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Circulating ANGPTL8/Betatrophin Concentrations Are Increased After Surgically Induced Weight Loss, but Not After Diet-Induced Weight Loss

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Abstract

Background

ANGPTL8/betatrophin is a secreted protein reported to be involved in β-cell replication that has recently been shown to be more related to lipid metabolism. Weight loss represents a clinical situation of improvement of glucose homeostasis and overall metabolic control. The aim of the present study was to analyze the impact of weight loss induced by either a conventional dietary treatment or bariatric surgery on ANGPTL8/betatrophin concentrations.

Methods

Serum concentrations of ANGPTL8/betatrophin were measured by ELISA in 158 subjects before and 1 year after weight loss induced either by conventional dietary treatment (n = 38) or bariatric surgery (sleeve gastrectomy, n = 20, or Roux-en-Y gastric bypass, n = 100).

Results

Massive surgery-induced weight loss after SG or RYGB was accompanied by a statistically significant increase in circulating levels of ANGPTL8/betatrophin (28.1 ± 13.9 to 40.3 ± 22.8 ng/mL, P = 0.001 after SG; 24.6 ± 10.9 to 41.7 ± 19.4 ng/mL, P < 0.001 after RYGB), while remaining unchanged 25.6 ± 13.3 to 25.4 ± 10.7 ng/mL (P = 0.891) after diet-induced weight loss. The change in ANGPTL8/betatrophin levels was positively correlated with the change in HDL-C concentrations.

Conclusions

Our study showed that serum ANGPTL8/betatrophin concentrations were increased in obese subjects after surgically induced weight loss, but not after weight loss achieved by conventional dietary treatment. The change in ANGPTL8/betatrophin concentrations emerged as a significant predictor of the change in HDL-C levels after weight loss.

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Abbreviations

ANGPTL8:

Angiopoietin-like protein 8

BMI:

Body mass index

SBP:

Systolic blood pressure

DBP:

Diastolic blood pressure

OGTT:

Oral glucose tolerance test

HOMA:

Homeostatic model assessment

PAL:

Physical activity level

QUICKI:

Quantitative insulin sensitivity check index

CRP:

C-reactive protein

ALT:

Alanine aminotransferase

γ-GT:

γ-Glutamyltransferase

WBC:

White blood cells

References

  1. Frühbeck G, Toplak H, Woodward E, et al. Obesity: the gateway to ill health - an EASO position statement on a rising public health, clinical and scientific challenge in Europe. Obes Facts. 2013;6:117–20.

    Article  PubMed  Google Scholar 

  2. Eckel RH, Kahn SE, Ferrannini E, et al. Obesity and type 2 diabetes: what can be unified and what needs to be individualized? J Clin Endocrinol Metab. 2011;96:1654–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Yumuk V, Frühbeck G, Oppert JM, et al. An EASO position statement on multidisciplinary obesity management in adults. Obes Facts. 2014;7:96–101.

    Article  PubMed  Google Scholar 

  4. de las Fuentes L, Waggoner AD, Mohammed BS, et al. Effect of moderate dietinduced weight loss and weight regain on cardiovascular structure and function. J Am Coll Cardiol. 2009;54:2376–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Geloneze B, Geloneze SR, Chaim E, et al. Metabolic surgery for non-obese type 2 diabetes: incretins, adipocytokines, and insulin secretion/resistance changes in a 1-year interventional clinical controlled study. Ann Surg. 2012;256:72–8.

    Article  PubMed  Google Scholar 

  6. Vest AR, Heneghan HM, Schauer PR, et al. Surgical management of obesity and the relationship to cardiovascular disease. Circulation. 2013;127:945–59.

    Article  PubMed  Google Scholar 

  7. Sjöström L, Narbro K, Sjöström CD, et al. Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med. 2007;357:741–52.

    Article  PubMed  Google Scholar 

  8. Mingrone G, Panunzi S, De Gaetano A, et al. Bariatric surgery versus conventional medical therapy for type 2 diabetes. N Engl J Med. 2012;366:1577–85.

    Article  CAS  PubMed  Google Scholar 

  9. Schauer PR, Bhatt DL, Kirwan JP, et al. Bariatric surgery versus intensive medical therapy for diabetes – 3-year outcomes. N Engl J Med. 2014;370:2002–13.

    Article  PubMed  Google Scholar 

  10. Frühbeck G. Bariatric and metabolic surgery: a shift in eligibility and success criteria. Nat Rev Endocrinol. 2015;11:465–77.

