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Erschienen in: Obesity Surgery 2/2021

28.09.2020 | Original Contributions

Roux-en-Y Gastric Bypass Surgery Has Early Differential Effects on Bile Acids and the Levels of Complement Component 3 and Acylation-Stimulating Protein

verfasst von: Olivier F. Noel, Xin Chu, Andrew D. Patterson, Michael A. Edwards, Christopher D. Still, Glenn S. Gerhard

Erschienen in: Obesity Surgery | Ausgabe 2/2021

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Abstract

Background

Bile acids have been implicated in the mechanism by which Roux-en-Y gastric bypass (RYGB) can induce remission of type 2 diabetes (T2D). Our goal was to identify circulating proteins whose levels changed after RYGB when dysglycemic parameters normalized.

Materials and Methods

This was a retrospective study of 26 participants who underwent RYGB. Blood proteins were identified using two-dimensional electrophoresis and mass spectroscopy. Complement proteins were measured using immunoassays and bile acids measured using ultra-high-performance liquid chromatography and mass spectroscopy.

Results

A total of 7/452 blood proteins were found to change 2 days after RYGB. Complement component 3 (C3) was selected because of its regulation by bile acids and the glucoregulatory function of its proteolytically processed product C3adesArg or acylation-stimulating protein (ASP). The median (inter-quartile range/IQR) C3 level was 47.4 (34.5, 65.9) mg/dL before surgery decreasing to 40.9 (13.4, 64.1) mg/dL within 2 days after surgery (p = 0.0292). The median (IQR) ASP level increased from 2.8 (0.9, 7.3) nM before surgery to 8.0 (5.3, 14.1) nM within 2 days after surgery (p = 0.0016). ASP levels increased in 14/17 (82%) with T2D remission and in 6/6 with normoglycemia but decreased in 3/3 with persistent T2D. Of ten bile acids measured, the levels of ursodeoxycholic acid (UDCA) were significantly decreased after RYGB and the levels of taurodeoxycholic acid (TDCA) were significantly decreased with T2D remission.

