Neuregulin, an Effector on Mitochondria Metabolism That Preserves Insulin Sensitivity

Gumà, Anna; Díaz-Sáez, Francisco; Camps, Marta; Zorzano, António

doi:10.3389/fphys.2020.00696

Cited by 20 publications

(14 citation statements)

References 135 publications

(181 reference statements)

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“…Decreased secretion of the adipokine neuregulin 4 (NRG-4) by BAT was recently described in 74 women with GDM (93). NRG-4 is a novel member of the neuregulin family which is predominantly secreted by BAT and has been suggested to play a vital role in regulating the mitochondrial oxidative machinery (94). Another recent study reported a direct inter-tissue communication between BAT and the placenta, via placental growth factor (PIGF), which manifests in increased UCP-1 expression and mitochondrial oxygen consumption in GDM BAT tissue when compared to normal pregnancy (95).…”

Section: Mitochondrial Dysfunctionmentioning

confidence: 99%

Mechanisms of Endothelial Dysfunction in Pre-eclampsia and Gestational Diabetes Mellitus: Windows Into Future Cardiometabolic Health?

et al. 2020

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Placental insufficiency and adipose tissue dysregulation are postulated to play key roles in the pathophysiology of both pre-eclampsia (PE) and gestational diabetes mellitus (GDM). A dysfunctional release of deleterious signaling motifs can offset an increase in circulating oxidative stressors, pro-inflammatory factors and various cytokines. It has been previously postulated that endothelial dysfunction, instigated by signaling from endocrine organs such as the placenta and adipose tissue, may be a key mediator of the vasculopathy that is evident in both adverse obstetric complications. These signaling pathways also have significant effects on long term maternal cardiometabolic health outcomes, specifically cardiovascular disease, hypertension, and type II diabetes. Recent studies have noted that both PE and GDM are strongly associated with lower maternal flow-mediated dilation, however the exact pathways which link endothelial dysfunction to clinical outcomes in these complications remains in question. The current diagnostic regimen for both PE and GDM lacks specificity and consistency in relation to clinical guidelines. Furthermore, current therapeutic options rely largely on clinical symptom control such as antihypertensives and insulin therapy, rather than that of early intervention or prophylaxis. A better understanding of the pathogenic origin of these obstetric complications will allow for more targeted therapeutic interventions. In this review we will explore the complex signaling relationship between the placenta and adipose tissue in PE and GDM and investigate how these intricate pathways affect maternal endothelial function and, hence, play a role in acute pathophysiology and the development of future chronic maternal health outcomes.

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Section: Mitochondrial Dysfunctionmentioning

confidence: 99%

Mechanisms of Endothelial Dysfunction in Pre-eclampsia and Gestational Diabetes Mellitus: Windows Into Future Cardiometabolic Health?

et al. 2020

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“…It has been recently reported that ω-3 fatty acids stimulate adipose tissue metabolism via activation of brown and beige adipose tissue, which play a crucial role in maintaining energy homeostasis through non-shivering thermogenesis [ 86 , 87 ]. Consequently, brown and beige adipose tissue release factors which mediate lipid metabolism and thermogenic activation [ 43 , 47 , 88 ]. One of these factors is NRG-4 [ 51 ], a member of the neuregulins family of ligands, which have been shown to regulate different aspects of glucose and lipid metabolism [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, NRG-4 levels positively correlated with ω-3 index, while as expected, lower AA/EPO ratio was associated with greater NRG-4 secretion. These findings indicate a possible role of NRG4 in the white adipose tissue browning, as well as possible increased lipid metabolism [ 46 , 47 , 51 ]. The benefits of NRG4 in response to ω-3 PUFA diet should be treated with caution, however, as no analyses of NRG-4 effect on brown adipocyte tissue thermogenesis were performed in this study.…”

Section: Discussionmentioning

confidence: 99%

“…Neuregulin-4 (NRG-4), a member of the neuregulin family (NRG1–NRG4), has recently been introduced as a novel adipocytokine with beneficial metabolic effect [ 43 , 44 , 45 , 46 ]. NRG-4 produces signals through the receptor tyrosine—protein kinases/human epidermal growth factor receptors (ErB/HER) and exerts pleiotropic effects that ultimately regulate energy metabolism and insulin sensitivity, as well as protects against oxidative stress [ 47 ]. It has been demonstrated that higher NRG-4 levels are associated with improvement in glucose homeostasis, maintenance of lipid balance, prevention of insulin resistance and weight gain [ 48 , 49 ].…”

