Skip to main content
Top
Published in: Endocrine 3/2020

01-06-2020 | Insulins | Original Article

Association of PPARγ gene expression with postprandial hypertriglyceridaemia and risk of type 2 diabetes mellitus

Authors: B. K. Mishra, B. D. Banerjee, V. Agrawal, S. V. Madhu

Published in: Endocrine | Issue 3/2020

Login to get access

Abstract

Purpose

Peroxisome proliferator-activated receptor γ (PPARγ) gene is strongly associated with type 2 diabetes mellitus, as well as postprandial lipemia, and plays an important role in Wnt dependent adipogenesis in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT). We aimed to study the expression of PPARγ gene in SAT and VAT to find out its correlation with postprandial hypertriglyceredemia and glucose intolerance.

Methods

Thirty subjects who were scheduled to undergo abdominal surgery were recruited in three groups (n = 10 in NGT, n = 10 in prediabetes, and n = 10 in T2DM). A standardized oral fat challenge was performed. Anthropometry, plasma glucose, HbA1c, and fasting serum insulin were also measured. SAT and VATs were collected during surgery for PPARγ gene expression studies by real-time PCR.

Results

PPARγ gene expression was 5.5-fold lower in T2DM and 1.7-fold lower in prediabetes as compared with NGT subjects in VAT. There was a significant negative correlation of expression of PPARγ gene in VAT {Tgauc (r = −0.57, p < 0.007), Peak Tg (r = −0.51, p < 0.01)} as well as in subcutaneous adipose tissue {Tgauc (r = −0.45, p < 0.02)} with PPTg responses measures.

