Effect of Pesticides on Peroxisome Proliferator-Activated Receptors (PPARs) and Their Association with Obesity and Diabetes

Table 2

In vitro studies of activation PPARs by pesticides.

PPAR subtype	Pesticide	Chemical classification	Type of pesticide	Cell culture	Item	Year	References
PPARα	Permethrin	Pyrethroid	Insecticide	Primary mouse and human hepatocytes cultures	Activation of PPARα	2020	Kondo et al. [125]
	Methiocarb	Carbamate	Insecticide	Cos-1 cells (transfected)	Activation of PPARα, CYP4A, PXR, CAR	2016	Fujino et al. [57]
	Carbaryl				Activation of PPARα, PXR, CAR
	Deltamethrin	Pyrethroid	Insecticide	Cos-1 cells (transfected)	None activate PPARα	2019	Fujino et al. [30]
	Cis-Permethrin Cypermethrin
	Paraquat	Bipyridine	Herbicide	Primary mouse hepatocytes cultures	Activation of PPARα, regulate lipid homeostasis and dismiss of stress	2004	Anderson et al. [66]
PPAR β/δ	2,4-D	Phenoxy	Herbicide	HepG2 cell line	Increase expres of PPARβ/δ, and CREB (regulator of gluconeogenesis)	2018	Sun et al. [26]
PPARγ	Endrin	Organochlorine	Insecticide	3T3-L1 cell line	Up-regulate PPARγ, C/EBPs, FAS, GLUT-4, Adiponectin	2022	Seok et al. [24]
	DDT	Organochlorine	Insecticide	Primary hepatocytes rat	Increase PPARγ	2021	Jellali et al. [36]
	Permethrin	Pyrethroid
	Chlorpyrifos	Organophosphate	Insecticide	3T3-L1 cell line	Enhance store lipid droplets, up-regulated transcription of PPARγ, C/EBPα and FABP4	2020	Blanco et al. [32]
	Permethrin	Pyrethroid	Insecticide	3T3-L1 cell line	TG accumulation and pre-adipocytes proliferation	2021	Kassotis et al. [126]
	Cypermethrin
	Chlorpyrifos
		Organophosphate
	Iprodione	Imide		Hepatocyte rat cell line	Up-regulate PPARγ	2020	Sohrabi et al. [37]
			Fungicide
	Flutolanil	Acid amides	Fungicide
	Paraquat	Bipyridine	Herbicide
	DDT	Organochlorine	Insecticide
	Endosulfan		Insecticide
	Methoxychlor		Insecticide
	Pentachlorophenol		Insecticide
	Quintozene		Fungicide
	Toxaphene		Insecticide
	Chlorpyrifos	Organophosphate	Insecticide
	Diazinon		Insecticide
	Fibronil	Phenylpyrazole	Fungicide
	Allethrin	Pyrethroid	Insecticide
	Bifenthrin		Fungicide
	Cyhalothrin		Insecticide
	Permethrin		Insecticide
	Resmethrin		Insecticide
	Atrazine	Triazine	Herbicide
	Paclobutrazol	Triazole	Herbicide
	Diuron	Ureas	Herbicide
	Endrin	Organochlorine	Insecticide	Hepatocyte rat cell line	Down-regulate PPARγ	2020	Sohrabi et al. [37]
	Propamocarb	Carbamate	Fungicide
	Rotenone	Heteropentacyclic compound	Insecticide
	Prallethrin	Pyrethroid	Insecticide	3T3-L1, OP9, BM-MSC cell lines	Lipid accumulation, activate PPARγ and stimulate the expression of Plin1	2020	Andrews et al. [38]
	Allethrin	Pyrethroid	Insecticide	3T3-L1, OP9, BM-MSC cell lines	Activate transcriptional function of PPARγ	2020	Andrews et al. [38]
	Fenthion	Organophosphate	Insecticide
	Fentin	Organotion	Fungicide
	Quinoxyfen	Quinoline	Fungicide
	2-Benzothiazole sulfonic acid	Benzothiazole	Fungicide	Mammalian cells	Bind to PPARγ	2020	Neale et. al. [127]
	MCPA	Phenoxy	Herbicide
	TBT	Organotion	Antifouling	THP-1cell line	Activation of PPARγ, increase lipid accumulation and expression of lipid metabolism genes	2021	Jie et al. [65]
	QpE	Phenoxy	Herbicide	3T3-L1 cell line	Induce accumulation of lipids via PPARγ	2019	Biserni et al. [39]
