Regulation of adipocyte differentiation and metabolism by lansoprazole
Lansoprazole (LPZ) is one of the most commonly prescribed drugs for treatment of acid-related diseases, and it is increasingly recognized for its potential application as an anti-diabetic therapy. Although LPZ target tissues remain poorly understood, possible sites of action include adipose tissue....
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| Veröffentlicht in: | Life sciences (1973) 2019-12, Vol.239, p.116897-116897, Article 116897 |
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| creator | Benchamana, Ameena Mori, Hiroyuki MacDougald, Ormond A. Soodvilai, Sunhapas |
| description | Lansoprazole (LPZ) is one of the most commonly prescribed drugs for treatment of acid-related diseases, and it is increasingly recognized for its potential application as an anti-diabetic therapy. Although LPZ target tissues remain poorly understood, possible sites of action include adipose tissue. In this study, we assessed effects of LPZ on adipocyte differentiation and function by using 3T3-L1 preadipocytes and HFD-induced obesity mice as an in vitro and in vivo model, respectively.
Oil red O staining and intracellular triacylglycerol content were used to determine lipid accumulation. Glucose uptake was performed to measure mature adipocyte function. Expression of adipocyte genes was determined by qRT-PCR and immunoblotting.
LPZ has dual effects on differentiation of 3T3-L1 cells. At low concentrations, LPZ enhanced adipocyte differentiation via induction of PPARγ and C/EBPα, two master adipogenic transcription factors, as well as lipogenic proteins, ACC1 and FASN. Increasing of adipocyte number subsequently increased basal and insulin-stimulated glucose uptake, and expression of Glut4 mRNA. Conversely, high concentrations of LPZ strongly inhibited differentiation and expression of PPARγ and C/EBPα, and maintained expression of preadipocytes markers, β-catenin and Pref-1. Inhibition of adipogenesis by LPZ reduced mature adipocyte number, Glut4 mRNA expression and insulin-stimulated glucose uptake. In addition, treatment with LPZ at 200 mg/kg significantly reduced body weight gain and total fat mass in HFD-induced obese mice.
These results indicate that effects of LPZ on adipocyte differentiation are dependent on concentration and are correlated with PPARγ and C/EBPα. |
| doi_str_mv | 10.1016/j.lfs.2019.116897 |
| format | Article |
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Oil red O staining and intracellular triacylglycerol content were used to determine lipid accumulation. Glucose uptake was performed to measure mature adipocyte function. Expression of adipocyte genes was determined by qRT-PCR and immunoblotting.
LPZ has dual effects on differentiation of 3T3-L1 cells. At low concentrations, LPZ enhanced adipocyte differentiation via induction of PPARγ and C/EBPα, two master adipogenic transcription factors, as well as lipogenic proteins, ACC1 and FASN. Increasing of adipocyte number subsequently increased basal and insulin-stimulated glucose uptake, and expression of Glut4 mRNA. Conversely, high concentrations of LPZ strongly inhibited differentiation and expression of PPARγ and C/EBPα, and maintained expression of preadipocytes markers, β-catenin and Pref-1. Inhibition of adipogenesis by LPZ reduced mature adipocyte number, Glut4 mRNA expression and insulin-stimulated glucose uptake. In addition, treatment with LPZ at 200 mg/kg significantly reduced body weight gain and total fat mass in HFD-induced obese mice.
