WITHDRAWN: Glutaminolysis-induced mTORC1 activation drives non-alcoholic steatohepatitis progression

Cabré, Noemí; Luciano-Mateo, Fedra; Chapski, Douglas J.; Baiges-Gayà, Gerard; Fernández-Arroyo, Salvador; Hernández-Aguilera, Anna; Castañé, Helena; Rodríguez-Tomàs, Elisabet; París, Marta; Sabench, Fàtima; Castillo, Daniel Del; Bas, Josep Maria del; Tomé, Mercedes; Bodineau, Clément; Sola-García, Alejandro; Martín-Montalvo, Aléjandro; Durán, Raúl V.; Vondriska, Thomas M.; Rosa‐Garrido, Manuel; Camps, Jordi; Menéndez, Javier A.; Joven, Jorge

doi:10.1016/j.jhep.2021.04.037

Cited by 4 publications

(3 citation statements)

References 37 publications

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“…Bariatric surgery is a common treatment in patients with morbid obesity, and offers a unique opportunity to investigate the metabolic derangements associated with NAFLD, especially when comparing the data obtained from a peri-surgical liver biopsy with those obtained from a percutaneous biopsy obtained post-surgery [123]. Recent results from our research group [124][125][126][127] showed that, one year post-bariatric surgery (laparoscopic sleeve gastrectomy), the prevalence of diabetes, hypertension, and NAFLD significantly decreased in patients with pre-surgery morbid obesity; the improvements in hepatic histology and function were greater in patients with NASH. We found significant pre-surgery differences in liver markers of oxidative stress and inflammation (including CCL2 and PON1) between patients with, and those without, NASH, which suggested a regulatory role of mitogen-activated protein kinases.…”

Section: Obesity and The Associated Liver Diseasementioning

confidence: 99%

On the Role of Paraoxonase-1 and Chemokine Ligand 2 (C-C motif) in Metabolic Alterations Linked to Inflammation and Disease. A 2021 Update

et al. 2021

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Infectious and many non-infectious diseases share common molecular mechanisms. Among them, oxidative stress and the subsequent inflammatory reaction are of particular note. Metabolic disorders induced by external agents, be they bacterial or viral pathogens, excessive calorie intake, poor-quality nutrients, or environmental factors produce an imbalance between the production of free radicals and endogenous antioxidant systems; the consequence being the oxidation of lipids, proteins, and nucleic acids. Oxidation and inflammation are closely related, and whether oxidative stress and inflammation represent the causes or consequences of cellular pathology, both produce metabolic alterations that influence the pathogenesis of the disease. In this review, we highlight two key molecules in the regulation of these processes: Paraoxonase-1 (PON1) and chemokine (C-C motif) ligand 2 (CCL2). PON1 is an enzyme bound to high-density lipoproteins. It breaks down lipid peroxides in lipoproteins and cells, participates in the protection conferred by HDL against different infectious agents, and is considered part of the innate immune system. With PON1 deficiency, CCL2 production increases, inducing migration and infiltration of immune cells in target tissues and disturbing normal metabolic function. This disruption involves pathways controlling cellular homeostasis as well as metabolically-driven chronic inflammatory states. Hence, an understanding of these relationships would help improve treatments and, as well, identify new therapeutic targets.

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Section: Obesity and The Associated Liver Diseasementioning

confidence: 99%

On the Role of Paraoxonase-1 and Chemokine Ligand 2 (C-C motif) in Metabolic Alterations Linked to Inflammation and Disease. A 2021 Update

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…Bariatric surgery is a common treatment in patients with morbid obesity, and offers a unique opportunity to investigate the metabolic derangements associated with NAFLD, especially when comparing the data obtained from a peri-surgical liver biopsy with those obtained from a percutaneous biopsy obtained post-surgery [123]. Recent results from our research group [124][125][126][127] showed that, one year post-bariatric surgery (laparoscopic sleeve gastrectomy), the prevalence of diabetes, hypertension and NAFLD significantly decreased in patients with pre-surgery morbid obesity; the improvements in hepatic histology and function were greater in patients with NASH. We found significant pre-surgery differences in liver markers of oxidative stress and inflammation (including CCL2 and PON1) between patients with, and those without, NASH; which suggested a regulatory role of mitogen-activated protein kinases.…”

