title: Nutritional strategy to prevent fatty liver and insulin resistance independent of obesity by reducing glucose-dependent insulinotropic polypeptide responses in mice.
abstract: OBJECTIVE
  High intake of carbohydrates, particularly sucrose, in western societies is associated with the development of non-alcoholic fatty liver (NAFL) and diabetes mellitus. It is unclear whether this is related primarily to the carbohydrate quantity or to the hormonal responses, particularly glucose-dependent insulinotropic polypeptide (GIP), which is released in the proximal intestine. Therefore, we investigated the role of GIP by comparing two glucose-fructose dimers, sucrose and Palatinose (isomaltulose), resorbed proximally or distally.
  
  
  METHODS
  The glycaemic and incretin responses to sucrose and Palatinose were studied by oral gavage and meal tests. We then analysed phenotypic and metabolic diet-induced changes in C57Bl/6J mice exposed to isoenergetic diets differing in carbohydrate type. Studies were repeated in GIP receptor knockout (Gipr(-/-)) mice and their wild-type littermates.
  
  
  RESULTS
  Compared with sucrose, Palatinose intake resulted in slower glucose absorption and reduced postprandial insulin and GIP levels. After 22 weeks, Palatinose feeding prevented hepatic steatosis (48.5%) compared with sucrose and improved glucose tolerance, without differences in body composition and food intake. Ablation of GIP signalling in Gipr(-/-) mice completely prevented the deleterious metabolic effects of sucrose feeding. Furthermore, our microarray analysis indicated that sucrose increased 2.3-fold the hepatic expression of Socs2, which is involved in the growth hormone signalling pathway and participates in the development of NAFL.
  
  
  CONCLUSIONS
  Our results suggest that the site of glucose absorption and the GIP response determine liver fat accumulation and insulin resistance. GIP may play a role in sucrose induced fatty liver by regulating the expression of Socs2.
authors.affiliation: Department of Clinical Nutrition, German Institute of Human Nutrition, Arthur-Scheunert-Allee 114-116, 14558, Nuthetal, Germany.
authors.forename: Farnaz
authors.initials: F
authors.lastname: Keyhani-Nejad
authors.forename: Martin
authors.initials: M
authors.lastname: Irmler
authors.forename: Frank
authors.initials: F
authors.lastname: Isken
authors.forename: Eva K
authors.initials: EK
authors.lastname: Wirth
authors.forename: Johannes
authors.initials: J
authors.lastname: Beckers
authors.forename: Andreas L
authors.initials: AL
authors.lastname: Birkenfeld
authors.forename: Andreas F H
authors.initials: AF
authors.lastname: Pfeiffer
mesh_terms: D000818:Animals; D004032:Diet; D005234:Fatty Liver / Q000473:pathology* / Q000517:prevention & control; D005749:Gastric Inhibitory Polypeptide / Q000378:metabolism*; D007333:Insulin Resistance; D007408:Intestinal Absorption; D007534:Isomaltose / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D051379:Mice; D011964:Receptors, Gastrointestinal Hormone / Q000378:metabolism; D013395:Sucrose / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D011964:Receptors, Gastrointestinal Hormone; D013395:Sucrose; D005749:Gastric Inhibitory Polypeptide; D007534:Isomaltose; C041086:gastric inhibitory polypeptide receptor; C008189:isomaltulose