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

Table 3

In vivo models of pesticide effect above the PPAR receptors.

PPAR subtype	Pesticide	Chemical classification	Type of pesticide	Model of study	Item	Year	References
PPARα	Methidathion	Organophosphate	Insecticide	Male B6C3F1 mice	These pesticides not active PPARα in a tumorigenesis process	2022	Rooney et al. [103]
	Fenthion
	Parathion
	Fibronil	Phenylpyrazole	Insecticide	Male albino rats	Up-regulated FABP, ACC1, and PPARα	2021	Wasef et al. [80]
	Carbendazim	Carbamate	Fungicide	Male zebrafish (Danio rerio)	Level of glucose decreased and PPARα, ACO, CPT1 were not affected	2020	Bao et al. [91]
	Boscalid	Anilide	Fungicide	Zebrafish (Danio rerio)	Decrease the content of TG and cholesterol by accelerating lipolysis; and inhibiting lipogenesis, via the regulation of PPARα	2019	Qian et al. [95]
	Permethrin	Pyrethroid	Insecticide	Female C57BL/6N wild-type or PPARα (KO) mice	Increase expression of PPARα in hepatocytes and KO mice the effect decreases	2019	Kondo et al. [63]
	Propaquizafop	Ariloxiphenoxypropionate	Herbicide	Male SD wild-type or PPARα (KO) rats	PPARα regulates the biochemical and histological changes in the liver in hepatocarcinogenesis	2018	Strupp et al. [98]
	Propamocarb	Carbamate	Fungicide	Male C57bL/6J mice	Decrease PPARα and increase hepatic bile acids with a change of energy metabolism and the gut microbiota	2018	Wu et al.^89
	2,4-D	Organochlorine	Herbicide	Male Sv/129 wild-type or PPARα-null mice	Induce testicular toxicity due to disruption of cholesterol/testosterone homeostasis in Leydig cells via PPARα	2016	Harada et al. [109]
	Oxadiazon	Oxadiazol	Herbicide	Male C3H/HeNCrl and CAR (KO) mice	PPARα and CAR are involved in the development of liver tumors	2016	Kuwata et al. [99]
	Toxaphene	Organochlorine	Insecticide	Male B6C3F1 mice	Induce mouse liver tumors, increase CAR, AhR but not PPARα target genes	2015	Wan et al. [102]
	Myclobutanil	Triazole	Fungicide	Male Wistar Han IGS rats	Perturb fatty acid and steroid metabolism in the liver predominantly through the CAR, PPARα, and PXR signaling pathways.	2009	Goetz and Dix [93]
	Propiconazole
	Triadimefon
	Methyl thiophanate	Thioallophanate	Fungicide	Male lizard (Podarcis sicula)	Increase AOX and PPARα	2006	Buono et al. [92]
PPARβ/δ	Atrazine	Triazine	Herbicide	Xenopus leavis tadpoles	Increase PPARβ/δ, which is associated with the conversion of lipid and proteins into energy	2011	Zaya et al. [94]
PPARγ	DDT	Organophosphate	Insecticide	Male SD rats	Decrease PPARγ expression	2022	Al-Obaidi [79]
	DDE
	Bromuconazole	Triazole	Fungicide	Male SD rats	Decrease the TG synthesis via inhibiting the PPARγ pathway	2021	Wu et al. [18]
	TBT	Organotion	Antifouling	Male C57BL/6 mice	Activate PPARγ, increase lipid accumulation and the expression of lipid metabolism	2021	Jie et al. [65]
	Dieldrin	Organochlorine	Insecticide	Male C57BL/6 mice	No affect the genes regulated by PPARγ in hepatocarcinogenesis	2020	Wang et al. [97]
	Paraquat	Dipiridile	Herbicide	Male Wistar rats	Activation of PPARγ with pioglitazone, decreases the concentrations of MDA (a lipid peroxidation marker)	2020	Amin et al. [107]
	Monocrotophos	Organophosphate	Insecticide	Male CFT-Wistar rats	Increase lipid content in the liver, PPARγ, ACC, and FAS	2020	Nagaraju et al. [85]
	TPT	Organotion	Antifouling	Xenopus tropicalis embryos	TPT exposure reversed some impacts induced by PPARγ overexpression	2018	Zhu et al. [110]
	TBT	Organotion	Antifouling	Female Wistar rats	Abnormal ovarian adipogenesis with increased cholesterol levels, lipid accumulation, PPARγ, C/EBP-β, and Lipin-1	2018	de Araújo et al. [77]
	TBT	Organotion	Antifouling	Male C57bL/6J mice	Increase mRNA expression of the PPARγ target genes Fabp4, Plin1	2017	Baker et al. [76]
	Mancozeb	Dithiocarbamate	Fungicide	Swiss albino mice	Affect PPARγ and increased the cholesterol and TG	2014	Bhaskar and Mohanty [78]
	Imidacloprid	Neonicotinoid	Insecticide		No affinity to PPARγ
