Palmitoleate attenuates diet induced insulin resistance and hepatic inflammation independently of...
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POSTER PRESENTATION Open Access Palmitoleate attenuates diet induced insulin resistance and hepatic inflammation independently of PPAR-a Camila O Souza 1* , Alexandre A de S Teixeira 1 , Edson A de Lima 1 , Helena A Batatinha 1 , Sandro M Hirabara 2 , William T Festuccia 3 , José Cesar Rosa Neto 1 From Metabolism, Diet and Disease 2014: Cancer and metabolism Washington DC, USA. 28-30 May 2014 Background Previous studies have showed that the lipokine palmitoleic acid (or palmitoleate) reduces diet induced muscle and liver inflammation and insulin resistance [1] and increases adipose tissue lipolysis, the latter through a mechanism that depends on PPAR-a [2]. Here we tested whether palmitoleate protects from the deleterious effects of a high fat diet (HFD) on glucose homeostasis and liver inflamma- tion and whether PPAR-a is involved in these actions. Materials and methods C57BL (C57) and PPAR- a knockout (KO) mice fed either with a balanced (BD) or HFD during 12 weeks were treated after the 10th week with oleic acid (OLA, 300mg/kg of b.w.) or palmitoleate (PMA, 300mg/kg of b.w.) and evaluated for glucose and insulin tolerances (GTT and ITT), glucose uptake and metabolism, serum levels of aspartate aminotransferase (AST) and hepatic triacylglycerol content and cytokines levels (ELISA) and gene expression (qRT-PCR). Results HFD promotes insulin resistance and hepatic steatosis in both C57 and KO as evidenced by the reduced (p<0.05) muscle insulin stimulated glucose uptake and incorpora- tion and increased (p<0.05) hepatic triacylglycerol content and plasma AST levels. Surprisingly, the hepatic steatosis induced by HFD was associated with liver inflammation in KO, but not C57 mice as shown by the increased (p<0.05) hepatic levels of IL1-b, IL-12 and TNF-a. In spite of these genotype specific phenotypes, HFD increased (p<0.05) TLR4 expression and decreased (p<0.05) the IL1-Ra expression similarly in both C57 and KO. Independently of mice genotype, palmitoleate markedly attenuated the insulin resistance induced by HFD as evidenced by the improved glucose tolerance and response to insulin in the ITT (p<0.05) and increased glucose uptake and incorpora- tion in muscle in vitro (p<0.05). Furthermore, palmitoleate reduced (p<0.05) the serum levels of AST in C57 and decreased (p<0.05) the hepatic levels of IL1-b and IL-12 in KO mice. Finally, palmitoleate reduced the hepatic TLR-4 expression (p<0.05) and increased IL-1Ra expression (p<0.05) in C57 but not in KO. Conclusions We concluded that palmitoleate attenuates diet induced insulin resistance, hepatic steatosis, inflammation and damage through mechanisms that do not depend on PPAR-a. Acknowledgements FAPESP, CNPq, CAPES. Authors’ details 1 Department of Cell and Developmental Biology, University of São Paulo, São Paulo, São Paulo, 05508-000, Brazil. 2 Institute of Physical Activity Sciences and Sports, Cruzeiro do Sul University, São Paulo, São Paulo, 01506-000, Brazil. 3 Department of Physiology and Biophysics, University of São Paulo, São Paulo, São Paulo, 05508-000, Brazil. Published: 28 May 2014 References 1. Cao H, Gerhold K, Mayers JR, et al: Identification of a lipokine, a lipid hormone linking adipose tissue to systemic metabolism. Cell 2008, 134:933-944. 1 Department of Cell and Developmental Biology, University of São Paulo, São Paulo, São Paulo, 05508-000, Brazil Full list of author information is available at the end of the article Souza et al. Cancer & Metabolism 2014, 2(Suppl 1):P52 http://www.cancerandmetabolism.com/content/2/S1/P52 Cancer & Metabolism © 2014 Souza et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Transcript of Palmitoleate attenuates diet induced insulin resistance and hepatic inflammation independently of...
