BAIBA attenuates insulin resistance and inflammation induced by palmitate or a high fat diet via an AMPK–PPARδ-dependent pathway in mice
Aims/hypothesis We explored the effects of β-aminoisobutyric acid (BAIBA) on hyperlipidaemic-condition-induced insulin resistance and inflammation as mediated through a signalling pathway involving AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor δ (PPARδ). Methods...
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| Veröffentlicht in: | Diabetologia 2015-09, Vol.58 (9), p.2096-2105 |
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| creator | Jung, Tae Woo Hwang, Hwan-Jin Hong, Ho Cheol Yoo, Hye Jin Baik, Sei Hyun Choi, Kyung Mook |
| description | Aims/hypothesis
We explored the effects of β-aminoisobutyric acid (BAIBA) on hyperlipidaemic-condition-induced insulin resistance and inflammation as mediated through a signalling pathway involving AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor δ (PPARδ).
Methods
Mouse skeletal muscle C2C12 cells and C57BL/6J mice were treated with palmitate or a high-fat diet (HFD) and BAIBA. Inflammation and the expression of genes associated with insulin signalling were determined by western blot and quantitative real-time PCR. Selected genes from candidate pathways were evaluated by small interfering (si)RNA knockdown and specific inhibitors.
Results
BAIBA treatment ameliorated impairment of insulin receptor substrate (IRS)-1/Akt-mediated insulin signalling in palmitate-treated C2C12 myocytes and in skeletal muscle of HFD-fed mice. In addition, BAIBA treatment reversed HFD-induced increases in body weight and improved impaired glucose tolerance in mice. In vitro and in vivo, inhibitory κBα (IκBα) phosphorylation, nuclear factor κB (NFκB) nuclear translocation and downstream inflammatory cytokines were significantly suppressed by BAIBA. Furthermore, BAIBA treatment significantly induced AMPK phosphorylation and expression of PPARδ in C2C12 myocytes and in skeletal muscle of mice. Both compound C, an AMPK inhibitor, and
Pparδ
(also known as
Ppard
) siRNA abrogated the inhibitory effects of BAIBA on palmitate-induced inflammation and insulin resistance. BAIBA significantly induced the expression of genes associated with fatty acid oxidation, such as carnitine palmitoyltransferase 1 (
Cpt1
), acyl-CoA oxidase (
Aco
; also known as
Acox1
) and fatty acid binding protein 3 (
Fabp3
); this effect of BAIBA was significantly reduced by compound C and
Pparδ
siRNA.
Conclusions/interpretation
These results are the first to demonstrate that BAIBA attenuates insulin resistance, suppresses inflammation and induces fatty acid oxidation via the AMPK–PPARδ pathway in skeletal muscle. |
| doi_str_mv | 10.1007/s00125-015-3663-z |
| format | Article |
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We explored the effects of β-aminoisobutyric acid (BAIBA) on hyperlipidaemic-condition-induced insulin resistance and inflammation as mediated through a signalling pathway involving AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor δ (PPARδ).
Methods
Mouse skeletal muscle C2C12 cells and C57BL/6J mice were treated with palmitate or a high-fat diet (HFD) and BAIBA. Inflammation and the expression of genes associated with insulin signalling were determined by western blot and quantitative real-time PCR. Selected genes from candidate pathways were evaluated by small interfering (si)RNA knockdown and specific inhibitors.
Results
BAIBA treatment ameliorated impairment of insulin receptor substrate (IRS)-1/Akt-mediated insulin signalling in palmitate-treated C2C12 myocytes and in skeletal muscle of HFD-fed mice. In addition, BAIBA treatment reversed HFD-induced increases in body weight and improved impaired glucose tolerance in mice. In vitro and in vivo, inhibitory κBα (IκBα) phosphorylation, nuclear factor κB (NFκB) nuclear translocation and downstream inflammatory cytokines were significantly suppressed by BAIBA. Furthermore, BAIBA treatment significantly induced AMPK phosphorylation and expression of PPARδ in C2C12 myocytes and in skeletal muscle of mice. Both compound C, an AMPK inhibitor, and
Pparδ
(also known as
Ppard
) siRNA abrogated the inhibitory effects of BAIBA on palmitate-induced inflammation and insulin resistance. BAIBA significantly induced the expression of genes associated with fatty acid oxidation, such as carnitine palmitoyltransferase 1 (
Cpt1
), acyl-CoA oxidase (
Aco
; also known as
Acox1
) and fatty acid binding protein 3 (
Fabp3
); this effect of BAIBA was significantly reduced by compound C and
Pparδ
siRNA.
