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The role of pioglitazone in antioxidant, anti-inflammatory, and insulin sensitivity in a high fat-carbohydrate diet-induced rat model of insulin resistance
We explored the cascade effects of a high fat-carbohydrate diet (HFCD) and pioglitazone (an anti-diabetic therapy used to treat type 2 diabetes mellitus (T2DM)) on lipid profiles, oxidative stress/antioxidant, insulin, and inflammatory biomarkers in a rat model of insulin resistance. Sixty albino ra...
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| Published in: | Brazilian journal of medical and biological research 2021-01, Vol.54 (8), p.e10782-e10782 |
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| creator | Al-Muzafar, H.M Alshehri, F.S Amin, K.A |
| description | We explored the cascade effects of a high fat-carbohydrate diet (HFCD) and pioglitazone (an anti-diabetic therapy used to treat type 2 diabetes mellitus (T2DM)) on lipid profiles, oxidative stress/antioxidant, insulin, and inflammatory biomarkers in a rat model of insulin resistance. Sixty albino rats (80-90 g) were randomly divided into three dietary groups; 1) standard diet; 2) HFCD diet for 12 weeks to induce an in vivo model of insulin resistance; and 3) HFCD diet plus pioglitazone. Blood and tissue samples were taken to assess hepatic function, lipid profiles, oxidative biomarkers, malondialdehyde (MDA) levels, antioxidant defense biomarkers, including reduced glutathione (GSH), superoxide dismutase (SOD), and the inflammatory markers interleukin-6 (IL-6) and tumor necrotic factor (TNF-[alpha]). HFCD-fed rats had significantly (Pp0.05) increased serum triacylglycerol (TG), total cholesterol (TC), low-density lipoprotein (LDL), alanine transaminase (ALT), and bilirubin levels, but decreased high-density lipoprotein (HDL) levels compared with the normal group. Moreover, serum leptin, resistin, TNF-[alpha], and IL-6 levels were increased significantly in HFCD animals compared with controls. Similarly, HFCD-induced insulin resistance caused antioxidant and cytokine disturbances, which are important therapy targets for pioglitazone. Importantly, administration of this drug ameliorated these changes, normalized leptin and resistin and inflammatory markers by reducing TNF-[alpha] levels. Metabolic cascades of elevated lipid profiles, oxidative stress, insulin, and inflammatory biomarkers are implicated in insulin resistance progression. HFCD induced metabolic cascades comprising hypertriglyceridemia, hyperglycemia, insulin resistance, obesity-associated hormones, and inflammatory biomarkers may be alleviated using pioglitazone. Key words: Pioglitazone; Type 2 diabetes mellitus; Antioxidants; Insulin resistance; Anti-inflammatory |
| doi_str_mv | 10.1590/1414-431X2020e10782 |
| format | article |
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Sixty albino rats (80-90 g) were randomly divided into three dietary groups; 1) standard diet; 2) HFCD diet for 12 weeks to induce an in vivo model of insulin resistance; and 3) HFCD diet plus pioglitazone. Blood and tissue samples were taken to assess hepatic function, lipid profiles, oxidative biomarkers, malondialdehyde (MDA) levels, antioxidant defense biomarkers, including reduced glutathione (GSH), superoxide dismutase (SOD), and the inflammatory markers interleukin-6 (IL-6) and tumor necrotic factor (TNF-[alpha]). HFCD-fed rats had significantly (Pp0.05) increased serum triacylglycerol (TG), total cholesterol (TC), low-density lipoprotein (LDL), alanine transaminase (ALT), and bilirubin levels, but decreased high-density lipoprotein (HDL) levels compared with the normal group. Moreover, serum leptin, resistin, TNF-[alpha], and IL-6 levels were increased significantly in HFCD animals compared with controls. Similarly, HFCD-induced insulin resistance