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01.02.2015 | Article

Nutritional strategy to prevent fatty liver and insulin resistance independent of obesity by reducing glucose-dependent insulinotropic polypeptide responses in mice

verfasst von: Farnaz Keyhani-Nejad, Martin Irmler, Frank Isken, Eva K. Wirth, Johannes Beckers, Andreas L. Birkenfeld, Andreas F. H. Pfeiffer

Erschienen in: Diabetologia | Ausgabe 2/2015

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Abstract

Aims/hypothesis

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/interpretation

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.

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Williams CD, Stengel J, Asike MI et al (2011) Prevalence of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis among a largely middle-aged population utilizing ultrasound and liver biopsy: a prospective study. Gastroenterology 140:124–131PubMedCrossRef

Krawczyk M, Bonfrate L, Portincasa P (2010) Nonalcoholic fatty liver disease. Best Pract Res Clin Gastroenterol 24:695–708PubMedCrossRef

Marchesini G, Bugianesi E, Forlani G et al (2003) Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome. Hepatology 37:917–923PubMedCrossRef

Birkenfeld AL, Shulman GI (2014) Nonalcoholic fatty liver disease, hepatic insulin resistance, and type 2 diabetes. Hepatology 59:713–723PubMedCrossRef

Rudovich NN, Weickert MO, Machann J, Pfeiffer AF (2010) Combination of acarbose and ezetimibe prevents non-alcoholic fatty liver disease: a break of intestinal insulin resistance? J Hepatol 52:952–953PubMedCrossRef

Sato K, Arai H, Mizuno A et al (2007) Dietary palatinose and oleic acid ameliorate disorders of glucose and lipid metabolism in Zucker fatty rats. J Nutr 137:1908–1915PubMed

Daly M (2003) Sugars, insulin sensitivity, and the postprandial state. Am J Clin Nutr 78:865S–872SPubMed

Kawai K, Yoshikawa H, Murayama Y, Okuda Y, Yamashita K (1989) Usefulness of palatinose as a caloric sweetener for diabetic patients. Horm Metab Res 21:338–340PubMedCrossRef

Isken F, Klaus S, Petzke KJ, Loddenkemper C, Pfeiffer AF, Weickert MO (2010) Impairment of fat oxidation under high- vs. low-glycemic index diet occurs before the development of an obese phenotype. Am J Physiol Endocrinol Metab 298:E287–E295PubMedCrossRef

10.

Mortensen K, Christensen LL, Holst JJ, Orskov C (2003) GLP-1 and GIP are colocalized in a subset of endocrine cells in the small intestine. Regul Pept 114:189–196PubMedCrossRef

11.

Yip RG, Wolfe MM (2000) GIP biology and fat metabolism. Life Sci 66:91–103PubMedCrossRef

12.

Shimotoyodome A, Suzuki J, Fukuoka D, Tokimitsu I, Hase T (2010) RS4-type resistant starch prevents high-fat diet-induced obesity via increased hepatic fatty acid oxidation and decreased postprandial GIP in C57BL/6J mice. Am J Physiol Endocrinol Metab 298:E652–E662PubMedCrossRef

13.

Musso G, Gambino R, Pacini G, De Michieli F, Cassader M (2009) Prolonged saturated fat-induced, glucose-dependent insulinotropic polypeptide elevation is associated with adipokine imbalance and liver injury in nonalcoholic steatohepatitis: dysregulated enteroadipocyte axis as a novel feature of fatty liver. Am J Clin Nutr 89:558–567PubMedCrossRef

14.

Isken F, Weickert MO, Tschop MH et al (2009) Metabolic effects of diets differing in glycaemic index depend on age and endogenous glucose-dependent insulinotrophic polypeptide in mice. Diabetologia 52:2159–2168PubMedCrossRef

15.

Haberer D, Thibault L, Langhans W, Geary N (2009) Beneficial effects on glucose metabolism of chronic feeding of isomaltulose versus sucrose in rats. Ann Nutr Metab 54:75–82PubMedCrossRef

16.

