scholarly journals A Study on Neonatal Intake of Oleanolic Acid and Metformin in Rats (Rattus norvegicus) with Metabolic Dysfunction: Implications on Lipid Metabolism and Glucose Transport

Molecules ◽  
2018 ◽  
Vol 23 (10) ◽  
pp. 2528 ◽  
Author(s):  
Mmahiine Molepo ◽  
Ademola Ayeleso ◽  
Trevor Nyakudya ◽  
Kennedy Erlwanger ◽  
Emmanuel Mukwevho
Keyword(s):  
Fatty Acids ◽  
Lipid Metabolism ◽  
Oral Administration ◽  
Free Fatty Acids ◽  
Glucose Transport ◽  
Oleanolic Acid ◽  
Metabolic Dysfunction ◽  
High Fructose Diet ◽  
Glut 4 ◽  
High Fructose

Metabolic syndrome, a cluster of different disorders which include diabetes, obesity and cardiovascular diseases, is a global epidemic that is growing at an alarming rate. The origins of disease can be traced back to early developmental stages of life. This has increased mortalities and continues to reduce life expectancies of individuals across the globe. The aim of this study was to investigate the sub-acute and long term effects of neonatal oral administration of oleanolic acid and metformin on lipids (free fatty acids, FFAs) and genes associated with lipid metabolism and glucose transport using a neonatal rat experimental model. In the first study, seven days old pups were randomly grouped into control—distilled water (DW); oleanolic acid (60 mg/kg), metformin (500 mg/kg), high fructose diet (20% w/v, HF), oleanolic acid (OA) + high fructose diet (OA + HF), and Metformin + high fructose diet (MET + HF) groups. The pups were treated for 7 days, and then terminated on postnatal day (PD) 14. In the second study, rat pups were initially treated similarly to study 1 and weaned onto normal rat chow and plain drinking water on PD 21 till they reached adulthood (PD112). Tissue and blood samples were collected for further analyses. Measurement of the levels of free fatty acids (FFAs) was done using gas chromatography-mass spectrometry. Quantitative polymerase chain reaction (qPCR) was used to analyze the gene expression of glut-4, glut-5, fas, acc-1, nrf-1 and cpt-1 in the skeletal muscle. The results showed that HF accelerated accumulation of saturated FFAs within skeletal muscles. The HF fed neonatal rats had increased stearic acid, which was associated with decreased glucose, suppressed expression of glut-4, glut-5, nrf-1 and cpt-1 genes, and increased expression of acc-1 (p < 0.01) and fas. OA + HF and MET + HF treated groups had increased mono- and polyunsaturated FFAs; oleic, and octadecadienoic acids than the HF group. These unsaturated FFAs were associated with increased glut-4, glut-5 and nrf-1 (p < 0.01) and decreased acc-1 and fas (p < 0.05) in both OA + HF and MET + HF treated groups. Conclusions: The present study shows that neonatal oral administration of oleanolic acid and metformin potentially protects against the development of fructose-induced metabolic dysfunction in the rats in both short and long time periods.

scholarly journals Long-Term Impact of Neonatal Intake of Oleanolic Acid on the Expression of AMP-Activated Protein Kinase, Adiponectin and Inflammatory Cytokines in Rats Fed with a High Fructose Diet

Nutrients ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 226 ◽  
Author(s):  
Mashudu Matumba ◽  
Ademola Ayeleso ◽  
Trevor Nyakudya ◽  
Kennedy Erlwanger ◽  
Novel Chegou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lipid Metabolism ◽  
Oleanolic Acid ◽  
Metabolic Diseases ◽  
Adiponectin Concentration ◽  
High Fructose Diet ◽  
Glucose And Lipid Metabolism ◽  
High Fructose ◽  
Tnf Α

AMP-activated protein kinase (AMPK) is known to regulate both glucose and lipid metabolism, which play vital roles in the development of metabolic syndrome. One way of regulating AMPK is through hormonal activation using adiponectin. Patients diagnosed with type-2 diabetes (T2D) and obesity exhibit low adiponectin concentration levels in their blood. Moreover, studies have also shown that inflammatory processes play a significant role in the etiology of these metabolic diseases. In this study, the long-term effects of neonatal intake of oleanolic acid (OA) on the AMPK gene, genes associated with glucose transport and lipid metabolism, adiponectin levels, and inflammatory biomarkers in rats fed with a high fructose diet were investigated. Seven day old pups were randomly divided into five groups and treated as follows; 0.5% dimethylsulphoxide v/v in distilled water vehicle control (CON), oleanolic acid (OA, 60 mg/kg), high fructose diet (HF, 20% w/v), high fructose diet combined with oleanolic acid (HF+OA), and high fructose diet combined with metformin (HF+MET, 500 mg/kg). The treatments were administered once daily until day 14. The rats were then weaned at day 21 and fed standard rat chow and had ad libitum access to plain drinking water until day 112. The quantitative polymerase chain reaction (qPCR) was used to analyze the gene expressions of AMPK, Glut-4, Cpt-1, AdipoR1, AdipoR2, TNF-α, and IL-6 in the skeletal muscles. Bio-Plex Pro magnetic bead-based assay was used to measure plasma levels of inflammatory markers (TNF-α, IL-6, VEGF, and MCP-1) while ELISA kits were used to measure adiponectin concentration in blood plasma. The results obtained in this study showed that neonatal supplementation with OA significantly increased AMPK gene expression approximately ~4-fold in OA fed rats compared to those that were fed with HF alone. In addition, glut-4 gene expression was also significantly higher in the OA treatment group compared to all the other experimental groups except the CON group whereas Cpt-1 gene was more expressed when OA was administered alone. Together, these results indicated that OA can play a role in glucose and lipid metabolism gene regulation. Furthermore, the results showed that the OA group had ~1.5-fold increase in adiponectin concentration when comparedto the HF group. Moreover, HF increased levels of inflammatory cytokines, which was attenuated by neonatal administration of OA. Plasma concentration and gene expression in the skeletal muscle for TNF-α and IL-6 were significantly increased in rats that were treated with HF alone when compared to all the other groups. On the contrary, the high levels of TNF-α and IL-6 were reduced when OA was administered. These findings suggest that intake of oleanolic acid during the neonatal stage of development could be a potential strategic intervention for the long-term prevention of metabolic diseases such as T2D and obesity.