caused antioxidant and cytokine disturbances, which are important therapy targets for pioglitazone. Importantly, administration of this drug ameliorated these changes, normalized leptin and resistin and inflammatory markers by reducing TNF-[alpha] levels. Metabolic cascades of elevated lipid profiles, oxidative stress, insulin, and inflammatory biomarkers are implicated in insulin resistance progression. HFCD induced metabolic cascades comprising hypertriglyceridemia, hyperglycemia, insulin resistance, obesity-associated hormones, and inflammatory biomarkers may be alleviated using pioglitazone. Key words: Pioglitazone; Type 2 diabetes mellitus; Antioxidants; Insulin resistance; Anti-inflammatory</description><identifier>ISSN: 0100-879X</identifier><identifier>ISSN: 1414-431X</identifier><identifier>EISSN: 1414-431X</identifier><identifier>EISSN: 1678-4510</identifier><identifier>DOI: 10.1590/1414-431X2020e10782</identifier><identifier>PMID: 34037093</identifier><language>eng</language><publisher>Ribeirao Preto: Associacao Brasileira de Divulgacao Cientifica (ABDC)</publisher><subject>Alanine ; Alanine transaminase ; Anti-inflammatory ; Anti-inflammatory diet ; Anti-inflammatory drugs ; Antioxidants ; Bilirubin ; BIOLOGY ; Biomarkers ; Cholesterol ; Diabetes mellitus (non-insulin dependent) ; Diabetes therapy ; Diet ; Glutathione ; High carbohydrate diet ; High density lipoprotein ; High fat diet ; Hyperglycemia ; Hypertriglyceridemia ; Hypoglycemic agents ; Inflammation ; Insulin ; Insulin resistance ; Interleukin 6 ; Interleukins ; Leptin ; Lipids ; Low density lipoprotein ; Low density lipoproteins ; Malondialdehyde ; MEDICINE, RESEARCH & EXPERIMENTAL ; Metabolism ; Oxidative stress ; Pioglitazone ; Rodents ; Superoxide ; Superoxide dismutase ; Transaminase ; Triglycerides ; Tumor necrosis factor-α ; Type 2 diabetes ; Type 2 diabetes mellitus</subject><ispartof>Brazilian journal of medical and biological research, 2021-01, Vol.54 (8), p.e10782-e10782</ispartof><rights>COPYRIGHT 2021 Associacao Brasileira de Divulgacao Cientifica (ABDC)</rights><rights>Copyright Revista Brasileira de Pesquisas Medicas 2021</rights><rights>This work is licensed under a Creative Commons Attribution 4.0 International License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c663t-ac06dc060e671195456682b68d42a9cffd8a3ecf71fb20eb1b087cdc1fb936603</citedby><cites>FETCH-LOGICAL-c663t-ac06dc060e671195456682b68d42a9cffd8a3ecf71fb20eb1b087cdc1fb936603</cites><orcidid>0000-0003-2487-8427 ; 0000-0001-5054-4610 ; 0000-0003-0015-2541</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,24150,27924,27925</link.rule.ids></links><search><creatorcontrib>Al-Muzafar, H.M</creatorcontrib><creatorcontrib>Alshehri, F.S</creatorcontrib><creatorcontrib>Amin, K.A</creatorcontrib><title>The role of pioglitazone in antioxidant, anti-inflammatory, and insulin sensitivity in a high fat-carbohydrate diet-induced rat model of insulin resistance</title><title>Brazilian journal of medical and biological research</title><addtitle>Braz J Med Biol Res</addtitle><description>We explored the cascade effects of a high fat-carbohydrate diet (HFCD) and pioglitazone (an anti-diabetic therapy used to treat type 2 diabetes mellitus (T2DM)) on lipid profiles, oxidative stress/antioxidant, insulin, and inflammatory biomarkers in a rat model of insulin resistance. Sixty albino rats (80-90 g) were randomly divided into three dietary groups; 1) standard diet; 2) HFCD diet for 12 weeks to induce an in vivo model of insulin resistance; and 3) HFCD diet plus pioglitazone. Blood and tissue samples were taken to assess hepatic function, lipid profiles, oxidative biomarkers, malondialdehyde (MDA) levels, antioxidant defense biomarkers, including reduced glutathione (GSH), superoxide dismutase (SOD), and the inflammatory markers interleukin-6 (IL-6) and tumor necrotic factor (TNF-[alpha]). HFCD-fed rats had significantly (Pp0.05) increased serum triacylglycerol (TG), total cholesterol (TC), low-density lipoprotein (LDL), alanine transaminase (ALT), and bilirubin levels, but decreased high-density lipoprotein (HDL) levels compared with the normal group. Moreover, serum leptin, resistin, TNF-[alpha], and IL-6 levels were increased significantly in HFCD animals compared with controls. Similarly, HFCD-induced insulin resistance caused antioxidant and cytokine disturbances, which are important therapy targets for pioglitazone. Importantly, administration of this drug ameliorated these changes, normalized leptin and resistin and inflammatory markers by reducing TNF-[alpha] levels. Metabolic cascades of elevated lipid profiles, oxidative stress, insulin, and inflammatory biomarkers are implicated in insulin resistance progression. HFCD induced metabolic cascades comprising hypertriglyceridemia, hyperglycemia, insulin resistance, obesity-associated hormones, and inflammatory biomarkers may be alleviated using pioglitazone. Key words: Pioglitazone; Type 2 diabetes mellitus; Antioxidants; Insulin resistance; Anti-inflammatory</description><subject>Alanine</subject><subject>Alanine transaminase</subject><subject>Anti-inflammatory</subject><subject>Anti-inflammatory diet</subject><subject>Anti-inflammatory drugs</subject><subject>Antioxidants</subject><subject>Bilirubin</subject><subject>BIOLOGY</subject><subject>Biomarkers</subject><subject>Cholesterol</subject><subject>Diabetes mellitus (non-insulin dependent)</subject><subject>Diabetes therapy</subject><subject>Diet</subject><subject>Glutathione</subject><subject>High carbohydrate diet</subject><subject>High density lipoprotein</subject><subject>High fat diet</subject><subject>Hyperglycemia</subject><subject>Hypertriglyceridemia</subject><subject>Hypoglycemic agents</subject><subject>Inflammation</subject><subject>Insulin</subject><subject>Insulin resistance</subject><subject>Interleukin 6</subject><subject>Interleukins</subject><subject>Leptin</subject><subject>Lipids</subject><subject>Low density lipoprotein</subject><subject>Low density lipoproteins</subject><subject>Malondialdehyde</subject><subject>MEDICINE, RESEARCH & EXPERIMENTAL</subject><subject>Metabolism</subject><subject>Oxidative stress</subject><subject>Pioglitazone</subject><subject>Rodents</subject><subject>Superoxide</subject><subject>Superoxide dismutase</subject><subject>Transaminase</subject><subject>Triglycerides</subject><subject>Tumor necrosis factor-α</subject><subject>Type 2 diabetes</subject><subject>Type 2 diabetes mellitus</subject><issn>0100-879X</issn><issn>1414-431X</issn><issn>1414-431X</issn><issn>1678-4510</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>DOA</sourceid><recordid>eNpdUk1v1DAQjRCIlsIv4BIJCXEgxY4dJ7kgVRUflSpxoEi9WY492XjlxMV2qi5_hT_LZLfssiiybE_eezOeeVn2mpJzWrXkA-WUF5zR25KUBCipm_JJdrqPPs1OCSWkaOr29iR7EeOakLIinD7PThgnrCYtO81-3wyQB-8g931-Z_3K2aR--QlyO-VqStY_WIP7--2lsFPv1Diq5MNmCRmExdkhNsIUbbL3Nm221HywqyHvVSq0Cp0fNiaoBLmxkFDFzBpMjpF89AbckvyvUIBoY1KThpfZs165CK8e97Psx-dPN5dfi-tvX64uL64LLQRLhdJEGFwERE1pW_FKiKbsRGN4qVrd96ZRDHRf077DRnW0I02tjcZry4Qg7Cy72ukar9byLthRhY30ysptwIeVVCFZ7UACBV63ynBR93gwnaZdCXXf9JwDthu1zndaUVtwXq79HCYsXn5fhiGXYeC48EgagiW3SPi4I9zN3QhGw5SCckdVHP-Z7CBX_l42lDdNU6PAu0eB4H_OEJMcbdTgnJrAz1GWFStLXrFtrjf_QffllZWgWH7F-QG1UvhinLjHvHoRlRdCcMaqshaHhx6h8DMwWo0G6i3Gjwhv_yEMoFwaonczWmyKx0C2A-rgYwzQ75tBiVycLxePS_T4w8H57A-novPY</recordid><startdate>20210101</startdate><enddate>20210101</enddate><creator>Al-Muzafar, H.M</creator><creator>Alshehri, F.S</creator><creator>Amin, K.A</creator><general>Associacao Brasileira de Divulgacao Cientifica (ABDC)</general><general>Revista Brasileira de Pesquisas Medicas</general><general>Associação Brasileira de Divulgação