title: Ghrelin receptor regulates HFCS-induced adipose inflammation and insulin resistance.
abstract: OBJECTIVE
  High fructose corn syrup (HFCS) is the most commonly used sweetener in the United States. Some studies show that HFCS consumption correlates with obesity and insulin resistance, while other studies are in disagreement. Owing to conflicting and insufficient scientific evidence, the safety of HFCS consumption remains controversial.
  
  
  METHODS
  We investigated the metabolic consequences of mice fed a (a) regular diet, (b) 'Western' high-fat diet or (c) regular diet supplemented with 8% HFCS in drinking water (to mimic soft drinks) for 10 months. Adipose tissue macrophages (ATMs) have emerged as a major pathogenic factor for obesity and insulin resistance. ATMs consist of proinflammatory F4/80(+)CD11c(+) macrophages and anti-inflammatory F4/80(+)CD11c(-) macrophages. In this study, we assessed the effects of HFCS on ATMs in intra-abdominal fat.
  
  
  RESULTS
  We found that HFCS feeding in mice induced more severe adipose inflammation and insulin resistance than even the higher-calorie-containing 'Western' high-fat diet, and these HFCS-induced deleterious effects were independent of calorie intake or body fat content. We showed that similar to 'Western' high-fat diet, HFCS triggered a robust increase of both proinflammatory ATMs and anti-inflammatory ATMs in intra-abdominal fat. Remarkably, however, the anti-inflammatory ATMs were much less abundant in HFCS-fed mice than in high-fat-fed mice. Furthermore, we showed that deletion of the ghrelin receptor (growth hormone secretagogue receptor, GHS-R) ameliorates HFCS-induced adipose inflammation and insulin resistance. HFCS-fed GHS-R-null mice exhibit decreased proinflammatory ATMs in intra-abdominal fat, reduced adipose inflammation and attenuated liver steatosis.
  
  
  CONCLUSIONS
  Our studies demonstrate that HFCS has detrimental effects on metabolism, suggesting that dietary guidelines on HFCS consumption for Americans may need to be revisited. GHS-R deletion mitigates the effects of HFCS on adipose inflammation and insulin resistance, suggesting that GHS-R antagonists may represent a novel therapy for insulin resistance.
authors.affiliation: 1] Division of Endocrinology, Department of Internal Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China [2] USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: X
authors.initials: X
authors.lastname: Ma
authors.affiliation: 1] USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA [2] State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.
authors.forename: L
authors.initials: L
authors.lastname: Lin
authors.affiliation: 1] USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA [2] Department of Reproductive Medicine, Tongji Hospital affiliated to Tongji Medical College, Huazhong Science and Technology University, Wuhan, China.
authors.forename: J
authors.initials: J
authors.lastname: Yue
authors.affiliation: USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: G
authors.initials: G
authors.lastname: Pradhan
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: G
authors.initials: G
authors.lastname: Qin
authors.affiliation: Preclinical Model Development Core, The Methodist Hospital Research Institute, Houston, TX, USA.
authors.forename: L J
authors.initials: LJ
authors.lastname: Minze
authors.affiliation: Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
authors.forename: H
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
authors.forename: D
authors.initials: D
authors.lastname: Sheikh-Hamad
authors.affiliation: USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: C W
authors.initials: CW
authors.lastname: Smith
authors.affiliation: 1] USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA [2] Huffington Center on Aging, Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Sun