	Glyphosate	Organophosphate	Herbicide	3T3-L1 cell line	Not induce accumulation of lipids via PPARγ	2018	Mesnage et al. [29]
	2,4-D	Phenoxy	Herbicide
	Dicamba	Chlorophenoxy	Herbicide
	Mesotrione	Triketone	Herbicide
	Isoxaflutole	Isoxazole	Herbicide
	Permethrin	Pyrethroid	Insecticide	3T3-L1 cell line	Induce adipogenesis via PPARγ	2019	Qi et al. [128]
	Fibronil	Phenylpyrazole	Fungicide
	Chlorantraniliprole	Ryanoid	Insecticide	3T3-L1 cell line	Induce adipogenesis, up-regulate C/EBPα, PPARγ and ACC	2019	Yuan et al. [23]
	Chlorpyrifos	Organophosphate	Insecticide	HTR8/SVneo cells	Reduce mRNA of PPARγ	2019	Ridano et al. [64]
	Flubendiamide	Ryanoid	Insecticide	3T3-L1 cell line	Enhance TG content, increase C/EBPα, PPARγ	2018	Sun et al. [129]
	Pyraclostrobin	Strobilurin	Fungicide	3T3-L1 cell line	TG accumulation, without activation of PPARγ, reduce LPL, CEBPα, GLUT4	2018	Luz et al. [40]
	Cis-Bifenthrin	Pyrethroid	Insecticide	HepG2 cell line	Lipid accumulation, induce expression of PPARγ, FAS	2018	Xiang et al. [58]
	QpE	Phenoxy	Herbicide	HepaRG (transfected)	Activate PPARγ	2018	Mesnage et al. [37]
	Isoxaflutole	Isoxazole	Herbicide
	Mesotrones	Triketone	Herbicide
	Glyphosate	Organophosphate	Herbicide		Not activate PPARγ
	Diazinon	Organophosphate	Insecticide	3T3-L1 cell line	Increase lipid accumulation, induce transcriptional factors of C/EBPα and PPARγ	2018	Smith et al. [33]
	Diflubenzuron Chlorfluazuron Flucycloxuron Noviflumuron	Benzoylurea	Insecticide	HepG2 cell line	Exhibited potent PPARγ agonistic activity	2018	Ning et al. [20]
	Flufenoxuron
	TBT	Organotion	Antifouling	Primary adipocytes culture of Onchrorynchus mykiss	Induce lipid accumulation, increase C/EBPα and PPARγ expression	2017	Lutfi et al. [43]
	TPT
	DDT / DDE	Organochlorine	Insecticide	3T3-L1 cell line	Increase lipid accumulation, PPARγ expression, FAS, C/EBPα, LPL	2016	Kim et al. [31]
	Fibronil	Phenylpyrazole	Insecticide	3T3-L1 cell line	Increase lipid accumulation and expression of PPARγ and C/EBPα genes	2016	Sun et al. [22]
Glyphosate	Organophosphate	Herbicide	3T3-L1 cell line	Increase lipid peroxidation, inhibit the induction of PPARγ during differentiation with the commercial presentation, not in pure form	2016	Martini et al. [56]
Deltamethrin	Pyrethroid	Insecticide	SH-SY5Y cell line	Decreased PPARγ expression and the receptor protects against pesticide cytotoxicity	2016	Ko et al. [68]
TBT	Organotion	Antifouling	MSC cells	Promote adipogenesis via PPARγ receptor but there are others receptors	2014	Biemann et al. [60]
Chlorpyrifos	Organophosphate	Insecticide	SH-SY5Y cell line	Activation of PPARγ, dismiss the oxidative stress, inflammation and death cell produced to the pesticide	2014	Lee et al. [69]
Rotenone	Heteropentacyclic compound	Insecticide	SH-SY5Y cell line	Activation of PPARγ via rosiglitazone and inhibits the effect of pesticide	2014	Corona et al. [70]
TBT	Organotion	Antifouling	MSC cells	Induce PPARγ, FABP4, lipid accumulation, stimulus cellular differentiation	2011	Yanik et al. [59]
TPT
Dibutyltin
TBT	Organotion	Antifouling	3T3-L1 cell line	Increase adipogenic activity but not via PPARγ	2011	Penza et al. [52]
Endrin	Organochlorine	Insecticide	3T3-L1 cell line	Bind to PPARγ, but preferably through to glucocorticoid receptor	2010	Sargis et al. [54]