Matsuo K, Arai H, Muto K et al (2007) The anti-obesity effect of the palatinose-based formula Inslow is likely due to an increase in the hepatic PPAR-alpha and adipocyte PPAR-gamma gene expressions. J Clin Biochem Nutr 40:234–241PubMedCentralPubMedCrossRef

17.

Rico-Bautista E, Flores-Morales A, Fernandez-Perez L (2006) Suppressor of cytokine signaling (SOCS) 2, a protein with multiple functions. Cytokine Growth Factor Rev 17:431–439PubMedCrossRef

18.

Zadjali F, Santana-Farre R, Vesterlund M et al (2012) SOCS2 deletion protects against hepatic steatosis but worsens insulin resistance in high-fat-diet-fed mice. FASEB J 26:3282–3291PubMedCrossRef

19.

Preitner F, Ibberson M, Franklin I et al (2004) Gluco-incretins control insulin secretion at multiple levels as revealed in mice lacking GLP-1 and GIP receptors. J Clin Invest 113:635–645PubMedCentralPubMedCrossRef

20.

Isken F, Klaus S, Osterhoff M, Pfeiffer AF, Weickert MO (2010) Effects of long-term soluble vs. insoluble dietary fiber intake on high-fat diet-induced obesity in C57BL/6J mice. J Nutr Biochem 21:278–284PubMedCrossRef

21.

Valentini L, Wirth EK, Schweizer U et al (2009) Circulating adipokines and the protective effects of hyperinsulinemia in inflammatory bowel disease. Nutrition 25:172–181PubMedCrossRef

22.

Rainer J, Sanchez-Cabo F, Stocker G, Sturn A, Trajanoski Z (2006) CARMAweb: comprehensive R- and bioconductor-based web service for microarray data analysis. Nucleic Acids Res 34:W498–W503PubMedCentralPubMedCrossRef

23.

Tollet-Egnell P, Flores-Morales A, Stavreus-Evers A, Sahlin L, Norstedt G (1999) Growth hormone regulation of SOCS-2, SOCS-3, and CIS messenger ribonucleic acid expression in the rat. Endocrinology 140:3693–3704PubMed

24.

Lina BA, Jonker D, Kozianowski G (2002) Isomaltulose (Palatinose): a review of biological and toxicological studies. Food Chem Toxicol 40:1375–1381PubMedCrossRef

25.

Arai H, Mizuno A, Matsuo K et al (2004) Effect of a novel palatinose-based liquid balanced formula (MHN-01) on glucose and lipid metabolism in male Sprague-Dawley rats after short- and long-term ingestion. Metabolism 53:977–983PubMedCrossRef

26.

Takeda E, Arai H, Yamamoto H, Okumura H, Taketani Y (2005) Control of oxidative stress and metabolic homeostasis by the suppression of postprandial hyperglycemia. J Med Invest 52(Suppl):259–265PubMedCrossRef

27.

Park JH, Kwon OD, Ahn SH, Lee S, Choi BK, Jung KY (2013) Fatty diets retarded the propulsive function of and attenuated motility in the gastrointestinal tract of rats. Nutr Res 33:228–234PubMedCrossRef

28.

Goff LM, Cowland DE, Hooper L, Frost GS (2013) Low glycaemic index diets and blood lipids: a systematic review and meta-analysis of randomised controlled trials. Nutrition, metabolism, and cardiovascular diseases. Nutr Metab Cardiovasc Dis 23:1–10PubMedCrossRef

29.

Kendall DM, Sobel BE, Coulston AM et al (2003) The insulin resistance syndrome and coronary artery disease. Coron Artery Dis 14:335–348PubMedCrossRef

30.

Cummings JH, Englyst HN (1995) Gastrointestinal effects of food carbohydrate. Am J Clin Nutr 61:938S–945SPubMed

31.

Chinda D, Nakaji S, Fukuda S et al (2004) The fermentation of different dietary fibers is associated with fecal clostridia levels in men. J Nutr 134:1881–1886PubMed

32.