Conclusions/interpretation
These results are the first to demonstrate that BAIBA attenuates insulin resistance, suppresses inflammation and induces fatty acid oxidation via the AMPK–PPARδ pathway in skeletal muscle.</description><identifier>ISSN: 0012-186X</identifier><identifier>EISSN: 1432-0428</identifier><identifier>DOI: 10.1007/s00125-015-3663-z</identifier><identifier>PMID: 26105792</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Active Transport, Cell Nucleus ; Aminoisobutyric Acids - chemistry ; AMP-Activated Protein Kinases - metabolism ; Animals ; Carnitine O-Palmitoyltransferase - metabolism ; Diabetes Mellitus - metabolism ; Diet, High-Fat - adverse effects ; Fatty Acids - chemistry ; Gene Expression Regulation ; Glucose Tolerance Test ; Human Physiology ; Inflammation - physiopathology ; Insulin - metabolism ; Insulin Resistance ; Internal Medicine ; Male ; Medicine ; Medicine & Public Health ; Metabolic Diseases ; Mice ; Mice, Inbred C57BL ; Muscle Fibers, Skeletal - metabolism ; NF-kappa B - metabolism ; Oxygen - chemistry ; Palmitates - adverse effects ; Receptors, Cytoplasmic and Nuclear - metabolism ; RNA, Small Interfering - metabolism ; Signal Transduction</subject><ispartof>Diabetologia, 2015-09, Vol.58 (9), p.2096-2105</ispartof><rights>Springer-Verlag Berlin Heidelberg 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c457t-f94e8b65eed4e63836b6dcd39af8e21f0a2d3e91bfe0a3c3e769e1f6cb6ea1fe3</citedby><cites>FETCH-LOGICAL-c457t-f94e8b65eed4e63836b6dcd39af8e21f0a2d3e91bfe0a3c3e769e1f6cb6ea1fe3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00125-015-3663-z$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00125-015-3663-z$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26105792$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jung, Tae Woo</creatorcontrib><creatorcontrib>Hwang, Hwan-Jin</creatorcontrib><creatorcontrib>Hong, Ho Cheol</creatorcontrib><creatorcontrib>Yoo, Hye Jin</creatorcontrib><creatorcontrib>Baik, Sei Hyun</creatorcontrib><creatorcontrib>Choi, Kyung Mook</creatorcontrib><title>BAIBA attenuates insulin resistance and inflammation induced by palmitate or a high fat diet via an AMPK–PPARδ-dependent pathway in mice</title><title>Diabetologia</title><addtitle>Diabetologia</addtitle><addtitle>Diabetologia</addtitle><description>Aims/hypothesis
We explored the effects of β-aminoisobutyric acid (BAIBA) on hyperlipidaemic-condition-induced insulin resistance and inflammation as mediated through a signalling pathway involving AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor δ (PPARδ).
Methods
Mouse skeletal muscle C2C12 cells and C57BL/6J mice were treated with palmitate or a high-fat diet (HFD) and BAIBA. Inflammation and the expression of genes associated with insulin signalling were determined by western blot and quantitative real-time PCR. Selected genes from candidate pathways were evaluated by small interfering (si)RNA knockdown and specific inhibitors.
Results
BAIBA treatment ameliorated impairment of insulin receptor substrate (IRS)-1/Akt-mediated insulin signalling in palmitate-treated C2C12 myocytes and in skeletal muscle of HFD-fed mice. In addition, BAIBA treatment reversed HFD-induced increases in body weight and improved impaired glucose tolerance in mice. In vitro and in vivo, inhibitory κBα (IκBα) phosphorylation, nuclear factor κB (NFκB) nuclear translocation and downstream inflammatory cytokines were significantly suppressed by BAIBA. Furthermore, BAIBA treatment significantly induced AMPK phosphorylation and expression of PPARδ in C2C12 myocytes and in skeletal muscle of mice. Both compound C, an AMPK inhibitor, and
Pparδ
(also known as
Ppard
) siRNA abrogated the inhibitory effects of BAIBA on palmitate-induced inflammation and insulin resistance. BAIBA significantly induced the expression of genes associated with fatty acid oxidation, such as carnitine palmitoyltransferase 1 (
Cpt1
), acyl-CoA oxidase (
Aco
; also known as
Acox1
) and fatty acid binding protein 3 (
Fabp3
); this effect of BAIBA was significantly reduced by compound C and
Pparδ
siRNA.