Conclusions

These data further support an association of C3 with glucose metabolism and implicate bile acids and ASP in the early remittive effects of RYGB on T2D.
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Literatur
1.
Zurück zum Zitat Goldfine AB, Patti ME. Diabetes improvement following Roux-en-Y gastric bypass: understanding dynamic changes in insulin secretion and action. Diabetes. 2014;63(5):1454–6.CrossRef Goldfine AB, Patti ME. Diabetes improvement following Roux-en-Y gastric bypass: understanding dynamic changes in insulin secretion and action. Diabetes. 2014;63(5):1454–6.CrossRef
2.
Zurück zum Zitat Allen RE, Hughes TD, Ng JL, et al. Mechanisms behind the immediate effects of Roux-en-Y gastric bypass surgery on type 2 diabetes. Theor Biol Med Model. 2013;10:45.CrossRef Allen RE, Hughes TD, Ng JL, et al. Mechanisms behind the immediate effects of Roux-en-Y gastric bypass surgery on type 2 diabetes. Theor Biol Med Model. 2013;10:45.CrossRef
3.
Zurück zum Zitat Hutch CR, Sandoval DA. Physiological and molecular responses to bariatric surgery: markers or mechanisms underlying T2DM resolution? Ann N Y Acad Sci. 2017;1391(1):5–19.CrossRef Hutch CR, Sandoval DA. Physiological and molecular responses to bariatric surgery: markers or mechanisms underlying T2DM resolution? Ann N Y Acad Sci. 2017;1391(1):5–19.CrossRef
4.
Zurück zum Zitat Flynn CR, Albaugh VL, Abumrad NN. Metabolic effects of bile acids: potential role in bariatric surgery. Cell Mol Gastroenterol Hepatol. 2019;8(2):235–46.CrossRef Flynn CR, Albaugh VL, Abumrad NN. Metabolic effects of bile acids: potential role in bariatric surgery. Cell Mol Gastroenterol Hepatol. 2019;8(2):235–46.CrossRef
5.
Zurück zum Zitat Wu Y, Zhou A, Tang L, et al. Bile acids: key regulators and novel treatment targets for type 2 diabetes. J Diabetes Res. 2020;2020:6138438.PubMedPubMedCentral Wu Y, Zhou A, Tang L, et al. Bile acids: key regulators and novel treatment targets for type 2 diabetes. J Diabetes Res. 2020;2020:6138438.PubMedPubMedCentral
6.
Zurück zum Zitat Ryan KK, Tremaroli V, Clemmensen C, et al. FXR is a molecular target for the effects of vertical sleeve gastrectomy. Nature. 2014;509(7499):183–8.CrossRef Ryan KK, Tremaroli V, Clemmensen C, et al. FXR is a molecular target for the effects of vertical sleeve gastrectomy. Nature. 2014;509(7499):183–8.CrossRef
7.
Zurück zum Zitat McGavigan AK, Garibay D, Henseler ZM, et al. TGR5 contributes to glucoregulatory improvements after vertical sleeve gastrectomy in mice. Gut. 2017;66(2):226–34. CrossRef McGavigan AK, Garibay D, Henseler ZM, et al. TGR5 contributes to glucoregulatory improvements after vertical sleeve gastrectomy in mice. Gut. 2017;66(2):226–34. CrossRef
8.
Zurück zum Zitat Li J, Pircher PC, Schulman IG, et al. Regulation of complement C3 expression by the bile acid receptor FXR. J Biol Chem. 2005;280(9):7427–34.CrossRef Li J, Pircher PC, Schulman IG, et al. Regulation of complement C3 expression by the bile acid receptor FXR. J Biol Chem. 2005;280(9):7427–34.CrossRef
9.
Zurück zum Zitat Ursini F, Abenavoli L. The emerging role of complement C3 as a biomarker of insulin resistance and cardiometabolic diseases: preclinical and clinical evidence. Rev Recent Clin Trials. 2018;13(1):61–8.CrossRef Ursini F, Abenavoli L. The emerging role of complement C3 as a biomarker of insulin resistance and cardiometabolic diseases: preclinical and clinical evidence. Rev Recent Clin Trials. 2018;13(1):61–8.CrossRef
10.
Zurück zum Zitat Maslowska M, Sniderman AD, Germinario R, et al. ASP stimulates glucose transport in cultured human adipocytes. Int J Obes Relat Metab Disord. 1997;21(4):261–6.CrossRef Maslowska M, Sniderman AD, Germinario R, et al. ASP stimulates glucose transport in cultured human adipocytes. Int J Obes Relat Metab Disord. 1997;21(4):261–6.CrossRef
11.
Zurück zum Zitat Wood GC, Chu X, Manney C, et al. An electronic health record-enabled obesity database. BMC Med Inform Decis Mak. 2012;12(1):45.CrossRef Wood GC, Chu X, Manney C, et al. An electronic health record-enabled obesity database. BMC Med Inform Decis Mak. 2012;12(1):45.CrossRef
12.
