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Genes, Vol. 11, Pages 720: Cardiac Transcriptome Analysis Reveals Nr4a1 Mediated Glucose Metabolism Dysregulation in Response to High-Fat Diet
ng Xia Chen Obesity is associated with an increased risk of developing cardiovascular disease (CVD), with limited alterations in cardiac genomic characteristics known. Cardiac transcriptome analysis was conducted to profile gene signatures in high-fat diet (HFD)-induced obese mice. A total of 184 differentially expressed genes (DEGs) were identified between groups. Based on the gene ontology (GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of DEGs, the critical role of closely interlocked glucose metabolism was determined in HFD-induced cardiac remodeling DEGs, inclu...
Source: Genes - June 28, 2020 Category: Genetics & Stem Cells Authors: Lihui Men Wenting Hui Xin Guan Tongtong Song Xuan Wang Siwei Zhang Xia Chen Tags: Article Source Type: research

Salt causes aging-associated hypertension via vascular Wnt5a under Klotho deficiency
Aging is associated with a high prevalence of hypertension due to elevated susceptibility of BP to dietary salt, but its mechanism is unknown. Serum levels of Klotho, an anti-aging factor, decline with age. We found that high salt (HS) increased BP in aged mice and young heterozygous Klotho-knockout mice and was associated with increased vascular expression of Wnt5a and p-MYPT1, which indicate RhoA activity. Not only the Wnt inhibitor LGK974 and the Wnt5a antagonist Box5 but Klotho supplementation inhibits HS-induced BP elevation, similarly to the Rho kinase inhibitor fasudil, associated with reduced p-MYPT1 expression in ...
Source: Journal of Clinical Investigation - June 29, 2020 Category: Biomedical Science Authors: Wakako Kawarazaki, Risuke Mizuno, Mitsuhiro Nishimoto, Nobuhiro Ayuzawa, Daigoro Hirohama, Kohei Ueda, Fumiko Kawakami-Mori, Shigeyoshi Oba, Takeshi Marumo, Toshiro Fujita Source Type: research

MAPK-interacting kinase 2 (MNK2) regulates adipocyte metabolism independently of its catalytic activity.
Abstract The mitogen-activated protein kinase (MAPK)-interacting kinases (MNKs) are serine/threonine protein kinases that are activated by the ERK1/2 (extracellular-regulated kinase) and p38α/β MAPK pathways. The MNKs have previously been implicated in metabolic disease and shown to mediate diet-induced obesity. In particular, knockout of MNK2 in mice protects from the weight gain induced by a high-fat diet. These and other data suggest that MNK2 regulates expansion of adipose tissue, a stable, long-term energy reserve that plays an important role in regulating whole-body energy homeostasis. Using the well-estab...
Source: The Biochemical Journal - July 9, 2020 Category: Biochemistry Authors: Merrett J, Xie J, Psaltis PJ, Proud CG Tags: Biochem J Source Type: research

Geniposide alleviates diabetic nephropathy of mice through AMPK/SIRT1/NF- κB pathway.
The objective of this study was to explore the antidiabetic nephropathy effects of GE both in high fat diet/streptozotocin-induced DN mice and in high glucose-induced podocyte model. Renal function in DN mice was evaluated by levels of serum creatinine (Scr) and blood urea nitrogen (BUN). Renal inflammation was appraised by pro-inflammatory cytokines: Tumor necrosis factor α (TNF-α), Interleukin 6 (IL-6) and IL-1β via ELISA assay. Renal histopathology analysis was conducted via hematoxylin and eosin, Masson and periodic acid-silver metheramine staining. Cellular viability was measured by Terminal deoxynucleotidyl transf...
Source: European Journal of Pharmacology - August 2, 2020 Category: Drugs & Pharmacology Authors: Li F, Chen Y, Li Y, Huang M, Zhao W Tags: Eur J Pharmacol Source Type: research

Endothelial Deficiency of Insulin-like Growth Factor -1 Receptor Reduces Endothelial Barrier Function and Promotes Atherosclerosis in Apoe-Deficient Mice.
Abstract Insulin-like growth factor-1 (IGF-1) decreases atherosclerosis in Apolipoprotein E (Apoe) -deficient mice when administered systemically. However, mechanisms for its atheroprotective effect are not fully understood. We generated endothelium-specific IGF-1 receptor (IGF1R) deficient mice on Apoe-deficient background to assess effects of IGF-1 on the endothelium in the context of hyperlipidemia-induced atherosclerosis. Endothelial deficiency of IGF1R promoted atherosclerotic burden, when animals were fed on high-fat diet for 12 weeks or normal chow for 12 months. Under normal chow feeding condition, the vas...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 13, 2020 Category: Physiology Authors: Higashi Y, Sukhanov S, Shai SY, Danchuk S, Snarski P, Li Z, Hou X, Hamblin MH, Woods TC, Wang M, Wang D, Yu H, Korthuis RJ, Yoshida T, Delafontaine P Tags: Am J Physiol Heart Circ Physiol Source Type: research

