Linagliptin alleviates hepatic steatosis and inflammation in a mouse model of non-alcoholic steatohepatitis

Medical Molecular Morphology - Tập 47 Số 3 - Trang 137-149 - 2014
Thomas Klein1, Masato Fujisawa2, Jan Peter Sandel1, Yuichiro Shibazaki2, Kyoko Wakamatsu2, Michael Mark1, Hiroyuki Yoneyama2
1Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany
2Stelic Institute of Regenerative Medicine, Stelic Institute & Co., Minato-city, Japan

Tóm tắt

Từ khóa


Tài liệu tham khảo

Klein T, Mark M, Schuppan D (2011) The dipeptidyl peptidase 4 inhibitor linagliptin is an effective therapeutic for metabolic liver disease in several rodent models of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Hepatology 54(4(Suppl)):369A

Klein T, Mark M (2012) Linagliptin is an effective therapeutic for non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Diabetes 61(Suppl 1):A265

Angulo P (2002) Nonalcoholic fatty liver disease. N Engl J Med 346:1221–1231

Nugent C, Younossi ZM (2007) Evaluation and management of obesity-related nonalcoholic fatty liver disease. Nat Clin Pract Gastroenterol Hepatol 4:432–441

Schuppan D, Gorrell MD, Klein T, Mark M, Afdhal NH (2010) The challenge of developing novel pharmacological therapies for non-alcoholic steatohepatitis. Liver Int 30:795–808

Ascha MS, Hanouneh IA, Lopez R, Tamimi TA, Feldstein AF, Zein NN (2010) The incidence and risk factors of hepatocellular carcinoma in patients with nonalcoholic steatohepatitis. Hepatology 51:1972–1978

Kudo H, Yata Y, Takahara T, Kawai K, Nakayama Y, Kanayama M, Oya T, Morita S, Sasahara M, Mann DA, Sugiyama T (2009) Telmisartan attenuates progression of steatohepatitis in mice: role of hepatic macrophage infiltration and effects on adipose tissue. Liver Int 29:988–996

Georgescu EF, Ionescu R, Niculescu M, Mogoanta L, Vancica L (2009) Angiotensin-receptor blockers as therapy for mild-to-moderate hypertension-associated non-alcoholic steatohepatitis. World J Gastroenterol 15:942–954

Georgescu EF (2008) Angiotensin receptor blockers in the treatment of NASH/NAFLD: could they be a first-class option? Adv Ther 25:1141–1174

Jin H, Yamamoto N, Uchida K, Terai S, Sakaida I (2007) Telmisartan prevents hepatic fibrosis and enzyme-altered lesions in liver cirrhosis rat induced by a choline-deficient L-amino acid-defined diet. Biochem Biophys Res Commun 364:801–807

Fujita K, Yoneda M, Wada K, Mawatari H, Takahashi H, Kirikoshi H, Inamori M, Nozaki Y, Maeyama S, Saito S, Iwasaki T, Terauchi Y, Nakajima A (2007) Telmisartan, an angiotensin II type 1 receptor blocker, controls progress of nonalcoholic steatohepatitis in rats. Dig Dis Sci 52:3455–3464

Yang L, Bataller R, Dulyx J, Coffman TM, Ginès P, Rippe RA, Brenner DA (2005) Attenuated hepatic inflammation and fibrosis in angiotensin type 1a receptor deficient mice. J Hepatol 43:317–323

Yilmaz Y, Atug O, Yonal O, Duman D, Ozdogan O, Imeryuz N, Kalayci C (2009) Dipeptidyl peptidase IV inhibitors: therapeutic potential in nonalcoholic fatty liver disease. Med Sci Monit 15:HY1–HY5

Balaban YH, Korkusuz P, Simsek H, Gokcan H, Gedikoglu G, Pinar A, Hascelik G, Asan E, Hamaloglu E, Tatar G (2007) Dipeptidyl peptidase IV (DDP IV) in NASH patients. Ann Hepatol 6:242–250

Kern M, Kloting N, Niessen HG, Thomas L, Stiller D, Mark M, Klein T, Bluher M (2012) Linagliptin improves insulin sensitivity and hepatic steatosis in diet-induced obesity. PLoS One 7:e38744

Klein T, Niessen HG, Ittrich C, Mayoux E, Mueller HP, Cheetham S, Stiller D, Kassubek J, Mark M (2012) Evaluation of body fat composition after linagliptin treatment in a rat model of diet-induced obesity: a magnetic resonance spectroscopy study in comparison with sibutramine. Diabetes Obes Metab 14:1050–1053