Conclusion

Reduced adipocyte expression of PPARγ gene and the resultant postprandial hypertriglyceredemia is associated with greater risk of diabetes and prediabetes.
Literature
3.
go back to reference M. Aslam, S. Aggarwal, K.K. Sharma, V. Galav, Postprandial hypertriglyceridemia predicts development of insulin resistance glucoseintolerance and type 2 diabete. PLoS ONE 11(1), 1–15 (2016)CrossRef M. Aslam, S. Aggarwal, K.K. Sharma, V. Galav, Postprandial hypertriglyceridemia predicts development of insulin resistance glucoseintolerance and type 2 diabete. PLoS ONE 11(1), 1–15 (2016)CrossRef
4.
go back to reference M. Axelsen, U. Smith, J.W. Eriksson, M.R. Taskinen, P.A. Jansson, Postprandial hypertriglyceridemia and insulin resistance in normoglycemic first-degree relatives of patients with type 2 diabetes. Ann. Intern. Med. 131(1), 27–31 (1999)PubMedCrossRef M. Axelsen, U. Smith, J.W. Eriksson, M.R. Taskinen, P.A. Jansson, Postprandial hypertriglyceridemia and insulin resistance in normoglycemic first-degree relatives of patients with type 2 diabetes. Ann. Intern. Med. 131(1), 27–31 (1999)PubMedCrossRef
6.
go back to reference B.E. Rios-Gonzalez, K.E. Luevano-Ortega, A.M. Saldana-Cruz, J.R. Gonzalez-Garcia, M.T. Magana-Torres, Polymorphisms of seven genes involved in lipid metabolism in an unselected Mexican population. J. Genet. 90(3), e114–e119 (2011)PubMed B.E. Rios-Gonzalez, K.E. Luevano-Ortega, A.M. Saldana-Cruz, J.R. Gonzalez-Garcia, M.T. Magana-Torres, Polymorphisms of seven genes involved in lipid metabolism in an unselected Mexican population. J. Genet. 90(3), e114–e119 (2011)PubMed
7.
go back to reference P. Perez-Martinez, J. Delgado-Lista, F. Perez-Jimenez, J. Lopez-Miranda, Update on genetics of postprandial lipemia. Atheroscler. Suppl. 11(1), 39–43 (2010)PubMedCrossRef P. Perez-Martinez, J. Delgado-Lista, F. Perez-Jimenez, J. Lopez-Miranda, Update on genetics of postprandial lipemia. Atheroscler. Suppl. 11(1), 39–43 (2010)PubMedCrossRef
8.
go back to reference F. Cardona, S. Morcillo, M. Gonzalo-Marín, L. Garrido-Sanchez, M. Macias-Gonzalez, F.J. Tinahones, Pro12Ala sequence variant of the PPARG gene is associated with postprandial hypertriglyceridemia in non-E3/E3 patients with the metabolic syndrome. Clin. Chem. 52(10), 1920–1925 (2006)PubMedCrossRef F. Cardona, S. Morcillo, M. Gonzalo-Marín, L. Garrido-Sanchez, M. Macias-Gonzalez, F.J. Tinahones, Pro12Ala sequence variant of the PPARG gene is associated with postprandial hypertriglyceridemia in non-E3/E3 patients with the metabolic syndrome. Clin. Chem. 52(10), 1920–1925 (2006)PubMedCrossRef
9.
go back to reference U. Edvardsson, PPARs in the Regulation of Gene Expression and Lipid Metabolism in the Liver, Department of Physiology Wallenberg Laboratory for Cardiovascular Research. The Sahlgrenska Academy at Göteborg University (Intellecta DocuSys AB, Göteborg, 2005) U. Edvardsson, PPARs in the Regulation of Gene Expression and Lipid Metabolism in the Liver, Department of Physiology Wallenberg Laboratory for Cardiovascular Research. The Sahlgrenska Academy at Göteborg University (Intellecta DocuSys AB, Göteborg, 2005)
11.
go back to reference G. Castillo, S. Hauser, J.K. Rosenfield, B.M. Spiegelman, Role and regulation of PPARy during Adipogenesis. J. Anim. Sci. 77(Suppl 3), 9 (1999)CrossRef G. Castillo, S. Hauser, J.K. Rosenfield, B.M. Spiegelman, Role and regulation of PPARy during Adipogenesis. J. Anim. Sci. 77(Suppl 3), 9 (1999)CrossRef
14.
go back to reference P.J. Gianaros, K. Salomon, F. Zhou, J.F. Owens, L.H. Kuller, K.A.Matthews, Decreased Expression of adipogenic genes in obese subjects with type 2 diabetes. Obesity 67(4), 553–560 (2008) P.J. Gianaros, K. Salomon, F. Zhou, J.F. Owens, L.H. Kuller, K.A.Matthews, Decreased Expression of adipogenic genes in obese subjects with type 2 diabetes. Obesity 67(4), 553–560 (2008)
