Estrogen receptor-associated receptor α and peroxisome proliferator-activated receptor γ in metabolism and disease (Review)

Huang,Wei-Yi; Sun,Peng-Ming

doi:10.3892/mmr.2020.11795

Estrogen receptor-associated receptor α and peroxisome proliferator-activated receptor γ in metabolism and disease (Review)

Authors:
- Wei-Yi Huang
- Peng-Ming Sun
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Affiliations: Laboratory of Gynecologic Oncology, Fujian Provincial Maternity and Children's Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350001, P.R. China
Published online on: December 22, 2020 https://doi.org/10.3892/mmr.2020.11795
Article Number: 156

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Abstract

Estrogen receptor‑associated receptor α (ERRα) is an orphan nuclear receptor that lacks corresponding ligands. ERRα recruits co‑regulators to regulate gene transcription and plays an important role in human physiological functions. Peroxisome proliferator‑activated receptor γ (PPARγ) is also a nuclear receptor that regulates the expression of target genes via a ligand‑dependent mechanism, thereby participating in a series of physiological processes. Both ERRα and PPARγ are involved in the process of energy metabolism and tumorigenesis. In the present review, a concise overview of the important roles governed by ERRα and PPARγ in metabolism and their association with various disease are provided.

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1	Giguère V, Yang N, Segui P and Evans RM: Identification of a new class of steroid hormone receptors. Nature. 331:91–94. 1988. View Article : Google Scholar : PubMed/NCBI
2	Wu Z, Puigserver P, Andersson U, Zhang C, Adelmant G, Mootha V, Troy A, Cinti S, Lowell B, Scarpulla RC, et al: Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell. 98:115–124. 1999. View Article : Google Scholar : PubMed/NCBI
3	Mootha VK, Handschin C, Arlow D, Xie X, St Pierre J, Sihag S, Yang W, Altshuler D, Puigserver P, Patterson N, et al: Erralpha and Gabpa/b specify PGC-1alpha-dependent oxidative phosphorylation gene expression that is altered in diabetic muscle. Proc Natl Acad Sci USA. 101:6570–6575. 2004. View Article : Google Scholar : PubMed/NCBI
4	Huss JM, Torra IP, Staels B, Giguère V and Kelly DP: Estrogen-related receptor alpha directs peroxisome proliferator-activated receptor alpha signaling in the transcriptional control of energy metabolism in cardiac and skeletal muscle. Mol Cell Biol. 24:9079–9091. 2004. View Article : Google Scholar : PubMed/NCBI
5	Emmett MJ, Lim HW, Jager J, Richter HJ, Adlanmerini M, Peed LC, Briggs ER, Steger DJ, Ma T, Sims CA, et al: Histone deacetylase 3 prepares brown adipose tissue for acute thermogenic challenge. Nature. 546:544–548. 2017. View Article : Google Scholar : PubMed/NCBI
6	Dufour CR, Levasseur MP, Pham NH, Eichner LJ, Wilson BJ, Charest-Marcotte A, Duguay D, Poirier-Héon JF, Cermakian N and Giguère V: Genomic convergence among ERRα, PROX1, and BMAL1 in the control of metabolic clock outputs. PLoS Genet. 7:e10021432011. View Article : Google Scholar : PubMed/NCBI
7	Giguère V: To ERR in the estrogen pathway. Trends Endocrinol Metab. 13:220–225. 2002. View Article : Google Scholar : PubMed/NCBI
8	Ranhotra HS: The estrogen-related receptor alpha: The oldest, yet an energetic orphan with robust biological functions. J Recept Signal Transduct Res. 30:193–205. 2010. View Article : Google Scholar : PubMed/NCBI
