Oleic acid increases the transcriptional activity of FoxO1 by promoting its nuclear translocation and β-catenin binding in pancreatic β-cells

Publication date: Available online 27 June 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Magdalena Jazurek-Ciesiolka, Justyna Janikiewicz, Pawel Dobrzyn, Anna Dziewulska, Kamil Kozinski, Agnieszka DobrzynAbstractIn the setting of metabolic overload, chronic elevations of free fatty acids in blood and tissues are associated with pancreatic β-cell lipotoxicity and failure. Ultimately, obesity combined with insulin resistance increases the dysfunctional demand of β-cells and contributes to the development of type 2 diabetes. Forkhead box O1 (FoxO1) is a potent transcriptional regulator of pancreatic β-cell function and tolerance to lipid stress. The present study examined the effects of stearoyl-CoA desaturase 1 (SCD1)-metabolized precursors and products, notably oleic acid, on the compensatory capacity of β-cells and their relationship with regulation of the FoxO1 and Wnt pathways. The trioleate-induced compromise of insulin sensitivity blunted the compensatory response of pancreatic β-cells in primary rat islets. These events were associated with increases in the nuclear accumulation and transcriptional activity of FoxO1. Such effects were also observed in INS-1E cells that were subjected to oleate treatment. The overexpression of human SCD1 that was accompanied by endogenously generated oleic acid also led to an increase in the nuclear abundance of FoxO1. The mechanism of the oleate-mediated subcellular localiz...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - Category: Molecular Biology Source Type: research

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ConclusionsWe conclude that the β-adrenergic pathway is still functionally intact upon the inhibition of PI3Kα, showing that the activation of downstream insulin effectors is not required for the acute effects of β-adrenoceptor agonists on glucose homeostasis or thermogenesis.Graphical abstract
Source: Molecular Metabolism - Category: Endocrinology Source Type: research
ConclusionsWe conclude that the β-adrenergic pathway is still functionally intact upon the inhibition of PI3Kα, showing that the activation of downstream insulin effectors is not required for the acute effects of β-adrenoceptor agonists on glucose homeostasis or thermogenesis.
Source: Molecular Metabolism - Category: Endocrinology Source Type: research
Albiflorin (AF) is a small molecule (MW 481) isolated from Paeoniae radix, a plant used as a remedy for various conditions with pathogenesis shared by metabolic diseases. Reported here is our characterization of its therapeutic profiles in three mouse models with distinctive pathological features of metabolic syndrome (MetS). Our results firstly showed that AF alleviated high fat (HF) induced obesity and associated glucose intolerance, suggesting its therapeutic efficacy for MetS. In the type 2 diabetes (T2D) model induced by a combination of HF and low doses of streptozotocin, AF lowered hyperglycaemia and improved insuli...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
We examined human lung tissue from COPD patients and normal control subjects, and found a substantial increase in p16-expressing alveolar cells in COPD patients. Using a transgenic mouse deficient for p16, we demonstrated that lungs of mice lacking p16 were structurally and functionally resistant to CS-induced emphysema due to activation of IGF1/Akt regenerative and protective signaling. Fat Tissue Surrounds Skeletal Muscle to Accelerate Atrophy in Aging and Obesity https://www.fightaging.org/archives/2019/09/fat-tissue-surrounds-skeletal-muscle-to-accelerate-atrophy-in-aging-and-obesity/ Researchers her...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
by Teresa Buenaventura, Stavroula Bitsi, William E. Laughlin, Thomas Burgoyne, Zekun Lyu, Affiong I. Oqua, Hannah Norman, Emma R. McGlone, Andrey S. Klymchenko, Ivan R. Corr êa Jr, Abigail Walker, Asuka Inoue, Aylin Hanyaloglu, Jak Grimes, Zsombor Koszegi, Davide Calebiro, Guy A. Rutter, Stephen R. Bloom, Ben Jones, Alejandra Tomas The glucagon-like peptide-1 receptor (GLP-1R), a key pharmacological target in type 2 diabetes (T2D) and obesity, undergoes rapid endocytosis after stimulation by endogenous and therapeutic agonists. We have previously highlighted the relevance of this process in fine-tuning GLP-1R respon...
Source: PLoS Biology: Archived Table of Contents - Category: Biology Authors: Source Type: research
Alessandro Poggi1*, Roberto Benelli2, Roberta Venè1, Delfina Costa1, Nicoletta Ferrari1, Francesca Tosetti1 and Maria Raffaella Zocchi3 1Molecular Oncology and Angiogenesis Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy 2Immunology Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy 3Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy It is well established that natural killer (NK) cells are involved in both innate and adaptive immunity. Indeed, they can recognize molecules induced at the cell surface by stress signals ...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Conclusion Taken together, evidence from animal and human studies demonstrates that the brain detects levels of circulating nutrients and hormones and consequently organizes an outward response that contributes to the regulation of whole-body glucose homeostasis. However, there are major knowledge gaps about the exact nature of this response and its relative importance compared to peripheral processes. As we have seen, animal studies have provided an anatomical map of CNS glucose regulation and have identified important neurons and neural circuits involved. Additionally, the CNS sensing of key nutrients and hormones has b...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
Ali Mahzari1, Songpei Li1, Xiu Zhou1,2, Dongli Li2, Sherouk Fouda1, Majid Alhomrani1, Wala Alzahrani1, Stephen R. Robinson1 and Ji-Ming Ye1,2* 1Lipid Biology and Metabolic Disease Laboratory, School of Health and Biomedical Sciences, RMIT University, Melbourne, VIC, Australia 2School of Biotechnology and Health Sciences, Wuyi University, Jiangmen, China The present study investigated the effects of matrine on non-alcoholic steatohepatitis (NASH) in mice induced by a methionine choline-deficient (MCD) diet and the mechanism involved. The study was performed in C57B/6J mice fed a MCD diet for 6 weeks to induce NAS...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Conclusion The periconceptional environment and lifestyle factors modify sperm epigenome. This alteration might be maintained in the zygote and throughout development, thereby leading to the inheritance of newly acquired pathologies. The role of sperm miRNA, not only as innovative markers of fertility issues but also as vectors involved in the inheritance of paternal diseases, appears to be crucial. Overweight and obesity seem to alter sperm miRNA profile, thereby leading to transmission of different miRNA profiles in zygote, with consequences on embryo development. In long term, metabolic disorders have been described in...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
Conclusions In conclusion, articles in this Research Topic made a very significant contribution to our understanding of the role played by environmental factors, dysbiotic conditions, and infections in triggering diseases. Since this is a rapidly expanding area of research, many other factors contributing to the onset of these diseases are not covered here. We are confident, however, that further studies will expand the list as well as bring a better understanding of mechanisms involved in the onset of autoimmune and autoinflammatory diseases. Author Contributions All authors listed have made a substantial, direct and i...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
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