15.
go back to reference Q. Guo, S.P. Sahoo, P.R. Wang, D.P. Milot, M.C. Ippolito, M.S. Wu et al. A novel peroxisome proliferator-activated receptor α/γ dual agonist demonstrates favorable effects on lipid homeostasis. Endocrinology 145(4), 1640–1648 (2004)PubMedCrossRef Q. Guo, S.P. Sahoo, P.R. Wang, D.P. Milot, M.C. Ippolito, M.S. Wu et al. A novel peroxisome proliferator-activated receptor α/γ dual agonist demonstrates favorable effects on lipid homeostasis. Endocrinology 145(4), 1640–1648 (2004)PubMedCrossRef
16.
go back to reference A. Chawla, E.J. Schwarz, D.D. Dimaculangan, M.A. Lazar, Peroxisome proliferator-activated receptor (PPAR) gamma: adipose-predominant expression and induction early in adipocyte differentiation. Endocrinology 135(2), 798–800 (1994)PubMedCrossRef A. Chawla, E.J. Schwarz, D.D. Dimaculangan, M.A. Lazar, Peroxisome proliferator-activated receptor (PPAR) gamma: adipose-predominant expression and induction early in adipocyte differentiation. Endocrinology 135(2), 798–800 (1994)PubMedCrossRef
17.
go back to reference U. Smith, B.B. Kahn, Adipose tissue regulates insulin sensitivity: role of adipogenesis, de novo lipogenesis and novel lipids. J. Intern. Med. 280(5), 465–475 (2016)PubMedPubMedCentralCrossRef U. Smith, B.B. Kahn, Adipose tissue regulates insulin sensitivity: role of adipogenesis, de novo lipogenesis and novel lipids. J. Intern. Med. 280(5), 465–475 (2016)PubMedPubMedCentralCrossRef
18.
go back to reference L.A. Muir, C.K. Neeley, K.A. Meyer, N.A. Baker, A.M. Brosius, A.R. Washabaugh et al. Adipose tissue fibrosis, hypertrophy, and hyperplasia: Correlations with diabetes in human obesity. Obesity 24(3), 597–605 (2016)PubMedCrossRef L.A. Muir, C.K. Neeley, K.A. Meyer, N.A. Baker, A.M. Brosius, A.R. Washabaugh et al. Adipose tissue fibrosis, hypertrophy, and hyperplasia: Correlations with diabetes in human obesity. Obesity 24(3), 597–605 (2016)PubMedCrossRef
19.
go back to reference B. Gustafson, S. Hedjazifar, S. Gogg, A. Hammarstedt, U. Smith, Insulin resistance and impaired adipogenesis.Trends Endocrinol. Metab 26(4), 193–200 (2015)PubMedCrossRef B. Gustafson, S. Hedjazifar, S. Gogg, A. Hammarstedt, U. Smith, Insulin resistance and impaired adipogenesis.Trends Endocrinol. Metab 26(4), 193–200 (2015)PubMedCrossRef
20.
go back to reference M.M. Ibrahim, Subcutaneous and visceral adipose tissue: structural and functional differences. Obes. Rev. 11(1), 11–18 (2010)PubMedCrossRef M.M. Ibrahim, Subcutaneous and visceral adipose tissue: structural and functional differences. Obes. Rev. 11(1), 11–18 (2010)PubMedCrossRef
21.
go back to reference A. Lüdtke, J. Buettner, W. Wu, A. Muchir, A. Schroeter, S. Zinn-Justin et al. Peroxisome proliferator-activated receptor-γ C190S mutation causes partial lipodystrophy. J. Clin. Endocrinol. Metab. 92(6), 2248–2255 (2007)PubMedCrossRef A. Lüdtke, J. Buettner, W. Wu, A. Muchir, A. Schroeter, S. Zinn-Justin et al. Peroxisome proliferator-activated receptor-γ C190S mutation causes partial lipodystrophy. J. Clin. Endocrinol. Metab. 92(6), 2248–2255 (2007)PubMedCrossRef
22.
go back to reference G. Medina-Gomez, S.L. Gray, L. Yetukuri, K. Shimomura, S. Virtue, M. Campbell et al. PPAR gamma 2 prevents lipotoxicity by controlling adipose tissue expandability and peripheral lipid metabolism. PLoS Genet. 3(4), e64 (2007)PubMedPubMedCentralCrossRef G. Medina-Gomez, S.L. Gray, L. Yetukuri, K. Shimomura, S. Virtue, M. Campbell et al. PPAR gamma 2 prevents lipotoxicity by controlling adipose tissue expandability and peripheral lipid metabolism. PLoS Genet. 3(4), e64 (2007)PubMedPubMedCentralCrossRef
24.
