The Preliminary Investigation of GLP-1 Receptor Agonist on Liver Steatosis in Obese Mice
Abstract
To investigate the effects of glucagon-like peptide-1 (GLP-1) receptor agonist, exenatide,on liver function and steatosis in obese mice. Methods Male c57BL/6J mice (8 weeks old) were divided into high-fat-diet group (for obesity model construction) and chow diet group. 12 weeks later, mice of high-fat diet group were randomly divided into high-dose exenatide group 〔H group, intraperitoneal injection 0.02 μg/（g·d）, high-fat-diet〕, low-dose exenatide group 〔L group, intraperitoneal injection 0.01 μg/（g·d）, high-fat-diet〕, saline group （NS group, intraperitoneal injection of saline, high-fat-diet）, diet control group (D group, shifted to chow diet) and high-fat control group (M group, high-fat-diet) for 4-week treatments ,respectively. The body mass and serum biochemical indicators of were detected. Liver tissues were stained with HE, and steatosis score was measured. Results After 4-week treatments, H group showed more body mass loss than L group and D group ( P<0.05). The serum alanine aminotransferase (ALT) level of NG group was higher than that of H, L,M, and NS groups ( P<0.05). Serum cholesterol and triglyceride declined to normal levels by diet intervention or drug treatment. High-dose exenatide treatment ran a risk of increasing serum uric acid level. The serum levels of aspartate aminotransferase (AST), glucose, homeostasis model assessment-insulin resistance (HOMA-IR), lipase,
Keywords: Obesity, GLP-1 receptor agonist, Hepaticsteatosis
Full Text:
PDFReferences
DE LAPERTOSA SB. FRECHTEL G, HARDY Е, et al. The effects of exenatide twice daily compared to insulin lispro added to basal insulin in Latin American patients with type 2 diabetes; a retrospective analysis of the 4В trial. Diabetes Res Clin Pract, 2016 ( 122): 38-45 [2016-10-01]. http;//dx. doi. org/10. 1016/j. diabres. 2016. 10. 001. doi: 10. 1016/j. diabres. 2016. 10. 001.
SU N,LI Y, XU T,et al. Exenatide in obese or overweight patients without diabetes: a systematic review and meta-analyses of randomized controlled trials. Int J Cardiol, 2016 (219);293-300[2016-03-08]. http://dx. doi. org/10. 1016/j. ijcard. 2016. 06. 028. doi; 10. 1016/j. ijcard. 2016. 06. 028. World health organization. Obesity. [2015-08-24]. http;// www. who. int/topics/obsity/en/.
KNOPFK, AABOE K, VILSBOLL T, et al. Impaired incretin effect and fasting hyperglucagonaemia characterizing type 2 diabetic subjects are early signs of dysmetabolism in obesity. Diabetes Obes Metab,2012,14(6) :500-510.
RANGANATH L, NORRIS F, MORGAN L, et al. Inhibition of carbohydrate-mediated glucagon-like peptide-1 ( 7-36) amide secretion by circulating non-esterified fatty acids. Clin Sci (Lond), 1999,96(4) ;335-342.
BERGENSTAL RM. LI Y. PORTER TK. et al. Exenatide once weekly improved glycaemic control, cardiometabolic risk factors and a composite index of an HbAlc <7%, without weight gain or hypoglycaemia, over 52 weeks. Diabetes Obes Metab,2013,15(3);264-271.
OWENS I)R. MONNIER L. BOLLI GB. Differential effects of GLP-1 receptor agonists on components of dysglycaemia in individuals with type 2 diabetes mellitus. Diabetes Metab, 2013,39(6): 485-496.
YUANGH. SONG WL, HUANG YY. et at. Efficacy and tolerability of exenatide monotherapy in obese patients with newly diagnosed type 2 diabetes; a randomized, 26 weeks metformin controlled, parallel-group study. Chin Med J (Engl), 2012,125(15); 2677-2681.
SEGHIERI M, REBELOS E, GASTALDELLI A, et al. Direct effect of GLP-1 infusion on endogenous glucose production in humans. Diabetologia,2013,56(1): 156-161.