Conclusions/interpretation
These results are the first to demonstrate that BAIBA attenuates insulin resistance, suppresses inflammation and induces fatty acid oxidation via the AMPK–PPARδ pathway in skeletal muscle.</description><subject>Active Transport, Cell Nucleus</subject><subject>Aminoisobutyric Acids - chemistry</subject><subject>AMP-Activated Protein Kinases - metabolism</subject><subject>Animals</subject><subject>Carnitine O-Palmitoyltransferase - metabolism</subject><subject>Diabetes Mellitus - metabolism</subject><subject>Diet, High-Fat - adverse effects</subject><subject>Fatty Acids - chemistry</subject><subject>Gene Expression Regulation</subject><subject>Glucose Tolerance Test</subject><subject>Human Physiology</subject><subject>Inflammation - physiopathology</subject><subject>Insulin - metabolism</subject><subject>Insulin Resistance</subject><subject>Internal Medicine</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metabolic Diseases</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Muscle Fibers, Skeletal - metabolism</subject><subject>NF-kappa B - metabolism</subject><subject>Oxygen - chemistry</subject><subject>Palmitates - adverse effects</subject><subject>Receptors, Cytoplasmic and Nuclear - metabolism</subject><subject>RNA, Small Interfering - metabolism</subject><subject>Signal Transduction</subject><issn>0012-186X</issn><issn>1432-0428</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU1uFDEQhS1ERIbAAdggL9mY-Kfb3b3sRPxEBGWEQGJnue1yxlG3e7DdoMmKPUuuwjk4RE6CRxNYsipV1fueVPUQesboS0Zpc5ooZbwmlNVESCnI7QO0YpXghFa8fYhW-zVhrfx8jB6ndEMpFXUlH6FjLhmtm46v0I-z_uKsxzpnCIvOkLAPaRl9wBGST1kHA1gHW8Zu1NOks59DaexiwOJhh7d6nHwuJJ4j1njjrzfY6Yyth4y_el1g3L9fv7v7_nO97j_8_kUsbCFYCLmwefNN74odnryBJ-jI6THB0_t6gj69fvXx_C25vHpzcd5fElPVTSauq6AdZA1gK5CiFXKQ1ljRadcCZ45qbgV0bHBAtTACGtkBc9IMEjRzIE7Qi4PvNs5fFkhZTT4ZGEcdYF6SYg3lsq4a2hUpO0hNnFOK4NQ2-knHnWJU7TNQhwxUyUDtM1C3hXl-b78ME9h_xN-nFwE_CFJZhWuI6mZeYign_8f1D8RulkM</recordid><startdate>20150901</startdate><enddate>20150901</enddate><creator>Jung, Tae Woo</creator><creator>Hwang, Hwan-Jin</creator><creator>Hong, Ho Cheol</creator><creator>Yoo, Hye Jin</creator><creator>Baik, Sei Hyun</creator><creator>Choi, Kyung Mook</creator><general>Springer Berlin Heidelberg</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>7X8</scope></search><sort><creationdate>20150901</creationdate><title>BAIBA attenuates insulin resistance and inflammation induced by palmitate or a high fat diet via an AMPK–PPARδ-dependent pathway in mice</title><author>Jung, Tae Woo ; Hwang, Hwan-Jin ; Hong, Ho Cheol ; Yoo, Hye Jin ; Baik, Sei Hyun ; Choi, Kyung Mook</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c457t-f94e8b65eed4e63836b6dcd39af8e21f0a2d3e91bfe0a3c3e769e1f6cb6ea1fe3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Active Transport, Cell Nucleus</topic><topic>Aminoisobutyric Acids - chemistry</topic><topic>AMP-Activated Protein Kinases - metabolism</topic><topic>Animals</topic><topic>Carnitine O-Palmitoyltransferase - metabolism</topic><topic>Diabetes Mellitus - metabolism</topic><topic>Diet, High-Fat - adverse effects</topic><topic>Fatty Acids - chemistry</topic><topic>Gene Expression Regulation</topic><topic>Glucose Tolerance Test</topic><topic>Human Physiology</topic><topic>Inflammation - physiopathology</topic><topic>Insulin - metabolism</topic><topic>Insulin Resistance</topic><topic>Internal Medicine</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Metabolic Diseases</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Muscle Fibers, Skeletal - metabolism</topic><topic>NF-kappa B - metabolism</topic><topic>Oxygen - chemistry</topic><topic>Palmitates - adverse effects</topic><topic>Receptors, Cytoplasmic and Nuclear - metabolism</topic><topic>RNA, Small Interfering - metabolism</topic><topic>Signal Transduction</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jung, Tae Woo</creatorcontrib><creatorcontrib>Hwang, Hwan-Jin</creatorcontrib><creatorcontrib>Hong, Ho