go back to reference C. Knouff, J. Auwerx, Peroxisome proliferator-activated receptor-γ calls for activation in moderation: Lessons from genetics and pharmacology. Endocr. Rev. 25(6), 899–918 (2004)PubMedCrossRef C. Knouff, J. Auwerx, Peroxisome proliferator-activated receptor-γ calls for activation in moderation: Lessons from genetics and pharmacology. Endocr. Rev. 25(6), 899–918 (2004)PubMedCrossRef
25.
go back to reference S.V. Madhu, M. Aslam, V. Galav, S.K. Bhattacharya, A.A. Jafri, Atorvastatin prevents type 2 diabetes mellitus-an experimental study. Eur. J. Pharm. 728(April), 135–140 (2014)CrossRef S.V. Madhu, M. Aslam, V. Galav, S.K. Bhattacharya, A.A. Jafri, Atorvastatin prevents type 2 diabetes mellitus-an experimental study. Eur. J. Pharm. 728(April), 135–140 (2014)CrossRef
26.
go back to reference S.J. Li, Y.Y. Wu, W. Li, S.J. Wang, Y.M. Fan, Ultrastructural observation in a case of mucinous nevus. J. Ger. Soc. Dermatol. 16(6), 778–780 (2018) S.J. Li, Y.Y. Wu, W. Li, S.J. Wang, Y.M. Fan, Ultrastructural observation in a case of mucinous nevus. J. Ger. Soc. Dermatol. 16(6), 778–780 (2018)
27.
go back to reference D. Care, S.S. Suppl, Classification and diagnosis of diabetes: standards of medical care in Diabetesd2018. Diabetes Care 41(January), S13–S27 (2018) D. Care, S.S. Suppl, Classification and diagnosis of diabetes: standards of medical care in Diabetesd2018. Diabetes Care 41(January), S13–S27 (2018)
28.
go back to reference K.J. Livak, T.D. Schmittgen, Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25(4), 402–408 (2001)CrossRef K.J. Livak, T.D. Schmittgen, Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25(4), 402–408 (2001)CrossRef
29.
go back to reference C.J. Yen, B.A. Beamer, C. Negri, K. Silver, K.A. Brown, D.P. Yarnall et al. Molecular scanning of the human peroxisome proliferator activated receptor gamma (hPPAR gamma) gene in diabetic Caucasians: identification of a Pro12Ala PPAR gamma 2 missense mutation. Biochem. Biophys. Res. Commun. 241(2), 270–274 (1997)PubMedCrossRef C.J. Yen, B.A. Beamer, C. Negri, K. Silver, K.A. Brown, D.P. Yarnall et al. Molecular scanning of the human peroxisome proliferator activated receptor gamma (hPPAR gamma) gene in diabetic Caucasians: identification of a Pro12Ala PPAR gamma 2 missense mutation. Biochem. Biophys. Res. Commun. 241(2), 270–274 (1997)PubMedCrossRef
30.
go back to reference S.V. Madhu, S. Kant, S. Srivastava, R. Kant, S.B. Sharma, D.P. Bhadoria, Postprandial lipaemia in patients with impaired fasting glucose, impaired glucose tolerance and diabetes mellitus. Diabetes Res. Clin. Pract. 80(3), 380–385 (2008)PubMedCrossRef S.V. Madhu, S. Kant, S. Srivastava, R. Kant, S.B. Sharma, D.P. Bhadoria, Postprandial lipaemia in patients with impaired fasting glucose, impaired glucose tolerance and diabetes mellitus. Diabetes Res. Clin. Pract. 80(3), 380–385 (2008)PubMedCrossRef
31.
go back to reference K. Fujiki, F. Kano, K. Shiota, M. Murata, Expression of the peroxisome proliferator activated receptor γ gene is repressed by DNA methylation in visceral adipose tissue of mouse models of diabetes. BMC Biol. 7, 1–14 (2009)CrossRef K. Fujiki, F. Kano, K. Shiota, M. Murata, Expression of the peroxisome proliferator activated receptor γ gene is repressed by DNA methylation in visceral adipose tissue of mouse models of diabetes. BMC Biol. 7, 1–14 (2009)CrossRef
32.
go back to reference A. Vidal-Puig, M. Jimenez-Liñan, B.B. Lowell, A. Hamann, E. Hu, B. Spiegelman et al. Regulation of PPARγ gene expression by nutrition and obesity in rodents. J. Clin. Investig. 97(11), 2553–2561 (1996)PubMedCrossRef A. Vidal-Puig, M. Jimenez-Liñan, B.B. Lowell, A. Hamann, E. Hu, B. Spiegelman et al. Regulation of PPARγ gene expression by nutrition and obesity in rodents. J. Clin. Investig. 97(11), 2553–2561 (1996)PubMedCrossRef
33.