9	Issemann I and Green S: Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators. Nature. 347:645–650. 1990. View Article : Google Scholar : PubMed/NCBI
10	Juge-Aubry C, Pernin A, Favez T, Burger AG, Wahli W, Meier CA and Desvergne B: DNA binding properties of peroxisome proliferator-activated receptor subtypes on various natural peroxisome proliferator response elements. Importance of the 5-flanking region. J Biol Chem. 272:25252–25259. 1997. View Article : Google Scholar : PubMed/NCBI
11	Vamecq J and Latruffe N: Medical significance of peroxisome proliferator-activated receptors. Lancet. 354:141–148. 1999. View Article : Google Scholar : PubMed/NCBI
12	Chandra V, Huang P, Hamuro Y, Raghuram S, Wang Y, Burris TP and Rastinejad F: Structure of the intact PPAR-gamma-RXR- nuclear receptor complex on DNA. Nature. 456:350–356. 2008. View Article : Google Scholar : PubMed/NCBI
13	Burns KA and Vanden Heuvel JP: Modulation of PPAR activity via phosphorylation. Biochim Biophys Acta. 1771:952–960. 2007. View Article : Google Scholar : PubMed/NCBI
14	Bookout AL, Jeong Y, Downes M, Yu RT, Evans RM and Mangelsdorf DJ: Anatomical profiling of nuclear receptor expression reveals a hierarchical transcriptional network. Cell. 126:789–799. 2006. View Article : Google Scholar : PubMed/NCBI
15	Bonnelye E, Vanacker JM, Dittmar T, Begue A, Desbiens X, Denhardt DT, Aubin JE, Laudet V and Fournier B: The ERR-1 orphan receptor is a transcriptional activator expressed during bone development. Mol Endocrinol. 11:905–916. 1997. View Article : Google Scholar : PubMed/NCBI
16	Heard DJ, Norby PL, Holloway J and Vissing H: Human ERRgamma, a third member of the estrogen receptor-related receptor (ERR) subfamily of orphan nuclear receptors: Tissue-specific isoforms are expressed during development and in the adult. Mol Endocrinol. 14:382–392. 2000. View Article : Google Scholar : PubMed/NCBI
17	Bonnelye E, Vanacker JM, Spruyt N, Alric S, Fournier B, Desbiens X and Laudet V: Expression of the estrogen-related receptor 1 (ERR-1) orphan receptor during mouse development. Mech Dev. 65:71–85. 1997. View Article : Google Scholar : PubMed/NCBI
18	Carnesecchi J and Vanacker JM: Estrogen-related receptors and the control of bone cell fate. Mol Cell Endocrinol. 432:37–43. 2016. View Article : Google Scholar : PubMed/NCBI
19	Likhite N, Yadav V, Milliman EJ, Sopariwala DH, Lorca S, Narayana NP, Sheth M, Reineke EL, Giguère V and Narkar V: Loss of estrogen-related receptor alpha facilitates angiogenesis in endothelial cells. Mol Cell Biol. 39:392019. View Article : Google Scholar
20	Sun P, Sehouli J, Denkert C, Mustea A, Könsgen D, Koch I, Wei L and Lichtenegger W: Expression of estrogen receptor-related receptors, a subfamily of orphan nuclear receptors, as new tumor biomarkers in ovarian cancer cells. J Mol Med (Berl). 83:457–467. 2005. View Article : Google Scholar : PubMed/NCBI
21	Johnston SD, Liu X, Zuo F, Eisenbraun TL, Wiley SR, Kraus RJ and Mertz JE: Estrogen-related receptor alpha 1 functionally binds as a monomer to extended half-site sequences including ones contained within estrogen-response elements. Mol Endocrinol. 11:342–352. 1997. View Article : Google Scholar : PubMed/NCBI
22	Wende AR, Huss JM, Schaeffer PJ, Giguère V and Kelly DP: PGC-1alpha coactivates PDK4 gene expression via the orphan nuclear receptor ERRalpha: A mechanism for transcriptional control of muscle glucose metabolism. Mol Cell Biol. 25:10684–10694. 2005. View Article : Google Scholar : PubMed/NCBI