Section: Obesity and The Associated Liver Diseasementioning

confidence: 99%

On the Role of Paraoxonase-1, Chemokine (C-C motif) Ligand 2 and Metabolism in Oxidation, Inflammation and Disease. A 2021 Update

Camps¹,

Castañé²,

Rodríguez-Tomàs³

et al. 2021

Preprint

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Infectious as well as most non-infectious diseases share certain common molecular mechanisms. Among them, oxidative stress and the subsequent inflammatory reaction are of particular note. Metabolic disorders induced by external agents, be they bacterial or viral pathogens, excessive calorie intake, poor-quality nutrients, or environmental factors, produce an imbalance between the production of free radicals and endogenous antioxidant systems; the consequence being the oxidation of lipids, proteins and nucleic acids. Oxidation and inflammation are closely related, and whether oxidative stress and inflammation represent the causes or consequences of cellular pathology, they produce metabolic alterations that influence the pathogenesis of the disease. In this review we highlight two key molecules in the regulation of these processes: Paraoxonase-1 (PON1) and chemokine (C-C motif) ligand 2 (CCL2). PON1 is an enzyme bound to high-density lipoproteins. It breaks down lipid peroxides in lipoproteins and cells, participates in the protection conferred by HDL against different infectious agents, and is considered part of the innate immune system. With PON1 deficiency, CCL2 production increases, which induces migration and infiltration of immune cells in target tissues, and is involved in disturbing normal metabolic function. This disruption involves pathways controlling cellular homeostasis as well as metabolically-driven chronic inflammatory states. Hence, an understanding of these relationships would help improve treatments and, as well, identify new therapeutic targets.

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“…DNA methylation is an epigenetic mechanism which regulates gene expression through chromatin structure changes. Equally influenced by environmental factors, genetic predisposition and the individual lifestyle, the level of gene methylation is dynamically changing in setting up stable gene expression profiles to adapt to the process of obesity ( Samblas et al, 2019 ; Cabre et al, 2021 ). A previous study analyzing the whole genome methylation and gene expression in non-diseased breast showed that obesity is connected with the genome-wide methylation changes in human tissue ( Hair et al, 2015a ).…”

Section: Introductionmentioning

confidence: 99%

Integrative Analysis of Gene Expression and DNA Methylation Depicting the Impact of Obesity on Breast Cancer

Xiong

Yang

et al. 2022

Front. Cell Dev. Biol.

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Obesity has been reported to be a risk factor for breast cancer, but how obesity affects breast cancer (BC) remains unclear. Although body mass index (BMI) is the most commonly used reference for obesity, it is insufficient to evaluate the obesity-related pathophysiological changes in breast tissue. The purpose of this study is to establish a DNA-methylation-based biomarker for BMI (DM-BMI) and explore the connection between obesity and BC. Using DNA methylation data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), we developed DM-BMI to evaluate the degree of obesity in breast tissues. In tissues from non-BC and BC population, the DM-BMI model exhibited high accuracy in BMI prediction. In BC tissues, DM-BMI correlated with increased adipose tissue content and BC tissues with increased DM-BMI exhibited higher expression of pro-inflammatory adipokines. Next, we identified the gene expression profile relating to DM-BMI. Using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, we observed that the DM-BMI-related genes were mostly involved in the process of cancer immunity. DM-BMI is positively correlated with T cell infiltration in BC tissues. Furthermore, we observed that DM-BMI was positively correlated with immune checkpoint inhibitors (ICI) response markers in BC. Collectively, we developed a new biomarker for obesity and discovered that BC tissues from obese individuals exhibit an increased degree of immune cell infiltration, indicating that obese BC patients might be the potential beneficiaries for ICI treatment.

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WITHDRAWN: Glutaminolysis-induced mTORC1 activation drives non-alcoholic steatohepatitis progression

Cited by 4 publications

References 37 publications

On the Role of Paraoxonase-1 and Chemokine Ligand 2 (C-C motif) in Metabolic Alterations Linked to Inflammation and Disease. A 2021 Update

On the Role of Paraoxonase-1 and Chemokine Ligand 2 (C-C motif) in Metabolic Alterations Linked to Inflammation and Disease. A 2021 Update

On the Role of Paraoxonase-1, Chemokine (C-C motif) Ligand 2 and Metabolism in Oxidation, Inflammation and Disease. A 2021 Update

Integrative Analysis of Gene Expression and DNA Methylation Depicting the Impact of Obesity on Breast Cancer

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