Peripheral, But Not Central, Administration of Adiponectin Reduces Visceral Adiposity and Upregulates the Expression of Uncoupling Protein in Agouti Yellow (Ay/a) Obese Mice

Peripheral, But Not Central, Administration of Adiponectin Reduces Visceral Adiposity and Upregulates the Expression of Uncoupling Protein in Agouti Yellow ( A y /a ) Obese Mice Takayuki Masaki 1 , Seiichi Chiba 1 , Tohru Yasuda 1 , Tetsuo Tsubone 1 , Tetsuya Kakuma 1 , Iichiro Shimomura 2 , Tohru F...

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Veröffentlicht in:Diabetes (New York, N.Y.) N.Y.), 2003-09, Vol.52 (9), p.2266-2273
Hauptverfasser: MASAKI, Takayuki, CHIBA, Seiichi, YASUDA, Tohru, TSUBONE, Tetsuo, KAKUMA, Tetsuya, SHIMOMURA, Iichiro, FUNAHASHI, Tohru, MATSUZAWA, Yuji, YOSHIMATSU, Hironobu
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container_title Diabetes (New York, N.Y.)
container_volume 52
creator MASAKI, Takayuki
CHIBA, Seiichi
YASUDA, Tohru
TSUBONE, Tetsuo
KAKUMA, Tetsuya
SHIMOMURA, Iichiro
FUNAHASHI, Tohru
MATSUZAWA, Yuji
YOSHIMATSU, Hironobu
description Peripheral, But Not Central, Administration of Adiponectin Reduces Visceral Adiposity and Upregulates the Expression of Uncoupling Protein in Agouti Yellow ( A y /a ) Obese Mice Takayuki Masaki 1 , Seiichi Chiba 1 , Tohru Yasuda 1 , Tetsuo Tsubone 1 , Tetsuya Kakuma 1 , Iichiro Shimomura 2 , Tohru Funahashi 3 , Yuji Matsuzawa 3 and Hironobu Yoshimatsu 1 1 Department of Internal Medicine, School of Medicine, Oita Medical University, Oita, Japan 2 Department of Medicine and Pathophysiology, Graduate School of Medicine, Osaka University, Osaka, Japan 3 Department of Internal Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan Address correspondence and reprint requests to Dr. Takayuki Masaki, Department of Internal Medicine, School of Medicine, Oita Medical University, Hasama, Oita, 879-5593, Japan. E-mail: masaki{at}oita-med.ac.jp Abstract To examine the peripheral and central roles of adiponectin in energy intake and expenditure, we investigated the effects of adiponectin on food intake, adiposity, sympathetic nerve activity (SNA), and mRNA expressions of uncoupling protein (UCP) in the brown adipose tissue (BAT), white adipose tissue (WAT) and skeletal muscle in agouti yellow ( A y /a ) obese mice. Intraperitoneal administration of adiponectin (1.5 mg/kg for 7 days) attenuated body weight gain and reduced visceral adiposity in A y /a obese mice compared with PBS-treated controls. In addition, adiponectin treatment increased the expression of UCP1 mRNA in BAT, UCP2 mRNA in WAT, and UCP3 mRNA in skeletal muscle compared with PBS-treated A y /a controls. Acute peripheral administration of adiponectin (1.5 mg/kg, one injection) also increased SNA in the BAT accompanied by an increase in rectal temperature. Finally, these above responses as well as expression of c-Fos–like immunohistochemistry in the hypothalamus were not induced by central application of adiponectin (0–15 μg/kg). Taken together, adiponectin effectively regulated visceral adiposity, SNA, and UCP mRNA expression peripherally, suggesting that this substance can be used as a therapeutic tool, administered peripherally, in the treatment of visceral obesity and related metabolic disorders. ARC, arcuate nucleus BAT, brown adipose tissue ICV, intracerebroventricular PVN, paraventricular nucleus SNA, sympathetic nerve activity UCP, uncoupling protein VMH, ventromedial hypothalamus WAT, white adipose tissue Footnotes Accepted June 18, 2003. Received March 18, 2003. DIABETES
doi_str_mv 10.2337/diabetes.52.9.2266