Section: Introductionmentioning

confidence: 99%

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The Effect of Omega-3 Fatty Acid Supplementation on Serum Adipocytokines, Lipid Profile and Biochemical Markers of Inflammation in Recreational Runners

Żebrowska¹,

Hall

Stolecka‐Warzecha

et al. 2021

Nutrients

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Background: The study aimed to evaluate the effects of a 3-week ω-3 PUFA supplementation on serum adipocytokines (i.e., adiponectin, leptin), neuregulin-4 (NRG4) and erythrocyte omega-3 (ω-3) fatty acid content, as well as the blood antioxidant defense capacity in non-elite endurance runners. Methods: Twenty-four runners were randomized into two groups: the supplemented group, who received omega free fatty acids extract containing 142 mg of EPA, 267 mg of DHA, 12 mg of vitamin E and 5 µg of vitamin D, each administrated at a dose of six capsules twice a day for three weeks, or the placebo group. Venous blood samples were withdrawn at the start and at the end of the study protocols to estimate serum biochemical variables. Results: A significantly higher ω-3 index and lower AA/EPA ratio was observed after ω-3 PUFA compared to pre-supplementation levels (p < 0.001 and p < 0.001, respectively). An increase in baseline adiponectin and NRG4 levels, as well as a decrease of leptin concentration and lipid profile improvement, were observed in subjects after a ω-3 PUFA diet. The increased ω-3 index had a significant effect on TNFα levels and a serum marker of antioxidant defense. Conclusions: The ω-3 PUFA extract with added vitamin E and D supplementation may have a positive effect on the function of the adipocyte tissue, as well as the ability to prevent cardiovascular complications in athletes.

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“…Another gene was NRG1 that is a member of the epidermal growth factor (EGF) family and binds to a class of receptor tyrosine kinases, ErbB receptors. NRG1 is implicated in the differentiation, proliferation, and survival of cells [67]. NRGs are local growth factors, while NRG1 has been found in plasma as a diagnostic marker for various maladies such as chronic heart failure (67) and acute lung injury associated with in ammation [68].…”

Section: Discussionmentioning

confidence: 99%

Identification of Shared Gene Signatures in Different Stages of Non-Alcoholic Fatty Liver Disease Using Integrated Microarray Dataset

Gh¹,

Arabfard²

2020

Preprint

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Purpose: Non-alcoholic fatty liver disease (NAFLD) is the most preventable type of chronic liver disease worldwide and a risk factor for developing cirrhosis or hepatocellular carcinoma (HCC) if untreated. Although experts have performed lots of efforts to find the underlying mechanisms of NAFLD, it remains a challenge to recognize them. The aim of this study is to distinguish common gene signature and pathways in the human liver during NAFLD progression through the systems biology method.Methods: In this study, the three microarray datasets, GSE48452, GSE63067 and GSE89632, were selected from the NCBI GEO database to explore differentially expressed genes (DEGs) among healthy controls, simple steatosis and non-alcoholic steatohepatitis (NASH) patients. Furthermore, protein-protein interaction (PPI) networks and pathway enrichment analysis were used to detect common genes and biological pathways in different stages of NAFLD.Results: The current study was included 47 healthy subjects, 36 patients with simple steatosis and 46 NASH patients. Common high degree genes among all three sets were CHI3L1, GFBP2, NRG1, PEG10 and FADS2. The top five genes in the hepatic PPI networks of three datasets were STAT3, JUN, CANX, FN1 and MYC. Signal transduction, immune response, and anti-apoptosis were the most important biological pathways between healthy vs. NASH, while cell communication, signal transduction and immune response were three top biological pathways between healthy vs. simple steatosis. Also, the most eminent biological pathways between NASH vs. simple steatosis were metabolism and energy pathways. Conclusion: The present study represented the unique and shared key genes and pathways between different stages of NAFLD, which may facilitate the understanding of the NAFLD mechanism and identify potential therapeutic targets in this disease.

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Neuregulin, an Effector on Mitochondria Metabolism That Preserves Insulin Sensitivity

Cited by 20 publications

References 135 publications

Mechanisms of Endothelial Dysfunction in Pre-eclampsia and Gestational Diabetes Mellitus: Windows Into Future Cardiometabolic Health?

Mechanisms of Endothelial Dysfunction in Pre-eclampsia and Gestational Diabetes Mellitus: Windows Into Future Cardiometabolic Health?

The Effect of Omega-3 Fatty Acid Supplementation on Serum Adipocytokines, Lipid Profile and Biochemical Markers of Inflammation in Recreational Runners

Identification of Shared Gene Signatures in Different Stages of Non-Alcoholic Fatty Liver Disease Using Integrated Microarray Dataset

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