scholarly journals Differential expression of gluconeogenic enzymes in early- and late-stage diabetes: the effect of Citrullus colocynthis (L.) Schrad. Seed extract on hyperglycemia and hyperlipidemia in Wistar-Albino rats model

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Arezoo Afshari ◽  
Fouzieh Salimi ◽  
Azin Nowrouzi ◽  
Masoumeh Babaie Khalili ◽  
Salar Bakhtiyari ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Fatty Acid Synthase ◽  
Regulatory Element ◽  
Albino Rats ◽  
Citrullus Colocynthis ◽  
Gene Expressions ◽  
Protein Carbonyl Content ◽  
Hepatic Expression ◽  
Ability To Act

Abstract Background The medicinal plant Citrullus colocynthis (L.) Schrad. (C. colocynthis) may benefit patients at different phases of diabetes by attuning to contrasting situations. Our primary objective was to find the mechanism(s) behind the antidiabetic/anti-hyperlipidemic effects of C.colocynthis seed aqueous extract (CCAE) in two different stages of type 2 diabetes (T2D) in rats. Methods Fasting blood sugar (FBS) levels, body weights, and the degree of impaired glucose tolerance (IGT) were measured in healthy nondiabetic control rats (Con), as well as rats with early and late stages of T2D, denoted as ET2D and LT2D, respectively. CCAE was intraperitoneally (IP) injected for 28 days. In the end, the hepatic mRNA expression levels of the following genes were determined by RT-PCR: glucose-6-phosphatase (G6Pase), phosphoenolpyruvate carboxykinase (PEPCK), insulin-dependent sterol regulatory element-binding protein-1c (SREBP-1c), acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), peroxisome proliferator-activated receptor alpha (PPARα), and carnitine palmitoyltransferase I (CPT1). The liver was examined by hematoxylin and eosin (H&E) and Oil-Red O staining. CCAE was partially analyzed by HPLC-DAD. Results ET2D and LT2D were characterized by differentially elevated FBS, deteriorated bodyweight, and significant IGT compared to Con. Hepatosteatoses of varying morphologies and higher hepatic expression of G6Pase than PRPCK in ET2D versus the opposite in LT2D further confirmed the divergent nature of metabolic aberrations. At the end of 28 days, the high levels of FBS, alkaline phosphatase (ALP), triglyceride (TG), urea, hepatic protein carbonyl content (PCC), and alanine and aspartate aminotransferases (AST and ALT, respectively) persisted in untreated LT2D. CCAE ameliorated oxidative stress and upregulated PPARα expression in diabetic groups and Con; it downregulated CPT1 expression in the LT2D group. CCAE’s ability to lower FBS and serum and hepatic TG in both ET2D and LT2D indicated its ability to act via different mechanisms. Ferulic acid (Fer A) and rutin hydrate (RH) were detected in CCAE. Conclusion CCAE lowered the FBS in ET2D via inhibiting the hepatic G6Pase expression (glycogenolysis). In LT2D, CCAE abated sugar levels by diverting PEPCK activity, preferably towards glyceroneogenesis than gluconeogenesis. The preserved triglyceride/fatty acid (TG/FA) cycle, the upregulated PPARα, and the downregulated CPT1 gene expressions reduced serum and hepatic TG.

scholarly journals A role for PPARα in the control of SREBP activity and lipid synthesis in the liver

2005 ◽  
Vol 389 (2) ◽  
pp. 413-421 ◽  
Author(s):  
Brian L. Knight ◽  
Abdel Hebbachi ◽  
David Hauton ◽  
Anna-Marie Brown ◽  
David Wiggins ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Cholesterol Synthesis ◽  
Fatty Acid Synthase ◽  
De Novo ◽  
Regulatory Element ◽  
Active Form ◽  
Dietary Cholesterol ◽  
Acid Oxidation ◽  
Mrna Levels ◽  
Hepatic Expression

Inclusion of the PPARα (peroxisome-proliferator-activated receptor α) activator WY 14,643 in the diet of normal mice stimulated the hepatic expression of not only genes of the fatty acid oxidation pathway, but also those of the de novo lipid synthetic pathways. Induction of fatty acid synthase mRNA by WY 14,643 was greater during the light phase of the diurnal cycle, when food intake was low and PPARα expression was high. Hepatic fatty acid pathway flux in vivo showed a similar pattern of increases. The abundance of mRNAs for genes involved in hepatic cholesterol synthesis was also increased by WY 14,643, but was associated with a decrease in cholesterogenic carbon flux. None of these changes were apparent in PPARα-null mice. Mice of both genotypes showed the expected decreases in 3-hydroxy-3-methylglutaryl-CoA reductase mRNA levels and cholesterol synthesis in response to an increase in dietary cholesterol. The increase in fatty acid synthesis due to WY 14,643 was not mediated by increased expression of SREBP-1c (sterol regulatory element binding protein-1c) mRNA, but by an increase in cleavage of the protein to the active form. An accompanying rise in stearoyl-CoA desaturase mRNA expression suggested that the increase in lipogenesis could have resulted from an alteration in membrane fatty acid composition that influenced SREBP activation.

