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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\u003EMeasurements of free fatty acid (FFA), also known to as non-esterified fatty acid, and glucose kinetics have shown that obese individuals have adipose tissue that is insulin resistant [Jensen MD, Nielsen S. \u003Cem\u003EMetabolism\u003C\/em\u003E 2007]. It is commonly thought that oversupply of FFA is a major contributor to the development of insulin resistance in obesity. This article discusses the known molecular mechanisms for the phenomenon of insulin resistance in adipose tissue and challenged the notion of oversupply of FFA in obesity.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EObesity\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ECardiometabolic Disorder\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EInsulin\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group clinical-trial\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EEndocrinology\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EDiabetes \u0026amp; Metabolic Syndrome\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EObesity\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ECardiometabolic Disorder\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EInsulin\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EMeasurements of free fatty acid (FFA), also known to as non-esterified fatty acid, and glucose kinetics have shown that obese individuals have adipose tissue that is insulin resistant [Jensen MD, Nielsen S. \u003Cem\u003EMetabolism\u003C\/em\u003E 2007]. It is commonly thought that oversupply of FFA is a major contributor to the development of insulin resistance in obesity. Once insulin resistance develops, lipolysis of stored triacylglycerol is increased, resulting in increased release of FFAs by adipocytes [Eckel RH et al. \u003Cem\u003ELancet\u003C\/em\u003E 2005]. Fredrik Karpe, MD, PhD, Oxford University, Oxford, United Kingdom, discussed the known molecular mechanisms for the phenomenon of insulin resistance in adipose tissue and challenged the notion of oversupply of FFA in obesity.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EA study comparing lean versus abdominally obese men from the Oxford Biobank found a clear difference in fat mass and insulin resistance but no difference in FFA concentrations between the 2 groups [McQuaid S et al. \u003Cem\u003EDiabetes\u003C\/em\u003E 2011]. A systematic literature review and comparison of patients from the Oxford Biobank found no relationship between body mass index (BMI) and FFA concentrations [Karpe F et al. \u003Cem\u003EDiabetes\u003C\/em\u003E 2011]. Additionally, an analysis of several large studies found that hyperinsulinemia was associated with a decreased release of FFA from adipose tissue [Karpe F et al. \u003Cem\u003EDiabetes\u003C\/em\u003E 2011]. In fact, adipose tissue in obese (and insulin resistant) individuals almost invariably supply less FFA per unit fat mass than in lean individuals.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EProf. Karpe and fellow researchers investigated whether excess fat deposition in non-adipose tissue is due to excess fatty acid delivery from adipose tissue or to impaired adipose tissue fat storage [McQuaid S et al. \u003Cem\u003EDiabetes\u003C\/em\u003E 2011]. Using stable-isotope fatty acid tracers to assess FFA delivery over a diurnal cycle, they found that the FFA Ra (rate of appearance) was significantly higher in abdominally obese versus lean men (p=0.009), but when the data were normalized per lean body mass, the difference disappeared. When expressed per total fat mass, the obese men had significantly lower FFA Ra compared with lean men (p=0.029). It therefore appears that adipose tissue in obese individuals down-regulate FFA supply to the systemic circulation as part of an adequate metabolic adaptation despite an element of insulin resistance.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EIn the same study, lean men had a progressive increase in meal fat deposition into adipose tissue with each meal (13%, 35%, and 47%, first to third meal; p\u0026lt;0.001). Abdominally obese men did not have a significant increase in adipose tissue fat storage with sequential feeding (6%, 25%, and 18%, first to third meal; p=0.12). The difference was statistically significant for the last meal (p=0.001). As the up-regulation of fat storage is an insulin-sensitive process, it therefore seems that obese individuals have a defect in immediate fat storage. The transcriptional signature of adipose tissue from the obese men was consistent with impaired fat storage function. Klimcakova and colleagues demonstrated that lipolysis, lipogenesis, glycolysis, and mitochondrial genes are highly downregulated in obese adipose tissue [Klimcakova E et al. \u003Cem\u003EJ Clin Endocrinol Metab\u003C\/em\u003E 2011].\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EAccording to Prof. Karpe, analysis of available evidence shows that adipose tissues and organs do not oversecrete FFA but instead adapt extremely well to obesity. Adipose tissue can be insulin resistant but in terms of regulation of lipolysis, this is balanced by hyperinsulinemia. Human adipose tissue adapts to obesity, hyperplasia, and hyperinsulinemia by down-regulating metabolic processes. Increased release of FFA is not an obvious feature in the development of insulin resistance, while adipose tissue fat storage is decreased in obese individuals leading to ectopic fat deposition, with the liver as the prime target.\u003C\/p\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2013 MD Conference Express\u00ae\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\/13\/16\/11.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_openurl.js?nznm5e\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}