β-Adrenergic-AMPK Pathway Phosphorylates Acetyl-CoA Carboxylase in a High-epinephrine Rat Model, SPORTS
We established a new animal model called SPORTS (Spontaneously-Running Tokushima-Shikoku) rats, which show high-epinephrine (Epi) levels. Recent reports show that Epi activates adenosine monophosphate (AMP)–activated protein kinase (AMPK) in adipocytes. Acetyl-CoA carboxylase (ACC) is the rate-limit...
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| creator | Hattori, Atsushi Mawatari, Kazuaki Tsuzuki, Satomi Yoshioka, Emiko Toda, Satomi Yoshida, Masaki Yasui, Sonoko Furukawa, Hiroko Morishima, Masaki Ono, Katasushige Ohnishi, Takamasa Nakano,Masayuki Harada, Nagakatsu Takahashi, Akira Nayaya, Yutaka |
| description | We established a new animal model called SPORTS (Spontaneously-Running Tokushima-Shikoku) rats, which show high-epinephrine (Epi) levels. Recent reports show that Epi activates adenosine monophosphate (AMP)–activated protein kinase (AMPK) in adipocytes. Acetyl-CoA carboxylase (ACC) is the rate-limiting enzyme in fatty acid synthesis, and the enzymatic activity is suppressed when its Ser-79 is phosphorylated by AMPK. The aim of this study was to investigate the in vivo effect of Epi on ACC and abdominal visceral fat accumulation. We divided both 6-week male control and SPORTS rats into two groups, which were fed either normal diet or high fat and sucrose (HFS) diet for 16 weeks. At the end of diet treatment, retroperitoneal fat was collected for western blotting and histological analysis. Food intake was not different among the groups, but SPORTS rats showed significantly lower weight gain than control rats in both diet groups. After 10 weeks of diet treatment, glucose tolerance tests (GTTs) revealed that SPORTS rats had increased insulin sensitivity. Furthermore, SPORTS rats had lower quantities of both abdominal fat and plasma triglyceride (TG). In abdominal fat, elevated ACC Ser-79 phosphorylation was observed in SPORTS rats and suppressed by an antagonist of β-adrenergic receptor (AR), propranolol, or an inhibitor of AMPK, Compound C. From these results, high level of Epi induced ACC phosphorylation mediated through β-AR and AMPK signaling pathways in abdominal visceral fat of SPORTS rats, which may contribute to reduce abdominal visceral fat accumulation and increase insulin sensitivity. Our results suggest that β-AR-regulated ACC activity would be a target for treating lifestyle-related diseases, such as obesity. |
| doi_str_mv | 10.1038/oby.2009.145 |
| format | Article |
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Recent reports show that Epi activates adenosine monophosphate (AMP)–activated protein kinase (AMPK) in adipocytes. Acetyl-CoA carboxylase (ACC) is the rate-limiting enzyme in fatty acid synthesis, and the enzymatic activity is suppressed when its Ser-79 is phosphorylated by AMPK. The aim of this study was to investigate the in vivo effect of Epi on ACC and abdominal visceral fat accumulation. We divided both 6-week male control and SPORTS rats into two groups, which were fed either normal diet or high fat and sucrose (HFS) diet for 16 weeks. At the end of diet treatment, retroperitoneal fat was collected for western blotting and histological analysis. Food intake was not different among the groups, but SPORTS rats showed significantly lower weight gain than control rats in both diet groups. After 10 weeks of diet treatment, glucose tolerance tests (GTTs) revealed that SPORTS rats had increased insulin sensitivity. Furthermore, SPORTS rats had lower quantities of both abdominal fat and plasma triglyceride (TG). In abdominal fat, elevated ACC Ser-79 phosphorylation was observed in SPORTS rats and suppressed by an antagonist of β-adrenergic receptor (AR), propranolol, or an inhibitor of AMPK, Compound C. From these results, high level of Epi induced ACC phosphorylation mediated through β-AR and AMPK signaling pathways in abdominal visceral fat of SPORTS rats, which may contribute to reduce abdominal visceral fat accumulation and increase insulin sensitivity. Our results suggest that β-AR-regulated ACC activity would be a target for treating lifestyle-related diseases, such as obesity.