Tolylfluanid	Sulfamide	Fungicide
TPT	Organotion	Antifouling		Activate PPARγ
TBT	Organotion	Antifouling	3T3-L1 cell line	Promote adipogenesis and lipid accumulation	2006	Grün et al. [130]
TBT	Organotion	Antifouling	3T3-L1 cell line	Accumulation of lipid but not via PPARγ and increase aP2	2005	Inadera & Shimomura [45]
TBT	Organotion	Antifouling	3T3-L1 cell line	Activate PPARγ, accumulation of TG and increase adipocyte differentiation	2005	Kanayama et al. [44]
TPT
DDT	Organochlorine	Insecticide	3T3-L1 cell line	Induction of C/EBPα, PPARγ, increase phenotype of adipocytes	2002	Moreno-Aliaga & Matsumura [46]
Endrin	Organochlorine	Insecticide	3T3-L1 cell line	Inhibition of adipocyte differentiation, inhibit C/EBPα but not C/EBPβ and C/EBPδ, reduce PPARγ	1999	Moreno-Aliaga & Matsumura [51]
PPARα and PPARγ	DDE	Organochlorine	Insecticide	3T3-L1 cell line	No affect PPARα neither PPARγ, reduce lipid accumulation inhibit adipocyte differentiation	2012	Taxvig et al. [49]
	Chlorpyrifos	Organophosphate	Insecticide
	Mancozeb	Dithiocarbamate	Fungicide
	Prochoraz	Ureas	Fungicide
	Deltamethrin	Pyrethroid	Insecticide	3T3-L1 cell line	Activate PPARγ but not PPARα, reduce lipid accumulation	2012	Taxvig et al. [49]
	Aldrin	Organochlorine	Insecticide	CV-1 cell line transfected with PPARα and PPARγ mouse
	α-BHC		Insecticide
	β-BHC		Insecticide
	γ-BHC		Insecticide
	δ-BHC		Insecticide
	Captan		Fungicide
	cis-Chlordane		Insecticide
	trans-Chlordane		Insecticide
	Chlorobenzilate		Insecticide
	Chloropropylate		Insecticide
	Chlorothalonil		Fungicide
	o,p´-DDT		Insecticide
	p,p´-DDT		Insecticide
	p,p´-DDE		Insecticide
	p,p´-DDD		Insecticide		None have agonistic activity to PPARα and PPARγ	2006	Takeuchi et al. [25]
	Dichlobenil		Herbicide
	Dicofol		Insecticide
	Dieldrin		Insecticide
	α-Endosulfan		Insecticide
	β-Endosulfan		Insecticide
	Endosulfan sulfate		Insecticide
	Endrin		Insecticide
	Folpet		Fungicide
	Fthalide		Fungicide
	Heptachlor		Insecticide
	Heptachlor epoxide		Insecticide
	Methoxychlor		Insecticide
	Pentachlorophenol		Insecticide
	Quintozene		Fungicide
	Acifluorfen	Diphenyl ethers	Herbicide	CV-1 cell line transfected with PPARα and PPARγ mouse	None have agonistic activity to PPARα and PPARγ	2006	Takeuchi et al. [25]
	Acifluorfen-methyl		Herbicide
	Bifenox		Herbicide
	Chlomethoxyfen		Herbicide
	Chlornitrofen		Herbicide
	CNP-amino		Herbicide
	Chloroxurone		Herbicide
	Diclofop-methyl		Herbicide	CV-1 cell line transfected with PPARα and PPARγ mouse	Induce PPARα and PPARγ	2006	Takeuchi et al. [25]
	Fluazifop-butyl		Herbicide	CV-1 cell line transfected with PPARα and PPARγ mouse	None have agonistic activity to PPARα and PPARγ	2006	Takeuchi et al. [25]
	Nitrofen		Herbicide
	Oxyfluorfen		Herbicide
	Acephate	Organophosphate	Insecticide
				CV-1 cell line transfected with PPARα and PPARγ mouse	None have agonistic activity to PPARα and PPARγ	2006	Takeuchi et al. [25]
				Anilofos	Herbicide
				Bromophos-ethyl	Insecticide
				Bromophos-methyl	Insecticide
				Butamifos	Herbicide
				Chlorpyrifos	Insecticide
				Chlorpyrifos-methyl	Insecticide
				Cyanofenphos	Insecticide
				Cyanophos	Insecticide
				Diazinon	Insecticide
	Dichlofenthion		Insecticide
	Dichlorvos		Insecticide
	Dimethoate		Insecticide
	Dioxabenzofos		Insecticide
	Disulfoton		Insecticide