POSTER PRESENTATION Open Access
Palmitoleate attenuates diet induced insulinresistance and hepatic inflammationindependently of PPAR-aCamila O Souza1*, Alexandre A de S Teixeira1, Edson A de Lima1, Helena A Batatinha1, Sandro M Hirabara2,William T Festuccia3, José Cesar Rosa Neto1
From Metabolism, Diet and Disease 2014: Cancer and metabolismWashington DC, USA. 28-30 May 2014
BackgroundPrevious studies have showed that the lipokine palmitoleicacid (or palmitoleate) reduces diet induced muscle andliver inflammation and insulin resistance [1] and increasesadipose tissue lipolysis, the latter through a mechanismthat depends on PPAR-a [2]. Here we tested whetherpalmitoleate protects from the deleterious effects of a highfat diet (HFD) on glucose homeostasis and liver inflamma-tion and whether PPAR-a is involved in these actions.
Materials and methodsC57BL (C57) and PPAR-a knockout (KO) mice fedeither with a balanced (BD) or HFD during 12 weekswere treated after the 10th week with oleic acid (OLA,300mg/kg of b.w.) or palmitoleate (PMA, 300mg/kg ofb.w.) and evaluated for glucose and insulin tolerances(GTT and ITT), glucose uptake and metabolism, serumlevels of aspartate aminotransferase (AST) and hepatictriacylglycerol content and cytokines levels (ELISA) andgene expression (qRT-PCR).
ResultsHFD promotes insulin resistance and hepatic steatosis inboth C57 and KO as evidenced by the reduced (p<0.05)muscle insulin stimulated glucose uptake and incorpora-tion and increased (p<0.05) hepatic triacylglycerol contentand plasma AST levels. Surprisingly, the hepatic steatosisinduced by HFD was associated with liver inflammation inKO, but not C57 mice as shown by the increased (p<0.05)hepatic levels of IL1-b, IL-12 and TNF-a. In spite of thesegenotype specific phenotypes, HFD increased (p<0.05)
TLR4 expression and decreased (p<0.05) the IL1-Raexpression similarly in both C57 and KO. Independentlyof mice genotype, palmitoleate markedly attenuated theinsulin resistance induced by HFD as evidenced by theimproved glucose tolerance and response to insulin in theITT (p<0.05) and increased glucose uptake and incorpora-tion in muscle in vitro (p<0.05). Furthermore, palmitoleatereduced (p<0.05) the serum levels of AST in C57 anddecreased (p<0.05) the hepatic levels of IL1-b and IL-12 inKO mice. Finally, palmitoleate reduced the hepatic TLR-4expression (p<0.05) and increased IL-1Ra expression(p<0.05) in C57 but not in KO.
ConclusionsWe concluded that palmitoleate attenuates diet inducedinsulin resistance, hepatic steatosis, inflammation anddamage through mechanisms that do not depend onPPAR-a.
AcknowledgementsFAPESP, CNPq, CAPES.
Authors’ details1Department of Cell and Developmental Biology, University of São Paulo,São Paulo, São Paulo, 05508-000, Brazil. 2Institute of Physical Activity Sciencesand Sports, Cruzeiro do Sul University, São Paulo, São Paulo, 01506-000,Brazil. 3Department of Physiology and Biophysics, University of São Paulo,São Paulo, São Paulo, 05508-000, Brazil.
Published: 28 May 2014
References1. Cao H, Gerhold K, Mayers JR, et al: Identification of a lipokine, a lipid
hormone linking adipose tissue to systemic metabolism. Cell 2008,134:933-944.
1Department of Cell and Developmental Biology, University of São Paulo,São Paulo, São Paulo, 05508-000, BrazilFull list of author information is available at the end of the article
Souza et al. Cancer & Metabolism 2014, 2(Suppl 1):P52http://www.cancerandmetabolism.com/content/2/S1/P52 Cancer &
Metabolism
© 2014 Souza et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative CommonsAttribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproductionin any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
2. Bolsoni-Lopes A, Festuccia WT, Farias TS, et al: Palmitoleic acid (n-7)increases white adipocyte lipolysis and lipase content in aPPARalphadependent manner. Am J Physiol Endocrinol Metab 2013, 305:E1093-E1102.
doi:10.1186/2049-3002-2-S1-P52Cite this article as: Souza et al.: Palmitoleate attenuates diet inducedinsulin resistance and hepatic inflammation independently of PPAR-a.Cancer & Metabolism 2014 2(Suppl 1):P52.
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