scholarly journals Effect ofα-linolenic acid and DHA intake on lipogenesis and gene expression involved in fatty acid metabolism in growing-finishing pigs

2016 ◽  
Vol 116 (1) ◽  
pp. 7-18 ◽  
Author(s):  
A. De Tonnac ◽  
E. Labussière ◽  
A. Vincent ◽  
J. Mourot
Keyword(s):  
Fatty Acid ◽  
Linolenic Acid ◽  
Fatty Acid Synthase ◽  
Regulatory Element ◽  
Control Diet ◽  
Fatty Acid Desaturase ◽  
Finishing Pigs ◽  
Gene Expressions ◽  
Quadratic Effects ◽  
Coa Reductase

AbstractThe regulation of lipogenesis mechanisms related to consumption ofn-3 PUFA is poorly understood. The aim of the present study was to find out whetherα-linolenic acid (ALA) or DHA uptake can have an effect on activities and gene expressions of enzymes involved in lipid metabolism in the liver, subcutaneous adipose tissue andlongissimus dorsi(LD) muscle of growing–finishing pigs. Six groups of ten pigs received one of six experimental diets supplemented with rapeseed oil in the control diet, extruded linseed, microalgae or a mixture of both to implement different levels of ALA and DHA with the same content in totaln-3. Results were analysed for linear and quadratic effects of DHA intake. The results showed that activities of malic enzyme (ME) and fatty acid synthase (FAS) decreased linearly in the liver with dietary DHA. Although the expression of the genes of these enzymes and their activities were poorly correlated,MEandFASexpressions also decreased linearly with DHA intake. The intake of DHA down-regulates the expressions of other genes involved in fatty acid (FA) metabolism in some tissues of pigs, such asfatty acid desaturase 2andsterol-regulatory element binding transcription factor 1in the liver and2,4-dienoyl CoA reductase 2in the LD muscle. FA oxidation in the LD muscle and FA synthesis decreased in the liver with increasing amount of dietary DHA, whereas a retroconversion of DHA into EPA seems to be set up in this last tissue.

Placental Accumulation of Triacylglycerols in Gestational Diabetes Mellitus and Its Association with Altered Fetal Growth are Related to the Differential Expressions of Proteins of Lipid Metabolism

2020 ◽  
Author(s):  
Manoharan Balachandiran ◽  
Zachariah Bobby ◽  
Gowri Dorairajan ◽  
Sajini Elizabeth Jacob ◽  
Victorraj Gladwin ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Fetal Growth ◽  
Fatty Acid Synthase ◽  
Regulatory Element ◽  
Acid Oxidation ◽  
Placental Proteins

Abstract Introduction Gestational diabetes mellitus (GDM) exhibit altered placental lipid metabolism. The molecular basis of this altered metabolism is not clear. Altered placental expression of proteins of lipogenesis and fatty acid oxidation may be involved in the placental accumulation of triacylglycerols (TG). The present study was aimed at investigating the differential expressions of placental proteins related to lipid metabolism among GDM women in comparison with control pregnant women (CPW) and to correlate them with maternal and fetal lipid parameters as well as altered fetal growth. Materials and Methods Maternal blood, cord blood, and placental samples were collected from GDM and CPW. The biochemical parameters, glucose, lipid profile and free fatty acids (FFA) were measured. The placental TG content was measured. Differential placental expressions of proteins; phosphatidylinositol-3-kinase (PI3K) p85α, PI3K p110α,liver X receptor alpha (LXRα), sterol regulatory element binding protein1(SREBP1), fatty acid synthase (FAS), stearyl CoA desaturase1 (SCD1), lipoprotein lipase (LPL),Peroxisome proliferator-activated receptor (PPAR)α and PPARγ were analysed by western blotting and immunohistochemistry. Results Placental protein expressions of PI3K p110α, LXRα, FAS, SCD1, and LPL were found to be significantly higher, whereas PPARα and PPARγ were lower in GDM women compared with CPW. The placental TG content and cord plasma FFA were increased in GDM women compared with CPW. The placental TG content positively correlated with Ponderal index of GDM new-borns. Conclusion Differential expressions of placental proteins related to lipid metabolism in GDM might have led to placental TG accumulation. This might have contributed to the fetal overgrowth in GDM.