go back to reference C. Leyvraz, C. Verdumo, M. Suter, A. Paroz, J.M. Calmes, P.M. Marques-Vidal et al. Changes in gene expression profile in human subcutaneous adipose tissue during significant weight loss. Obes. Facts 5(3), 440–451 (2012)PubMedCrossRef C. Leyvraz, C. Verdumo, M. Suter, A. Paroz, J.M. Calmes, P.M. Marques-Vidal et al. Changes in gene expression profile in human subcutaneous adipose tissue during significant weight loss. Obes. Facts 5(3), 440–451 (2012)PubMedCrossRef
34.
go back to reference T.O. Hammes, Costa CDS, F. Rohden, R. Margis, AlmeidaJ.C. De, A.V. Padoin et al. Parallel down-regulation of FOXO1, PPARγ and adiponectin mRNA expression in visceral adipose tissue of class III obese individuals. Obes. Facts 5(3), 452–459 (2012)PubMedCrossRef T.O. Hammes, Costa CDS, F. Rohden, R. Margis, AlmeidaJ.C. De, A.V. Padoin et al. Parallel down-regulation of FOXO1, PPARγ and adiponectin mRNA expression in visceral adipose tissue of class III obese individuals. Obes. Facts 5(3), 452–459 (2012)PubMedCrossRef
35.
go back to reference A. Wagener, H.F. Goessling, A.O. Schmitt, S. Mauel, A.D. Gruber, R. Reinhardt et al. Genetic and diet effects on Ppar-α and Ppar-γ signaling pathways in the Berlin Fat Mouse Inbred line with genetic predisposition for obesity. Lipids Health Dis. 9(ii), 1–10 (2010) A. Wagener, H.F. Goessling, A.O. Schmitt, S. Mauel, A.D. Gruber, R. Reinhardt et al. Genetic and diet effects on Ppar-α and Ppar-γ signaling pathways in the Berlin Fat Mouse Inbred line with genetic predisposition for obesity. Lipids Health Dis. 9(ii), 1–10 (2010)
36.
go back to reference M. Hatami, M. Saidijam, R. Yadegarzari, S. Borzuei, A. Soltanian, M.S. Arian et al. Peroxisome proliferator-activated receptor-gamma gene expression and its association with oxidative stress in patients with metabolic syndrome. Chonnam Med. J. 52(3), 201–206 (2016)PubMedPubMedCentralCrossRef M. Hatami, M. Saidijam, R. Yadegarzari, S. Borzuei, A. Soltanian, M.S. Arian et al. Peroxisome proliferator-activated receptor-gamma gene expression and its association with oxidative stress in patients with metabolic syndrome. Chonnam Med. J. 52(3), 201–206 (2016)PubMedPubMedCentralCrossRef
37.
go back to reference K. Ruschke, L. Fishbein, A. Dietrich, N. Klöting, A. Tönjes, A. Oberbach, et al. Markers and mediates beneficial effects of physical training. Eur J Endocrinol 162(3), 515–523 (2010)PubMedCrossRef K. Ruschke, L. Fishbein, A. Dietrich, N. Klöting, A. Tönjes, A. Oberbach, et al. Markers and mediates beneficial effects of physical training. Eur J Endocrinol 162(3), 515–523 (2010)PubMedCrossRef
39.
go back to reference Y. Lecarpentier, V. Claes, A. Vallée, J.L. Hébert, Interactions between PPAR gamma and the canonical Wnt/beta-catenin pathway in type 2 diabetes and colon cancer. PPAR Res. 2017, 1–9 (2017) Y. Lecarpentier, V. Claes, A. Vallée, J.L. Hébert, Interactions between PPAR gamma and the canonical Wnt/beta-catenin pathway in type 2 diabetes and colon cancer. PPAR Res. 2017, 1–9 (2017)
40.
go back to reference D. Ren, T.N. Collingwood, E.J. Rebar, A.P. Wolffe, H.S. Camp, PPARγ knockdown by engineered transcription factors: Exogenous PPARγ2 but not PPARγ1 reactivates adipogenesis. Genes Dev. 16(1), 27–32 (2002)PubMedPubMedCentralCrossRef D. Ren, T.N. Collingwood, E.J. Rebar, A.P. Wolffe, H.S. Camp, PPARγ knockdown by engineered transcription factors: Exogenous PPARγ2 but not PPARγ1 reactivates adipogenesis. Genes Dev. 16(1), 27–32 (2002)PubMedPubMedCentralCrossRef
Metadata
Title
Association of PPARγ gene expression with postprandial hypertriglyceridaemia and risk of type 2 diabetes mellitus
Authors
B. K. Mishra
B. D. Banerjee
V. Agrawal
S. V. Madhu
Publication date
01-06-2020
Publisher
Springer US
Published in
Endocrine / Issue 3/2020
Print ISSN: 1355-008X
Electronic ISSN: 1559-0100
DOI
https://doi.org/10.1007/s12020-020-02257-w

Other articles of this Issue 3/2020

Endocrine 3/2020 Go to the issue