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Total 281 results found since Jan 2013.

Modulation of Sirt1/NF- κB interaction of evogliptin attributed to inhibition of vascular inflammatory response leading to attenuation of atherosclerotic plaque formation.
This study demonstrates that the protective effect of evogliptin on atherosclerotic progression via inhibition of vascular inflammation. The findings imply that evogliptin has potential for anti-atherosclerosis therapy that targets arterial inflammation. PMID: 31421133 [PubMed - as supplied by publisher]
Source: Biochemical Pharmacology - August 13, 2019 Category: Drugs & Pharmacology Authors: Anh Nguyen P, Soon Won J, Khalilur Rahman M, Ju Bae E, Kyung Cho M Tags: Biochem Pharmacol Source Type: research

Hypoxia exacerbates non-alcoholic fatty liver disease via HIF-2 α/PPARα pathway.
This study aimed to investigate whether hypoxia can affect non-alcoholic fatty liver disease (NAFLD) progression and the associated mechanisms, specifically regarding the HIF-2α / PPARα pathway in vitro and vivo. Recent studies have reported that, compared with HIF-1α, HIF-2α has different effects on lipid metabolism. We propose hypoxia may exacerbate NAFLD by the HIF-2α upregulation-induced suppression of PPARα in the liver. To verify this hypothesis, a steatotic human hepatocyte (L02) cell line treated with free fatty acids and a mouse model of NAFLD fed a high-fat diet were used. Steatotic hepatocytes were treated...
Source: American Journal of Physiology. Endocrinology and Metabolism - August 19, 2019 Category: Physiology Authors: Chen J, Chen J, Fu H, Li Y, Wang L, Luo S, Lu H Tags: Am J Physiol Endocrinol Metab Source Type: research

FcgRIII Deficiency and FcgRIIb Defeciency Promote Renal Injury in Diabetic Mice.
Abstract The immune system is involved in the development of diabetes complications and IgG Fc gamma receptors (FcgRs) are key immune receptors responsible for the effective control of both humoral and innate immunity. We investigated the effects of members of the FcgR superfamily into both the streptozotocin plus high fat-induced type 2 diabetes and high fat diet (HFD) models. FcgRIII-/- diabetic mice and FcgRIIb-/- diabetic mice had elevated levels of serum creatinine compared with wildtype (WT) diabetic mice. Renal histology of diabetic FcgRIII knockout and FcgRIIb knockout mice showed mesangial expansion and G...
Source: Biomed Res - September 21, 2019 Category: Research Authors: Zhang R, Wang T, Yin Q, Zhang J, Li L, Guo R, Han Q, Li H, Wang Y, Wang J, Gurung P, Lu Y, Cheng J, Bai L, Zhang J, Liu F Tags: Biomed Res Int Source Type: research

Novel Interaction of Antioxidant-1 with TRAF4: Role in Inflammatory Responses in Endothelial Cells.
We reported that in proinflammatory cytokine TNFa-stimulated endothelial cells (ECs), cytosolic Cu chaperone Atox1 functions as a Cu-dependent transcription factor for NOX organizer p47phox, thereby increasing ROS-dependent inflammatory gene expression. However, the role and mechanism of Atox1 nuclear translocation in inflamed ECs remain unclear. Using enface staining and nuclear fractionation, here we show that Atox1 was localized in the nucleus in inflamed aortas from ApoE-/- mice with Angiotensin II infusion on a high fat diet, while it was found in cytosol in those from control mice. In cultured human ECs, TNFα stimul...
Source: Am J Physiol Cell Ph... - September 24, 2019 Category: Cytology Authors: Das A, Sudhahar V, Ushio-Fukai M, Fukai T Tags: Am J Physiol Cell Physiol Source Type: research

Allyl isothiocyanate ameliorates lipid accumulation and inflammation in nonalcoholic fatty liver disease via the Sirt1/AMPK and NF- κB signaling pathways.
CONCLUSION: AITC significantly ameliorates hepatic steatosis and inflammation by activating the Sirt1/AMPK pathway and inhibiting the NF-κB pathway. Therefore, AITC is a potential therapeutic agent for NAFLD. PMID: 31558861 [PubMed - in process]
Source: World Journal of Gastroenterology : WJG - September 13, 2019 Category: Gastroenterology Authors: Li CX, Gao JG, Wan XY, Chen Y, Xu CF, Feng ZM, Zeng H, Lin YM, Ma H, Xu P, Yu CH, Li YM Tags: World J Gastroenterol Source Type: research