Regulation of fatty acid synthase expression in breast cancer by sterol regulatory element binding protein-1c

2003 ◽  
Vol 282 (2) ◽  
pp. 132-137 ◽  
Author(s):  
Y.u-A.n Yang ◽  
Patrice J. Morin ◽  
Wan Fang Han ◽  
Tinghua Chen ◽  
Daniel M. Bornman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
Binding Protein ◽  
Regulatory Element ◽  
Element Binding Protein ◽  
Sterol Regulatory Element

Regulation of the SREBP transcription factors by mTORC1

2011 ◽  
Vol 39 (2) ◽  
pp. 495-499 ◽  
Author(s):  
Caroline A. Lewis ◽  
Beatrice Griffiths ◽  
Claudio R. Santos ◽  
Mario Pende ◽  
Almut Schulze
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
Target Genes ◽  
De Novo ◽  
Regulatory Element ◽  
Cholesterol Biosynthesis ◽  
Mammalian Target Of Rapamycin ◽  
Lipid Biosynthesis ◽  
De Novo Lipogenesis ◽  
Genes Encoding

In recent years several reports have linked mTORC1 (mammalian target of rapamycin complex 1) to lipogenesis via the SREBPs (sterol-regulatory-element-binding proteins). SREBPs regulate the expression of genes encoding enzymes required for fatty acid and cholesterol biosynthesis. Lipid metabolism is perturbed in some diseases and SREBP target genes, such as FASN (fatty acid synthase), have been shown to be up-regulated in some cancers. We have previously shown that mTORC1 plays a role in SREBP activation and Akt/PKB (protein kinase B)-dependent de novo lipogenesis. Our findings suggest that mTORC1 plays a crucial role in the activation of SREBP and that the activation of lipid biosynthesis through the induction of SREBP could be part of a regulatory pathway that co-ordinates protein and lipid biosynthesis during cell growth. In the present paper, we discuss the increasing amount of data supporting the potential mechanisms of mTORC1-dependent activation of SREBP as well as the implications of this signalling pathway in cancer.

scholarly journals Effect of Breed on Transcriptional and Protein Expression of Lipogenic Enzymes in Tail and Subcutaneous Adipose Tissue from Two Grazing Breeds of Lambs

Animals ◽  
2019 ◽  
Vol 9 (2) ◽  
pp. 64
Author(s):  
María Gallardo ◽  
Luis Arias-Darraz ◽  
Juan Cárcamo
Keyword(s):  
Fatty Acid ◽  
Protein Expression ◽  
Mrna Expression ◽  
Fatty Acid Synthase ◽  
Regulatory Element ◽  
Subcutaneous Fat ◽  
Human Consumption ◽  
Meat Industry ◽  
Lipogenic Enzymes ◽  
Expression Levels

This experiment was carried out to determine the effect of breed on mRNA and protein expression levels of lipogenic enzymes acetyl-CoA carboxylase α (ACC), fatty acid synthase (FAS), stearoyl-CoA desaturase 1 (SCD1) plus sterol regulatory element binding transcription factor 1c (SREBP1c) in the subcutaneous fat (SCF) from the back of the animal, and tail fat (TF) of both Chilota and Suffolk Down lambs grazing Calafatal. Eight Chilota and six Suffolk Down 2-month-old male lambs were allocated to graze a “Calafatal”, a typical secondary succession of Chiloé Archipelago, Chile. After 62 d, lambs were slaughtered according to Chile’s meat industry standards. Fatty acid profile, RT-qPCR, and Western blot analyses from SCF and TF samples were performed. Although the mRNA expression levels of ACC, FAS, SCD1 and SREBP1c in SCF did not differ significantly between breeds (p > 0.05), a trend to higher mRNA expression of FAS and SREBP1c in TF from Chilota lambs was observed (p = 0.06). On the other hand, FAS levels in SCF were higher in Chilota than in Suffolk Down lambs (p < 0.02), although Suffolk Down showed higher fat contents and saturated fatty acid (SFA) proportions than Chilota lambs (p < 0.01). The FAS protein expression in TF was similar in both breeds (p > 0.05). Although the fat content was higher in Suffolk Down than in Chilota lambs (p < 0.01), the SFA proportions were similar in both breeds. Finally, it can be concluded that although mRNA expression of enzymes was similar in both breeds, there were differences in some protein levels in the SCF, partially related with the fatty acid profiles, thus affecting the selection of lamb breed either for human consumption or experimental purposes.

scholarly journals Arazyme Suppresses Hepatic Steatosis and Steatohepatitis in Diet-Induced Non-Alcoholic Fatty Liver Disease-Like Mouse Model