These results indicate that effects of LPZ on adipocyte differentiation are dependent on concentration and are correlated with PPARγ and C/EBPα.</description><identifier>ISSN: 0024-3205</identifier><identifier>EISSN: 1879-0631</identifier><identifier>DOI: 10.1016/j.lfs.2019.116897</identifier><identifier>PMID: 31644894</identifier><language>eng</language><publisher>Netherlands: Elsevier Inc</publisher><subject>3T3-L1 Cells ; Adipocytes ; Adipocytes - drug effects ; Adipocytes - metabolism ; Adipocytes - physiology ; Adipogenesis ; Adipogenesis - drug effects ; Adipose tissue ; Animals ; Anti-diabetic ; Body fat ; Body weight ; Body weight gain ; CCAAT-Enhancer-Binding Protein-alpha - metabolism ; Cell differentiation ; Cell Differentiation - drug effects ; Diabetes mellitus ; Diet, High-Fat ; Differentiation ; Gene expression ; Glucose ; Glucose Transporter Type 4 - metabolism ; Immunoblotting ; In vivo methods and tests ; Insulin ; Insulin - metabolism ; Lansoprazole ; Lansoprazole - metabolism ; Lansoprazole - pharmacology ; Lipid Metabolism - drug effects ; Lipids ; Lipogenesis ; Low concentrations ; Male ; Medical treatment ; Metabolism ; Mice ; Mice, Inbred C57BL ; Obesity ; Obesity - metabolism ; PPAR gamma - metabolism ; Preadipocytes ; Proton pump inhibitor ; Transcription factors ; Triglycerides ; Triglycerides - metabolism ; Weight reduction ; β-Catenin</subject><ispartof>Life sciences (1973), 2019-12, Vol.239, p.116897-116897, Article 116897</ispartof><rights>2019 Elsevier Inc.</rights><rights>Copyright © 2019 Elsevier Inc. All rights reserved.</rights><rights>Copyright Elsevier BV Dec 15, 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c545t-f85a7ad4336ef62499e8bfe6e1b381b3fa88c0c230c02da3c55beecc15e86ea73</citedby><cites>FETCH-LOGICAL-c545t-f85a7ad4336ef62499e8bfe6e1b381b3fa88c0c230c02da3c55beecc15e86ea73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.lfs.2019.116897$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,315,781,785,886,3551,27929,27930,46000</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31644894$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Benchamana, Ameena</creatorcontrib><creatorcontrib>Mori, Hiroyuki</creatorcontrib><creatorcontrib>MacDougald, Ormond A.</creatorcontrib><creatorcontrib>Soodvilai, Sunhapas</creatorcontrib><title>Regulation of adipocyte differentiation and metabolism by lansoprazole</title><title>Life sciences (1973)</title><addtitle>Life Sci</addtitle><description>Lansoprazole (LPZ) is one of the most commonly prescribed drugs for treatment of acid-related diseases, and it is increasingly recognized for its potential application as an anti-diabetic therapy. Although LPZ target tissues remain poorly understood, possible sites of action include adipose tissue. In this study, we assessed effects of LPZ on adipocyte differentiation and function by using 3T3-L1 preadipocytes and HFD-induced obesity mice as an in vitro and in vivo model, respectively.
Oil red O staining and intracellular triacylglycerol content were used to determine lipid accumulation. Glucose uptake was performed to measure mature adipocyte function. Expression of adipocyte genes was determined by qRT-PCR and immunoblotting.
LPZ has dual effects on differentiation of 3T3-L1 cells. At low concentrations, LPZ enhanced adipocyte differentiation via induction of PPARγ and C/EBPα, two master adipogenic transcription factors, as well as lipogenic proteins, ACC1 and FASN. Increasing of adipocyte number subsequently increased basal and insulin-stimulated glucose uptake, and expression of Glut4 mRNA. Conversely, high concentrations of LPZ strongly inhibited differentiation and expression of PPARγ and C/EBPα, and maintained expression of preadipocytes markers, β-catenin and Pref-1. Inhibition of adipogenesis by LPZ reduced mature adipocyte number, Glut4 mRNA expression and insulin-stimulated glucose uptake. In addition, treatment with LPZ at 200 mg/kg significantly reduced body weight gain and total fat mass in HFD-induced obese mice.