23	Yoon JC, Puigserver P, Chen G, Donovan J, Wu Z, Rhee J, Adelmant G, Stafford J, Kahn CR, Granner DK, et al: Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1. Nature. 413:131–138. 2001. View Article : Google Scholar : PubMed/NCBI
24	Kitamura K, Erlangga JS, Tsukamoto S, Sakamoto Y, Mabashi-Asazuma H and Iida K: Daidzein promotes the expression of oxidative phosphorylation- and fatty acid oxidation-related genes via an estrogen-related receptor α pathway to decrease lipid accumulation in muscle cells. J Nutr Biochem. 77:1083152020. View Article : Google Scholar : PubMed/NCBI
25	Cartoni R, Léger B, Hock MB, Praz M, Crettenand A, Pich S, Ziltener JL, Luthi F, Dériaz O, Zorzano A, et al: Mitofusins 1/2 and ERRalpha expression are increased in human skeletal muscle after physical exercise. J Physiol. 567:349–358. 2005. View Article : Google Scholar : PubMed/NCBI
26	Soriano FX, Liesa M, Bach D, Chan DC, Palacín M and Zorzano A: Evidence for a mitochondrial regulatory pathway defined by peroxisome proliferator-activated receptor-gamma coactivator-1 alpha, estrogen-related receptor-alpha, and mitofusin 2. Diabetes. 55:1783–1791. 2006. View Article : Google Scholar : PubMed/NCBI
27	Rangwala SM, Li X, Lindsley L, Wang X, Shaughnessy S, Daniels TG, Szustakowski J, Nirmala NR, Wu Z and Stevenson SC: Estrogen-related receptor alpha is essential for the expression of antioxidant protection genes and mitochondrial function. Biochem Biophys Res Commun. 357:231–236. 2007. View Article : Google Scholar : PubMed/NCBI
28	Herzog B, Cardenas J, Hall RK, Villena JA, Budge PJ, Giguère V, Granner DK and Kralli A: Estrogen-related receptor alpha is a repressor of phosphoenolpyruvate carboxykinase gene transcription. J Biol Chem. 281:99–106. 2006. View Article : Google Scholar : PubMed/NCBI
29	Ranhotra HS: Estrogen-related receptor alpha and mitochondria: Tale of the titans. J Recept Signal Transduct Res. 35:386–390. 2015. View Article : Google Scholar : PubMed/NCBI
30	Vega RB and Kelly DP: A role for estrogen-related receptor alpha in the control of mitochondrial fatty acid beta-oxidation during brown adipocyte differentiation. J Biol Chem. 272:31693–31699. 1997. View Article : Google Scholar : PubMed/NCBI
31	LeBleu VS, O'Connell JT, Gonzalez Herrera KN, Wikman H, Pantel K, Haigis MC, Machado de Carvalho F, Damascena A, Domingos Chinen LT, Rocha RM, et al: PGC-1α mediates mitochondrial biogenesis and oxidative phosphorylation in cancer cells to promote metastasis. Nat Cell Biol. 16:992–1003, 1001-1015. 2014. View Article : Google Scholar : PubMed/NCBI
32	Villena JA and Kralli A: ERRalpha: A metabolic function for the oldest orphan. Trends Endocrinol Metab. 19:269–276. 2008. View Article : Google Scholar : PubMed/NCBI
33	Aprile M, Ambrosio MR, D'Esposito V, Beguinot F, Formisano P, Costa V and Ciccodicola A: PPARG in human adipogenesis: Differential contribution of canonical transcripts and dominant negative isoforms. PPAR Res. 2014:5378652014. View Article : Google Scholar : PubMed/NCBI
34	Salgia MM, Elix CC, Pal SK and Jones JO: Different roles of peroxisome proliferator-activated receptor gamma isoforms in prostate cancer. Am J Clin Exp Urol. 7:98–109. 2019.PubMed/NCBI
35	Braissant O, Foufelle F, Scotto C, Dauça M and Wahli W: Differential expression of peroxisome proliferator-activated receptors (PPARs): Tissue distribution of PPAR-alpha, -beta, and -gamma in the adult rat. Endocrinology. 137:354–366. 1996. View Article : Google Scholar : PubMed/NCBI