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E-mail: masaki{at}oita-med.ac.jp Abstract To examine the peripheral and central roles of adiponectin in energy intake and expenditure, we investigated the effects of adiponectin on food intake, adiposity, sympathetic nerve activity (SNA), and mRNA expressions of uncoupling protein (UCP) in the brown adipose tissue (BAT), white adipose tissue (WAT) and skeletal muscle in agouti yellow ( A y /a ) obese mice. Intraperitoneal administration of adiponectin (1.5 mg/kg for 7 days) attenuated body weight gain and reduced visceral adiposity in A y /a obese mice compared with PBS-treated controls. In addition, adiponectin treatment increased the expression of UCP1 mRNA in BAT, UCP2 mRNA in WAT, and UCP3 mRNA in skeletal muscle compared with PBS-treated A y /a controls. Acute peripheral administration of adiponectin (1.5 mg/kg, one injection) also increased SNA in the BAT accompanied by an increase in rectal temperature. Finally, these above responses as well as expression of c-Fos–like immunohistochemistry in the hypothalamus were not induced by central application of adiponectin (0–15 μg/kg). Taken together, adiponectin effectively regulated visceral adiposity, SNA, and UCP mRNA expression peripherally, suggesting that this substance can be used as a therapeutic tool, administered peripherally, in the treatment of visceral obesity and related metabolic disorders. ARC, arcuate nucleus BAT, brown adipose tissue ICV, intracerebroventricular PVN, paraventricular nucleus SNA, sympathetic nerve activity UCP, uncoupling protein VMH, ventromedial hypothalamus WAT, white adipose tissue Footnotes Accepted June 18, 2003. Received March 18, 2003. DIABETES</description><identifier>ISSN: 0012-1797</identifier><identifier>EISSN: 1939-327X</identifier><identifier>DOI: 10.2337/diabetes.52.9.2266</identifier><identifier>PMID: 12941765</identifier><identifier>CODEN: DIAEAZ</identifier><language>eng</language><publisher>Alexandria, VA: American Diabetes Association</publisher><subject>Adiponectin ; Adipose tissue ; Adipose Tissue, Brown - drug effects ; Adipose tissues ; Animals ; Biological and medical sciences ; Blood Glucose - drug effects ; Body Temperature - drug effects ; Body Weight - drug effects ; Carrier Proteins - genetics ; Diabetes ; Diabetes mellitus ; Diabetes. Impaired glucose tolerance ; Eating - drug effects ; Endocrine pancreas. 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E-mail: masaki{at}oita-med.ac.jp Abstract To examine the peripheral and central roles of adiponectin in energy intake and expenditure, we investigated the effects of adiponectin on food intake, adiposity, sympathetic nerve activity (SNA), and mRNA expressions of uncoupling protein (UCP) in the brown adipose tissue (BAT), white adipose tissue (WAT) and skeletal muscle in agouti yellow ( A y /a ) obese mice. Intraperitoneal administration of adiponectin (1.5 mg/kg for 7 days) attenuated body weight gain and reduced visceral adiposity in A y /a obese mice compared with PBS-treated controls. In addition, adiponectin treatment increased the expression of UCP1 mRNA in BAT, UCP2 mRNA in WAT, and UCP3 mRNA in skeletal muscle compared with PBS-treated A y /a controls. Acute peripheral administration of adiponectin (1.5 mg/kg, one injection) also increased SNA in the BAT accompanied by an increase in rectal temperature. Finally, these above responses as well as expression of c-Fos–like immunohistochemistry in the hypothalamus were not induced by central application of adiponectin (0–15 μg/kg). Taken together, adiponectin