BUNCK MC, CORNER A, ELIASSON B, et al. Effects of exenatide on measures of p-cell function after 3 years in metformin-treated patients with type 2 diabetes. Diabetes Care,2011,34(9):2041-204 7.
ARMSTRONG MJ, HULL D. GUOK, et al. Glucagon-like peptide 1 decreases lipotoxicity in non-alcoholic steatohepatitis. J Hepatol,2016,64(2):399-408.
PETIT JM, CERCUEIL JP, LOFFROY R, et al. Effect of liraglutide therapy on liver fat content in patients with inadequately controlled type 2 diabetes. J Clin Endocrinol
Metab, 2016; jc20162775 [ 2016-10-04 ]. http://press. endocrine, org/doi/pdf/10. 1210/jc. 2016-2775. doi: http:// dx. doi. org/10. 1210/jc. 2016-2775.
CHAURASIA В. К ADD AI VA. LANCASTER G. et al. Adipocyte ceramides regulate subcutaneous adipose browning, inflammation, and metabolism. Cell Metab.2016.24(6):820-834.
SO A. THORENS B. Uric acid transport and disease. J Clin Invest,2010,120(6): 1791-1799.
NAKAJIMA K. OSHIDA H. MUNEYUKI T, et al. Independent association between low serum amylase and non¬alcoholic fatty liver disease in asymptomatic adults: a cross- sectional observa-tional study. BMJ Open.2013(3); e002235 [ 2013-01-03 ]. https; / / www. ncbi. nlm. nib. gov/pmc/ articles/PMC354 926 l/pdf/bmjopen-2012-002235. pdf. doi: 10. 1136/bmjopen-2012-002235.
LEI H, WANG J. LU P, et al. BMP10 inhibited the growth and migration of gastric cancer cells. Tumour Biol. 2016, 37 (3):3025-3031.
LIU H. BAG Г), XIA X, et al. An unconventional role of BMP-Smadl signaling in DNA damage response:a mechanism for tumor suppression. J Cell Biochem. 2014, 115 ( 3); 450- 456.
BRETON G, YASSINE-DIAB B, COHN L, et al. SiRNA knockdown of PD-L1 and PD-L2 in monocyte-derived dendritic cells only modestly improves proliferative responses to Gag by CD8( + ) T cells from HIV-l-infected individuals. J Clin Immunol,2009,29(5) :637-645.
TANIGUCHI T, OGASAWARA К. TAKAOKA A, etal. IRF family of transcription factors as regulators of host defense. Annu Rev Immunol, 2001 ( 19) ; 623-655 [ 2016-07- 21 ]. http; //www. annualreviews. org/doi/10. 1146/annurev. immunol. 19. 1. 623.
BYRD-LEIFER CA, BLOCK EF, TAKEDA К , etal. The role of MyD88 and TLR4 in the LPS-mimetic activity of Taxol. Eur J Immunol.2001,31(8);2448-2457.
ZIMMER SM. LIU J. CLAYTON JL, et al. Paclitaxel binding to human and murine MD-2. J Biol Chem, 2008. 283
KARAKHANOVA S, MEISEL S, RING S. et al. ERK/p38 MAP-kinases and PI3K are involved in the differential regulation of B7-H1 expression in DC subsets. Eur J Immunol,2010,40(1) ;254-266.
LEE SJ, JANG BC, LEE SW. el at. Interferon regulatory factor-1 is prerequisite to the constitutive expression and IFN- gamma-induced upregulation of B7-H1 (CD274). FEBSLett* 2006,580(3):755-762.
KLEINERT H, SCHWARZ PM. FORSTERMANN U. Regulation of the expression of inducible nitric oxide synthase. Biol Chem,2003,384(10/11): 1343-1364.
LI B. YANG Y, JIANG S, et al. Adenovirus-mediated overexpression of BMP-9 inhibits human osteosarcoma cell growth and migration through downregulation of the Р13К/ АКТ pathway. Int J Oncol.2012,41(5): 1809-1819. SABADO RL, BHARDWAJ N. Directing dendritic cell immunotherapy towards successful cancer treatment. Immunotherapy,2010,2( 1);37-56.
Refbacks
- There are currently no refbacks.