High mobility group box-1 release from H2O2-injured hepatocytes due to sirt1 functional inhibition.
CONCLUSION: The functional inhibition between Parp1 and Sirt1 leads to HMGB1 hyperacetylation, which leads to its translocation from the nucleus to the cytoplasm and finally outside the cell. PMID: 31576091 [PubMed - in process]
Source: World Journal of Gastroenterology : WJG - September 27, 2019 Category: Gastroenterology Authors: Ye TJ, Lu YL, Yan XF, Hu XD, Wang XL Tags: World J Gastroenterol Source Type: research

Deficiency of the autophagy gene ATG16L1 induces insulin resistance through KLHL9/KLHL13/CUL3-mediated IRS1 degradation Protein Synthesis and Degradation
We examined mouse embryonic fibroblasts lacking Atg16l1 (ATG16L1 KO mouse embryonic fibroblasts (MEFs)), an essential autophagy gene, and observed deficient insulin and insulin-like growth factor-1 signaling. ATG16L1 KO MEFs displayed reduced protein content of insulin receptor substrate-1 (IRS1), pivotal to insulin signaling, whereas IRS1myc overexpression recovered downstream insulin signaling. Endogenous IRS1 protein content and insulin signaling were restored in ATG16L1 KO mouse embryonic fibroblasts (MEF) upon proteasome inhibition. Through proximity-dependent biotin identification (BioID) and co-immunoprecipitation, ...
Source: Journal of Biological Chemistry - October 31, 2019 Category: Chemistry Authors: Scott Frendo-Cumbo, Javier R. Jaldin-Fincati, Etienne Coyaud, Estelle M. N. Laurent, Logan K. Townsend, Joel M. J. Tan, Ramnik J. Xavier, Nicolas J. Pillon, Brian Raught, David C. Wright, John Hunter Brumell, Amira Klip Tags: Signal Transduction Source Type: research

DEL-1 ameliorates high-fat diet-induced insulin resistance in mouse skeletal muscle through SIRT1/SERCA2-mediated ER stress suppression.
Abstract Inflammation and endoplasmic reticulum (ER) stress are associated with the development of insulin resistance and diabetes. Developmental endothelial locus-1 (DEL-1) enhances efferocytosis by macrophage and suppresses inflammatory response. However, effects of DEL-1 on ER stress-mediated insulin resistance in skeletal muscle remain unclear. Here, DEL-1 treatment augmented SIRT1 expression in C2C12 myocytes, thereby increasing SERCA2 expression in a dose-dependent fashion, and attenuated ER stress and insulin resistance under palmitate treatment condition. SIRT1/SERCA2 knockdown abrogated effects of DEL-1 o...
Source: Biochemical Pharmacology - November 24, 2019 Category: Drugs & Pharmacology Authors: Long Sun J, Park J, Lee T, Hoon Jeong J, Woo Jung T Tags: Biochem Pharmacol Source Type: research

Identification of a hormone response element that mediates suppression of APOF by LXR and PPARα agonists
Publication date: Available online 6 December 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of LipidsAuthor(s): Yan Liu, Lahoucine Izem, Richard E. MortonAbstractApolipoprotein F (ApoF) regulates cholesteryl ester transfer protein activity. We previously observed that hepatic APOF mRNA levels are decreased by high fat, cholesterol-enriched diets. Here we show in human liver C3A cells that APOF mRNA levels are reduced by agonists of LXR and PPARα nuclear receptors. This negative regulation requires co-incubation with the RXR agonist, retinoic acid. Bioinformatic analysis of the ~2 kb sequen...
Source: Biochimica et Biophysica Acta (BBA) Molecular and Cell Biology of Lipids - December 7, 2019 Category: Lipidology Source Type: research

Role of ATP-binding cassette transporter A1 in suppressing lipid accumulation by glucagon-like peptide-1 agonist in hepatocytes
ConclusionsOur data reveals that exendin-4 stimulates hepatic ABCA1 expression and reduces lipid accumulation by the CaMKK/CaMKIV/PREB pathway, suggesting that ABCA1 and PREB might be the therapeutic targets in fatty liver disease.Graphical abstract
Source: Molecular Metabolism - January 7, 2020 Category: Endocrinology Source Type: research