PL - 023 Effects of Oleanolic Acid on Omega-3 and 6 Fatty Acids Metabolism in Rats fed with High Fructose Diet

2018 ◽  
Vol 1 (1) ◽  
Author(s):  
Sandile Fuku
Keyword(s):  
Gene Expression ◽  
Lipid Metabolism ◽  
Oleanolic Acid ◽  
Therapeutic Potential ◽  
Gas Chromatography Mass Spectrometry ◽  
Omega 3 ◽  
Expression Levels ◽  
High Fructose Diet ◽  
High Fructose ◽  
Anti Inflammatory

Objective The present study investigated the effect of OA on metabolism of omega 3 and 6 together with genes associated with lipid metabolism in high fructose diet fed Sprague Dawley rats.  Methods Real Time PCR qPCR was conducted to evaluate gene expressions levels. Gas Chromatography Mass Spectrometry (GS-MS): Lipid metabolism metabolites were assesed. Measurement of gene expression using qPCR analysis: Expressions levels of glucose transport and lipid metabolism genes were assessed.  Measurements of inflammatory markers concentration in Blood plasma:TNF-α and adiponectin concentrations were determined. Results It was found that high fructose diet decreased gene ex pression levels of NRF-1 and GLUT-4 genes, however administration of OA increased expression levels of these genes.  Furthermore, adiponectin concentration was lowered in HFD group however this was reversed when HFD was accompanied by OA administration.  This increase in concentration of the anti-inflammatory molecule followed the increase in adiponectin receptor, AdipoR1 gene expression in skeletal muscle tissue. The results on lipid metabolism metabolites were consistent the observed molecular events, the anti-inflammatory signaling molecules (EPA and DHA) were five times higher in HF+OA than they were in HFD. High FAS,ACC-2 gene expression levels in HFD group, low 2 expression levels these genes together with increased CPT-1 in OA treated groups coincided with increased levels of arachidonic acid and linoleic acid levels in HFD, threefold increase compared to the control, and decreased levels in OA treated rats.  Conclusions  Supplementation of diet with oleanolic acid produces DHA and EPA, thus modulating anti-inflammatory response and modulating effects of exercise in reversing diabetes.  We provided evidence to effect that diet has a therapeutic potential in managing metabolic syndrome related diseases.

Kombuchas from green and black teas reduce oxidative stress, liver steatosis and inflammation, and improve glucose metabolism in Wistar rats fed a high-fat high-fructose diet

2021 ◽  
Author(s):  
Rodrigo Cardoso ◽  
Luiza Dias Moreira ◽  
Mirian Costa ◽  
Renata Celi Lopes Toledo ◽  
Mariana Grancieri ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Metabolism ◽  
Glucose Metabolism ◽  
Wistar Rats ◽  
Liver Steatosis ◽  
Black Tea ◽  
High Fat ◽  
High Fructose Diet ◽  
High Fructose ◽  
Green And Black Tea

The aim of this study was to evaluate the effect of green and black tea kombuchas consumption on adiposity, lipid metabolism, liver steatosis, oxidative stress, and inflammation in Wistar rats...

Curcumin ameliorates protein expression changes involved in mitochondrial fatty acids metabolism in heart of mice fed a high-fructose diet

2020 ◽  
Author(s):  
Cecilia Gabriela Meléndez-Salcido ◽  
Katya Vargas-Ortiz ◽  
Oscar Gerardo Silva-Gaona ◽  
María Cristina León-García ◽  
Luz Arcelia Ortega-Hernández ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fatty Acids ◽  
Beneficial Effect ◽  
Therapeutic Potential ◽  
Cardiometabolic Disease ◽  
Control Group ◽  
Standard Diet ◽  
High Fructose Diet ◽  
High Fructose ◽  
Fatty Acids Metabolism

