Summary
Vertical sleeve gastrectomy (VSG) is becoming more and more popular among the world. Despite its dramatic efficacy, however, the mechanism of VSG remains largely undetermined. This study aimed to test interferon (IFN)-γ secretion n of mesenteric lymph nodes in obese mice (ob/ob mice), a model of VSG, and its relationship with farnesoid X receptor (FXR) expression in the liver and small intestine, and to investigate the weight loss mechanism of VSG. The wild type (WT) mice and ob/ob mice were divided into four groups: A (WT+Sham), B (WT+VSG), C (ob/ob+Sham), and D (ob/ob+VSG). Body weight values were monitored. The IFN-γ expression in mesenteric lymph nodes of ob/ob mice pre- and post-operation was detected by flow cytometry (FCM). The FXR expression in the liver and small intestine was detected by Western blotting. The mouse AML-12 liver cells were stimulated with IFN-γ at different concentrations in vitro. The changes of FXR expression were also examined. The results showed that the body weight of ob/ob mice was significantly declined from (40.6±2.7) g to (27.5±3.8) g on the 30th day after VSG (P<0.05). At the same time, VSG induced a higher level secretion of IFN-γ in mesenteric lymph nodes of ob/ob mice than that pre-operation (P<0.05). The FXR expression levels in the liver and small intestine after VSG were respectively 0.97±0.07 and 0.84±0.07 fold of GAPDH, which were significantly higher than pre-operative levels of 0.50±0.06 and 0.48±0.06 respectively (P<0.05). After the stimulation of AML-12 liver cells in vitro by different concentrations of IFN-γ (0, 10, 25, 50, 100, and 200 ng/mL), the relative FXR expression levels were 0.22±0.04, 0.31±0.04, 0.39±0.05, 0.38±0.05, 0.56±0.06, and 0.35±0.05, respectively, suggesting IFN-γ could distinctly promote the FXR expression in a dose-dependent manner in comparison to those cells without IFN-γ stimulation (P<0.05). It was concluded that VSG induces a weight loss in ob/ob mice by increasing IFN-γ secretion of mesenteric lymph nodes, which then increases the FXR expression of the liver and small intestine.
Similar content being viewed by others
References
Buchwald H, Avidor Y, Braunwald E, et al. Bariatric surgery: a systematic review and meta-analysis. JAMA, 2004, 292(14): 1724–1737
Schauer PR, Bhatt DL, Kirwan JP, et al. Bariatric surgery versus intensive medical therapy for diabetes-3-year outcomes. N Engl J Med, 2014, 370(21): 2002–2013
Ryan KK, Tremaroli V, Clemmensen C, et al. FXR is a molecular target for the effects of vertical sleeve gastrectomy. Nature, 2014, 509(7499): 183–188
Xia Z, Wang G, Li H, et al. Influence of bariatric surgery on the expression of nesfatin-1 in rats with type 2 diabetes mellitus. Curr Pharm Des, 2015, 21,(11): 1464–1471
Yip S, Plank LD, Murphy R. Gastric bypass and sleeve gastrectomy for type 2 diabetes: a systematic review and meta-analysis of outcomes. Obes Surg, 2013, 23(12): 1994–2003
Stefater MA, Wilson-Perez HE, Chambers AP, et al. All bariatric surgeries are not created equal: insights from mechanistic comparisons. Endocr Rev, 2012, (4): 595–622
Myronovych A, Kirby M, Ryan kk, et al. Vertical sleeve gastrectomy reduces hepatic steatosis while increasing serum bile acids in a weight-loss-independent manner. Obesity (Silver Spring), 2013, 22(2): 390–400
Kohli R, Bradley D, Setchell KD, et al. Weight loss induced by Roux-en-Y gastric bypass but not laparoscopic adjustable gastric banding increases circulating bile acids. J Clin Endocrinol Metab, 2013, 98(4): E708–712
Gerhard GS, Styer AM, Wood GC, et al. A role for fibroblast growth factor 19 and bile acids in diabetes remission after Roux-en-Y gastric bypass. Diabetes Care, 2013, 36(7): 1859–1864
de Aguiar Vallim TQ, Tarling EJ, Edwards PA. Pleiotropic roles of bile acids in metabolism. Cell Metab, 2013, 17(5): 657–669
Keating N, Keely SJ. Bile acids in regulation of intestinal physiology. Curr Gastroenterol Rep, 2009, 11(5): 375–382
Fiorucci S, Mencarelli A, Palladino G, et al. Bile-acid-activated receptors: targeting TGR5 and farnesoid-X-receptor in lipid and glucose disorders. Trends Pharmacol Sci, 2009, 30(11): 570–580
Furet J-P, Kong LC, Tap J, et al. Differential adaptation of human gut microbiota to bariatric surgery induced weight loss: links with metabolic and low-grade inflammation markers. Diabetes, 2010, 59(12): 3049–3057
Ley RE, Backhed F, Turnbaugh P, et al. Obesity alters gut microbial ecology. Proc Natl Acd Sci USA, 2005, 102(31): 11070–11075
Liou AP, Paziuk M, Luevano JM Jr, et al. Conserved shifts in the gut microbiota due to gastric bypass reduce host weight and adiposity. Sci Transl Med, 2013, 5(178): 178ra41
Graessler J, Qin Y, Zhong H, et al. Metagenomic sequencing of the human gut microbiome before and after bariatric surgery in obese patients with type 2 diabetes:correlation with inflammatory and metabolic parameters. Pharmacogenomics J, 2012, 13(6): 514–522