Cheol</creatorcontrib><creatorcontrib>Yoo, Hye Jin</creatorcontrib><creatorcontrib>Baik, Sei Hyun</creatorcontrib><creatorcontrib>Choi, Kyung Mook</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Diabetologia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jung, Tae Woo</au><au>Hwang, Hwan-Jin</au><au>Hong, Ho Cheol</au><au>Yoo, Hye Jin</au><au>Baik, Sei Hyun</au><au>Choi, Kyung Mook</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>BAIBA attenuates insulin resistance and inflammation induced by palmitate or a high fat diet via an AMPK–PPARδ-dependent pathway in mice</atitle><jtitle>Diabetologia</jtitle><stitle>Diabetologia</stitle><addtitle>Diabetologia</addtitle><date>2015-09-01</date><risdate>2015</risdate><volume>58</volume><issue>9</issue><spage>2096</spage><epage>2105</epage><pages>2096-2105</pages><issn>0012-186X</issn><eissn>1432-0428</eissn><abstract>Aims/hypothesis
We explored the effects of β-aminoisobutyric acid (BAIBA) on hyperlipidaemic-condition-induced insulin resistance and inflammation as mediated through a signalling pathway involving AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor δ (PPARδ).
Methods
Mouse skeletal muscle C2C12 cells and C57BL/6J mice were treated with palmitate or a high-fat diet (HFD) and BAIBA. Inflammation and the expression of genes associated with insulin signalling were determined by western blot and quantitative real-time PCR. Selected genes from candidate pathways were evaluated by small interfering (si)RNA knockdown and specific inhibitors.
Results
BAIBA treatment ameliorated impairment of insulin receptor substrate (IRS)-1/Akt-mediated insulin signalling in palmitate-treated C2C12 myocytes and in skeletal muscle of HFD-fed mice. In addition, BAIBA treatment reversed HFD-induced increases in body weight and improved impaired glucose tolerance in mice. In vitro and in vivo, inhibitory κBα (IκBα) phosphorylation, nuclear factor κB (NFκB) nuclear translocation and downstream inflammatory cytokines were significantly suppressed by BAIBA. Furthermore, BAIBA treatment significantly induced AMPK phosphorylation and expression of PPARδ in C2C12 myocytes and in skeletal muscle of mice. Both compound C, an AMPK inhibitor, and
Pparδ
(also known as
Ppard
) siRNA abrogated the inhibitory effects of BAIBA on palmitate-induced inflammation and insulin resistance. BAIBA significantly induced the expression of genes associated with fatty acid oxidation, such as carnitine palmitoyltransferase 1 (
Cpt1
), acyl-CoA oxidase (
Aco
; also known as
Acox1
) and fatty acid binding protein 3 (
Fabp3
); this effect of BAIBA was significantly reduced by compound C and
Pparδ
siRNA.
Conclusions/interpretation
These results are the first to demonstrate that BAIBA attenuates insulin resistance, suppresses inflammation and induces fatty acid oxidation via the AMPK–PPARδ pathway in skeletal muscle.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>26105792</pmid><doi>10.1007/s00125-015-3663-z</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Active Transport, Cell Nucleus Aminoisobutyric Acids - chemistry AMP-Activated Protein Kinases - metabolism Animals Carnitine O-Palmitoyltransferase - metabolism Diabetes Mellitus - metabolism Diet, High-Fat - adverse effects Fatty Acids - chemistry Gene Expression Regulation Glucose Tolerance Test Human Physiology Inflammation - physiopathology Insulin - metabolism Insulin Resistance Internal Medicine Male Medicine Medicine & Public Health Metabolic Diseases Mice Mice, Inbred C57BL Muscle Fibers, Skeletal - metabolism NF-kappa B - metabolism Oxygen - chemistry Palmitates - adverse effects Receptors, Cytoplasmic and Nuclear - metabolism RNA, Small Interfering - metabolism Signal Transduction |
| title | BAIBA attenuates insulin resistance and inflammation induced by palmitate or a high fat diet via an AMPK–PPARδ-dependent pathway in mice |
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