These results indicate that effects of LPZ on adipocyte differentiation are dependent on concentration and are correlated with PPARγ and C/EBPα.</description><subject>3T3-L1 Cells</subject><subject>Adipocytes</subject><subject>Adipocytes - drug effects</subject><subject>Adipocytes - metabolism</subject><subject>Adipocytes - physiology</subject><subject>Adipogenesis</subject><subject>Adipogenesis - drug effects</subject><subject>Adipose tissue</subject><subject>Animals</subject><subject>Anti-diabetic</subject><subject>Body fat</subject><subject>Body weight</subject><subject>Body weight gain</subject><subject>CCAAT-Enhancer-Binding Protein-alpha - metabolism</subject><subject>Cell differentiation</subject><subject>Cell Differentiation - drug effects</subject><subject>Diabetes mellitus</subject><subject>Diet, High-Fat</subject><subject>Differentiation</subject><subject>Gene expression</subject><subject>Glucose</subject><subject>Glucose Transporter Type 4 - metabolism</subject><subject>Immunoblotting</subject><subject>In vivo methods and tests</subject><subject>Insulin</subject><subject>Insulin - metabolism</subject><subject>Lansoprazole</subject><subject>Lansoprazole - metabolism</subject><subject>Lansoprazole - pharmacology</subject><subject>Lipid Metabolism - drug effects</subject><subject>Lipids</subject><subject>Lipogenesis</subject><subject>Low concentrations</subject><subject>Male</subject><subject>Medical treatment</subject><subject>Metabolism</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Obesity</subject><subject>Obesity - metabolism</subject><subject>PPAR gamma - metabolism</subject><subject>Preadipocytes</subject><subject>Proton pump inhibitor</subject><subject>Transcription factors</subject><subject>Triglycerides</subject><subject>Triglycerides - metabolism</subject><subject>Weight reduction</subject><subject>β-Catenin</subject><issn>0024-3205</issn><issn>1879-0631</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU1L5TAUhoM46PXjB7iRghs3vZPvpgiCiDoDwsAwrkOanmgubXNNWuH6641URV3M4pDFec57zpsXoSOClwQT-XO17FxaUkzqJSFS1dUWWhBV1SWWjGyjBcaUl4xisYv2UlphjIWo2A7aZURyrmq-QNd_4X7qzOjDUARXmNavg92MULTeOYgwjH5umqEtehhNEzqf-qLZFJ0ZUlhH8xw6OEA_nOkSHL69--ju-urf5a_y9s_N78uL29IKLsbSKWEq03LGJDhJeV2DahxIIA1TuZxRymJLGbaYtoZZIRoAa4kAJcFUbB-dz7rrqemhtfm-aDq9jr43caOD8fprZ_AP-j486QoLVVORBU7fBGJ4nCCNuvfJQpfNQJiSzquVoFRKntGTb-gqTHHI9jLFWM0lVTJTZKZsDClFcB_HEKxfU9IrnVPSrynpOaU8c_zZxcfEeywZOJsByH_55CHqZD0MFlofwY66Df4_8i9k66R-</recordid><startdate>20191215</startdate><enddate>20191215</enddate><creator>Benchamana, Ameena</creator><creator>Mori, Hiroyuki</creator><creator>MacDougald, Ormond A.</creator><creator>Soodvilai, Sunhapas</creator><general>Elsevier Inc</general><general>Elsevier BV</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7U7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20191215</creationdate><title>Regulation of adipocyte differentiation and metabolism by lansoprazole</title><author>Benchamana, Ameena ; Mori, Hiroyuki ; MacDougald, Ormond A. ; Soodvilai, Sunhapas</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c545t-f85a7ad4336ef62499e8bfe6e1b381b3fa88c0c230c02da3c55beecc15e86ea73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>3T3-L1 Cells</topic><topic>Adipocytes</topic><topic>Adipocytes - drug effects</topic><topic>Adipocytes - metabolism</topic><topic>Adipocytes - physiology</topic><topic>Adipogenesis</topic><topic>Adipogenesis - drug effects</topic><topic>Adipose tissue</topic><topic>Animals</topic><topic>Anti-diabetic</topic><topic>Body fat</topic><topic>Body weight</topic><topic>Body weight gain</topic><topic>CCAAT-Enhancer-Binding Protein-alpha - metabolism</topic><topic>Cell differentiation</topic><topic>Cell Differentiation - drug effects</topic><topic>Diabetes mellitus</topic><topic>Diet, High-Fat</topic><topic>Differentiation</topic><topic>Gene expression</topic><topic>Glucose</topic><topic>Glucose Transporter Type 4 - metabolism</topic><topic>Immunoblotting</topic><topic>In vivo methods and tests</topic><topic>Insulin</topic><topic>Insulin - metabolism</topic><topic>Lansoprazole</topic><topic>Lansoprazole - metabolism</topic><topic>Lansoprazole - pharmacology</topic><topic>Lipid Metabolism - drug effects</topic><topic>Lipids</topic><topic>Lipogenesis</topic><topic>Low