</description><identifier>ISSN: 1930-7381</identifier><identifier>EISSN: 1930-739X</identifier><identifier>DOI: 10.1038/oby.2009.145</identifier><identifier>PMID: 19444233</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>abdominal fat ; acetyl-CoA carboxylase ; Acetyl-CoA Carboxylase - metabolism ; adenosine monophosphate ; adipocytes ; Adrenergic beta-Antagonists - pharmacology ; AMP-Activated Protein Kinases - metabolism ; Analysis of Variance ; animal models ; Animals ; antagonists ; Blood Glucose - metabolism ; Blotting, Western ; Body Weight - drug effects ; Body Weight - physiology ; Eating ; enzyme activity ; Enzyme-Linked Immunosorbent Assay ; Epinephrine - metabolism ; fatty acids ; food intake ; Glucose Tolerance Test ; glucose tolerance tests ; high fat diet ; Insulin - blood ; insulin resistance ; Intra-Abdominal Fat - drug effects ; Intra-Abdominal Fat - metabolism ; Male ; males ; obesity ; Obesity - metabolism ; phosphorylation ; Phosphorylation - drug effects ; propranolol ; Propranolol - pharmacology ; Pyrazoles - pharmacology ; Pyrimidines - pharmacology ; Rats ; Receptors, Adrenergic, beta - metabolism ; signal transduction ; sports ; sucrose ; triacylglycerols ; Up-Regulation - drug effects ; visceral fat ; weight gain ; Western blotting</subject><ispartof>Obesity (Silver Spring, Md.), 2010-01, Vol.18 (1), p.48-54</ispartof><rights>2010 North American Association for the Study of Obesity (NAASO)</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3812-f7c9535189145dd64c1013f6579b9a152d307fbc4968ba98104ac835d825feb23</citedby><cites>FETCH-LOGICAL-c3812-f7c9535189145dd64c1013f6579b9a152d307fbc4968ba98104ac835d825feb23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1038%2Foby.2009.145$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1038%2Foby.2009.145$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1416,1432,27915,27916,45565,45566,46400,46824</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19444233$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hattori, Atsushi</creatorcontrib><creatorcontrib>Mawatari, Kazuaki</creatorcontrib><creatorcontrib>Tsuzuki, Satomi</creatorcontrib><creatorcontrib>Yoshioka, Emiko</creatorcontrib><creatorcontrib>Toda, Satomi</creatorcontrib><creatorcontrib>Yoshida, Masaki</creatorcontrib><creatorcontrib>Yasui, Sonoko</creatorcontrib><creatorcontrib>Furukawa, Hiroko</creatorcontrib><creatorcontrib>Morishima, Masaki</creatorcontrib><creatorcontrib>Ono, Katasushige</creatorcontrib><creatorcontrib>Ohnishi, Takamasa</creatorcontrib><creatorcontrib>Nakano,Masayuki</creatorcontrib><creatorcontrib>Harada, Nagakatsu</creatorcontrib><creatorcontrib>Takahashi, Akira</creatorcontrib><creatorcontrib>Nayaya, Yutaka</creatorcontrib><title>β-Adrenergic-AMPK Pathway Phosphorylates Acetyl-CoA Carboxylase in a High-epinephrine Rat Model, SPORTS</title><title>Obesity (Silver Spring, Md.)