Científica</general><scope>AAYXX</scope><scope>CITATION</scope><scope>INF</scope><scope>7QG</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>7X8</scope><scope>5PM</scope><scope>GPN</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0003-2487-8427</orcidid><orcidid>https://orcid.org/0000-0001-5054-4610</orcidid><orcidid>https://orcid.org/0000-0003-0015-2541</orcidid></search><sort><creationdate>20210101</creationdate><title>The role of pioglitazone in antioxidant, anti-inflammatory, and insulin sensitivity in a high fat-carbohydrate diet-induced rat model of insulin resistance</title><author>Al-Muzafar, H.M ; 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Sixty albino rats (80-90 g) were randomly divided into three dietary groups; 1) standard diet; 2) HFCD diet for 12 weeks to induce an in vivo model of insulin resistance; and 3) HFCD diet plus pioglitazone. Blood and tissue samples were taken to assess hepatic function, lipid profiles, oxidative biomarkers, malondialdehyde (MDA) levels, antioxidant defense biomarkers, including reduced glutathione (GSH), superoxide dismutase (SOD), and the inflammatory markers interleukin-6 (IL-6) and tumor necrotic factor (TNF-[alpha]). HFCD-fed rats had significantly (Pp0.05) increased serum triacylglycerol (TG), total cholesterol (TC), low-density lipoprotein (LDL), alanine transaminase (ALT), and bilirubin levels, but decreased high-density lipoprotein (HDL) levels compared with the normal group. Moreover, serum leptin, resistin, TNF-[alpha], and IL-6 levels were increased significantly in HFCD animals compared with controls. Similarly, HFCD-induced insulin resistance caused antioxidant and cytokine disturbances, which are important therapy targets for pioglitazone. Importantly, administration of this drug ameliorated these changes, normalized leptin and resistin and inflammatory markers by reducing TNF-[alpha] levels. Metabolic cascades of elevated lipid profiles, oxidative stress, insulin, and inflammatory biomarkers are implicated in insulin resistance progression. HFCD induced metabolic cascades comprising hypertriglyceridemia, hyperglycemia, insulin resistance, obesity-associated hormones, and inflammatory biomarkers may be alleviated using pioglitazone. Key words: Pioglitazone; Type 2 diabetes mellitus; Antioxidants; Insulin resistance; Anti-inflammatory</abstract><cop>Ribeirao Preto</cop><pub>Associacao Brasileira de Divulgacao Cientifica (ABDC)</pub><pmid>34037093</pmid><doi>10.1590/1414-431X2020e10782</doi><orcidid>https://orcid.org/0000-0003-2487-8427</orcidid><orcidid>https://orcid.org/0000-0001-5054-4610</orcidid><orcidid>https://orcid.org/0000-0003-0015-2541</orcidid><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0100-879X |
| ispartof | Brazilian journal of medical and biological research, 2021-01, Vol.54 (8), p.e10782-e10782 |
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| source | SciELO Brazil |
| subjects | Alanine Alanine transaminase Anti-inflammatory Anti-inflammatory diet Anti-inflammatory drugs Antioxidants Bilirubin BIOLOGY Biomarkers Cholesterol Diabetes mellitus (non-insulin dependent) Diabetes therapy Diet Glutathione High carbohydrate diet High density lipoprotein High fat diet Hyperglycemia Hypertriglyceridemia Hypoglycemic agents Inflammation Insulin Insulin resistance Interleukin 6 Interleukins Leptin Lipids Low density lipoprotein Low density lipoproteins Malondialdehyde MEDICINE, RESEARCH & EXPERIMENTAL Metabolism Oxidative stress Pioglitazone Rodents Superoxide Superoxide dismutase Transaminase Triglycerides Tumor necrosis factor-α Type 2 diabetes Type 2 diabetes mellitus |
| title | The role of pioglitazone in antioxidant, anti-inflammatory, and insulin sensitivity in a high fat-carbohydrate diet-induced rat model of insulin resistance |
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