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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/cdn\/css\/http\/css_Xg7z6oCTVgud_Q0huYz9x9iiD5H_2YPSJ5z2ZViSWdY.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003EThis article discusses the complex communication between adipocytes and hepatocytes, noting that understanding this crosstalk is important, since it affects the pathophysiology of type 2 diabetes mellitus. Ultimately one needs to consider three domains: the adipose domain, the mediator domain, and the liver domain.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003ECardiometabolic Disorder\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EObesity\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EAssaf Rudich, MD, Ben-Gurion University of Negev, Beer-Sheva, Israel, discussed the complex communication between adipocytes and hepatocytes, noting that understanding this crosstalk is important, since it affects the pathophysiology of type 2 diabetes mellitus. Until very recently, when adipocyte-hepatocyte crosstalk was discussed, the focus was on mediators. There is new evidence, however, that indicates that this is a more complex process, and to understand it, we need to consider three domains: the adipose domain, the mediator domain, and the liver domain.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EAs people become obese, they develop various adipose stresses that are sensed by a specific stress signaling pathway, which, in turn, causes a cascade that translates the stress into a functional alteration of adipose tissue. This alteration causes a change in the mediators (ie, free fatty acids [FFAs], adipokines, cytokines). Hypothesizing on the results of this process, Prof. Rudich noted that it is possible that FFAs participate early on in the natural history of liver disease, in what is sometimes called the \u201cfirst hit\u201d (ie, insulin resistance and steatosis) and that adipokines, via various adipokine- and cytokine-specific pathways, contribute more to the \u201csecond hit,\u201d which is the deterioration of steatosis to nonalcoholic steatohepatitis, fibrosis, and cirrhosis. Having defined this pathway, Prof. Rudich suggested that in order to affect it directly, research should be focused on trying to alleviate the stress of adipose tissue in response to obesity and eliminate the activation of the stress response in adipose tissue (\u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E).\u003C\/p\u003E\u003Cdiv id=\u0022F1\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/10\/9\/37\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Role of the Adipocyte in Liver Hepatic Insulin Resistance \u0026#x2013; From a Paradigm Shift to Paradigm Synthesis.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-909053648\u0022 data-figure-caption=\u0022Role of the Adipocyte in Liver Hepatic Insulin Resistance \u0026#x2013; From a Paradigm Shift to Paradigm Synthesis.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 1.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/10\/9\/37\/F1.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/10\/9\/37\/F1.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 1.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/10\/9\/37\/F1.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/11564\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption attrib\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 1.\u003C\/span\u003E \n            \u003Cp id=\u0022p-4\u0022 class=\u0022first-child\u0022\u003ERole of the Adipocyte in Liver Hepatic Insulin Resistance \u2013 From a Paradigm Shift to Paradigm Synthesis.\u003C\/p\u003E\n         \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-1\u0022\u003EReproduced with permission from A. Rudich, MD.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-5\u0022\u003EObesity can impact cardiac remodeling in a variety of ways. Gary Sweeney, PhD, York University, Toronto, Canada, and Institut Pasteur Korea, reviewed some of the ways in which adipokines directly influence the function of cardiomyocytes. He focused on two important but contrasting adipokines: adiponectin, which decreases in obese individuals, and leptin, which increases in obese individuals [Matsuzawa Y. \u003Cem\u003ENat Rev Cardiol\u003C\/em\u003E 2006; Banerji MA et al. \u003Cem\u003EJ Clin Endocrinol Metab\u003C\/em\u003E 1999].