effectively regulated visceral adiposity, SNA, and UCP mRNA expression peripherally, suggesting that this substance can be used as a therapeutic tool, administered peripherally, in the treatment of visceral obesity and related metabolic disorders. ARC, arcuate nucleus BAT, brown adipose tissue ICV, intracerebroventricular PVN, paraventricular nucleus SNA, sympathetic nerve activity UCP, uncoupling protein VMH, ventromedial hypothalamus WAT, white adipose tissue Footnotes Accepted June 18, 2003. Received March 18, 2003. DIABETES</description><subject>Adiponectin</subject><subject>Adipose tissue</subject><subject>Adipose Tissue, Brown - drug effects</subject><subject>Adipose tissues</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Blood Glucose - drug effects</subject><subject>Body Temperature - drug effects</subject><subject>Body Weight - drug effects</subject><subject>Carrier Proteins - genetics</subject><subject>Diabetes</subject><subject>Diabetes mellitus</subject><subject>Diabetes. Impaired glucose tolerance</subject><subject>Eating - drug effects</subject><subject>Endocrine pancreas. Apud cells (diseases)</subject><subject>Endocrinopathies</subject><subject>Gene Expression - drug effects</subject><subject>Hypothalamus - drug effects</subject><subject>Hypothalamus - metabolism</subject><subject>Ingestion</subject><subject>Injections, Intraperitoneal</subject><subject>Injections, Intraventricular</subject><subject>Insulin - blood</subject><subject>Intercellular Signaling Peptides and Proteins</subject><subject>Ion Channels</subject><subject>Liver - drug effects</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Membrane Proteins - genetics</subject><subject>Membrane Transport Proteins</subject><subject>Metabolic diseases</subject><subject>Mice</subject><subject>Mice, Obese</subject><subject>Mitochondrial Proteins</subject><subject>Muscle, Skeletal - drug effects</subject><subject>Muscle, Skeletal - physiology</subject><subject>Obesity</subject><subject>Obesity - drug therapy</subject><subject>Obesity - physiopathology</subject><subject>Physiological aspects</subject><subject>Proteins - genetics</subject><subject>Proteins - pharmacology</subject><subject>Proto-Oncogene Proteins c-fos - metabolism</subject><subject>RNA, Messenger - analysis</subject><subject>Triglycerides - blood</subject><subject>Uncoupling Protein 1</subject><subject>Uncoupling Protein 2</subject><subject>Up-Regulation - drug effects</subject><subject>Viscera</subject><issn>0012-1797</issn><issn>1939-327X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNptkt2KEzEUxwdR3Lr6Al5IEBQXnW4-ZprJZS3rKlS7iBW9CpnMmWmWaTJOMuz2oXxHU1splXJCQk5-5yN_TpI8J3hMGeOXlVElBPDjnI7FmNLJ5EEyIoKJlFH-42EywpjQlHDBz5In3t9ijCfRHidnhIqM8Ek-Sn7fQG-6FfSqfYfeDwF9cQHNwIa_jmm1Ntb4eAnGWeTq6DGds6CDsegrVIMGj74br7cJdo_ehA1StkLLrodmaFXsEIUVoKv76PB-n2hptRu61tgG3fQuQMwX17RxQzDoJ7Stu0NvpptLdYEWJXhAn42Gp8mjWrUenu3P82T54erb7GM6X1x_mk3nqc6LPKQqy4sMKyigrCtW6AkjZZWXWjBVKq0yzqmuMMeZEITirARCea4rXXJe1JpTdp683uXtevdrAB_kevvHtlUW3OAlZ7lgXLAIvvwPvHVDb2NvkpJJVsQNRyjdQY1qQRpbuyiobsBuRYti1ia6pwRznmcFKyI_PsFHq2Bt9MmAi6OAyAS4D40avJfF9fyYTU-x2rUtNCCjjLPFMU93vO6d9z3UsuvNWvUbSbDcjqH8N4Yyp1LI7RjGoBd7WYZyDdUhZD93EXi1B5TXqq17ZbXxBy7HgtM8i9zbHbcyzerO9HCodqLsHwd29lE</recordid><startdate>20030901</startdate><enddate>20030901</enddate><creator>MASAKI, Takayuki</creator><creator>CHIBA, Seiichi</creator><creator>YASUDA, Tohru</creator><creator>TSUBONE, Tetsuo</creator><creator>KAKUMA, Tetsuya</creator><creator>SHIMOMURA, Iichiro</creator><creator>FUNAHASHI, Tohru</creator><creator>MATSUZAWA, Yuji</creator><creator>YOSHIMATSU, Hironobu</creator><general>American Diabetes Association</general><scope>IQODW</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>8GL</scope><scope>3V.