scholarly journals C/EBPbeta knockdown prevents fatty acid induced inflammatory gene progression, macrophage infiltration and insulin resistance in vivo and in vitro

2009 ◽  
Vol 23 (S1) ◽  
Author(s):  
Shaikh Mizanoor Rahman ◽  
Rachel Janssen ◽  
B.A. Houssaye ◽  
Jed Friedman
Keyword(s):  
Insulin Resistance ◽  
Fatty Acid ◽  
Macrophage Infiltration ◽  
Inflammatory Gene

scholarly journals PEG-BHD1028 Peptide Regulates Insulin Resistance and Fatty Acid β-Oxidation, and Mitochondrial Biogenesis by Binding to Two Heterogeneous Binding Sites of Adiponectin Receptors, AdipoR1 and AdipoR2

2021 ◽  
Vol 22 (2) ◽  
pp. 884
Author(s):  
In Kyung Lee ◽  
Gyuyoup Kim ◽  
Do-Hwi Kim ◽  
Brian B. Kim
Keyword(s):  
Insulin Resistance ◽  
Fatty Acid ◽  
Mitochondrial Biogenesis ◽  
Binding Sites ◽  
Action Spectrum ◽  
C2c12 Cells ◽  
In Vivo Models ◽  
Insulin Resistant

Adiponectin plays multiple critical roles in modulating various physiological processes by binding to its receptors. The functions of PEG-BHD1028, a potent novel peptide agonist to AdipoRs, was evaluated using in vitro and in vivo models based on the reported action spectrum of adiponectin. To confirm the design concept of PEG-BHD1028, the binding sites and their affinities were analyzed using the SPR (Surface Plasmon Resonance) assay. The results revealed that PEG-BHD1028 was bound to two heterogeneous binding sites of AdipoR1 and AdipoR2 with a relatively high affinity. In C2C12 cells, PEG-BHD1028 significantly activated AMPK and subsequent pathways and enhanced fatty acid β-oxidation and mitochondrial biogenesis. Furthermore, it also facilitated glucose uptake by lowering insulin resistance in insulin-resistant C2C12 cells. PEG-BHD1028 significantly reduced the fasting plasma glucose level in db/db mice following a single s.c. injection of 50, 100, and 200 μg/Kg and glucose tolerance at a dose of 50 μg/Kg with significantly decreased insulin production. The animals received 5, 25, and 50 μg/Kg of PEG-BHD1028 for 21 days significantly lost their weight after 18 days in a range of 5–7%. These results imply the development of PEG-BHD1028 as a potential adiponectin replacement therapeutic agent.

scholarly journals MLK3 promotes metabolic dysfunction induced by saturated fatty acid-enriched diet

2013 ◽  
Vol 305 (4) ◽  
pp. E549-E556 ◽  
Author(s):  
Vidya Gadang ◽  
Rohit Kohli ◽  
Andriy Myronovych ◽  
David Y. Hui ◽  
Diego Perez-Tilve ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Saturated Fatty Acid ◽  
Saturated Fatty Acids ◽  
Low Grade ◽  
Metabolic Dysfunction ◽  
Jnk Activation

Saturated fatty acids activate the c-Jun NH2-terminal kinase (JNK) pathway, resulting in chronic low-grade inflammation and the development of insulin resistance. Mixed-lineage kinase 3 (MLK3) is a mitogen-activated protein kinase kinase kinase (MAP3K) that mediates JNK activation in response to saturated fatty acids in vitro; however, the exact mechanism for diet-induced JNK activation in vivo is not known. Here, we have used MLK3-deficient mice to examine the role of MLK3 in a saturated-fat diet model of obesity. MLK3-KO mice fed a high-fat diet enriched in medium-chain saturated fatty acids for 16 wk had decreased body fat compared with wild-type (WT) mice due to increased energy expenditure independently of food consumption and physical activity. Moreover, MLK3 deficiency attenuated palmitate-induced JNK activation and M1 polarization in bone marrow-derived macrophages in vitro, and obesity induced JNK activation, macrophage infiltration into adipose tissue, and expression of proinflammatory cytokines in vivo. In addition, loss of MLK3 improved insulin resistance and decreased hepatic steatosis. Together, these data demonstrate that MLK3 promotes saturated fatty acid-induced JNK activation in vivo and diet-induced metabolic dysfunction.

scholarly journals Effects of a natural PTP1B inhibitor from Rhodomela confervoides on the amelioration of fatty acid-induced insulin resistance in hepatocytes and hyperglycaemia in STZ-induced diabetic rats