Zurück zum Zitat Patterson AD, Maurhofer O, Beyoglu D, et al. Aberrant lipid metabolism in hepatocellular carcinoma revealed by plasma metabolomics and lipid profiling. Cancer Res. 2011;71(21):6590–600.CrossRef Patterson AD, Maurhofer O, Beyoglu D, et al. Aberrant lipid metabolism in hepatocellular carcinoma revealed by plasma metabolomics and lipid profiling. Cancer Res. 2011;71(21):6590–600.CrossRef
13.
Zurück zum Zitat Dagda RK, Sultana T, Lyons-Weiler J. Evaluation of the consensus of four peptide identification algorithms for tandem mass spectrometry based proteomics. J Proteomics Bioinform. 2010;3:39–47.CrossRef Dagda RK, Sultana T, Lyons-Weiler J. Evaluation of the consensus of four peptide identification algorithms for tandem mass spectrometry based proteomics. J Proteomics Bioinform. 2010;3:39–47.CrossRef
14.
Zurück zum Zitat Daily K, Patel VR, Rigor P, et al. MotifMap: integrative genome-wide maps of regulatory motif sites for model species. BMC Bioinformatics. 2011;12:495.CrossRef Daily K, Patel VR, Rigor P, et al. MotifMap: integrative genome-wide maps of regulatory motif sites for model species. BMC Bioinformatics. 2011;12:495.CrossRef
15.
Zurück zum Zitat Al Haj Ahmad RM, Al-Domi HA. Complement 3 serum levels as a pro-inflammatory biomarker for insulin resistance in obesity. Diabetes Metab Syndr. 2016;11:S229-S232 Al Haj Ahmad RM, Al-Domi HA. Complement 3 serum levels as a pro-inflammatory biomarker for insulin resistance in obesity. Diabetes Metab Syndr. 2016;11:S229-S232
16.
Zurück zum Zitat Ricklin D, Lambris JD. Complement in immune and inflammatory disorders: pathophysiological mechanisms. J Immunol. 2013;190(8):3831–8.CrossRef Ricklin D, Lambris JD. Complement in immune and inflammatory disorders: pathophysiological mechanisms. J Immunol. 2013;190(8):3831–8.CrossRef
17.
Zurück zum Zitat Cianflone K, Maslowska M, Sniderman AD. Acylation stimulating protein (ASP), an adipocyte autocrine: new directions. Semin Cell Dev Biol. 1999;10(1):31–41.CrossRef Cianflone K, Maslowska M, Sniderman AD. Acylation stimulating protein (ASP), an adipocyte autocrine: new directions. Semin Cell Dev Biol. 1999;10(1):31–41.CrossRef
18.
Zurück zum Zitat 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):1859–64.CrossRef 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):1859–64.CrossRef
19.
Zurück zum Zitat Abranches MV, Oliveira FC, Conceicao LL, et al. Obesity and diabetes: the link between adipose tissue dysfunction and glucose homeostasis. Nutr Res Rev. 2015;28(2):121–32.CrossRef Abranches MV, Oliveira FC, Conceicao LL, et al. Obesity and diabetes: the link between adipose tissue dysfunction and glucose homeostasis. Nutr Res Rev. 2015;28(2):121–32.CrossRef
20.
Zurück zum Zitat Hotamisligil GS. Inflammation and metabolic disorders. Nature. 2006;444(7121):860–7.CrossRef Hotamisligil GS. Inflammation and metabolic disorders. Nature. 2006;444(7121):860–7.CrossRef
21.
Zurück zum Zitat Hernandez-Mijares A, Banuls C, Bellod L, et al. Effect of weight loss on C3 and C4 components of complement in obese patients. Eur J Clin Investig. 2012;42(5):503–9.CrossRef Hernandez-Mijares A, Banuls C, Bellod L, et al. Effect of weight loss on C3 and C4 components of complement in obese patients. Eur J Clin Investig. 2012;42(5):503–9.CrossRef
22.
Zurück zum Zitat King BC, Kulak K, Krus U, et al. Complement component C3 is highly expressed in human pancreatic islets and prevents beta cell death via ATG16L1 interaction and autophagy regulation. Cell Metab. 2019;29(1):202–10. e6CrossRef King BC, Kulak K, Krus U, et al. Complement component C3 is highly expressed in human pancreatic islets and prevents beta cell death via ATG16L1 interaction and autophagy regulation. Cell Metab. 2019;29(1):202–10. e6CrossRef
23.
Zurück zum Zitat Kalant D, Cain SA, Maslowska M, et al. The chemoattractant receptor-like protein C5L2 binds the C3a des-Arg77/acylation-stimulating protein. J Biol Chem. 2003;278(13):11123–9.CrossRef Kalant D, Cain SA, Maslowska M, et al. The chemoattractant receptor-like protein C5L2 binds the C3a des-Arg77/acylation-stimulating protein. J Biol Chem. 2003;278(13):11123–9.CrossRef
24.
Zurück zum Zitat Fisette A, Munkonda MN, Oikonomopoulou K, et al. C5L2 receptor disruption enhances the development of diet-induced insulin resistance in mice. Immunobiology. 2013;218(1):127–33.CrossRef Fisette A, Munkonda MN, Oikonomopoulou K, et al. C5L2 receptor disruption enhances the development of diet-induced insulin resistance in mice. Immunobiology. 2013;218(1):127–33.CrossRef
