SULF2 Strongly Prediposes to Fasting and Postprandial Triglycerides in Patients with Obesity and Type 2 Diabetes Mellitus

H.C. Hassing; R.P. Surendran; B. Derudas; A. Verrijken; S.M. Francque; H.L. Mooij; S.J.B. Moens; L.M. 't Hart; G. Nijpels; J.M. Dekker; K.J. Williams; E.S.G. Stroes; L.F. van Gaal; B. Staels; M. Nieuwdorp; G.M. Dallinga-Thie

doi:https://doi.org/10.1002/oby.20682

SULF2 Strongly Prediposes to Fasting and Postprandial Triglycerides in Patients with Obesity and Type 2 Diabetes Mellitus

H.C. Hassing, R.P. Surendran, B. Derudas, A. Verrijken, S.M. Francque, H.L. Mooij, S.J.B. Moens, L.M. 't Hart, G. Nijpels, J.M. Dekker, K.J. Williams, E.S.G. Stroes, L.F. van Gaal, B. Staels, M. Nieuwdorp, G.M. Dallinga-Thie

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22 Citations (Scopus)

Abstract

Hepatic overexpression of sulfatase-2 (SULF2), a heparan sulfate remodeling enzyme, strongly contributes to high triglyceride (TG) levels in obese, type 2 diabetic (T2DM) db/db mice. Nevertheless, data in humans are lacking. Here, the association of human hepatic SULF2 expression and SULF2 gene variants with TG metabolism in patients with obesity and/or T2DM was investigated. Liver biopsies from 121 obese subjects were analyzed for relations between hepatic SULF2 mRNA levels and plasma TG. Associations between seven SULF2 tagSNPs and TG levels were assessed in 210 obese T2DM subjects with dyslipidemia. Replication of positive findings was performed in 1,316 independent obese T2DM patients. Postprandial TRL clearance was evaluated in 29 obese T2DM subjects stratified by SULF2 genotype. Liver SULF2 expression was significantly associated with fasting plasma TG (r = 0.271; P = 0.003) in obese subjects. The SULF2 rs2281279(A>G) SNP was reproducibly associated with lower fasting plasma TG levels in obese T2DM subjects (P < 0.05). Carriership of the minor G allele was associated with lower levels of postprandial plasma TG (P < 0.05) and retinyl esters levels (P < 0.001). These findings implicate SULF2 as potential therapeutic target in the atherogenic dyslipidemia of obesity and T2DM

Original language	English
Pages (from-to)	1309-1316
Journal	Obesity
Volume	22
Issue number	5
DOIs	https://doi.org/10.1002/oby.20682
Publication status	Published - 2014

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Hassing, H. C., Surendran, R. P., Derudas, B., Verrijken, A., Francque, S. M., Mooij, H. L., Moens, S. J. B., 't Hart, L. M., Nijpels, G., Dekker, J. M., Williams, K. J., Stroes, E. S. G., van Gaal, L. F., Staels, B., Nieuwdorp, M., & Dallinga-Thie, G. M. (2014). SULF2 Strongly Prediposes to Fasting and Postprandial Triglycerides in Patients with Obesity and Type 2 Diabetes Mellitus. Obesity, 22(5), 1309-1316. https://doi.org/10.1002/oby.20682

@article{748b7396a34542bd88e81110d1a2f608,

title = "SULF2 Strongly Prediposes to Fasting and Postprandial Triglycerides in Patients with Obesity and Type 2 Diabetes Mellitus",

abstract = "Hepatic overexpression of sulfatase-2 (SULF2), a heparan sulfate remodeling enzyme, strongly contributes to high triglyceride (TG) levels in obese, type 2 diabetic (T2DM) db/db mice. Nevertheless, data in humans are lacking. Here, the association of human hepatic SULF2 expression and SULF2 gene variants with TG metabolism in patients with obesity and/or T2DM was investigated. Liver biopsies from 121 obese subjects were analyzed for relations between hepatic SULF2 mRNA levels and plasma TG. Associations between seven SULF2 tagSNPs and TG levels were assessed in 210 obese T2DM subjects with dyslipidemia. Replication of positive findings was performed in 1,316 independent obese T2DM patients. Postprandial TRL clearance was evaluated in 29 obese T2DM subjects stratified by SULF2 genotype. Liver SULF2 expression was significantly associated with fasting plasma TG (r = 0.271; P = 0.003) in obese subjects. The SULF2 rs2281279(A>G) SNP was reproducibly associated with lower fasting plasma TG levels in obese T2DM subjects (P < 0.05). Carriership of the minor G allele was associated with lower levels of postprandial plasma TG (P < 0.05) and retinyl esters levels (P < 0.001). These findings implicate SULF2 as potential therapeutic target in the atherogenic dyslipidemia of obesity and T2DM",