Adiponectin treatment improves insulin resistance in mice by regulating the expression of the mitochondrial-derived peptide MOTS-c and its response to exercise via APPL1 –SIRT1–PGC-1α
Conclusions/interpretationOur findings showed that the APPL1 –SIRT1–PGC-1α pathway regulates the production and/or secretion of skeletal muscle MOTS-c by mediating adiponectin signalling. Our study provides an insight into the cellular and molecular pathways underlying the pathogenesis of diabetes and shows that MOTS-c is a potential novel therapeutic ta rget in the treatment of diabetes.Graphical abstract
Source: Diabetologia - September 2, 2020 Category: Endocrinology Source Type: research

GPR120 regulates pancreatic polypeptide secretion from male mouse islets via PLC-mediated calcium mobilization.
In this study, GPR120-IRES-EGFP knockin (KI) mouse was generated to identify GPR120-expressing cells with enhance green fluorescence proteins (EGFP). EGFP-positive cells collected from the KI mouse islets by flow cytometry had significantly higher expression of pancreatic polypeptide (PP) evidenced by RT-qPCR. Single cell RT-PCR and immunocytochemical double staining also demonstrated the co-expression of GPR120 with PP in mouse islets. GPR120 specific agonist, TUG-891, significantly increased plasma PP levels in mice. TUG-891 significantly increased PP levels in islet medium in vitro, which was markedly attenuated by GPR1...
Source: Endocrinology - September 1, 2020 Category: Endocrinology Authors: Zhao YF, Li XC, Liang XY, Zhao YY, Xie R, Zhang LJ, Zhang XC, Chen C Tags: Endocrinology Source Type: research

Thioredoxin-interacting protein: a critical link between autophagy disorders and pancreatic β-cell dysfunction
This study aimed to elucidate the influence of TXNIP on the autophagy of β-cell. In this study, C57BL/6 mice and TXNIP−/− mice were fed with a standard diet (SD) or a high-fat and high-sugar diet (HFSD), and then we analysed biochemical and autophagy related indexes in the mice. We infected MIN6 cells with LV-TXNIP and siRNA TXNIP, then the cells were treated with free fatty acid (FFA), autophagic activator rapamycin (RAP), inhibitors of autophagy chloroquine (CQ) and bafilomycin A1(BAF), finally, we examined the changes of autophagy in MIN6 cells. The results showed that HFSD led to β-cell dysfunction and autophagy ...
Source: Endocrine - September 5, 2020 Category: Endocrinology Source Type: research

Improved Glucose Intolerance Through a Distinct Mouse Olfactory Receptor 23 ‐Induced Signaling Pathway Mediating Glucose Uptake In Myotubes and Adipocytes
ConclusionsThese findings suggest that MOR23 is a novel factor for the regulation of glucose uptake and whole ‐body glucose homeostasis and has therapeutic potential for diabetes treatment.This article is protected by copyright. All rights reserved
Source: Molecular Nutrition and Food Research - September 10, 2020 Category: Food Science Authors: Wesuk Kang, Kelun Zhang, Tao Tong, Taesun Park Tags: Research Article Source Type: research

Caspase-11/4 and gasdermin D-mediated pyroptosis contributes to podocyte injury in mouse diabetic nephropathy.
In this study we investigated whether pyroptosis, a newly discovered cell death pathway was involved in DN. Diabetic mice were generated by high-fat diet/STZ injections. We showed that the expression levels of caspase-11 and cleavage of gasdermin D (GSDMD-N) in podocytes were significantly elevated, accompanied by reduced expression of podocyte makers nephrin and podocin, loss and fusion in podocyte foot processes, increased inflammatory cytokines NF-κB, IL-1β, and IL-18, macrophage infiltration, glomerular matrix expansion and increased urinary albumin to creatinine ratio (UACR). All these changes in diabetic mice were ...
Source: Acta Pharmacologica Sinica - September 22, 2020 Category: Drugs & Pharmacology Authors: Cheng Q, Pan J, Zhou ZL, Yin F, Xie HY, Chen PP, Li JY, Zheng PQ, Zhou L, Zhang W, Liu J, Lu LM Tags: Acta Pharmacol Sin Source Type: research