25.
Zurück zum Zitat Fisette A, Poursharifi P, Oikonomopoulou K, et al. Paradoxical glucose-sensitizing yet proinflammatory effects of acute ASP administration in mice. Mediat Inflamm. 2013;2013:713284.CrossRef Fisette A, Poursharifi P, Oikonomopoulou K, et al. Paradoxical glucose-sensitizing yet proinflammatory effects of acute ASP administration in mice. Mediat Inflamm. 2013;2013:713284.CrossRef
26.
Zurück zum Zitat Nestvold TK, Nielsen EW, Ludviksen JK, et al. Lifestyle changes followed by bariatric surgery lower inflammatory markers and the cardiovascular risk factors C3 and C4. Metab Syndr Relat Disord. 2015;13(1):29–35.CrossRef Nestvold TK, Nielsen EW, Ludviksen JK, et al. Lifestyle changes followed by bariatric surgery lower inflammatory markers and the cardiovascular risk factors C3 and C4. Metab Syndr Relat Disord. 2015;13(1):29–35.CrossRef
27.
Zurück zum Zitat Munkonda MN, Martin J, Poirier P, et al. Acylation stimulating protein reduction precedes insulin sensitization after BPD-DS bariatric surgery in severely obese women. Nutr Diabetes. 2012;2:e41.CrossRef Munkonda MN, Martin J, Poirier P, et al. Acylation stimulating protein reduction precedes insulin sensitization after BPD-DS bariatric surgery in severely obese women. Nutr Diabetes. 2012;2:e41.CrossRef
28.
Zurück zum Zitat Faraj M, Havel PJ, Phelis S, et al. Plasma acylation-stimulating protein, adiponectin, leptin, and ghrelin before and after weight loss induced by gastric bypass surgery in morbidly obese subjects. J Clin Endocrinol Metab. 2003;88(4):1594–602.CrossRef Faraj M, Havel PJ, Phelis S, et al. Plasma acylation-stimulating protein, adiponectin, leptin, and ghrelin before and after weight loss induced by gastric bypass surgery in morbidly obese subjects. J Clin Endocrinol Metab. 2003;88(4):1594–602.CrossRef
29.
Zurück zum Zitat Torres-Duran M, Lopez-Campos JL, Barrecheguren M, et al. Alpha-1 antitrypsin deficiency: outstanding questions and future directions. Orphanet J Rare Dis. 2018;13(1):114.CrossRef Torres-Duran M, Lopez-Campos JL, Barrecheguren M, et al. Alpha-1 antitrypsin deficiency: outstanding questions and future directions. Orphanet J Rare Dis. 2018;13(1):114.CrossRef
30.
Zurück zum Zitat Xie ZB, Zhang YF, Jin C, et al. LRG-1 promotes pancreatic cancer growth and metastasis via modulation of the EGFR/p38 signaling. J Exp Clin Cancer Res. 2019;38(1):75.CrossRef Xie ZB, Zhang YF, Jin C, et al. LRG-1 promotes pancreatic cancer growth and metastasis via modulation of the EGFR/p38 signaling. J Exp Clin Cancer Res. 2019;38(1):75.CrossRef
31.
Zurück zum Zitat Meneses MJ, Silvestre R, Sousa-Lima I, et al. Paraoxonase-1 as a regulator of glucose and lipid homeostasis: impact on the onset and progression of metabolic disorders. Int J Mol Sci. 2019;19:20(16). Meneses MJ, Silvestre R, Sousa-Lima I, et al. Paraoxonase-1 as a regulator of glucose and lipid homeostasis: impact on the onset and progression of metabolic disorders. Int J Mol Sci. 2019;19:20(16).
32.
Zurück zum Zitat Madsbad S, Dirksen C, Holst JJ. Mechanisms of changes in glucose metabolism and bodyweight after bariatric surgery. Lancet Diabetes Endocrinol. 2014;2(2):152–64.CrossRef Madsbad S, Dirksen C, Holst JJ. Mechanisms of changes in glucose metabolism and bodyweight after bariatric surgery. Lancet Diabetes Endocrinol. 2014;2(2):152–64.CrossRef
33.
Zurück zum Zitat Albaugh VL, Banan B, Ajouz H, et al. Bile acids and bariatric surgery. Mol Asp Med. 2017;56:75–89.CrossRef Albaugh VL, Banan B, Ajouz H, et al. Bile acids and bariatric surgery. Mol Asp Med. 2017;56:75–89.CrossRef
Metadaten
Titel
Roux-en-Y Gastric Bypass Surgery Has Early Differential Effects on Bile Acids and the Levels of Complement Component 3 and Acylation-Stimulating Protein
verfasst von
Olivier F. Noel
Xin Chu
Andrew D. Patterson
Michael A. Edwards
Christopher D. Still
Glenn S. Gerhard
Publikationsdatum
28.09.2020
Verlag
Springer US
Erschienen in
Obesity Surgery / Ausgabe 2/2021
Print ISSN: 0960-8923
Elektronische ISSN: 1708-0428
DOI
https://doi.org/10.1007/s11695-020-04993-4

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