RSC Advances ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 3429-3437 ◽  
Author(s):  
Shuju Guo ◽  
Lijun Wang ◽  
Dong Chen ◽  
Bo Jiang
Keyword(s):  
Insulin Resistance ◽  
Fatty Acid ◽  
Diabetic Rats ◽  
Rhodomela Confervoides

A natural bromophenol BPN was identified as a competitive PTP1B inhibitor both in vitro and in vivo.

scholarly journals Are Fried Foods Unhealthy? The Dietary Peroxidized Fatty Acid, 13-HPODE, Induces Intestinal Inflammation In Vitro and In Vivo

Antioxidants ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 926 ◽  
Author(s):  
Esra’a Keewan ◽  
Chandrakala Aluganti Narasimhulu ◽  
Michael Rohr ◽  
Simran Hamid ◽  
Sampath Parthasarathy
Keyword(s):  
Gene Expression ◽  
Fatty Acid ◽  
Intestinal Epithelium ◽  
Intestinal Inflammation ◽  
Inflammatory Disorder ◽  
Inflammatory Gene Expression ◽  
Inflammatory Gene ◽  
Gut Mucosa

Inflammatory Bowel Disease (IBD) is a chronic inflammatory disorder characterized by progressive inflammation and the erosion of the gut mucosa. Although the exact cause of IBD is unknown, multiple factors contribute to its complex pathogenesis. Diet is one such factor and a strong correlation exists between the western-style, high fat diets (HFDs) and IBD incidence rates. In this study, we propose that the peroxidized fatty acid components of HFDs could contribute to inflammation of the gut. The inflammatory nature of peroxidized linoleic acid (13-HPODE), was confirmed in vitro by analyzing pro-inflammatory gene expression in Caco-2 cells via RT-PCR and ELISA. Additionally, peroxide induced apoptosis was tested by Annexin-V fluorescent staining, while permeability was tested by FITC-dextran flux and TEER. The 13-HPODE-induced inflammation of intestinal epithelium was evaluated in vivo by analyzing pro-inflammatory cytokines under acute and chronic conditions after feeding 13-HPODE to C57BL/6J mice. Our data show that 13-HPODE significantly induced pro-inflammatory gene expression of TNF-α and MCP-1 in vitro, most notably in differentiated Caco-2 cells. Further, acute and chronic 13-HPODE treatments of mice similarly induced pro-inflammatory cytokine expression in the epithelium of both the proximal and distal small intestines, resident immune cells in Peyer’s patches and peritoneal macrophages. The results of this study not only confirm the pro-inflammatory properties of peroxidized fats on the gut mucosa, but for the first time demonstrate their ability to differentially induce pro-inflammatory gene expression and influence permeability in the intestinal epithelium and mucosal cells. Collectively, our results suggest that the immunogenic properties of HFD’s in the gut may be partly caused by peroxide derivatives, providing potential insight into how these diets contribute to exacerbations of IBD.

scholarly journals FOXE1-Dependent Regulation of Macrophage Chemotaxis by Thyroid Cells In Vitro and In Vivo

2021 ◽  
Vol 22 (14) ◽  
pp. 7666
Author(s):  
Sara C. Credendino ◽  
Marta De Menna ◽  
Irene Cantone ◽  
Carmen Moccia ◽  
Matteo Esposito ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Immune Cells ◽  
Cancer Susceptibility ◽  
Macrophage Infiltration ◽  
M2 Macrophage ◽  
Thyroid Cells ◽  
Transcriptional Alterations ◽  
Cancer Phenotypes

Forkhead box E1 (FOXE1) is a lineage-restricted transcription factor involved in thyroid cancer susceptibility. Cancer-associated polymorphisms map in regulatory regions, thus affecting the extent of gene expression. We have recently shown that genetic reduction of FOXE1 dosage modifies multiple thyroid cancer phenotypes. To identify relevant effectors playing roles in thyroid cancer development, here we analyse FOXE1-induced transcriptional alterations in thyroid cells that do not express endogenous FOXE1. Expression of FOXE1 elicits cell migration, while transcriptome analysis reveals that several immune cells-related categories are highly enriched in differentially expressed genes, including several upregulated chemokines involved in macrophage recruitment. Accordingly, FOXE1-expressing cells induce chemotaxis of co-cultured monocytes. We then asked if FOXE1 was able to regulate macrophage infiltration in thyroid cancers in vivo by using a mouse model of cancer, either wild type or with only one functional FOXE1 allele. Expression of the same set of chemokines directly correlates with FOXE1 dosage, and pro-tumourigenic M2 macrophage infiltration is decreased in tumours with reduced FOXE1. These data establish a novel link between FOXE1 and macrophages recruitment in the thyroid cancer microenvironment, highlighting an unsuspected function of this gene in the crosstalk between neoplastic and immune cells that shape tumour development and progression.