Inhibition of inflammation-mediated DPP-4 expression by linagliptin increases M2 macrophages in atherosclerotic lesions.
CONCLUSIONS: Linagliptin increased M2 macrophage polarization by inhibiting DPP-4 expression and activity. These findings may indicate the beneficial effects of DPP-4 inhibitors on the progression of diabetic macrovascular complications. PMID: 31964532 [PubMed - as supplied by publisher]
Source: Biochemical and Biophysical Research communications - January 17, 2020 Category: Biochemistry Authors: Nishida S, Matsumura T, Senokuchi T, Murakami-Nishida S, Ishii N, Morita Y, Yagi Y, Motoshima H, Kondo T, Araki E Tags: Biochem Biophys Res Commun Source Type: research

Obesity-induced reduced expression of the lncRNA ROIT impairs insulin transcription by downregulation of Nkx6.1 methylation
Conclusions/interpretationThese findings functionally suggest a novel link between obesity and beta cell dysfunction via ROIT. Elucidating a precise mechanism for the effect of obesity on lncRNA expression will broaden our understanding of the pathophysiological development of diabetes and facilitate the design of better tools for diabetes prevention and treatment.Data availabilityThe raw RNA sequencing data are available from the NCBI Gene Expression Omnibus (GEO series accession number GSE139991).
Source: Diabetologia - January 31, 2020 Category: Endocrinology Source Type: research

Resveratrol protects against nonalcoholic fatty liver disease by improving lipid metabolism and redox homeostasis via the PPAR α pathway
This study investigated the preventive and therapeutic effects of RSV on high-fat diet (HFD)-induced NAFLD in rats and palmitate acid (PA)-induced hepatocyte steatosis in HepG2 cells. Hepatocytes were incubated with inhibitors of peroxisome proliferator-activated receptor α (PPARα) or short interfering RNAs (siRNAs) targeting PPARα, AMP-activated protein kinase (AMPK), and protein kinase A (PKA) to determine the underlying mechanisms. We found that RSV noticeably ameliorated HFD-induced hepatic steatosis in rats and inhibited PA-induced lipid accumulation in HepG2 cells. Moreover, RSV improved lipid metabolism, enhanced...
Source: Applied Physiology, Nutrition, and Metabolism - June 6, 2019 Category: Physiology Authors: Yujie Huang Hedong Lang Ka Chen Yong Zhang Yanxiang Gao Li Ran Long Yi Mantian Mi Qianyong Zhang Source Type: research

Resveratrol improves high-fat diet-induced insulin resistance in mice by downregulating the lncRNA NONMMUT008655.2.
The objective of this study was to investigate whether RSV improves high-fat diet-induced insulin resistance in mice by regulating thelncRNANONMMUT008655.2 in vivo and in vitro. To this end, animal and cell insulin resistance models were developed. Specifically, C57BL/6J mice were fed a high-fat diet (HFD) and administered RSV for eight weeks. Additionally, mouse Hepa cells were treated with palmitic acid, transfected with siRNA NONMMUT008655.2, and treated with RSV. Treated mice and cells were then compared to normal controls that were not exposed to RSV. In the animal model, RSV was found to decrease the levels of fastin...
Source: American Journal of Translational Research - February 15, 2020 Category: Research Tags: Am J Transl Res Source Type: research

Stat3 activation induces insulin resistance via a muscle-specific E3 ubiquitin ligase Fbxo40.
Abstract Cellular mechanisms causing insulin resistance (IR) in chronic kidney disease (CKD) are poorly understood. One potential mechanism is that CKD-induced inflammation activates the signal transducer and activator of transcription 3 (Stat3) in muscle. We uncovered increased p-Stat3 in muscles of mice with CKD or mice fed high fat diet (HFD). Activated Stat3 stimulates the expression of Fbxo40, a muscle-specific E3 ubiquitin ligase that stimulates ubiquitin conjugation leading to degradation of insulin receptor substrate 1 (IRS1). Evidence that STAT3 activates Fbxo40 includes: 1) potential Stat3 binding sites ...
Source: Am J Physiol Endocri... - February 25, 2020 Category: Endocrinology Authors: Zhang L, Chen Z, Wang Y, Tweardy DJ, Mitch WE Tags: Am J Physiol Endocrinol Metab Source Type: research