</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8AF</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BEC</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>HCIFZ</scope><scope>K9-</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M2P</scope><scope>M7P</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>S0X</scope><scope>7X8</scope></search><sort><creationdate>20030901</creationdate><title>Peripheral, But Not Central, Administration of Adiponectin Reduces Visceral Adiposity and Upregulates the Expression of Uncoupling Protein in Agouti Yellow (Ay/a) Obese Mice</title><author>MASAKI, Takayuki ; CHIBA, Seiichi ; YASUDA, Tohru ; TSUBONE, Tetsuo ; KAKUMA, Tetsuya ; SHIMOMURA, Iichiro ; FUNAHASHI, Tohru ; MATSUZAWA, Yuji ; YOSHIMATSU, Hironobu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c585t-a45840ae8ebfd38c631bd5bc93abaca4772cd0704991204be1275cdcb778fc723</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Adiponectin</topic><topic>Adipose tissue</topic><topic>Adipose Tissue, Brown - drug effects</topic><topic>Adipose tissues</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Blood Glucose - drug effects</topic><topic>Body Temperature - drug effects</topic><topic>Body Weight - drug effects</topic><topic>Carrier Proteins - genetics</topic><topic>Diabetes</topic><topic>Diabetes mellitus</topic><topic>Diabetes. 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Allied Health Database</collection><collection>Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>eLibrary</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>SciTech Premium Collection</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Nursing &amp; Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Consumer Health Database</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>SIRS Editorial</collection><collection>MEDLINE - Academic</collection><jtitle>Diabetes (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>MASAKI, Takayuki</au><au>CHIBA, Seiichi</au><au>YASUDA, Tohru</au><au>TSUBONE, Tetsuo</au><au>KAKUMA, Tetsuya</au><au>SHIMOMURA, Iichiro</au><au>FUNAHASHI, Tohru</au><au>MATSUZAWA, Yuji</au><au>YOSHIMATSU, Hironobu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Peripheral, But Not Central, Administration of Adiponectin Reduces Visceral Adiposity and Upregulates the Expression of Uncoupling Protein in Agouti Yellow (Ay/a) Obese Mice</atitle><jtitle>Diabetes (New York, N.Y.)</jtitle><addtitle>Diabetes</addtitle><date>2003-09-01</date><risdate>2003</risdate><volume>52</volume><issue>9</issue><spage>2266</spage><epage>2273</epage><pages>2266-2273</pages><issn>0012-1797</issn><eissn>1939-327X</eissn><coden>DIAEAZ</coden><abstract>Peripheral, But Not Central, Administration of Adiponectin Reduces Visceral Adiposity and Upregulates the Expression of Uncoupling Protein in Agouti Yellow ( A y /a ) Obese Mice Takayuki Masaki 1 , Seiichi Chiba 1 , Tohru Yasuda 1 , Tetsuo Tsubone 1 , Tetsuya Kakuma 1 , Iichiro Shimomura 2 , Tohru Funahashi 3 , Yuji Matsuzawa 3 and Hironobu Yoshimatsu 1 1 Department of Internal Medicine, School of Medicine, Oita Medical University, Oita, Japan 2 Department of Medicine and Pathophysiology, Graduate School of Medicine, Osaka University, Osaka, Japan 3 Department of Internal Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan Address correspondence and reprint requests to Dr. Takayuki Masaki, Department of Internal Medicine, School