    Article  PubMed  Google Scholar 

  11. Quagliarini F, Wang Y, Kozlitina J, et al. Atypical angiopoietin-like protein that regulates ANGPTL3. Proc Natl Acad Sci U S A. 2012;109:19751–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Zhang R. Lipasin, a novel nutritionally-regulated liver-enriched factor that regulates serum triglyceride levels. Biochem Biophys Res Commun. 2012;424:786–92.

    Article  CAS  PubMed  Google Scholar 

  13. Ren G, Kim JY, Smas CM. Identification of RIFL, a novel adipocyte-enriched insulin target gene with a role in lipid metabolism. Am J Physiol Endocrinol Metab. 2012;303:E334–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Dong XY, Pang XW, Yu ST, et al. Identification of genes differentially expressed in human hepatocellular carcinoma by a modified suppression subtractive hybridization method. Int J Cancer. 2004;112:239–48.

    Article  CAS  PubMed  Google Scholar 

  15. Yi P, Park JS, Melton DA. Betatrophin: A hormone that controls pancreatic b cell proliferation. Cell. 2013;153:747–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Wang Y, Quagliarini F, Gusarova V, et al. Mice lacking ANGPTL8 (Betatrophin) manifest disrupted triglyceride metabolism without impaired glucose homeostasis. Proc Natl Acad Sci U S A. 2013;110:16109–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Gusarova V, Alexa CA, Na E, et al. ANGPTL8/betatrophin does not control pancreatic beta cell expansion. Cell. 2014;159:691–6.

    Article  CAS  PubMed  Google Scholar 

  18. Zhang R, Abou-Samra AB. A dual role of lipasin (betatrophin) in lipid metabolism and glucose homeostasis: consensus and controversy. Cardiovasc Diabetol. 2014;13:133.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Gómez-Ambrosi J, Pascual E, Catalán V, et al. Circulating betatrophin concentrations are decreased in human obesity and type 2 diabetes. J Clin Endocrinol Metab. 2014;99:E2004–9.

    Article  PubMed  Google Scholar 

  20. Chen X, Lu P, He W, et al. Circulating betatrophin levels are increased in patients with type 2 diabetes and associated with insulin resistance. J Clin Endocrinol Metab. 2015;100:E96–100.

    Article  CAS  PubMed  Google Scholar 

  21. Yamada H, Saito T, Aoki A, et al. Circulating betatrophin is elevated in patients with type 1 and type 2 diabetes. Endocr J. 2015;62:417–21.

    Article  CAS  PubMed  Google Scholar 

  22. Guo K, Lu J, Yu H, et al. Serum betatrophin concentrations are significantly increased in overweight but not in obese or type 2 diabetic individuals. Obesity (Silver Spring). 2015;23:793–7.

    Article  CAS  Google Scholar 

  23. Fu Z, Abou-Samra AB, Zhang R. An explanation for recent discrepancies in levels of human circulating betatrophin. Diabetologia. 2014;57:2232–4.

    Article  PubMed  Google Scholar 

  24. Johansson G, Westerterp KR. Assessment of the physical activity level with two questions: validation with doubly labeled water. Int J Obes (Lond). 2008;32:1031–3.

    Article  CAS  Google Scholar 

  25. Tokumoto S, Hamamoto Y, Fujimoto K, et al. Correlation of circulating betatrophin concentrations with insulin secretion capacity, evaluated by glucagon stimulation tests. Diabet Med. 2015;32:653–6.

    Article  CAS  PubMed  Google Scholar 

  26. Gómez-Ambrosi J, Salvador J, Rotellar F, et al. Increased serum amyloid A concentrations in morbid obesity decrease after gastric bypass. Obes Surg. 2006;16:262–9.

    Article  PubMed  Google Scholar 

  27. Catalán V, Gómez-Ambrosi J, Ramírez B, et al. Proinflammatory cytokines in obesity: impact of type 2 diabetes mellitus and gastric bypass. Obes Surg. 2007;17:1464–74.

    Article  PubMed  Google Scholar 

  28. Catalán V, Gómez-Ambrosi J, Rodríguez A, et al. Increased circulating and visceral adipose tissue expression levels of YKL-40 in obesity-associated type 2 diabetes are related to inflammation: impact of conventional weight loss and gastric bypass. J Clin Endocrinol Metab. 2011;96:200–9.

    Article  PubMed  Google Scholar 

  29. Schauer PR, Kashyap SR, Wolski K, et al. Bariatric surgery versus intensive medical therapy in obese patients with diabetes. N Engl J Med. 2012;366:1567–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Müller-Stich BP, Senft JD, Warschkow R, et al. Surgical versus medical treatment of type 2 diabetes mellitus in nonseverely obese patients: A systematic review and metaanalysis. Ann Surg. 2015;261:421–9.