	EPN		Insecticide
	Edifenphos		Fungicide
	Ethion		Insecticide
Ethoprophos	Insecticide
Fenamiphos	Nematicide
Fenchlorphos	Insecticide
Fenitrothion	Insecticide
Fenitrothion oxon	Insecticide
Fensulfothion	Insecticide
Fenthion	Insecticide
Glyphosate	Herbicide
Iprobenfos	Fungicide
Isofenphos	Insecticide		CV-1 cell line transfected with PPARα and PPARγ mouse	None have agonistic activity to PPARα and PPARγ	2006	Takeuchi et al. [25]
Isoxathion	Insecticide
Leptophos	Insecticide
Malathion	Insecticide
Mecarbam	Insecticide
Methamidophos	Insecticide
Methidathion	Insecticide
Methyl-parathion	Insecticide
Monocrotophos	Insecticide
Parathion	Insecticide
Phenthoate	Insecticide
Phorate	Insecticide
Phosalone	Insecticide
Phosmet	Insecticide
Piperophos	Fungicide
Pirimiphos-methyl	Insecticide
Profenofos	Insecticide
Propaphos	Insecticide
Prothiofos	Insecticide
Prothiofos oxon	Insecticide
Pyridaphenthion	Insecticide
Quinalphos	Insecticide		CV-1 cell line transfected with PPARα and PPARγ mouse	None have agonistic activity to PPARα and PPARγ	2006	Takeuchi et al. [25]
Terbufos	Insecticide
Tetrachlorvinphos	Insecticide
Thiometon	Insecticide
Tolclofos-methyl	Fungicide
Tolclofos-methyl oxon	Fungicide
Trichlorfon	Insecticide
Vamidothion	Insecticide
Cyfluthrin	Pyrethroid		Insecticide	CV-1 cell line transfected with PPARα and PPARγ mouse	None have agonistic activity to PPARα and PPARγ	2006	Takeuchi et al. [25]
Cyhalothrin			Insecticide
Cypermethrin			Insecticide
Deltamethrin			Insecticide
Etofenprox			Insecticide
Fenvalerate			Insecticide
Flucythrinate			Insecticide
Fluvalinate		Insecticide
Permethrin		Insecticide
Pyrethrin		Insecticide	CV-1 cell line transfected with PPARα and PPARγ mouse	Induce PPARα and PPARγ	2006	Takeuchi et al. [25]
Tefluthrin		Insecticide	CV-1 cell line transfected with PPARα and PPARγ mouse	None have agonistic activity to PPARα and PPARγ	2006	Takeuchi et al. [25]
Tralomethrin		Insecticide
Bendiocarb	Carbamate	Insecticide	CV-1 cell line transfected with PPARα and PPARγ mouse	None have agonistic activity to PPARα and PPARγ	2006	Takeuchi et al. [25]
Benomyl		Fungicide
Carbaryl		Insecticide
Carbendazim		Fungicide
Carbofuran		Insecticide
Chlorpropham		Herbicide
Diethofencarb		Fungicide
Dimepiperate		Herbicide
Esprocarb		Herbicide
Ethiofencarb		Insecticide
Fenobucarb		Insecticide
Isoprocarb		Insecticide
Methiocarb		Insecticide
Methomyl		Insecticide
Molinate		Herbicide
Oxamyl		Insecticide
Phenmedipham		Herbicide
Pirimicarb		Insecticide
Pyributicarb		Herbicide
Thiobencarb		Herbicide
Thiobencarb sulfon		Herbicide
Thiram		Fungicide
Alachlor	Acid amides	Herbicide	CV-1 cell line transfected with PPARα and PPARγ mouse	None have agonistic activity to PPARα and PPARγ	2006	Takeuchi et al. [25]
Asulam		Herbicide
Cafenstrole		Herbicide
Flutolanil		Fungicide
Mefenacet		Herbicide
Mepronil		Fungicide
Metalaxyl		Fungicide
Metolachlor		Herbicide
Pretilachlor		Herbicide
Propyzamide		Herbicide
Thenylchlor		Herbicide
Anilazine	Triazine	Fungicide	CV-1 cell line transfected with PPARα and PPARγ mouse	None have agonistic activity to PPARα and PPARγ	2006	Takeuchi et al. [25]
Atrazine		Herbicide
Metribuzin		Herbicide
Prometon		Herbicide
Prometryn		Herbicide
Simazine		Herbicide
Simetryn		Herbicide
Bensulfuron-methyl	Ureas	Herbicide