Souza-Mello V, Gregorio BM, Cardoso-de-Lemos FS, de Carvalho L, Aguila MB, Mandarim-de-Lacerda CA (2010) Comparative effects of telmisartan, sitagliptin and metformin alone or in combination on obesity, insulin resistance, and liver and pancreas remodelling in C57BL/6 mice fed on a very high-fat diet. Clin Sci (Lond) 119:239–250

Shirakawa J, Fujii H, Ohnuma K, Sato K, Ito Y, Kaji M, Sakamoto E, Koganei M, Sasaki H, Nagashima Y, Amo K, Aoki K, Morimoto C, Takeda E, Terauchi Y (2011) Diet-induced adipose tissue inflammation and liver steatosis are prevented by DPP-4 inhibition in diabetic mice. Diabetes 60:1246–1257

Ding X, Saxena NK, Lin S, Gupta NA, Anania FA (2006) Exendin-4, a glucagon-like protein-1 (GLP-1) receptor agonist, reverses hepatic steatosis in ob/ob mice. Hepatology 43:173–181

Anstee QM, Goldin RD (2006) Mouse models in non-alcoholic fatty liver disease and steatohepatitis research. Int J Exp Pathol 87:1–16

Larter CZ, Yeh MM (2008) Animal models of NASH: getting both pathology and metabolic context right. J Gastroenterol Hepatol 23:1635–1648

Yilmaz Y, Yonal O, Deyneli O, Celikel CA, Kalayci C, Duman DG (2012) Effects of sitagliptin in diabetic patients with nonalcoholic steatohepatitis. Acta Gastroenterol Belg 75:240–244

Fujii M, Shibazaki Y, Wakamatsu K, Honda Y, Kawauchi Y, Suzuki K, Arumugam S, Watanabe K, Ichida T, Asakura H, Yoneyama H (2013) A murine model for non-alcoholic steatohepatitis showing evidence of association between diabetes and hepatocellular carcinoma. Med Mol Morphol. doi: 10.1007/s00795-013-0016-1

Eckhardt M, Langkopf E, Mark M, Tadayyon M, Thomas L, Nar H, Pfrengle W, Guth B, Lotz R, Sieger P, Fuchs H, Himmelsbach F (2007) 8-(3-(R)-aminopiperidin-1-yl)-7-but-2-ynyl-3-methyl-1-(4-methyl-quinazolin -2-ylmethyl)-3,7-dihydropurine-2,6-dione (BI 1356), a highly potent, selective, long-acting, and orally bioavailable DPP-4 inhibitor for the treatment of type 2 diabetes. J Med Chem 50:6450–6453

Thomas L, Eckhardt M, Langkopf E, Tadayyon M, Himmelsbach F, Mark M (2008) (R)-8-(3-amino-piperidin-1-yl)-7-but-2-ynyl-3-methyl-1-(4-methyl-quinazolin-2-ylm ethyl)-3,7-dihydro-purine-2,6-dione (BI 1356), a novel xanthine-based dipeptidyl peptidase 4 inhibitor, has a superior potency and longer duration of action compared with other dipeptidyl peptidase-4 inhibitors. J Pharmacol Exp Ther 325:175–182

Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, Ferrell LD, Liu YC, Torbenson MS, Unalp-Arida A, Yeh M, McCullough AJ, Sanyal AJ (2005) Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 41:1313–1321

Yoneyama H, Matsuno K, Zhang Y, Murai M, Itakura M, Ishikawa S, Hasegawa G, Naito M, Asakura H, Matsushima K (2001) Regulation by chemokines of circulating dendritic cell precursors, and the formation of portal tract-associated lymphoid tissue, in a granulomatous liver disease. J Exp Med 193:35–49

Matsuno K, Ezaki T, Kudo S, Uehara Y (1996) A life stage of particle-laden rat dendritic cells in vivo: their terminal division, active phagocytosis, and translocation from the liver to the draining lymph. J Exp Med 183:1865–1878

Fujioka N, Mukaida N, Harada A, Akiyama M, Kasahara T, Kuno K, Ooi A, Mai M, Matsushima K (1995) Preparation of specific antibodies against murine IL-1ra and the establishment of IL-1ra as an endogenous regulator of bacteria-induced fulminant hepatitis in mice. J Leukoc Biol 58:90–98

