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.
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Data availability
Data will be available on reasonable request.
References
World Health Organization. Genetics and Diabetes (World Health, 1999), pp. 1–15. http://www.who.int/genomics/about/Diabetis-fin.pdf
G. Cristian, G.C.I. Paul, Genetic factors involved in the pathogenesis of type 2 diabetes. Genet. Diabetes 23(2), 131–192 (2010). http://www.acad.ro/sectii2002/proceedingsChemistry/doc2012-1/06Guja.pdf
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)
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)
S. Madhu, B. Sinha, M. Aslam, G. Mehrotra, S. Dwivedi, Postprandial triglyceride responses and endothelial function in prediabetic first-degree relatives of patients with diabetes. J. Clin. Lipidol. 11(6), 1415–1420 (2017). https://doi.org/10.1016/j.jacl.2017.08.001
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)
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)
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)
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)
S.F.A. Grant, G. Thorleifsson, I. Reynisdottir, R. Benediktsson, A. Manolescu, J. Sainz et al. The risk of type 2 diabetes in 5, 164 Indians. Nat. Genet. 38(3), 320–323 (2006). http://www.ncbi.nlm.nih.gov/pubmed/16415884
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)
B.M. Spiegelman, PPAR-gamma: adipogenic regulator and thiazolidinedione receptor. Diabetes 47(4), 507 LP–507514 (1998). http://diabetes.diabetesjournals.org/content/47/4/507.abstract
S.S. Choi, J. Park, J.H. Choi, Revisiting PPARγ as a target for the treatment of metabolic disorders. BMB Rep. 47(11), 599–608 (2014)
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)
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)
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)
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)
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)
B. Gustafson, S. Hedjazifar, S. Gogg, A. Hammarstedt, U. Smith, Insulin resistance and impaired adipogenesis.Trends Endocrinol. Metab 26(4), 193–200 (2015)
M.M. Ibrahim, Subcutaneous and visceral adipose tissue: structural and functional differences. Obes. Rev. 11(1), 11–18 (2010)
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)
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)
I. Takada, A.P. Kouzmenko, S. Kato, Wnt and PPARγ signaling in osteoblastogenesis and adipogenesis. Nat. Rev. Rheumatol. 5(July), 442 (2009). https://doi.org/10.1038/nrrheum.2009.137
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)
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)
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)
D. Care, S.S. Suppl, Classification and diagnosis of diabetes: standards of medical care in Diabetesd2018. Diabetes Care 41(January), S13–S27 (2018)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
K. Ylitalo, I. Nuotio, J. Viikari, J. Auwerx, H. Vidal, M.-R. Taskinen, C3, hormone-sensitive lipase, and peroxisome proliferator-activated receptor [gamma] expression in adipose tissue of familial combined hyperlipidemia patients. Metabolism. 51(5), 664–670 (2002). http://www.sciencedirect.com/science/article/pii/S0026049502797631
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)
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)
Acknowledgements
This work was supported by Indian Council of Medical Research, New Delhi (Grant No. 5/4/5-3/Diab.-16-NCD-II).
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Prior Presentation Parts of this study were presented in abstract form at the RSSDI DC 14th Annual Conference 2018, 21st October 2018 at Hotel the Lalit, New Delhi.
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Mishra, B.K., Banerjee, B.D., Agrawal, . et al. Association of PPARγ gene expression with postprandial hypertriglyceridaemia and risk of type 2 diabetes mellitus. Endocrine 68, 549–556 (2020). https://doi.org/10.1007/s12020-020-02257-w
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DOI: https://doi.org/10.1007/s12020-020-02257-w