concentrations</topic><topic>Male</topic><topic>Medical treatment</topic><topic>Metabolism</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Obesity</topic><topic>Obesity - metabolism</topic><topic>PPAR gamma - metabolism</topic><topic>Preadipocytes</topic><topic>Proton pump inhibitor</topic><topic>Transcription factors</topic><topic>Triglycerides</topic><topic>Triglycerides - metabolism</topic><topic>Weight reduction</topic><topic>β-Catenin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Benchamana, Ameena</creatorcontrib><creatorcontrib>Mori, Hiroyuki</creatorcontrib><creatorcontrib>MacDougald, Ormond A.</creatorcontrib><creatorcontrib>Soodvilai, Sunhapas</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Life sciences (1973)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Benchamana, Ameena</au><au>Mori, Hiroyuki</au><au>MacDougald, Ormond A.</au><au>Soodvilai, Sunhapas</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Regulation of adipocyte differentiation and metabolism by lansoprazole</atitle><jtitle>Life sciences (1973)</jtitle><addtitle>Life Sci</addtitle><date>2019-12-15</date><risdate>2019</risdate><volume>239</volume><spage>116897</spage><epage>116897</epage><pages>116897-116897</pages><artnum>116897</artnum><issn>0024-3205</issn><eissn>1879-0631</eissn><abstract>Lansoprazole (LPZ) is one of the most commonly prescribed drugs for treatment of acid-related diseases, and it is increasingly recognized for its potential application as an anti-diabetic therapy. Although LPZ target tissues remain poorly understood, possible sites of action include adipose tissue. In this study, we assessed effects of LPZ on adipocyte differentiation and function by using 3T3-L1 preadipocytes and HFD-induced obesity mice as an in vitro and in vivo model, respectively.
Oil red O staining and intracellular triacylglycerol content were used to determine lipid accumulation. Glucose uptake was performed to measure mature adipocyte function. Expression of adipocyte genes was determined by qRT-PCR and immunoblotting.
LPZ has dual effects on differentiation of 3T3-L1 cells. At low concentrations, LPZ enhanced adipocyte differentiation via induction of PPARγ and C/EBPα, two master adipogenic transcription factors, as well as lipogenic proteins, ACC1 and FASN. Increasing of adipocyte number subsequently increased basal and insulin-stimulated glucose uptake, and expression of Glut4 mRNA. Conversely, high concentrations of LPZ strongly inhibited differentiation and expression of PPARγ and C/EBPα, and maintained expression of preadipocytes markers, β-catenin and Pref-1. Inhibition of adipogenesis by LPZ reduced mature adipocyte number, Glut4 mRNA expression and insulin-stimulated glucose uptake. In addition, treatment with LPZ at 200 mg/kg significantly reduced body weight gain and total fat mass in HFD-induced obese mice.
These results indicate that effects of LPZ on adipocyte differentiation are dependent on concentration and are correlated with PPARγ and C/EBPα.</abstract><cop>Netherlands</cop><pub>Elsevier Inc</pub><pmid>31644894</pmid><doi>10.1016/j.lfs.2019.116897</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Access via ScienceDirect (Elsevier) |
| subjects | 3T3-L1 Cells Adipocytes Adipocytes - drug effects Adipocytes - metabolism Adipocytes - physiology Adipogenesis Adipogenesis - drug effects Adipose tissue Animals Anti-diabetic Body fat Body weight Body weight gain CCAAT-Enhancer-Binding Protein-alpha - metabolism Cell differentiation Cell Differentiation - drug effects Diabetes mellitus Diet, High-Fat Differentiation Gene expression Glucose Glucose Transporter Type 4 - metabolism Immunoblotting In vivo methods and tests Insulin Insulin - metabolism Lansoprazole Lansoprazole - metabolism Lansoprazole - pharmacology Lipid Metabolism - drug effects Lipids Lipogenesis Low concentrations Male Medical treatment Metabolism Mice Mice, Inbred C57BL Obesity Obesity - metabolism PPAR gamma - metabolism Preadipocytes Proton pump inhibitor Transcription factors Triglycerides Triglycerides - metabolism Weight reduction β-Catenin |
| title | Regulation of adipocyte differentiation and metabolism by lansoprazole |
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