scholarly journals Synthesis, Quantification, and Characterization of Fatty Acid Amides from In Vitro and In Vivo Sources

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2543
Author(s):  
Ruidong Ni ◽  
Suzeeta Bhandari ◽  
Perry R. Mitchell ◽  
Gabriela Suarez ◽  
Neel B. Patel ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Fatty Acid ◽  
Apis Mellifera ◽  
Chemical Synthesis ◽  
Acid Amide ◽  
Fatty Acid Amides ◽  
Fatty Acid Amide

Fatty acid amides are a diverse family of underappreciated, biologically occurring lipids. Herein, the methods for the chemical synthesis and subsequent characterization of specific members of the fatty acid amide family are described. The synthetically prepared fatty acid amides and those obtained commercially are used as standards for the characterization and quantification of the fatty acid amides produced by biological systems, a fatty acid amidome. The fatty acid amidomes from mouse N18TG2 cells, sheep choroid plexus cells, Drosophila melanogaster, Bombyx mori, Apis mellifera, and Tribolium castaneum are presented.

scholarly journals Antidiabetic Properties of Naringenin: A Citrus Fruit Polyphenol

Biomolecules ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. 99 ◽  
Author(s):  
Danja J. Den Hartogh ◽  
Evangelia Tsiani
Keyword(s):  
Insulin Resistance ◽  
Animal Studies ◽  
Citrus Fruit ◽  
Epidemiological Studies ◽  
Personal Health ◽  
Current Review ◽  
Vegetables And Fruits

Type 2 diabetes mellitus (T2DM) is a metabolic disease characterized by insulin resistance and hyperglycemia and is associated with personal health and global economic burdens. Current strategies/approaches of insulin resistance and T2DM prevention and treatment are lacking in efficacy resulting in the need for new preventative and targeted therapies. In recent years, epidemiological studies have suggested that diets rich in vegetables and fruits are associated with health benefits including protection against insulin resistance and T2DM. Naringenin, a citrus flavanone, has been reported to have antioxidant, anti-inflammatory, hepatoprotective, nephroprotective, immunomodulatory and antidiabetic properties. The current review summarizes the existing in vitro and in vivo animal studies examining the anti-diabetic effects of naringenin.

scholarly journals Effect of a Rumen-Protected Microencapsulated Supplement from Linseed Oil on the Growth Performance, Meat Quality, and Fatty Acid Composition in Korean Native Steers

Animals ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 1253
Author(s):  
Chae-Hyung Sun ◽  
Jae-Sung Lee ◽  
Jalil Ghassemi Nejad ◽  
Won-Seob Kim ◽  
Hong-Gu Lee
Keyword(s):  
Fatty Acid Composition ◽  
Fatty Acid ◽  
Growth Performance ◽  
Meat Quality ◽  
Acid Composition ◽  
Linseed Oil ◽  
Control Group ◽  
Ruminal Fluid

We evaluated the effects of a rumen-protected microencapsulated supplement from linseed oil (MO) on ruminal fluid, growth performance, meat quality, and fatty acid composition in Korean native steers. In an in vitro experiment, ruminal fluid was taken from two fistulated Holstein dairy cows. Different levels of MO (0%, 1%, 2%, 3%, and 4%) were added to the diet. In an in vivo experiment, eight steers (average body weight = 597.1 ± 50.26 kg; average age = 23.8 ± 0.12 months) were assigned to two dietary groups, no MO (control) and MO (3% MO supplementation on a DM basis), for 186 days. The in vitro study revealed that 3% MO is an optimal dose, as there were decreases in the neutral detergent fiber and acid detergent fiber digestibility at 48 h (p < 0.05). The in vivo study showed increases in the feed efficiency and average daily gain in the 3% MO group compared to the control group on days 1 to 90 (p < 0.05). Regarding meat quality, the shear force produced by the longissimus thoracis muscle in steers from the 3% MO group was lower than that produced by the control group (p < 0.05). Interestingly, in terms of the fatty acid profile, higher concentrations of C22:6n3 were demonstrated in the subcutaneous fat and higher concentrations of C18:3n3, C20:3n3, and C20:5n3 were found in the intramuscular fat from steers fed with 3% MO (p < 0.05). Our results indicate that supplementation with 3% MO supplements improves the growth performance and meat quality modulated by the omega-3 fatty acid content of meat in Korean native steers.

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