Greischel A, Binder R, Baierl J (2010) The dipeptidyl peptidase-4 inhibitor linagliptin exhibits time- and dose-dependent localization in kidney, liver, and intestine after intravenous dosing: results from high resolution autoradiography in rats. Drug Metab Dispos 38:1443–1448

Graefe-Mody U, Retlich S, Friedrich C (2012) Clinical pharmacokinetics and pharmacodynamics of linagliptin. Clin Pharmacokinet 51:411–427

He M, Su H, Gao W, Johansson SM, Liu Q, Wu X, Liao J, Young AA, Bartfai T, Wang MW (2010) Reversal of obesity and insulin resistance by a non-peptidic glucagon-like peptide-1 receptor agonist in diet-induced obese mice. PLoS One 5:e14205

Sharma S, Mells JE, Fu PP, Saxena NK, Anania FA (2011) GLP-1 analogs reduce hepatocyte steatosis and improve survival by enhancing the unfolded protein response and promoting macroautophagy. PLoS One 6:e25269

Svegliati-Baroni G, Saccomanno S, Rychlicki C, Agostinelli L, De Minicis S, Candelaresi C, Faraci G, Pacetti D, Vivarelli M, Nicolini D, Garelli P, Casini A, Manco M, Mingrone G, Risaliti A, Frega GN, Benedetti A, Gastaldelli A (2011) Glucagon-like peptide-1 receptor activation stimulates hepatic lipid oxidation and restores hepatic signalling alteration induced by a high-fat diet in nonalcoholic steatohepatitis. Liver Int 31:1285–1297

Stienstra R, Saudale F, Duval C, Keshtkar S, Groener JE, van Rooijen N, Staels B, Kersten S, Muller M (2010) Kupffer cells promote hepatic steatosis via interleukin-1beta-dependent suppression of peroxisome proliferator-activated receptor alpha activity. Hepatology 51:511–522

Sachithanandan N, Fam BC, Fynch S, Dzamko N, Watt MJ, Wormald S, Honeyman J, Galic S, Proietto J, Andrikopoulos S, Hevener AL, Kay TW, Steinberg GR (2010) Liver-specific suppressor of cytokine signaling-3 deletion in mice enhances hepatic insulin sensitivity and lipogenesis resulting in fatty liver and obesity. Hepatology 52:1632–1642

Yoneyama H, Ichida T (2005) Recruitment of dendritic cells to pathological niches in inflamed liver. Med Mol Morphol 38:136–141

Yoneyama H, Kawasaki S, Matsushima K (2000) Regulation of Th1 and Th2 immune responses by chemokines. Springer Semin Immunopathol 22:329–344

Fadini GP, Boscaro E, Albiero M, Menegazzo L, Frison V, de Kreutzenberg S, Agostini C, Tiengo A, Avogaro A (2010) The oral dipeptidyl peptidase-4 inhibitor sitagliptin increases circulating endothelial progenitor cells in patients with type 2 diabetes: possible role of stromal-derived factor-1α. Diabetes Care 33:1607–1609

Menten P, Struyf S, Schutyser E, Wuyts A, De Clercq E, Schols D, Proost P, Van Damme J (1999) The LD78β isoform of MIP-1α is the most potent CCR5 agonist and HIV-1-inhibiting chemokine. J Clin Invest 104:R1–R5

Proost P, Menten P, Struyf S, Schutyser E, De Meester I, Van Damme J (2000) Cleavage by CD26/dipeptidyl peptidase IV converts the chemokine LD78β into a most efficient monocyte attractant and CCR1 agonist. Blood 96:1674–1680

Mells JE, Fu PP, Sharma S, Olson D, Cheng L, Handy JA, Saxena NK, Sorescu D, Anania FA (2012) Glp-1 analog, liraglutide, ameliorates hepatic steatosis and cardiac hypertrophy in C57BL/6J mice fed a Western diet. Am J of Physiol Gastrointest Liver Physiol 302:G225–G235

Kroller-Schon S, Knorr M, Hausding M, Oelze M, Schuff A, Schell R, Sudowe S, Scholz A, Daub S, Karbach S, Kossmann S, Gori T, Wenzel P, Schulz E, Grabbe S, Klein T, Munzel T, Daiber A (2012) Glucose-independent improvement of vascular dysfunction in experimental sepsis by dipeptidyl-peptidase 4 inhibition. Cardiovasc Res 96:140–149