High Fructose Corn Syrup (HFCS) in Soft Drinks Induces Severe Adipose Inflammation and Insulin Resis

• 作 者: Yuxiang Sun
• 机 构: Baylor College of Medicine Houston USA
• 出 处: MIT`s 1st Annual World Congress of Diabetes-2012(2012第一届糖尿病大
• 发表日期: 2012年8期

　　Adipose inflammation and insulin resistance play causal roles for type 2 diabetes.HFCS is the most-used sweetener in the United States, substantially replacing sucrose.In this study, we compared the metabolic effects of mice fed regular diet, high fat diet (HFD), or regular diet supplemented with 8% HFCS in drinking water (to mimic soft drinks).We found that HFD-fed mice consumed the most total calories, and showed the most weight gain and fat deposition.Surprisingly, HFCS-fed mice exhibited the most severe insulin resistance;disproportionately greater in relation to their calorie intake and body fat content.Adipose tissue macrophages (ATMs) have emerged as a major pathogenic factor for obesity and insulin resistance.ATMs consist of pro-inflammatory M1 macrophages and anti-inflammatory M2 macrophages.Like HFD, HFCS induced robust increases of both M1 and M2 ATMs in visceral fat, but the number of M2 ATMs was much lower in HFCS-fed mice than in HFD-fed mice.Ghrelin is an orexigenic hormone, promoting adiposity and insulin resistance.The biologically relevant receptor of ghrelin is Growth Hormone Secretagogue Receptor (GHS-R).To elucidate whether ghrelin/GHS-R signaling affects macrophages in adipose tissues, we investigated the effects of GHS-R in HFCS-induced adipose inflammation, liver steatosis and insulin resistance using our Ghsr-null mice.The Ghsr-null mice exhibited lower M1 ATMs and pro-inflammatory cytokine expression, but no difference in M2 ATMs, in visceral fat.In vitro, our data further revealed that GHS-R gene knockdown in macrophage RAW264.7 cells resulted in reduced pro-inflammatory cytokines,suggesting that GHS-R has direct effect in macrophages.Thus, HFCS consumption has additional detrimental effects on adipose inflammation beyond the extra calories from HFCS, and GHS-R antagonists may represent novel drugs for ameliorating adipose inflammation and insulin resistance.