</title><addtitle>Obesity (Silver Spring)</addtitle><description>We established a new animal model called SPORTS (Spontaneously-Running Tokushima-Shikoku) rats, which show high-epinephrine (Epi) levels. Recent reports show that Epi activates adenosine monophosphate (AMP)–activated protein kinase (AMPK) in adipocytes. Acetyl-CoA carboxylase (ACC) is the rate-limiting enzyme in fatty acid synthesis, and the enzymatic activity is suppressed when its Ser-79 is phosphorylated by AMPK. The aim of this study was to investigate the in vivo effect of Epi on ACC and abdominal visceral fat accumulation. We divided both 6-week male control and SPORTS rats into two groups, which were fed either normal diet or high fat and sucrose (HFS) diet for 16 weeks. At the end of diet treatment, retroperitoneal fat was collected for western blotting and histological analysis. Food intake was not different among the groups, but SPORTS rats showed significantly lower weight gain than control rats in both diet groups. After 10 weeks of diet treatment, glucose tolerance tests (GTTs) revealed that SPORTS rats had increased insulin sensitivity. Furthermore, SPORTS rats had lower quantities of both abdominal fat and plasma triglyceride (TG). In abdominal fat, elevated ACC Ser-79 phosphorylation was observed in SPORTS rats and suppressed by an antagonist of β-adrenergic receptor (AR), propranolol, or an inhibitor of AMPK, Compound C. From these results, high level of Epi induced ACC phosphorylation mediated through β-AR and AMPK signaling pathways in abdominal visceral fat of SPORTS rats, which may contribute to reduce abdominal visceral fat accumulation and increase insulin sensitivity. Our results suggest that β-AR-regulated ACC activity would be a target for treating lifestyle-related diseases, such as obesity.</description><subject>abdominal fat</subject><subject>acetyl-CoA carboxylase</subject><subject>Acetyl-CoA Carboxylase - metabolism</subject><subject>adenosine monophosphate</subject><subject>adipocytes</subject><subject>Adrenergic beta-Antagonists - pharmacology</subject><subject>AMP-Activated Protein Kinases - metabolism</subject><subject>Analysis of Variance</subject><subject>animal models</subject><subject>Animals</subject><subject>antagonists</subject><subject>Blood Glucose - metabolism</subject><subject>Blotting, Western</subject><subject>Body Weight - drug effects</subject><subject>Body Weight - physiology</subject><subject>Eating</subject><subject>enzyme activity</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Epinephrine - metabolism</subject><subject>fatty acids</subject><subject>food intake</subject><subject>Glucose Tolerance Test</subject><subject>glucose tolerance tests</subject><subject>high fat diet</subject><subject>Insulin - blood</subject><subject>insulin resistance</subject><subject>Intra-Abdominal Fat - drug effects</subject><subject>Intra-Abdominal Fat - metabolism</subject><subject>Male</subject><subject>males</subject><subject>obesity</subject><subject>Obesity - metabolism</subject><subject>phosphorylation</subject><subject>Phosphorylation - drug effects</subject><subject>propranolol</subject><subject>Propranolol - pharmacology</subject><subject>Pyrazoles - pharmacology</subject><subject>Pyrimidines - pharmacology</subject><subject>Rats</subject><subject>Receptors, Adrenergic, beta - metabolism</subject><subject>signal transduction</subject><subject>sports</subject><subject>sucrose</subject><subject>triacylglycerols</subject><subject>Up-Regulation - drug effects</subject><subject>visceral fat</subject><subject>weight gain</subject><subject>Western blotting</subject><issn>1930-7381</issn><issn>1930-739X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kM1u1DAUha2Kqi2FHWvwjk0zvf7Jj5dhBBS11Yw6rQQry3GcSVAmDnZGJa_VB-kz4SijsuvGtq6-c-7xQegDgQUBll3aYlxQALEgPD5CZ0QwiFImfr55eWfkFL31_jcATyAmJ-iUCM45ZewM1c9PUV460xm3bXSU366v8VoN9aMa8bq2vq-tG1s1GI9zbYaxjZY2x0vlCvs3zL3BTYcVvmq2dWT6pjN97cKJ79SAb21p2gu8Wa_u7jfv0HGlWm_eH-5z9PDt6_3yKrpZff-xzG8iHXLSqEq1iFlMMhG-U5YJ1wQIq5I4FYVQJKYlg7QqNBdJViiREeBKZywuMxpXpqDsHH2efXtn_-yNH-Su8dq0reqM3XuZMpYQSPlEXsykdtZ7ZyrZu2an3CgJyKlaGaqVU7UyZAn4x4PxvtiZ8j986DIAZAYem9aMr5rJ1ZdfNKVTBjxrOjXsnXkRBXhi572fZqRSVqqta7x82FAgCQCkCQjB_gEYYpb8</recordid><startdate>201001</startdate><enddate>201001</enddate><creator>Hattori, Atsushi</creator><creator>Mawatari, Kazuaki</creator><creator>Tsuzuki, Satomi</creator><creator>Yoshioka, Emiko</creator><creator>Toda, Satomi</creator><creator>Yoshida, Masaki</creator><creator>Yasui, Sonoko</creator><creator>Furukawa, Hiroko</creator><creator>Morishima, Masaki</creator><creator>Ono, Katasushige</creator><creator>Ohnishi, Takamasa</creator><creator>Nakano,Masayuki</creator><creator>Harada, Nagakatsu</creator><creator>Takahashi, Akira</creator><creator>Nayaya, Yutaka</creator><general>Blackwell