	Paraquat	Dipiridile	Herbicide	Male Wistar rats	Atorvastatin reduces the inflammation produced by pesticide, via PPARγ	2014	Malekinejad et al. [131]
	Pronamide	Benzamide	Herbicide	Male CD-1 mice	The MoA of hepatocarcinogenesis although to PPARγ and CAR	2014	LeBaron et al. [100]
	Nitrofen	Diphenyl ether	Herbicide	Pregnant rats and their fetus	Down-regulated PPARγ and altered late gestation possibly due to impair lung development and maturation	2012	Gosemann et al. [132]
	Paraquat	Dipiridile	Herbicide	PPARγ heterozygous mice (PPAR^clox/lox/aP2-Cre)	Reduce expression of PPARγ, improve insulin sensitivity, and increased resistance to paraquat-induce oxidative stress	2008	Luo et al. [105]
	TBT	Organotion	Antifouling	Pregnant C57BL/6J mice and their pups	Increase the number of adipocytes and lipid accumulation through RXR and PPARγ	2006	Grün et al. [130]
PPARα PPARγ	Imidacloprid	Neonicotinoids	Insecticide	Zebrafish (Danio rerio)	Inhibit the growth of zebrafish and alters the levels of glycolipid metabolism and oxidative stress; reduce the expression of PPARα and PPARγ	2021	Luo et al. [96]
	Endosulfan sulfate	Organochlorine	Insecticide	Pregnant CD-1 mice and their male pups	In high and low-fat diet, PPARα and its target gene Cpt1a are increased, but not modify PPARγ	2021	Yan et al. [87]
	Chlorpyrifos	Organophosphate	Insecticide	Male zebrafish (Danio rerio)	Decrease PPARα and PPARγ, due to lipid metabolism disorders that are associated with gut oxidative stress and microbiota dysbiosis	2019	Wang et al. [86]
	Atrazine	Triazine	Herbicide	Male Kunming mice	Induce nephrotoxicity via modulating CYP450, PPARα, PPARγ, AhR, CAR, and PXR	2018	Xia et al. [108]
	Lambda cyhalothrin	Pyrethroid	Insecticide	Male albino rats	Up-regulate mRNA expression levels of PPARα, PPARγ, TNF-α FAS, and SREBP-1C	2016	Moustafa and Hussein [81]
	Triphenyltin	Organotion	Antifouling	Wood frog (Lithobates sylvaticus)	In chronic exposure, increase the expression of PPARα, PPARγ, FAS, and LPL	2013	Higley et al. [75]
PPARα PPARγ PPARβ/δ	Glyphosate	Organophosphate	Herbicide	Tilapia (Oreochromis niloticus)	Increase lipid content, alter redox status in liver, the genes involved in ion transport, lipid metabolism, and PPAR signaling pathway	2022	Jia et al. [74]
	Allethrin	Pyrethroids	Insecticide	Male Sprague Dawley rats	No activation of nuclear receptor in liver	2019	Fujino et al. [30]
	Bioresmethrin
	Cis-permetryn
	Cypermethrin
	Deltamethrin
	Fenvalerate
	Trans-permetryn
	Phenothrin
	Difenoconazole	Triazole	Fungicide	Marine medaka (Oryzias melastigma)	Increase the expression of receptor PPARα, PPARβ/δ, PPARγ, and increase lipid levels in muscle but not in liver	2016	Dong et al. [73]
	Paclobutrazol	Triazole	Fungicide	Male rockfish (Sebasticus marmoratus)	Increase total lipid, TG, TC, free fatty acid and up-regulate PPARα, PPARβ/δ, PPARγ, AR, FAS, FABP4, ACC	2013	Sun et al. [72]
	Atrazine	Triazine	Herbicide	CFI mice	No interact with the receptors α, β/δ, or γ	2003	Devos et al. [104]
	Diclofop	Ariloxiphenoxypropionate	Herbicide	Male Wistar rats (Pzh:WIS)	Increase the number of peroxisome and are a rodent PP	2001	Palut et al. [101]
	Oxadiazon	Oxadiazol	Herbicide	Male SD rats	Peroxisome proliferation only occurred in rats and mice maybe to PPARs activation	1996	Richert et al. [83]
				Male CD1 mice
				Male beagle dogs

Abbreviations: 2,4-D, 2,4-Dichlorophenoxyacetic acid; ACC, acetyl Co-A carboxylase; ACO, acyl-CoA oxidase; AhR, aryl hydrocarbon receptor; AR, androgen receptor; AOX, alternative oxidase; C/EBP-β, CCAAT enhancer binding protein beta; CAR, constitutive androstane receptor; CPT-1, carnitine palmitoyltransferase I; FABP4, fatty acid-binding protein 4; FAS, fatty acid synthase; KO, knock out; LPL, lipoprotein lipase; MDA, malondialdehyde; PP, peroxisome proliferator; 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; SD, Sprague Dawley; SREBP-1C, sterol regulatory element-binding protein 1; TBT, tributyltin; TC, total cholesterol; TG, triglycerides; TNF-α, tumor necrosis factor alpha; TPT, Triphenyltin.