of Medicine, Oita Medical University, Hasama, Oita, 879-5593, Japan. E-mail: masaki{at}oita-med.ac.jp Abstract To examine the peripheral and central roles of adiponectin in energy intake and expenditure, we investigated the effects of adiponectin on food intake, adiposity, sympathetic nerve activity (SNA), and mRNA expressions of uncoupling protein (UCP) in the brown adipose tissue (BAT), white adipose tissue (WAT) and skeletal muscle in agouti yellow ( A y /a ) obese mice. Intraperitoneal administration of adiponectin (1.5 mg/kg for 7 days) attenuated body weight gain and reduced visceral adiposity in A y /a obese mice compared with PBS-treated controls. In addition, adiponectin treatment increased the expression of UCP1 mRNA in BAT, UCP2 mRNA in WAT, and UCP3 mRNA in skeletal muscle compared with PBS-treated A y /a controls. Acute peripheral administration of adiponectin (1.5 mg/kg, one injection) also increased SNA in the BAT accompanied by an increase in rectal temperature. Finally, these above responses as well as expression of c-Fos–like immunohistochemistry in the hypothalamus were not induced by central application of adiponectin (0–15 μg/kg). Taken together, adiponectin effectively regulated visceral adiposity, SNA, and UCP mRNA expression peripherally, suggesting that this substance can be used as a therapeutic tool, administered peripherally, in the treatment of visceral obesity and related metabolic disorders. ARC, arcuate nucleus BAT, brown adipose tissue ICV, intracerebroventricular PVN, paraventricular nucleus SNA, sympathetic nerve activity UCP, uncoupling protein VMH, ventromedial hypothalamus WAT, white adipose tissue Footnotes Accepted June 18, 2003. Received March 18, 2003. DIABETES</abstract><cop>Alexandria, VA</cop><pub>American Diabetes Association</pub><pmid>12941765</pmid><doi>10.2337/diabetes.52.9.2266</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record>
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identifier ISSN: 0012-1797
ispartof Diabetes (New York, N.Y.), 2003-09, Vol.52 (9), p.2266-2273
issn 0012-1797
1939-327X
language eng
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source MEDLINE; EZB-FREE-00999 freely available EZB journals
subjects Adiponectin
Adipose tissue
Adipose Tissue, Brown - drug effects
Adipose tissues
Animals
Biological and medical sciences
Blood Glucose - drug effects
Body Temperature - drug effects
Body Weight - drug effects
Carrier Proteins - genetics
Diabetes
Diabetes mellitus
Diabetes. Impaired glucose tolerance
Eating - drug effects
Endocrine pancreas. Apud cells (diseases)
Endocrinopathies
Gene Expression - drug effects
Hypothalamus - drug effects
Hypothalamus - metabolism
Ingestion
Injections, Intraperitoneal
Injections, Intraventricular
Insulin - blood
Intercellular Signaling Peptides and Proteins
Ion Channels
Liver - drug effects
Male
Medical sciences
Membrane Proteins - genetics
Membrane Transport Proteins
Metabolic diseases
Mice
Mice, Obese
Mitochondrial Proteins
Muscle, Skeletal - drug effects
Muscle, Skeletal - physiology
Obesity
Obesity - drug therapy
Obesity - physiopathology
Physiological aspects
Proteins - genetics
Proteins - pharmacology
Proto-Oncogene Proteins c-fos - metabolism
RNA, Messenger - analysis
Triglycerides - blood
Uncoupling Protein 1
Uncoupling Protein 2
Up-Regulation - drug effects
Viscera
title Peripheral, But Not Central, Administration of Adiponectin Reduces Visceral Adiposity and Upregulates the Expression of Uncoupling Protein in Agouti Yellow (Ay/a) Obese Mice
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