Publishing Ltd</general><scope>FBQ</scope><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>201001</creationdate><title>β-Adrenergic-AMPK Pathway Phosphorylates Acetyl-CoA Carboxylase in a High-epinephrine Rat Model, SPORTS</title><author>Hattori, Atsushi ; Mawatari, Kazuaki ; Tsuzuki, Satomi ; Yoshioka, Emiko ; Toda, Satomi ; Yoshida, Masaki ; Yasui, Sonoko ; Furukawa, Hiroko ; Morishima, Masaki ; Ono, Katasushige ; Ohnishi, Takamasa ; Nakano,Masayuki ; Harada, Nagakatsu ; Takahashi, Akira ; Nayaya, Yutaka</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3812-f7c9535189145dd64c1013f6579b9a152d307fbc4968ba98104ac835d825feb23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>abdominal fat</topic><topic>acetyl-CoA carboxylase</topic><topic>Acetyl-CoA Carboxylase - metabolism</topic><topic>adenosine monophosphate</topic><topic>adipocytes</topic><topic>Adrenergic beta-Antagonists - pharmacology</topic><topic>AMP-Activated Protein Kinases - metabolism</topic><topic>Analysis of Variance</topic><topic>animal models</topic><topic>Animals</topic><topic>antagonists</topic><topic>Blood Glucose - metabolism</topic><topic>Blotting, Western</topic><topic>Body Weight - drug effects</topic><topic>Body Weight - physiology</topic><topic>Eating</topic><topic>enzyme activity</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Epinephrine - metabolism</topic><topic>fatty acids</topic><topic>food intake</topic><topic>Glucose Tolerance Test</topic><topic>glucose tolerance tests</topic><topic>high fat diet</topic><topic>Insulin - blood</topic><topic>insulin resistance</topic><topic>Intra-Abdominal Fat - drug effects</topic><topic>Intra-Abdominal Fat - metabolism</topic><topic>Male</topic><topic>males</topic><topic>obesity</topic><topic>Obesity - metabolism</topic><topic>phosphorylation</topic><topic>Phosphorylation - drug effects</topic><topic>propranolol</topic><topic>Propranolol - pharmacology</topic><topic>Pyrazoles - pharmacology</topic><topic>Pyrimidines - pharmacology</topic><topic>Rats</topic><topic>Receptors, Adrenergic, beta - metabolism</topic><topic>signal transduction</topic><topic>sports</topic><topic>sucrose</topic><topic>triacylglycerols</topic><topic>Up-Regulation - drug effects</topic><topic>visceral fat</topic><topic>weight gain</topic><topic>Western blotting</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hattori, Atsushi</creatorcontrib><creatorcontrib>Mawatari, Kazuaki</creatorcontrib><creatorcontrib>Tsuzuki, Satomi</creatorcontrib><creatorcontrib>Yoshioka, Emiko</creatorcontrib><creatorcontrib>Toda, Satomi</creatorcontrib><creatorcontrib>Yoshida, Masaki</creatorcontrib><creatorcontrib>Yasui, Sonoko</creatorcontrib><creatorcontrib>Furukawa, Hiroko</creatorcontrib><creatorcontrib>Morishima, Masaki</creatorcontrib><creatorcontrib>Ono, Katasushige</creatorcontrib><creatorcontrib>Ohnishi, Takamasa</creatorcontrib><creatorcontrib>Nakano,Masayuki</creatorcontrib><creatorcontrib>Harada, Nagakatsu</creatorcontrib><creatorcontrib>Takahashi, Akira</creatorcontrib><creatorcontrib>Nayaya, Yutaka</creatorcontrib><collection>AGRIS</collection><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>Obesity (Silver Spring, Md.