36	Meirhaeghe A, Fajas L, Gouilleux F, Cottel D, Helbecque N, Auwerx J and Amouyel P: A functional polymorphism in a STAT5B site of the human PPAR gamma 3 gene promoter affects height and lipid metabolism in a French population. Arterioscler Thromb Vasc Biol. 23:289–294. 2003. View Article : Google Scholar : PubMed/NCBI
37	Martin H: Role of PPAR-gamma in inflammation. Prospects for therapeutic intervention by food components. Mutat Res. 669:1–7. 2009. View Article : Google Scholar : PubMed/NCBI
38	Tanis SP, Colca JR, Parker TT, Artman GD III, Larsen SD, McDonald WG, Gadwood RC, Kletzien RF, Zeller JB, Lee PH, et al: PPARγ-sparing thiazolidinediones as insulin sensitizers. Design, synthesis and selection of compounds for clinical development. Bioorg Med Chem. 26:5870–5884. 2018. View Article : Google Scholar : PubMed/NCBI
39	Finch ER, Tukaramrao DB, Goodfield LL, Quickel MD, Paulson RF and Prabhu KS: Activation of PPARγ by endogenous prostaglandin J2 mediates the antileukemic effect of selenium in murine leukemia. Blood. 129:1802–1810. 2017. View Article : Google Scholar : PubMed/NCBI
40	Michalik L, Desvergne B, Dreyer C, Gavillet M, Laurini RN and Wahli W: PPAR expression and function during vertebrate development. Int J Dev Biol. 46:105–114. 2002.PubMed/NCBI
41	Lapsys NM, Kriketos AD, Lim-Fraser M, Poynten AM, Lowy A, Furler SM, Chisholm DJ and Cooney GJ: Expression of genes involved in lipid metabolism correlate with peroxisome proliferator-activated receptor gamma expression in human skeletal muscle. J Clin Endocrinol Metab. 85:4293–4297. 2000. View Article : Google Scholar : PubMed/NCBI
42	Iwata M, Haruta T, Usui I, Takata Y, Takano A, Uno T, Kawahara J, Ueno E, Sasaoka T, Ishibashi O, et al: Pioglitazone ameliorates tumor necrosis factor-alpha-induced insulin resistance by a mechanism independent of adipogenic activity of peroxisome proliferator - activated receptor-gamma. Diabetes. 50:1083–1092. 2001. View Article : Google Scholar : PubMed/NCBI
43	Ricote M, Huang J, Fajas L, Li A, Welch J, Najib J, Witztum JL, Auwerx J, Palinski W and Glass CK: Expression of the peroxisome proliferator-activated receptor gamma (PPARgamma) in human atherosclerosis and regulation in macrophages by colony stimulating factors and oxidized low density lipoprotein. Proc Natl Acad Sci USA. 95:7614–7619. 1998. View Article : Google Scholar : PubMed/NCBI
44	Jiang C, Ting AT and Seed B: PPAR-gamma agonists inhibit production of monocyte inflammatory cytokines. Nature. 391:82–86. 1998. View Article : Google Scholar : PubMed/NCBI
45	Yamashita H, Kawasawa YI, Shuman L, Zheng Z, Tran T, Walter V, Warrick JI, Chen G, Al-Ahmadie H, Kaag M, et al: Repression of transcription factor AP-2 alpha by PPARγ reveals a novel transcriptional circuit in basal-squamous bladder cancer. Oncogenesis. 8:692019. View Article : Google Scholar : PubMed/NCBI
46	Fan W and Evans R: PPARs and ERRs: Molecular mediators of mitochondrial metabolism. Curr Opin Cell Biol. 33:49–54. 2015. View Article : Google Scholar : PubMed/NCBI
47	Teng CT, Li Y, Stockton P and Foley J: Fasting induces the expression of PGC-1α and ERR isoforms in the outer stripe of the outer medulla (OSOM) of the mouse kidney. PLoS One. 6:e269612011. View Article : Google Scholar : PubMed/NCBI
48	Angajala A, Lim S, Phillips JB, Kim JH, Yates C, You Z and Tan M: Diverse roles of mitochondria in immune responses: novel insights into immuno-metabolism. Front Immunol. 9:16052018. View Article : Google Scholar : PubMed/NCBI
