Abstract
Background
Type 2 diabetes (T2D) resolves rapidly after bariatric surgery, even before substantial weight is lost. However, the molecular pathways underlying this phenomenon remain unclear. Microarray data has shown that numerous genes are differentially expressed in blood after bariatric surgery, including resistin and leptin. Resistin and leptin are circulating hormones derived from adipose tissue, which are associated with obesity and insulin resistance. This study examined expression of these genes before and after bariatric surgery in diabetic and nondiabetic obese patients.
Methods
The study included 16 obese patients who underwent bariatric surgery, either Roux-en-Y gastric bypass (RYGB) or adjustable gastric banding. Eight patients had T2D. Preoperative blood samples were collected in PAXgene tubes to stabilize mRNA. Postoperative samples were collected 3 months after surgery. Total RNA was isolated and cDNA was synthesized. Real-time quantitative PCR was used to quantify mRNA. Results were analyzed using Student’s t test with a P < 0.05 considered significant.
Results
Postoperatively, five diabetic patients had discontinued hypoglycemic medications and one showed improved glycemic control. Both leptin and resistin mRNA levels were elevated in the diabetic group but decreased after surgery to levels near those of the nondiabetic group. Greater downregulation of resistin and leptin expression occurred in patients who lost more excess body weight (EBW), while patients who lost less than 10% EBW had a mean increase in expression of the two genes. Downregulation of both genes was more pronounced after RYGB compared to gastric banding.
Conclusions
Downregulation of resistin and leptin gene expression after bariatric surgery may play a role in normalizing obesity-associated insulin resistance. Interestingly, downregulation is greater after RYGB and in patients who lose a greater proportion of EBW. Targeted therapies for obesity and diabetes may be developed by understanding the pathways by which these adipocytokines contribute to obesity and T2D.
Similar content being viewed by others
References
Kelesidis T, Kelesidis I, Chou S, Mantzoros CS (2010) Narrative review: the role of leptin in human physiology: emerging clinical applications. Ann Int Med 152:93–100
Verna EC, Berk PD (2008) Role of fatty acids in the pathogenesis of obesity and fatty liver: impact of bariatric surgery. Semin Liver Dis 28:407–426
McTernan PG, McTernan CL, Chetty R, Jenner K, Fisher FM, Lauer MN, Crocker J, Barnett AH, Kumar S (2002) Increased resistin gene and protein expression in human abdominal adipose tissue. J Clin Endocrinol Metab 87:2407
Yannakoulia M, Yiannakouris N, Bluher S, Matalas AL, Klimis-Zacas D, Mantzoros CS (2003) Body fat mass and macronutrient intake in relation to circulating soluble leptin receptor, free leptin index, adiponectin, and resistin concentrations in healthy humans. J Clin Endocrinol Metab 88:1730–1736
Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM, Patel HR, Ahima RS, Lazar MA (2001) The hormone resistin links obesity to diabetes. Nature 409:307–312
Won JC, Park CY, Lee WY, Lee ES, Oh SW, Park SW (2009) Association of plasma levels of resistin with subcutaneous fat mass and markers of inflammation but not with metabolic determinants or insulin resistance. J Korean Med Sci 24:695–700
Rabe K, Lehrke M, Parhofer KG, Broedl UC (2008) Adipokines and insulin resistance. Mol Med 14:741–751
Tsiotra PC, Tsigos C, Anastasiou E, Yfanti E, Boutati E, Souvatzoglou E, Kyrou I, Raptis SA (2008) Peripheral mononuclear cell resistin mRNA expression is increased in type 2 diabetic women. Mediators Inflamm 2008:892864