Endothelial HMGB1 Is a Critical Regulator of LDL Transcytosis via an SREBP2-SR-BI Axis.
CONCLUSIONS: Endothelial HMGB1 regulates LDL transcytosis by prolonging the half-life of SREBP2, enhancing SR-BI expression. Translocation of HMGB1 to the nucleus in response to LDL requires SR-BI. PMID: 33054399 [PubMed - as supplied by publisher]
Source: Arteriosclerosis, Thrombosis and Vascular Biology - October 15, 2020 Category: Cardiology Authors: Ghaffari S, Jang E, Nabi FN, Sanwal R, Khosraviani N, Wang C, Steinberg BE, Goldenberg NM, Ikeda J, Lee WL Tags: Arterioscler Thromb Vasc Biol Source Type: research

GPR40-Deficiency Is Associated with Hepatic FAT/CD36 Upregulation, Steatosis, Inflammation and Cell Injury in C57BL/6 Mice.
In this study, we fed wild-type or GPR40 knockout C57BL/6 mice high-fat diet (HFD) for 20 weeks and then assessed the effect of GPR40-deficiency on HFD-induced NAFLD. Assays on metabolic parameters showed that HFD increased bodyweight, glucose, insulin, insulin resistance, cholesterol and alanine aminotransferase (ALT), and GPR40-deficiency did not mitigate the HFD-induced metabolic abnormalities. In contrast, we found that GPR40-deficiency was associated with increased bodyweight, insulin, insulin resistance, cholesterol and ALT in control mice fed low fat diet (LFD). Surprisingly, histology and Oil Red O staining showed ...
Source: American Journal of Physiology. Endocrinology and Metabolism - October 26, 2020 Category: Physiology Authors: Lu Z, Li Y, Syn WK, Li AJ, Ritter S, Wank SA, Lopes-Virella MF, Huang Y Tags: Am J Physiol Endocrinol Metab Source Type: research

Mangiferin protect oxidative stress against deoxynivalenol induced damages through Nrf2 signaling pathways in endothelial cells.
Abstract Several cereal grains contain a mycotoxin food contaminant called Deoxynivalenol (DON), which presents a significant health risk as it is one of the most commonly found mycotoxins. The current paper examines the ameliorative effect of mangiferin (MAN) in vascular endothelial cells induced through activating the Nrf2 signaling pathway on dietary DON-induced oxidative changes. The study infers that the intercellular reactive oxygen species (ROS) levels and malondialdehyde decrease due to MAN. Other effects include: In human umbilical vein endothelial cells (HUVECs), the oxidative stress-induced cell damage ...
Source: Clinical and Experimental Pharmacology and Physiology - October 30, 2020 Category: Drugs & Pharmacology Authors: Al-Saeedi FJ Tags: Clin Exp Pharmacol Physiol Source Type: research

TXNIP/VDUP1 attenuates steatohepatitis via autophagy and fatty acid oxidation.
Abstract Impaired macroautophagy/autophagy has been implicated in experimental and human nonalcoholic steatohepatitis (NASH). However, the mechanism underlying autophagy dysregulation in NASH is largely unknown. Here, we investigated the role and mechanism of TXNIP/VDUP1 (thioredoxin interacting protein), a key mediator of cellular stress responses, in the pathogenesis of NASH. Hepatic TXNIP expression was upregulated in nonalcoholic fatty liver disease (NAFLD) patients and in methionine choline-deficient (MCD) diet-fed mice, as well as in palmitic acid (PA)-treated hepatocytes. Upregulation of hepatic TXNIP was p...
Source: Autophagy - November 16, 2020 Category: Cytology Authors: Park HS, Song JW, Park JH, Lim BK, Moon OS, Son HY, Lee JH, Gao B, Won YS, Kwon HJ Tags: Autophagy Source Type: research

Alisol B 23-acetate activates ABCG5/G8 in the jejunum via the LXR α/ACAT2 pathway to relieve atherosclerosis in ovariectomized ApoE-/- mice.
In conclusion, we confirmed that AB23A can reduce the absorption of dietary lipids in the jejunum by affecting the LXRα-ACAT2-ABCG5/G8 pathway and ultimately exert an anti-atherosclerotic effect. PMID: 33234731 [PubMed - as supplied by publisher]
Source: Aging - November 25, 2020 Category: Biomedical Science Authors: Yu XC, Fu Y, Bi YH, Zhang WW, Li J, Ji T, Chao Y, Meng QH, Chen Q, Ma MH, Zhang YH, Shan J, Bian HM Tags: Aging (Albany NY) Source Type: research