\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003ECardiac remodeling involves various processes that influence the function of the heart, including hypertrophy, apoptosis, fibrosis, and metabolism, all of which are affected by adipokines. Specifically, adiponectin attenuates both myocardial infarction (MI) and angiotension II-induced cardiac hypertrophy [Fuijoka D et al. \u003Cem\u003EAm J Physiol Heart Circ Physiol\u003C\/em\u003E 2006; Wang C et al. \u003Cem\u003ECell Physiol\u003C\/em\u003E 2010]. In animal studies and in vitro, adiponectin has been shown to have antiapoptotic effects on cardiomyocytes [Wang Y et al. \u003Cem\u003EAm J Physiol Endocrinol Metab\u003C\/em\u003E 2010; Shibata R et al. \u003Cem\u003ENat Med\u003C\/em\u003E 2005]. Both leptin and adiponectin can affect myocardial matrix remodeling by acting on the cardiomyocytes, fibroblasts, endothelial cells, and smooth muscle cells [Schram K \u0026amp; Sweeney G. \u003Cem\u003ETrends in Cardiovasc Med\u003C\/em\u003E 2008]. Adiponectin has also been shown to protect against MI and angiotensin II-induced cardiac fibrosis, and it can affect metabolism by increasing uptake of both glucose and fatty acid (\u003Ca id=\u0022xref-fig-2-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F2\u0022\u003EFigure 2\u003C\/a\u003E) [Fujita K et al. \u003Cem\u003EArterioscler Thromb Vasc Biol\u003C\/em\u003E 2008; Palanivel R et al. Cardiovasc Res 2007; Fang X et al. \u003Cem\u003EAm J Physiol Endocrinol Metab\u003C\/em\u003E 2010].\u003C\/p\u003E\u003Cdiv id=\u0022F2\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/10\/9\/37\/F2.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Summary of Effects of Adiponectin on Major Components of Cardiac Remodeling in Heart Failure.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-909053648\u0022 data-figure-caption=\u0022Summary of Effects of Adiponectin on Major Components of Cardiac Remodeling in Heart Failure.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 2.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/10\/9\/37\/F2.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/10\/9\/37\/F2.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 2.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/10\/9\/37\/F2.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/11568\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption attrib\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 2.\u003C\/span\u003E \n            \u003Cp id=\u0022p-7\u0022 class=\u0022first-child\u0022\u003ESummary of Effects of Adiponectin on Major Components of Cardiac Remodeling in Heart Failure.\u003C\/p\u003E\n         \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-2\u0022\u003EReproduced with permission from G. Sweeney, PhD.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-8\u0022\u003ERandy Seeley, PhD, Metabolic Diseases Institute, University of Cincinnati, Cincinnati, Ohio, USA, discussed a new hypothesis, which suggests that disparities in response to high-fat diets (HFDs) may be the result of differences in how quickly individuals can build adipose tissue blood vessels (ie, angiogenesis). Support for this theory comes from research that was originally done at the MD Anderson Cancer Center, showing that targeting a proapoptotic peptide to prohibitin in the adipose vasculature of mice caused ablation of white fat [Kolonin MG et al. \u003Cem\u003ENat Med\u003C\/em\u003E 2004]. The result was resorption of established white adipose tissue and normalization of metabolism, leading to rapid obesity reversal without detectable adverse effects. Dr. Seeley and colleagues have recently published the results of additional work using this peptide, showing that in mice, treatment with a proapoptotic peptide completely reversed HFD-induced obesity and reduced body weight in those who were on an HFD but not in those who were on a low-fat diet. Fat loss was due to reduced food intake (independent of the action of leptin) rather than a change in energy expenditure (\u003Ca id=\u0022xref-fig-3-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F3\u0022\u003EFigure 3\u003C\/a\u003E) [Kim DH et al. \u003Cem\u003EDiabetes\u003C\/em\u003E 2010]. New, unpublished data from Dr. Seeley\u0027s laboratory indicate that glucose metabolism is also improved in mice that are treated with the proapoptotic peptide.\u003C\/p\u003E\u003Cdiv id=\u0022F3\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/10\/9\/37\/F3.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Proapoptopic Peptide Decreases Body Weight.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-909053648\u0022 data-figure-caption=\u0022Proapoptopic Peptide Decreases Body Weight.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 3.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/10\/9\/37\/F3.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/10\/9\/37\/F3.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 3.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/10\/9\/37\/F3.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/11571\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption attrib\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 3.\u003C\/span\u003E \n            \u003Cp id=\u0022p-9\u0022 class=\u0022first-child\u0022\u003EProapoptopic Peptide Decreases Body Weight.\u003C\/p\u003E\n         \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-3\u0022\u003EReproduced with permission from R. Seeley, PhD.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2010 MD Conference Express\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/10\/9\/37.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_figures.js?nzmocp\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzmocp\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}