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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 Jan 22; 11(2)N

Abstract

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.

Authors+Show Affiliations

Department of Biochemistry, Faculty of Natural and Agricultural Science, North West University, Mafikeng Campus, Private Bag X2046, Mmabatho 2735, South Africa. mgmatumba@gmail.com.Department of Biochemistry, Faculty of Science, Adeleke University, P.M.B. 250, Ede, Osun State 232101, Nigeria. ademola.ayeleso@adelekeuniversity.edu.ng.Department of Human Anatomy and Physiology, Faculty of Health Sciences, University of Johannesburg, Doornfontein, Johannesburg 2028, South Africa. trevorn@uj.ac.za.School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Parktown, Johannesburg 2193, South Africa. kennedy.erlwanger@wits.ac.za.DST-NRF Centre of Excellence for Biomedical Tuberculosis Research and South African Medical Research Council Centre for Tuberculosis Research, Department of Biomedical Sciences, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg 7505, South Africa. novel@sun.ac.za.Department of Biochemistry, Faculty of Natural and Agricultural Science, North West University, Mafikeng Campus, Private Bag X2046, Mmabatho 2735, South Africa. emmanuel.mukwevho@nwu.ac.za.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30678182

Citation

Matumba, Mashudu Given, et al. "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, vol. 11, no. 2, 2019.
Matumba MG, Ayeleso AO, Nyakudya T, et al. 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;11(2).
Matumba, M. G., Ayeleso, A. O., Nyakudya, T., Erlwanger, K., Chegou, N. N., & Mukwevho, E. (2019). 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, 11(2). https://doi.org/10.3390/nu11020226
Matumba MG, et al. 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 Jan 22;11(2) PubMed PMID: 30678182.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Matumba,Mashudu Given, AU - Ayeleso,Ademola Olabode, AU - Nyakudya,Trevor, AU - Erlwanger,Kennedy, AU - Chegou,Novel N, AU - Mukwevho,Emmanuel, Y1 - 2019/01/22/ PY - 2018/10/23/received PY - 2018/12/06/revised PY - 2018/12/07/accepted PY - 2019/1/26/entrez PY - 2019/1/27/pubmed PY - 2019/4/10/medline KW - AMPK KW - adiponectin KW - high fructose diet KW - inflammatory cytokines KW - metabolic syndrome KW - obesity KW - oleanolic acid KW - type-2 diabetes JF - Nutrients JO - Nutrients VL - 11 IS - 2 N2 - 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. SN - 2072-6643 UR - https://www.unboundmedicine.com/medline/citation/30678182/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_ L2 - http://www.mdpi.com/resolver?pii=nu11020226 DB - PRIME DP - Unbound Medicine ER -