49	Wei W, Wang X, Yang M, Smith LC, Dechow PC, Sonoda J, Evans RM and Wan Y: PGC1beta mediates PPARgamma activation of osteoclastogenesis and rosiglitazone-induced bone loss. Cell Metab. 11:503–516. 2010. View Article : Google Scholar : PubMed/NCBI
50	Scarpulla RC: Metabolic control of mitochondrial biogenesis through the PGC-1 family regulatory network. Biochim Biophys Acta. 1813:1269–1278. 2011. View Article : Google Scholar : PubMed/NCBI
51	Xia Y, Buja LM, Scarpulla RC and McMillin JB: Electrical stimulation of neonatal cardiomyocytes results in the sequential activation of nuclear genes governing mitochondrial proliferation and differentiation. Proc Natl Acad Sci USA. 94:11399–11404. 1997. View Article : Google Scholar : PubMed/NCBI
52	Huss JM, Kopp RP and Kelly DP: Peroxisome proliferator-activated receptor coactivator-1alpha (PGC-1alpha) coactivates the cardiac-enriched nuclear receptors estrogen-related receptor-alpha and -gamma. Identification of novel leucine-rich interaction motif within PGC-1alpha. J Biol Chem. 277:40265–40274. 2002. View Article : Google Scholar : PubMed/NCBI
53	Fliegner D, Westermann D, Riad A, Schubert C, Becher E, Fielitz J, Tschöpe C and Regitz-Zagrosek V: Up-regulation of PPARgamma in myocardial infarction. Eur J Heart Fail. 10:30–38. 2008. View Article : Google Scholar : PubMed/NCBI
54	Gandhi GR, Stalin A, Balakrishna K, Ignacimuthu S, Paulraj MG and Vishal R: Insulin sensitization via partial agonism of PPARγ and glucose uptake through translocation and activation of GLUT4 in PI3K/p-Akt signaling pathway by embelin in type 2 diabetic rats. Biochim Biophys Acta. 1830:2243–2255. 2013. View Article : Google Scholar : PubMed/NCBI
55	Xia H, Dufour CR and Giguère V: ERRα as a bridge between transcription and function: Role in liver metabolism and disease. Front Endocrinol (Lausanne). 10:2062019. View Article : Google Scholar : PubMed/NCBI
56	Mootha VK, Lindgren CM, Eriksson KF, Subramanian A, Sihag S, Lehar J, Puigserver P, Carlsson E, Ridderstråle M, Laurila E, et al: PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat Genet. 34:267–273. 2003. View Article : Google Scholar : PubMed/NCBI
57	Schreiber SN, Emter R, Hock MB, Knutti D, Cardenas J, Podvinec M, Oakeley EJ and Kralli A: The estrogen-related receptor alpha (ERRalpha) functions in PPARgamma coactivator 1alpha (PGC-1alpha)-induced mitochondrial biogenesis. Proc Natl Acad Sci USA. 101:6472–6477. 2004. View Article : Google Scholar : PubMed/NCBI
58	Rutanen J, Yaluri N, Modi S, Pihlajamäki J, Vänttinen M, Itkonen P, Kainulainen S, Yamamoto H, Lagouge M, Sinclair DA, et al: SIRT1 mRNA expression may be associated with energy expenditure and insulin sensitivity. Diabetes. 59:829–835. 2010. View Article : Google Scholar : PubMed/NCBI
59	B'chir W, Dufour CR, Ouellet C, Yan M, Tam IS, Andrzejewski S, Xia H, Nabata K, St-Pierre J and Giguère V: Divergent role of estrogen-related receptor α in lipid- and fasting-induced hepatic steatosis in mice. Endocrinology. 159:2153–2164. 2018. View Article : Google Scholar : PubMed/NCBI
60	Chaveroux C, Eichner LJ, Dufour CR, Shatnawi A, Khoutorsky A, Bourque G, Sonenberg N and Giguère V: Molecular and genetic crosstalks between mTOR and ERRα are key determinants of rapamycin-induced nonalcoholic fatty liver. Cell Metab. 17:586–598. 2013. View Article : Google Scholar : PubMed/NCBI
61	Sakamoto T, Matsuura TR, Wan S, Ryba DM, Kim JU, Won KJ, Lai L, Petucci C, Petrenko N, Musunuru K, et al: A Critical Role for Estrogen-Related Receptor Signaling in Cardiac Maturation. Circ Res. 126:1685–1702. 2020. View Article : Google Scholar : PubMed/NCBI