Tonouchi H, Yamaji T, Uchida M et al (2011) Studies on absorption and metabolism of palatinose (isomaltulose) in rats. Br J Nutr 105:10–14PubMedCrossRef

33.

Naitoh R, Miyawaki K, Harada N et al (2008) Inhibition of GIP signaling modulates adiponectin levels under high-fat diet in mice. Biochem Biophys Res Commun 376:21–25PubMedCrossRef

34.

McClean PL, Irwin N, Cassidy RS, Holst JJ, Gault VA, Flatt PR (2007) GIP receptor antagonism reverses obesity, insulin resistance, and associated metabolic disturbances induced in mice by prolonged consumption of high-fat diet. Am J Physiol Endocrinol Metab 293:E1746–E1755PubMedCrossRef

35.

Knight ZA, Hannan KS, Greenberg ML, Friedman JM (2010) Hyperleptinemia is required for the development of leptin resistance. PLoS One 5:e11376PubMedCentralPubMedCrossRef

36.

Frederich RC, Hamann A, Anderson S, Lollmann B, Lowell BB, Flier JS (1995) Leptin levels reflect body lipid content in mice: evidence for diet-induced resistance to leptin action. Nat Med 1:1311–1314PubMedCrossRef

37.

Kadowaki T, Yamauchi T (2005) Adiponectin and adiponectin receptors. Endocr Rev 26:439–451PubMedCrossRef

38.

Shimabukuro M, Koyama K, Chen G et al (1997) Direct antidiabetic effect of leptin through triglyceride depletion of tissues. Proc Natl Acad Sci U S A 94:4637–4641PubMedCentralPubMedCrossRef

39.

Elam MB, Cowan GS Jr, Rooney RJ et al (2009) Hepatic gene expression in morbidly obese women: implications for disease susceptibility. Obesity (Silver Spring) 17:1563–1573CrossRef

40.

Tateno C, Kataoka M, Utoh R et al (2011) Growth hormone-dependent pathogenesis of human hepatic steatosis in a novel mouse model bearing a human hepatocyte-repopulated liver. Endocrinology 152:1479–1491PubMedCrossRef

41.

Fan Y, Menon RK, Cohen P et al (2009) Liver-specific deletion of the growth hormone receptor reveals essential role of growth hormone signaling in hepatic lipid metabolism. J Biol Chem 284:19937–19944PubMedCentralPubMedCrossRef

42.

Umahara M, Okada S, Ohshima K, Mori M (2003) Glucose-dependent insulinotropic polypeptide induced growth hormone secretion in acromegaly. Endocr J 50:643–650PubMedCrossRef

43.

Occhi G, Losa M, Albiger N et al (2011) The glucose-dependent insulinotropic polypeptide receptor is overexpressed amongst GNAS1 mutation-negative somatotropinomas and drives growth hormone (GH)-promoter activity in GH3 cells. J Neuroendocrinol 23:641–649PubMedCrossRef

44.

Kraus D, Yang Q, Kong D et al (2014) Nicotinamide N-methyltransferase knockdown protects against diet-induced obesity. Nature 508:258–262PubMedCrossRef

Titel: Nutritional strategy to prevent fatty liver and insulin resistance independent of obesity by reducing glucose-dependent insulinotropic polypeptide responses in mice
verfasst von: Farnaz Keyhani-Nejad
Martin Irmler
Frank Isken
Eva K. Wirth
Johannes Beckers
Andreas L. Birkenfeld
Andreas F. H. Pfeiffer
Publikationsdatum: 01.02.2015
Verlag: Springer Berlin Heidelberg
Erschienen in: Diabetologia / Ausgabe 2/2015
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-014-3423-5

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Nutritional strategy to prevent fatty liver and insulin resistance independent of obesity by reducing glucose-dependent insulinotropic polypeptide responses in mice

Abstract

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Methods

Results

Conclusions/interpretation

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