, inflammation, pyroptosis, and autophagy in lung tissues. Results showed that miR-34a down-regulation ameliorated lung injury in septic mice as reflected by decreased lung injury scores (decrease from 3.00 ± 0.32 to 2.00 ± 0.32) and wet-to-dry ratio (0.36-fold decrease). MiR-34a down-regulation also decreased reactive oxygen species accumulation (0.36-fold decrease), and promoted superoxide dismutase activity and the expression of SIRT1 (1.24-fold increase), heme oxygenase-1 and nuclear factor erythroid 2 like 2 to inhibit oxidative stress in septic mice. Moreover, miR-34a down-regulation suppressed inflammatory response and pyroptosis in septic mice, as evidenced by decreased level of pro-inflammatory factors including tumor necrosis factor α, interleukin-6 (IL-6), IL-1β, and IL-18, activity of caspase-1 (0.51-fold decrease) and expression of nucleotide-binding domain and leucine-rich repeat protein-3 (0.48-fold decrease), apoptosis-associated speck-like protein containing a CARD, cleaved-caspase-1, and cleaved-gasdermin D (0.36-fold decrease), and increased level of anti-inflammatory factors IL-10. MiR-34a down-regulation also enhanced autophagy in septic mice as evidenced by more autolysosomes and elevated expressions of ATG4B (0.90-fold increase), beclin1, ATG9, and LC3 II/I. Among these experiments, miR-34a up-regulation showed opposite effects on oxidative stress, inflammatory response, pyroptosis, and autophagy in septic mice. Additionally, miR-34a could bind to the 3′-untranslated region of SIRT1 and ATG4B. In conclusion, our findings demonstrated that miR-34a was implicated in oxidative stress, inflammation, pyroptosis, and autophagy in the development of sepsis. MiR-34a inhibition had a potential to alleviate sepsis-induced lung injury.

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Maresin1 Alleviates Metabolic Dysfunction in Septic Mice: A ¹H NMR-Based Metabolomics Analysis

Cited by 23 publications

References 40 publications

Maresin 1 Improves Cognitive Decline and Ameliorates Inflammation in a Mouse Model of Alzheimer’s Disease

Maresin 1 Improves Cognitive Decline and Ameliorates Inflammation in a Mouse Model of Alzheimer’s Disease

Decreased Plasma Maresin 1 Concentration Is Associated with Diabetic Foot Ulcer

MicroRNA-34a Inhibition Alleviates Lung Injury in Cecal Ligation and Puncture Induced Septic Mice

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Maresin1 Alleviates Metabolic Dysfunction in Septic Mice: A 1H NMR-Based Metabolomics Analysis

Cited by 23 publications

References 40 publications

Maresin 1 Improves Cognitive Decline and Ameliorates Inflammation in a Mouse Model of Alzheimer’s Disease

Maresin 1 Improves Cognitive Decline and Ameliorates Inflammation in a Mouse Model of Alzheimer’s Disease

Decreased Plasma Maresin 1 Concentration Is Associated with Diabetic Foot Ulcer

MicroRNA-34a Inhibition Alleviates Lung Injury in Cecal Ligation and Puncture Induced Septic Mice

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Maresin1 Alleviates Metabolic Dysfunction in Septic Mice: A ¹H NMR-Based Metabolomics Analysis