62	Mitra MS, Schilling JD, Wang X, Jay PY, Huss JM, Su X and Finck BN: Cardiac lipin 1 expression is regulated by the peroxisome proliferator activated receptor γ coactivator 1α/estrogen related receptor axis. J Mol Cell Cardiol. 51:120–128. 2011. View Article : Google Scholar : PubMed/NCBI
63	Gomez-Arroyo J, Mizuno S, Szczepanek K, Van Tassell B, Natarajan R, dos Remedios CG, Drake JI, Farkas L, Kraskauskas D, Wijesinghe DS, et al: Metabolic gene remodeling and mitochondrial dysfunction in failing right ventricular hypertrophy secondary to pulmonary arterial hypertension. Circ Heart Fail. 6:136–144. 2013. View Article : Google Scholar : PubMed/NCBI
64	Watson PA, Birdsey N, Huggins GS, Svensson E, Heppe D and Knaub L: Cardiac-specific overexpression of dominant-negative CREB leads to increased mortality and mitochondrial dysfunction in female mice. Am J Physiol Heart Circ Physiol. 299:H2056–H2068. 2010. View Article : Google Scholar : PubMed/NCBI
65	Sun PM, Gao M, Wei LH, Mustea A, Wang JL, Könsgen D, Lichtenegger W and Sehouli J: An estrogen receptor alpha-dependent regulation of estrogen receptor-related receptor alpha in the proliferation of endometrial carcinoma cells. Int J Gynecol Cancer. 16 (Suppl 2):564–568. 2006. View Article : Google Scholar : PubMed/NCBI
66	Stein RA, Gaillard S and McDonnell DP: Estrogen-related receptor alpha induces the expression of vascular endothelial growth factor in breast cancer cells. J Steroid Biochem Mol Biol. 114:106–112. 2009. View Article : Google Scholar : PubMed/NCBI
67	Cheung CP, Yu S, Wong KB, Chan LW, Lai FM, Wang X, Suetsugi M, Chen S and Chan FL: Expression and functional study of estrogen receptor-related receptors in human prostatic cells and tissues. J Clin Endocrinol Metab. 90:1830–1844. 2005. View Article : Google Scholar : PubMed/NCBI
68	Fujimoto J and Sato E: Clinical implication of estrogen-related receptor (ERR) expression in uterine endometrial cancers. J Steroid Biochem Mol Biol. 116:71–75. 2009. View Article : Google Scholar : PubMed/NCBI
69	Kraus RJ, Ariazi EA, Farrell ML and Mertz JE: Estrogen-related receptor alpha 1 actively antagonizes estrogen receptor-regulated transcription in MCF-7 mammary cells. J Biol Chem. 277:24826–24834. 2002. View Article : Google Scholar : PubMed/NCBI
70	Ma JH, Qi J, Lin SQ, Zhang CY, Liu FY, Xie WD and Li X: STAT3 targets ERR-α to promote epithelial-mesenchymal transition, migration, and invasion in triple-negative breast cancer cells. Mol Cancer Res. 17:2184–2195. 2019. View Article : Google Scholar : PubMed/NCBI
71	Fujimura T, Takahashi S, Urano T, Kumagai J, Ogushi T, Horie-Inoue K, Ouchi Y, Kitamura T, Muramatsu M and Inoue S: Increased expression of estrogen-related receptor alpha (ERRalpha) is a negative prognostic predictor in human prostate cancer. Int J Cancer. 120:2325–2330. 2007. View Article : Google Scholar : PubMed/NCBI
72	Hong F, Pan S, Guo Y, Xu P and Zhai Y: PPARs as nuclear receptors for nutrient and energy metabolism. Molecules. 24:25452019. View Article : Google Scholar
73	Fougerat A, Montagner A, Loiseau N, Guillou H and Wahli W: Peroxisome proliferator-activated receptors and their novel ligands as candidates for the treatment of non-alcoholic fatty liver disease. Cells. 9:92020. View Article : Google Scholar
74	Shi Y, Zou Y, Shen Z, Xiong Y, Zhang W, Liu C and Chen S: Trace elements, PPARs, and metabolic syndrome. Int J Mol Sci. 21:212020. View Article : Google Scholar