Zhang H, DiBaise JK, Zuccolo A, et al. Human gut microbiota in obesity and after gastric bypass. Proc Natl Acad Sci USA, 2009, 106(7): 2365–2370
Stefater MA, Wilson-Perez HE, Chambers AP, et al. All bariatric surgeries are not created equal: insights from mechanistic comparisons. Endocr Rev, 2012, 33(4): 595–622
Nakatani H, Kasama K, Oshiro T, et al. Serum bile acid along with plasma incretins and serum high molecular weight adiponectin levels are increased after bariatric surgery. Metabolism, 2009, 58(10): 1400–1407
Kliewer SA, Stimmel JB, Willson TM, et al. Bile acids: natural ligands for an orphan nuclear receptor. Science, 1999, 284(5418): 1365–1368
Makishima M, Okamoto AY, Repa JJ, et al. Identification of a nuclear receptor for bile acids. Science, 1999, 284(5418): 1362–1365
Lefebvre P, Cariou B, Lien F, et al. Role of bile acids and bile acid receptors in metabolic regulation. Physiol Rev, 2009, 89(1) 147–191
Cariou B, K van Harmelen, D Duran-Sandoval, et al. The farnesoid X receptor modulates adiposity and peripheral insulin sensitivity in mice. J Biol Chem, 2006, 281(16): 11039–11049
Dong X, Zhao H, Ma X. Reduction in bile acids pool causes delayed liver regeneration accompanied by down-regulated expression of FXR and c-Jun mRNA in rats. J Huazhong Univ Sci Technolog Med Sci, 2010, 30(1): 55–60
Zhang Y, FY Lee, G Barrera, et al. Activation of the nuclear receptor FXR improves hyperglycemia and hyperlipidemia in diabetic mice. Proc Natl Acad Sci USA, 2006, 103(40): 1006–1011
Porez G, Prawitt J, Gross B, et al. Bile acid receptors as targets for the treatment of dyslipidemia and cardiovascular disease. J, Lipid Res, 2012, 53(9): 1723–1737
Zhang Y, Kast-Woelbern HR, Edwards PA. Natural structural variants of the nuclear receptor farnesoid X receptor affect transcriptional activation. J Biol Chem, 2003, 278(11): 104–110
Duran-Sandoval D, Mautino G, Mar G, et al. Glucose regulates the expression of the farnesoid X receptor in liver. Diabetes, 2004, 53(4): 890–898
Cao R, Cronk ZXW, et al. Bile acids regulate hepatic gluconeogenic and farnesoid X receptor via Gi-protein-coupled receptors and the AKT pathway. J Lipid Res, 2010, 51(8): 2234–2244
Chambers AP, Kirchner H, Wilson-Perezet HE, et al. The effects of vertical sleeve gastrectomy in rodents are ghrelin independent. Gastroenterology, 2013, 144(1): 50–52
Wilson-Perez HE, Chambers AP, Kirchner H, et al. Vertical sleeve gastrectomy is effective in two genetic mouse models of glucagon-like peptide-1 receptor deficiency. Diabetes, 2013, 62(7): 2380–2385
Pories WJ. Bariatric surgery: risks and rewards. J Clin Endocrinol Metab, 2008, 93(11): S89–96
Insull W Jr. Clinical utility of bile acid sequestrants in the treatment of dyslipidemia: a scientific review. South Med J, 2006, 99(3): 257–273
Turnbaugh PT, Hamady M, Yatsunenko T, et al. A core gut microbiome in obese and lean twins. Nature, 2009, 457(7228): 480–484
Bäckhed F, Manchester JK, Semenkovich C, et al. Mechanism underlying the resistance to diet-induced obesity in germ-free mice. Proc, Natl, Acad, Sci, USA, 2007, 104(3): 979–984
Neyrinck AM, Possemiers S, Verstraete W, et al. Dietary modulation of clostridial cluster XIVa gut bacteria (Roseburia spp.) by chitinglucan fiber improves host metabolic alterations induced by high-fat diet in mice. J Nutr Biochem, 2012, 23,(1): 51–59
Brodziak F, Meharg C, Blaut M, et al. Differences in mucosal gene expression in the colon of two inbred mouse strains after colonization with commensal gut bacteria. PLos One, 2013, 8(8): e72317
Dewulf EM, Cani PD, Claus SP, et al. Insight into the prebiotic concept: lessons from an exploratory, double blind intervention study with insulin-type fructans in obese women. Gut, 2012, 62(8): 1112–1121
Hao Z, Münzberg H, Rezai-Zadeh K, et al. Leptin deficient ob/ob mice and diet-induced obese mice responded differently to Roux-en-Y bypass surgery. Intern J Obesity, 2015, 39(5): 798–805
Author information
Authors and Affiliations
Corresponding author
Additional information
This study was supported by grants from the National Natural Science Foundation of China (No. 81200276), the Hubei Provincial Natural Science Foundation of China (No. 2015CFB710), the Health and Family Planning Youth Project Foundation of Hubei Province, China (No. WJ2015Q001), the Research Fund of Union Hospital of Huazhong University of Science and Technology, China (No. 000003396), and the Research Fund of Public Welfare in Health Industry, 2014, Health and Family Planning Commission of China (No. 201402015), 2014, Health Ministry of China.
Rights and permissions
About this article
Cite this article
Du, Jp., Wang, G., Hu, Cj. et al. IFN-γ secretion in gut of Ob/Ob mice after vertical sleeve gastrectomy and its function in weight loss mechanism. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 36, 377–382 (2016). https://doi.org/10.1007/s11596-016-1595-6
Received:
Revised:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11596-016-1595-6