Abstract Background: It has been proposed that curcumin modulates the gene expression of different signaling pathways, improve the fatty acids metabolism and exerts a potential beneficial effect on cardiometabolic disease, but this has not been thoroughly demonstrated. In the present study, we evaluated the effect of curcumin upon the expression of PPARα, CPT1, MCAD, VLCAD and ACAA2 in heart of mice fed a high-fructose diet (HFD). Methods: Twenty-four mice C57BL/6 were divided into four groups (n=6) and treated for 15 weeks. Control group (C) received standard diet (SD), Curcumin group (C+Cur), Fructose group (F) and Fructose with Curcumin group (F+Cur). The groups were treated with 0.75% w/w curcumin mixed in the SD and 30% w/v fructose in water, respectively. Heart proteins expression were analyzed by Western Blot. Results: Curcumin supplementation increased PPARα and ACAA2 expression and decreased CPT1 and MCAD expression in heart of mice fed a HFD. However, it did not modify the VLCAD expression. Conclusions: Curcumin regulated PPARα, CPT1 and MCAD expression and increased ACAA2 expression; suggesting a therapeutic potential in the prevention of alterations in mitochondrial fatty acids metabolism in heart of mice fed a HFD.

Rapid impairment of skeletal muscle glucose transport/phosphorylation by free fatty acids in humans

Diabetes ◽  
1999 ◽  
Vol 48 (2) ◽  
pp. 358-364 ◽  
Author(s):  
M. Roden ◽  
M. Krssak ◽  
H. Stingl ◽  
S. Gruber ◽  
A. Hofer ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acids ◽  
Free Fatty Acids ◽  
Glucose Transport ◽  
Muscle Glucose Transport

scholarly journals Free Fatty Acids Impair FGF21 Action in HepG2 Cells

2015 ◽  
Vol 37 (5) ◽  
pp. 1767-1778 ◽  
Author(s):  
Mohamed Asrih ◽  
Christophe Montessuit ◽  
Jacques Philippe ◽  
François R. Jornayvaz
Keyword(s):  
Gene Expression ◽  
Fatty Acids ◽  
Lipid Metabolism ◽  
Free Fatty Acids ◽  
Hepg2 Cells ◽  
Lipid Lowering ◽  
Fibroblast Growth Factor 21 ◽  
Beneficial Effects ◽  
Positive Effects

Background/Aims: Fibroblast growth factor 21 (FGF21) is a key mediator of glucose and lipid metabolism. However, the beneficial effects of exogenous FGF21 administration are attenuated in obese animals and humans with elevated levels of circulating free fatty acids (FFA). Methods: We investigated in vitro how FFA impact FGF21 effects on hepatic lipid metabolism. Results: In the absence of FFA, FGF21 reduced lipogenesis and increased lipid oxidation in HepG2 cells. Inhibition of lipogenesis was associated with a down regulation of SREBP-1c, FAS and SCD1. The lipid-lowering effect was associated with AMPK and ACC phosphorylation, and up regulation of CPT-1α expression. Further, FGF21 treatment reduced TNFα gene expression, suggesting a beneficial action of FGF21 on inflammation. In contrast, the addition of FFA abolished the positive effects of FGF21 on lipid metabolism. Conclusion: In the absence of FFA, FGF21 improves lipid metabolism in HepG2 cells and reduces the inflammatory cytokine TNFα. However, under high levels of FFA, FGF21 action on lipid metabolism and TNFα gene expression is impaired. Therefore, FFA impair FGF21 action in HepG2 cells potentially through TNFα.

scholarly journals Analysis of N6-Methyladenosine Methylation Modification in Fructose-Induced Non-Alcoholic Fatty Liver Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Yunchen Luo ◽  
Zhijian Zhang ◽  
Liping Xiang ◽  
Bing Zhou ◽  
Xuejiao Wang ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Leptin Receptor ◽  
Alcoholic Fatty Liver ◽  
High Fructose Diet ◽  
High Fructose ◽  
Deficient Mice ◽  
Alcoholic Fatty Liver Disease

Improvements in living standards have led to non-alcoholic fatty liver disease (NAFLD), one of the most common chronic liver diseases worldwide. Recent studies have shown that N6-methyladenosine (m6A), a type of RNA modification, is strongly associated with many important biological processes. However, the relationship between m6A methylation modifications and NAFLD remains poorly understood. In the present study, through methylated RNA immunoprecipitation sequencing and RNA transcriptome sequencing in high fructose diet-induced NAFLD mice, we found that hypermethylation-encoding genes were mainly enriched in lipid metabolism processes. We identified 266 overlapping and differentially expressed genes (DEGs) that changed at both the mRNA expression level and m6A modification level. Among them, 193 genes displayed increased expression and m6A modification, indicating that m6A RNA modifications tend to be positively correlated with NAFLD. We further compared the high fructose diet-induced NAFLD mouse model with leptin receptor-deficient mice and found that DEGs enriched in the lipid metabolism pathway were up-regulated in both groups. In contrast, DEGs associated with the immune inflammatory response were up-regulated in the high fructose diet group, but down-regulated in leptin receptor-deficient mice. Taken together, our results demonstrate that m6A methylation modifications may play an important role in the development of NAFLD.

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