Chen BH, Song Y, Ding EL, Roberts CK, Manson JE, Rifai N, Buring JE, Gaziano JM, Liu S (2009) Circulating levels of resistin and risk of type 2 diabetes in men and women: results from two prospective cohorts. Diabetes Care 32:329–334
McTernan PG, Kusminski CM, Kumar S (2006) Resistin. Curr Opin Lipidol 17:170–175
van Dielen FMH, van ‘t Veer C, Buurman WA, Greve JWM (2002) Leptin and soluble leptin receptor levels in obese and weight-losing individuals. J Clin Endocrinol Metab 87:1708–1716
Azuma K, Katsukawa F, Oguchi S, Murata M, Yamazaki H, Shimada A, Saruta T (2003) Correlation between serum resistin level and adiposity in obese individuals. Obes Res 11:997–1001
Degawa-Yamauchi M, Bovenkerk JE, Juliar BE, Watson W, Kerr K, Jones R, Zhu Q, Considine RV (2003) Serum resistin (FIZZ3) protein is increased in obese humans. J Clin Endocrinol Metab 88:5452–5455
Norata GD, Ongari M, Garlaschelli K, Raselli S, Grigore L, Catapano AL (2007) Plasma resistin levels correlate with determinants of the metabolic syndrome. Eur J Endocrinol 156:279–284
Chen CC, Li TC, Li CI, Liu CS, Wang HJ, Lin CC (2005) Serum resistin level among healthy subjects: relationship to anthropometric and metabolic parameters. Metabolism 54:471–475
Korner J, Leibel RL (2003) To eat or not to eat - how the gut talks to the brain. N Engl J Med 349:926–928
Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR, Ohannesian JP, Marco CC, McKee LJ, Bauer TL, Caro JF (1996) Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med 334:292–295
Lonnqvist F, Arner P, Nordfors L, Schalling M (1995) Overexpression of the obese (ob) gene in adipose tissue of human obese subjects. Nat Med 1:950–953
Faraj M, Havel PJ, Phelis S, Blank D, Sniderman AD, Cianflone K (2003) 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 88:1594–1602
Trakhtenbroit MA, Leichman JG, Algahim MF, Miller CC III, Moody FG, Lux TR, Taegtmeyer H (2009) Body weight, insulin resistance, and serum adipokine levels 2 years after 2 types of bariatric surgery. Am J Med 122:435–442
Moschen AR, Molnar C, Wolf AM, Weiss H, Graziadei I, Kaser S, Ebenbichler CF, Stadlmann S, Moser PL, Tilg H (2009) Effects of weight loss induced by bariatric surgery on hepatic adipocytokine expression. J Hepatol 51:765–777
Nijhuis J, van Dielen FMH, Fouraschen SMG, van den Broek MAJ, Rensen SSM, Buurman WA, Greve JWM (2007) Endothelial activation markers and their key regulators after restrictive bariatric surgery. Obesity 15:1395–1399
Santoro S, Milleo FQ, Malzoni CE, Klajner S, Borges PCM, Santo MA, Campos FG, Artoni RF (2008) Enterohormonal changes after digestive adaptation: five-year results of a surgical proposal to treat obesity and associated diseases. Obes Surg 18:17–26
Filkova M, Haluzik M, Gay S, Senolt L (2009) The role of resistin as a regulator of inflammation: implications for various human pathologies. Clin Immunol 133:157–170
Fantuzzi G (2005) Adipose tissue, adipokines, and inflammation. J Allergy Clin Immunol 115:911–919 (quiz 920)
Das SK, Roberts SB, Kehayias JJ, Wang J, Hsu LKG, Shikora SA, Saltzman E, McCrory MA (2003) Body composition assessment in extreme obesity and after massive weight loss induced by gastric bypass surgery. Am J Physiol Endocrinol Metab 284:E1080–E1088
Rubino F, Gagner M (2002) Potential of surgery for curing type 2 diabetes mellitus. Ann Surg 236:554–559
Disclosures
Drs. Edwards, Hindle, Fu, and Brody have no conflicts of interest or financial ties to disclose.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Edwards, C., Hindle, A.K., Fu, S. et al. Downregulation of leptin and resistin expression in blood following bariatric surgery. Surg Endosc 25, 1962–1968 (2011). https://doi.org/10.1007/s00464-010-1494-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00464-010-1494-z