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hattori, Atsushi</au><au>Mawatari, Kazuaki</au><au>Tsuzuki, Satomi</au><au>Yoshioka, Emiko</au><au>Toda, Satomi</au><au>Yoshida, Masaki</au><au>Yasui, Sonoko</au><au>Furukawa, Hiroko</au><au>Morishima, Masaki</au><au>Ono, Katasushige</au><au>Ohnishi, Takamasa</au><au>Nakano,Masayuki</au><au>Harada, Nagakatsu</au><au>Takahashi, Akira</au><au>Nayaya, Yutaka</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>β-Adrenergic-AMPK Pathway Phosphorylates Acetyl-CoA Carboxylase in a High-epinephrine Rat Model, SPORTS</atitle><jtitle>Obesity (Silver Spring, Md.)</jtitle><addtitle>Obesity (Silver Spring)</addtitle><date>2010-01</date><risdate>2010</risdate><volume>18</volume><issue>1</issue><spage>48</spage><epage>54</epage><pages>48-54</pages><issn>1930-7381</issn><eissn>1930-739X</eissn><abstract>We established a new animal model called SPORTS (Spontaneously-Running Tokushima-Shikoku) rats, which show high-epinephrine (Epi) levels. Recent reports show that Epi activates adenosine monophosphate (AMP)–activated protein kinase (AMPK) in adipocytes. Acetyl-CoA carboxylase (ACC) is the rate-limiting enzyme in fatty acid synthesis, and the enzymatic activity is suppressed when its Ser-79 is phosphorylated by AMPK. The aim of this study was to investigate the in vivo effect of Epi on ACC and abdominal visceral fat accumulation. We divided both 6-week male control and SPORTS rats into two groups, which were fed either normal diet or high fat and sucrose (HFS) diet for 16 weeks. At the end of diet treatment, retroperitoneal fat was collected for western blotting and histological analysis. Food intake was not different among the groups, but SPORTS rats showed significantly lower weight gain than control rats in both diet groups. After 10 weeks of diet treatment, glucose tolerance tests (GTTs) revealed that SPORTS rats had increased insulin sensitivity. Furthermore, SPORTS rats had lower quantities of both abdominal fat and plasma triglyceride (TG). In abdominal fat, elevated ACC Ser-79 phosphorylation was observed in SPORTS rats and suppressed by an antagonist of β-adrenergic receptor (AR), propranolol, or an inhibitor of AMPK, Compound C. From these results, high level of Epi induced ACC phosphorylation mediated through β-AR and AMPK signaling pathways in abdominal visceral fat of SPORTS rats, which may contribute to reduce abdominal visceral fat accumulation and increase insulin sensitivity. Our results suggest that β-AR-regulated ACC activity would be a target for treating lifestyle-related diseases, such as obesity.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>19444233</pmid><doi>10.1038/oby.2009.145</doi><tpages>7</tpages></addata></record> |
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| subjects | abdominal fat acetyl-CoA carboxylase Acetyl-CoA Carboxylase - metabolism adenosine monophosphate adipocytes Adrenergic beta-Antagonists - pharmacology AMP-Activated Protein Kinases - metabolism Analysis of Variance animal models Animals antagonists Blood Glucose - metabolism Blotting, Western Body Weight - drug effects Body Weight - physiology Eating enzyme activity Enzyme-Linked Immunosorbent Assay Epinephrine - metabolism fatty acids food intake Glucose Tolerance Test glucose tolerance tests high fat diet Insulin - blood insulin resistance Intra-Abdominal Fat - drug effects Intra-Abdominal Fat - metabolism Male males obesity Obesity - metabolism phosphorylation Phosphorylation - drug effects propranolol Propranolol - pharmacology Pyrazoles - pharmacology Pyrimidines - pharmacology Rats Receptors, Adrenergic, beta - metabolism signal transduction sports sucrose triacylglycerols Up-Regulation - drug effects visceral fat weight gain Western blotting |
| title | β-Adrenergic-AMPK Pathway Phosphorylates Acetyl-CoA Carboxylase in a High-epinephrine Rat Model, SPORTS |
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