author = "H.C. Hassing and R.P. Surendran and B. Derudas and A. Verrijken and S.M. Francque and H.L. Mooij and S.J.B. Moens and {'t Hart}, L.M. and G. Nijpels and J.M. Dekker and K.J. Williams and E.S.G. Stroes and {van Gaal}, L.F. and B. Staels and M. Nieuwdorp and G.M. Dallinga-Thie",

year = "2014",

doi = "https://doi.org/10.1002/oby.20682",

language = "English",

volume = "22",

pages = "1309--1316",

journal = "Obesity",

issn = "1930-7381",

publisher = "Wiley-Blackwell",

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Hassing, HC, Surendran, RP, Derudas, B, Verrijken, A, Francque, SM, Mooij, HL, Moens, SJB, 't Hart, LM, Nijpels, G, Dekker, JM, Williams, KJ, Stroes, ESG, van Gaal, LF, Staels, B, Nieuwdorp, M & Dallinga-Thie, GM 2014, 'SULF2 Strongly Prediposes to Fasting and Postprandial Triglycerides in Patients with Obesity and Type 2 Diabetes Mellitus', Obesity, vol. 22, no. 5, pp. 1309-1316. https://doi.org/10.1002/oby.20682

TY - JOUR

T1 - SULF2 Strongly Prediposes to Fasting and Postprandial Triglycerides in Patients with Obesity and Type 2 Diabetes Mellitus

AU - Hassing, H.C.

AU - Surendran, R.P.

AU - Derudas, B.

AU - Verrijken, A.

AU - Francque, S.M.

AU - Mooij, H.L.

AU - Moens, S.J.B.

AU - 't Hart, L.M.

AU - Nijpels, G.

AU - Dekker, J.M.

AU - Williams, K.J.

AU - Stroes, E.S.G.

AU - van Gaal, L.F.

AU - Staels, B.

AU - Nieuwdorp, M.

AU - Dallinga-Thie, G.M.

PY - 2014

Y1 - 2014

N2 - Hepatic overexpression of sulfatase-2 (SULF2), a heparan sulfate remodeling enzyme, strongly contributes to high triglyceride (TG) levels in obese, type 2 diabetic (T2DM) db/db mice. Nevertheless, data in humans are lacking. Here, the association of human hepatic SULF2 expression and SULF2 gene variants with TG metabolism in patients with obesity and/or T2DM was investigated. Liver biopsies from 121 obese subjects were analyzed for relations between hepatic SULF2 mRNA levels and plasma TG. Associations between seven SULF2 tagSNPs and TG levels were assessed in 210 obese T2DM subjects with dyslipidemia. Replication of positive findings was performed in 1,316 independent obese T2DM patients. Postprandial TRL clearance was evaluated in 29 obese T2DM subjects stratified by SULF2 genotype. Liver SULF2 expression was significantly associated with fasting plasma TG (r = 0.271; P = 0.003) in obese subjects. The SULF2 rs2281279(A>G) SNP was reproducibly associated with lower fasting plasma TG levels in obese T2DM subjects (P < 0.05). Carriership of the minor G allele was associated with lower levels of postprandial plasma TG (P < 0.05) and retinyl esters levels (P < 0.001). These findings implicate SULF2 as potential therapeutic target in the atherogenic dyslipidemia of obesity and T2DM

AB - Hepatic overexpression of sulfatase-2 (SULF2), a heparan sulfate remodeling enzyme, strongly contributes to high triglyceride (TG) levels in obese, type 2 diabetic (T2DM) db/db mice. Nevertheless, data in humans are lacking. Here, the association of human hepatic SULF2 expression and SULF2 gene variants with TG metabolism in patients with obesity and/or T2DM was investigated. Liver biopsies from 121 obese subjects were analyzed for relations between hepatic SULF2 mRNA levels and plasma TG. Associations between seven SULF2 tagSNPs and TG levels were assessed in 210 obese T2DM subjects with dyslipidemia. Replication of positive findings was performed in 1,316 independent obese T2DM patients. Postprandial TRL clearance was evaluated in 29 obese T2DM subjects stratified by SULF2 genotype. Liver SULF2 expression was significantly associated with fasting plasma TG (r = 0.271; P = 0.003) in obese subjects. The SULF2 rs2281279(A>G) SNP was reproducibly associated with lower fasting plasma TG levels in obese T2DM subjects (P < 0.05). Carriership of the minor G allele was associated with lower levels of postprandial plasma TG (P < 0.05) and retinyl esters levels (P < 0.001). These findings implicate SULF2 as potential therapeutic target in the atherogenic dyslipidemia of obesity and T2DM

U2 - https://doi.org/10.1002/oby.20682

DO - https://doi.org/10.1002/oby.20682

M3 - Article

C2 - 24339435

SN - 1930-7381

VL - 22

SP - 1309

EP - 1316

JO - Obesity

JF - Obesity

IS - 5

ER -