75	Thangavel N, Al Bratty M, Akhtar Javed S, Ahsan W and Alhazmi HA: Targeting peroxisome proliferator-activated receptors using thiazolidinediones: Strategy for design of novel antidiabetic drugs. Int J Med Chem. 2017:10697182017.PubMed/NCBI
76	Ribon V, Johnson JH, Camp HS and Saltiel AR: Thiazolidinediones and insulin resistance: Peroxisome proliferatoractivated receptor gamma activation stimulates expression of the CAP gene. Proc Natl Acad Sci USA. 95:14751–14756. 1998. View Article : Google Scholar : PubMed/NCBI
77	Schinner S, Dellas C, Schroder M, Heinlein CA, Chang C, Fischer J and Knepel W: Repression of glucagon gene transcription by peroxisome proliferator-activated receptor gamma through inhibition of Pax6 transcriptional activity. J Biol Chem. 277:1941–1948. 2002. View Article : Google Scholar : PubMed/NCBI
78	Tontonoz P, Nagy L, Alvarez JG, Thomazy VA and Evans RM: PPARgamma promotes monocyte/macrophage differentiation and uptake of oxidized LDL. Cell. 93:241–252. 1998. View Article : Google Scholar : PubMed/NCBI
79	Maréchal L, Laviolette M, Rodrigue-Way A, Sow B, Brochu M, Caron V and Tremblay A: The CD36-PPARγ pathway in metabolic disorders. Int J Mol Sci. 19:192018. View Article : Google Scholar
80	Chawla A, Barak Y, Nagy L, Liao D, Tontonoz P and Evans RM: PPAR-gamma dependent and independent effects on macrophage-gene expression in lipid metabolism and inflammation. Nat Med. 7:48–52. 2001. View Article : Google Scholar : PubMed/NCBI
81	Chandra M, Miriyala S and Panchatcharam M: PPARγ and its role in cardiovascular diseases. PPAR Res. 2017:64046382017. View Article : Google Scholar : PubMed/NCBI
82	Fukunaga Y, Itoh H, Doi K, Tanaka T, Yamashita J, Chun TH, Inoue M, Masatsugu K, Sawada N, Saito T, et al: Thiazolidinediones, peroxisome proliferator-activated receptor gamma agonists, regulate endothelial cell growth and secretion of vasoactive peptides. Atherosclerosis. 158:113–119. 2001. View Article : Google Scholar : PubMed/NCBI
83	Chang JS and Ha K: A truncated PPAR gamma 2 localizes to mitochondria and regulates mitochondrial respiration in brown adipocytes. PLoS One. 13:e01950072018. View Article : Google Scholar : PubMed/NCBI
84	Dong JT: Anticancer activities of PPARγ in breast cancer are context-dependent. Am J Pathol. 182:1972–1975. 2013. View Article : Google Scholar : PubMed/NCBI
85	Lin SJ, Lin CY, Yang DR, Izumi K, Yan E, Niu X, Chang HC, Miyamoto H, Wang N, Li G, et al: The differential effects of anti-diabetic thiazolidinedione on prostate cancer progression are linked to the TR4 nuclear receptor expression status. Neoplasia. 17:339–347. 2015. View Article : Google Scholar : PubMed/NCBI
86	Lakshmi SP, Reddy AT, Banno A and Reddy RC: PPAR agonists for the prevention and treatment of lung cancer. PPAR Res. 2017:82527962017. View Article : Google Scholar : PubMed/NCBI
87	Yousefnia S, Momenzadeh S, Seyed Forootan F, Ghaedi K and Nasr Esfahani MH: The influence of peroxisome proliferator-activated receptor γ (PPARγ) ligands on cancer cell tumorigenicity. Gene. 649:14–22. 2018. View Article : Google Scholar : PubMed/NCBI
88	Holland CM, Saidi SA, Evans AL, Sharkey AM, Latimer JA, Crawford RA, Charnock-Jones DS, Print CG and Smith SK: Transcriptome analysis of endometrial cancer identifies peroxisome proliferator-activated receptors as potential therapeutic targets. Mol Cancer Ther. 3:993–1001. 2004.PubMed/NCBI
89	Zhang GY, Ahmed N, Riley C, Oliva K, Barker G, Quinn MA and Rice GE: Enhanced expression of peroxisome proliferator-activated receptor gamma in epithelial ovarian carcinoma. Br J Cancer. 92:113–119. 2005. View Article : Google Scholar : PubMed/NCBI