Daimuron		Herbicide
Diflubenzuron		Insecticide
Diuron		Herbicide
Linuron		Herbicide
Pencycuron		Fungicide
Prochloraz		Fungicide	CV-1 cell line transfected with PPARα and PPARγ mouse	None have agonistic activity to PPARα and PPARγ	2006	Takeuchi et al. [25]
Propanil		Herbicide
Amitraz	Formamidine	Fungicide	CV-1 cell line transfected with PPARα and PPARγ mouse	None have agonistic activity to PPARα and PPARγ	2006	Takeuchi et al. [25]
Benfuresate	Benzofuran	Herbicide
Bentazone	Benzothiadiazole	Herbicide
Benzoximate	Organochlorine	Acaricide
Bitertanol	Triazole	Fungicide
Bromopropylate	Benzilate	Acaricide
Chinomethionat	Quinoxaline	Fungicide
Chloridazon	Pyridazinone	Herbicide
Dazomet	Thiadiazine	Insecticide
Diquat	Bipyridine	Herbicide
Fenarimol	Pyrimidine	Fungicide
Ferimzone	Pyrimidine	Fungicide
Fluazinam	Diarilamine	Fungicide
Imazalil	Conazole	Fungicide	CV-1 cell line transfected with PPARα and PPARγ mouse	Induce PPARα and PPARγ	2006	Takeuchi et al. [25]
Imidacloprid	Neonicotinoid	Insecticide
Iminoctadine	Guanidine	Fungicide
Indanofan	Sulfonylurea	Herbicide
Ioxynil	Nitrile	Herbicide	CV-1 cell line transfected with PPARα and PPARγ mouse	None have agonistic activity to PPARα and PPARγ	2006	Takeuchi et al. [25]
Iprodione	Imide	Fungicide
Isoprothiolane	Dithiolane	Fungicide
Lenacil	Uracyles	Herbicide
MCPA	Phenoxy	Herbicide
2,4-D	Phenoxy	Herbicide
Paraquat	Bipyridine	Herbicide
Pendimethalin	Dinitroaniline	Herbicide
Probenazole	Benoxthiazole	Fungicide
Procymidone	Dicarboximide	Fungicide
Propiconazole	Triazole	Fungicide
Pyrazolynate	Pyrazole	Herbicide
Pyrazoxyfen	Pyrazole	Herbicide
Pyroquilon	Pyrroloquinoline	Fungicide	CV-1 cell line transfected with PPARα and PPARγ mouse	None have agonistic activity to PPARα and PPARγ	2006	Takeuchi et al. [25]
Sethoxydim	Oxime	Herbicide
Thiabendazole	Benzimidazole	Fungicide
Thiocyclam	Nereistoxin	Insecticide
Thiophanate-methyl	Thioureas	Fungicide
Triadimefon	Triazole	Fungicide
Tricyclazole	Triazole	Fungicide
Triflumizole	Imidazole	Fungicide
Trifluralin	Dinitroaniline	Herbicide
Triforine	Piperazine	Fungicide
Vinclozolin	Dicarboximide	Fungicide
2,4-D MCPA	Phenoxy	Herbicide	COS-1 (transfected)	No transactivation receptors	1999	Maloney & Waxman [28]
PPARα, PPARβ/δ, PPARγ	Atrazine	Triazine	Herbicide	RK13 (rabbit kidney) transfected	No interaction with the receptors	2003	Devos et al. [104]

Abbreviations: 2,4-D, 2,4-dichlorphenoxyacetic acid; ACC, acetyl Co-A carboxylase; BM-MSC, bone marrow-derived mesenchymal stem cell; C/EBPα, CCAAT enhancer binding protein alpha; C/EBPβ, CCAAT enhancer binding protein beta; CAR, constitutive androstane receptor; CREB, CAMP responsive element binding protein 1; EPN, Ethyl p-nitrophenyl phenylphosphorothioate; FABP4, fatty acid-binding protein 4; FAS, fatty acid synthase; GLUT-4, glucose transporter type 4; LPL, lipoprotein lipase; MCPA, 4-Chloro-o-toloxyacetic acid; DDT, diclorodifeniltricloroetano; DDD, Dichlorodiphenyldichloroethane; DDE, Dichlorodiphenyldichloroethylene; PPARα, peroxisome proliferator-activated receptor alpha; PPARβ/δ, peroxisome proliferator-activated receptor beta or delta; PPARγ, peroxisome proliferator-activated receptor gamma; PXR, pregnane X receptor; QpE, Quizalofop-p-ethyl; TBT, Tributyltin; TG, triglycerides; TPT, Triphenyltin.