    Article  PubMed  Google Scholar 

  31. Rader DJ, Hovingh GK. HDL and cardiovascular disease. Lancet. 2014;384:618–25.

    Article  CAS  PubMed  Google Scholar 

  32. Mingrone G, Greco AV, Giancaterini A, et al. Sex hormone-binding globulin levels and cardiovascular risk factors in morbidly obese subjects before and after weight reduction induced by diet or malabsorptive surgery. Atherosclerosis. 2002;161:455–62.

    Article  CAS  PubMed  Google Scholar 

  33. Aminian A, Zelisko A, Kirwan JP, et al. Exploring the impact of bariatric surgery on high density lipoprotein. Surg Obes Relat Dis. 2015;11:238–47.

    Article  PubMed  Google Scholar 

  34. Dattilo AM, Kris-Etherton PM. Effects of weight reduction on blood lipids and lipoproteins: a meta-analysis. Am J Clin Nutr. 1992;56:320–8.

    CAS  PubMed  Google Scholar 

  35. LeCheminant JD, Smith BK, Westman EC, et al. Comparison of a reduced carbohydrate and reduced fat diet for LDL, HDL, and VLDL subclasses during 9-months of weight maintenance subsequent to weight loss. Lipids Health Dis. 2010;9:54.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Varady KA, Bhutani S, Klempel MC, et al. Comparison of effects of diet versus exercise weight loss regimens on LDL and HDL particle size in obese adults. Lipids Health Dis. 2011;10:119.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Yatsuya H, Jeffery RW, Erickson DJ, et al. Sex-specific HDL cholesterol changes with weight loss and their association with anthropometric variables: the LIFE study. Obesity (Silver Spring). 2011;19:429–35.

    Article  CAS  Google Scholar 

  38. Peloso GM, Auer PL, Bis JC, et al. Association of low-frequency and rare coding sequence variants with blood lipids and coronary heart disease in 56,000 whites and blacks. Am J Hum Genet. 2014;94:223–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Asztalos BF, Swarbrick MM, Schaefer EJ, et al. Effects of weight loss, induced by gastric bypass surgery, on HDL remodeling in obese women. J Lipid Res. 2010;51:2405–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Zvintzou E, Skroubis G, Chroni A, et al. Effects of bariatric surgery on HDL structure and functionality: results from a prospective trial. J Clin Lipidol. 2014;8:408–17.

    Article  PubMed  Google Scholar 

  41. Zhang R, Abou-Samra AB. A dual role of lipasin (betatrophin) in lipid metabolism and glucose homeostasis: consensus and controversy. Cardiovasc Diabetol. 2014;13:133.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Kingwell BA, Chapman MJ, Kontush A, et al. HDL-targeted therapies: progress, failures and future. Nat Rev Drug Discov. 2014;13:445–64.

    Article  CAS  PubMed  Google Scholar 

  43. Kontush A. HDL particle number and size as predictors of cardiovascular disease. Front Pharmacol. 2015;6:218.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

The authors gratefully acknowledge the valuable collaboration of all the members of the Nutrition Unit for their technical support. The authors also wish to thank all subjects who participated in this study.

This work was supported by grants from the Fondo de Investigación Sanitaria-FEDER, Instituto de Salud Carlos III (ISCIII) (PI12/00515, PI13/00460 and PI/14/00950) and the ISCIII, Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición, CIBEROBN, Spain. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Correspondence to Gema Frühbeck.

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Conflict of Interest

E.P.-C., J.G.-A., R.M., V.V., V.C., A.R., B.R., C.S., M.J.G, J.S., and G.F. declare that they have no conflict of interest.

Additional information

E. Pascual-Corrales and J. Gómez-Ambrosi contributed equally to this work.

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ESM 2

Effect of weight loss on ANGPTL8/betatrophin concentrations in obese patients matched by body adiposity change and gender before (Pre) and after (Post) a conventional dietary (Conv Diet) or surgical [sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB)] intervention. Box represents interquartile range and median inside, with whiskers showing 10/90 percentiles. Differences between pre and post weight loss were analyzed by paired two-tailed Student’s t tests. *P<0.05 and **P<0.01 vs pre weight loss values (PDF 18 kb)

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Pascual-Corrales, E., Gómez-Ambrosi, J., Moncada, R. et al. Circulating ANGPTL8/Betatrophin Concentrations Are Increased After Surgically Induced Weight Loss, but Not After Diet-Induced Weight Loss. OBES SURG 26, 1881–1889 (2016). https://doi.org/10.1007/s11695-015-2026-7

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