90	Davidson B, Hadar R, Stavnes HT, Trope' CG and Reich R: Expression of the peroxisome proliferator-activated receptors-alpha, -beta, and -gamma in ovarian carcinoma effusions is associated with poor chemoresponse and shorter survival. Hum Pathol. 40:705–713. 2009. View Article : Google Scholar : PubMed/NCBI
91	Luo S, Wang J, Ma Y, Yao Z and Pan H: PPARγ inhibits ovarian cancer cells proliferation through upregulation of miR-125b. Biochem Biophys Res Commun. 462:85–90. 2015. View Article : Google Scholar : PubMed/NCBI
92	Ogino S, Shima K, Baba Y, Nosho K, Irahara N, Kure S, Chen L, Toyoda S, Kirkner GJ, Wang YL, et al: Colorectal cancer expression of peroxisome proliferator-activated receptor gamma (PPARG, PPARgamma) is associated with good prognosis. Gastroenterology. 136:1242–1250. 2009. View Article : Google Scholar : PubMed/NCBI
93	Reka AK, Kurapati H, Narala VR, Bommer G, Chen J, Standiford TJ and Keshamouni VG: Peroxisome proliferator-activated receptor-gamma activation inhibits tumor metastasis by antagonizing Smad3-mediated epithelial-mesenchymal transition. Mol Cancer Ther. 9:3221–3232. 2010. View Article : Google Scholar : PubMed/NCBI
94	Dong YW, Wang XP and Wu K: Suppression of pancreatic carcinoma growth by activating peroxisome proliferator-activated receptor gamma involves angiogenesis inhibition. World J Gastroenterol. 15:441–448. 2009. View Article : Google Scholar : PubMed/NCBI
95	He Q, Pang R, Song X, Chen J, Chen H, Chen B, Hu P and Chen M: Rosiglitazone suppresses the growth and invasiveness of SGC-7901 gastric cancer cells and angiogenesis in vitro via PPARgamma dependent and independent mechanisms. PPAR Res. 2008:6498082008. View Article : Google Scholar : PubMed/NCBI
96	Wang YX: PPARs: Diverse regulators in energy metabolism and metabolic diseases. Cell Res. 20:124–137. 2010. View Article : Google Scholar : PubMed/NCBI
97	Szklarczyk D, Gable AL, Lyon D, Junge A, Wyder S, Huerta-Cepas J, Simonovic M, Doncheva NT, Morris JH, Bork P, et al: STRING v11: Protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res. 47:D607–D613. 2019. View Article : Google Scholar : PubMed/NCBI
98	Ijichi N, Ikeda K, Horie-Inoue K, Yagi K, Okazaki Y and Inoue S: Estrogen-related receptor alpha modulates the expression of adipogenesis-related genes during adipocyte differentiation. Biochem Biophys Res Commun. 358:813–818. 2007. View Article : Google Scholar : PubMed/NCBI
99	Prabhu DS and Rajeswari VD: PPAR-Gamma as putative gene target involved in Butein mediated anti-diabetic effect. Mol Biol Rep. 47:5273–5283. 2020. View Article : Google Scholar : PubMed/NCBI
100	Lebovitz HE: Thiazolidinediones: The forgotten diabetes medications. Curr Diab Rep. 19:1512019. View Article : Google Scholar : PubMed/NCBI
101	Heneka MT, Sastre M, Dumitrescu-Ozimek L, Hanke A, Dewachter I, Kuiperi C, O'Banion K, Klockgether T, Van Leuven F and Landreth GE: Acute treatment with the PPARgamma agonist pioglitazone and ibuprofen reduces glial inflammation and Abeta1-42 levels in APPV717I transgenic mice. Brain. 128:1442–1453. 2005. View Article : Google Scholar : PubMed/NCBI
102	Wuertz BR, Darrah L, Wudel J and Ondrey FG: Thiazolidinediones abrogate cervical cancer growth. Exp Cell Res. 353:63–71. 2017. View Article : Google Scholar : PubMed/NCBI
103	Sanghvi M, Moaddel R, Frazier C, Gandhari M and Wainer IW: Abstract 5500: Biochromatography for the screening of new drugs for the estrogen related receptors. Cancer Res. 70:55002010.