2019 ◽  
Vol 20 (9) ◽  
pp. 2325 ◽  
Author(s):  
Hua Li ◽  
Wonbeak Yoo ◽  
Hye-Mi Park ◽  
Soo-Youn Lim ◽  
Dong-Ha Shin ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Liver Disease ◽  
Fatty Liver ◽  
Hepatic Steatosis ◽  
Fatty Liver Disease ◽  
Fatty Acid Synthase ◽  
Regulatory Element ◽  
Diet Group ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Arazyme, a metalloprotease from the spider Nephila clavata, exerts hepatoprotective activity in CCL4-induced acute hepatic injury. This study investigated the hepatoprotective effects in high-fat diet (HFD)-induced non-alcoholic fatty liver disease-like C57BL/6J mice. The mice were randomly divided into four groups (n = 10/group): the normal diet group, the HFD group, the arazyme group (HFD with 0.025% arazyme), and the milk thistle (MT) group (HFD with 0.1% MT). Dietary supplementation of arazyme for 13 weeks significantly lowered plasma triglyceride (TG) and non-esterified fatty acid levels. Suppression of HFD-induced hepatic steatosis in the arazyme group was caused by the reduced hepatic TG and total cholesterol (TC) contents. Arazyme supplementation decreased hepatic lipogenesis-related gene expression, sterol regulatory element-binding transcription protein 1 (Srebf1), fatty acid synthase (Fas), acetyl-CoA carboxylase 1 (Acc1), stearoyl-CoA desaturase-1 (Scd1), Scd2, glycerol-3-phosphate acyltransferase (Gpam), diacylglycerol O-acyltransferase 1 (Dgat1), and Dgat2. Arazyme directly reduced palmitic acid (PA)-induced TG accumulation in HepG2 cells. Arazyme suppressed macrophage infiltration and tumor necrosis factor α (Tnfa), interleukin-1β (Il1b), and chemokine-ligand-2 (Ccl2) expression in the liver, and inhibited secretion of TNFα and expression of inflammatory mediators, Tnfa, Il1b, Ccl2, Ccl3, Ccl4, and Ccl5, in PA-induced RAW264.7 cells. Arazyme effectively protected hepatic steatosis and steatohepatitis by inhibiting SREBP-1-mediated lipid accumulation and macrophage-mediated inflammation.

scholarly journals Phloretin ameliorates hepatic steatosis through regulation of lipogenesis and Sirt1/AMPK signaling in obese mice

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Chian-Jiun Liou ◽  
Shu-Ju Wu ◽  
Szu-Chuan Shen ◽  
Li-Chen Chen ◽  
Ya-Ling Chen ◽  
...  
Keyword(s):  
Oleic Acid ◽  
Fatty Acid ◽  
Hepatic Steatosis ◽  
Lipid Accumulation ◽  
Hepg2 Cells ◽  
Fatty Acid Synthase ◽  
Regulatory Element ◽  
Liver Lipid ◽  
Obese Mice ◽  
Alcoholic Fatty Liver

Abstract Background Phloretin is isolated from apple trees and could increase lipolysis in 3T3-L1 adipocytes. Previous studies have found that phloretin could prevent obesity in mice. In this study, we investigated whether phloretin ameliorates non-alcoholic fatty liver disease (NAFLD) in high-fat diet (HFD)-induced obese mice, and evaluated the regulation of lipid metabolism in hepatocytes. Methods HepG2 cells were treated with 0.5 mM oleic acid to induce lipid accumulation, and then treated with phloretin to evaluate the molecular mechanism of lipogenesis. In another experiment, male C57BL/6 mice were fed normal diet or HFD (60% fat, w/w) for 16 weeks. After the fourth week, mice were treated with or without phloretin by intraperitoneal injection for 12 weeks. Results Phloretin significantly reduced excessive lipid accumulation and decreased sterol regulatory element-binding protein 1c, blocking the expression of fatty acid synthase in oleic acid-induced HepG2 cells. Phloretin increased Sirt1, and phosphorylation of AMP activated protein kinase to suppress acetyl-CoA carboxylase expression, reducing fatty acid synthesis in hepatocytes. Phloretin also reduced body weight and fat weight compared to untreated HFD-fed mice. Phloretin also reduced liver weight and liver lipid accumulation and improved hepatocyte steatosis in obese mice. In liver tissue from obese mice, phloretin suppressed transcription factors of lipogenesis and fatty acid synthase, and increased lipolysis and fatty acid β-oxidation. Furthermore, phloretin regulated serum leptin, adiponectin, triglyceride, low-density lipoprotein, and free fatty acid levels in obese mice. Conclusions These findings suggest that phloretin improves hepatic steatosis by regulating lipogenesis and the Sirt-1/AMPK pathway in the liver.

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