Review Article

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 subtypePesticideChemical classificationType of pesticideModel of studyItemYearReferences

PPARαMethidathionOrganophosphateInsecticideMale B6C3F1 miceThese pesticides not active PPARα in a tumorigenesis process2022Rooney et al. [103]
Fenthion
Parathion
FibronilPhenylpyrazoleInsecticideMale albino ratsUp-regulated FABP, ACC1, and PPARα2021Wasef et al. [80]
CarbendazimCarbamateFungicideMale zebrafish (Danio rerio)Level of glucose decreased and PPARα, ACO, CPT1 were not affected2020Bao et al. [91]
BoscalidAnilideFungicideZebrafish (Danio rerio)Decrease the content of TG and cholesterol by accelerating lipolysis; and inhibiting lipogenesis, via the regulation of PPARα2019Qian et al. [95]
PermethrinPyrethroidInsecticideFemale C57BL/6N wild-type or PPARα (KO) miceIncrease expression of PPARα in hepatocytes and KO mice the effect decreases2019Kondo et al. [63]
PropaquizafopAriloxiphenoxypropionateHerbicideMale SD wild-type or PPARα (KO) ratsPPARα regulates the biochemical and histological changes in the liver in hepatocarcinogenesis2018Strupp et al. [98]
PropamocarbCarbamateFungicideMale C57bL/6J miceDecrease PPARα and increase hepatic bile acids with a change of energy metabolism and the gut microbiota2018Wu et al.89
2,4-DOrganochlorineHerbicideMale Sv/129 wild-type or PPARα-null miceInduce testicular toxicity due to disruption of cholesterol/testosterone homeostasis in Leydig cells via PPARα2016Harada et al. [109]
OxadiazonOxadiazolHerbicideMale C3H/HeNCrl and CAR (KO) micePPARα and CAR are involved in the development of liver tumors2016Kuwata et al. [99]
ToxapheneOrganochlorineInsecticideMale B6C3F1 miceInduce mouse liver tumors, increase CAR, AhR but not PPARα target genes2015Wan et al. [102]
MyclobutanilTriazoleFungicideMale Wistar Han IGS ratsPerturb fatty acid and steroid metabolism in the liver predominantly through the CAR, PPARα, and PXR signaling pathways.2009Goetz and Dix [93]
Propiconazole
Triadimefon
Methyl thiophanateThioallophanateFungicideMale lizard (Podarcis sicula)Increase AOX and PPARα2006Buono et al. [92]
PPARβ/δAtrazineTriazineHerbicideXenopus leavis tadpolesIncrease PPARβ/δ, which is associated with the conversion of lipid and proteins into energy2011Zaya et al. [94]
PPARγDDTOrganophosphateInsecticideMale SD ratsDecrease PPARγ expression2022Al-Obaidi [79]
DDE
BromuconazoleTriazoleFungicideMale SD ratsDecrease the TG synthesis via inhibiting the PPARγ pathway2021Wu et al. [18]
TBTOrganotionAntifoulingMale C57BL/6 miceActivate PPARγ, increase lipid accumulation and the expression of lipid metabolism2021Jie et al. [65]
DieldrinOrganochlorineInsecticideMale C57BL/6 miceNo affect the genes regulated by PPARγ in hepatocarcinogenesis2020Wang et al. [97]
ParaquatDipiridileHerbicideMale Wistar ratsActivation of PPARγ with pioglitazone, decreases the concentrations of MDA (a lipid peroxidation marker)2020Amin et al. [107]
MonocrotophosOrganophosphateInsecticideMale CFT-Wistar ratsIncrease lipid content in the liver, PPARγ, ACC, and FAS2020Nagaraju et al. [85]
TPTOrganotionAntifoulingXenopus tropicalis embryosTPT exposure reversed some impacts induced by PPARγ overexpression2018Zhu et al. [110]
TBTOrganotionAntifoulingFemale Wistar ratsAbnormal ovarian adipogenesis with increased cholesterol levels, lipid accumulation, PPARγ, C/EBP-β, and Lipin-12018de Araújo et al. [77]
TBTOrganotionAntifoulingMale C57bL/6J miceIncrease mRNA expression of the PPARγ target genes Fabp4, Plin12017Baker et al. [76]
MancozebDithiocarbamateFungicideSwiss albino miceAffect PPARγ and increased the cholesterol and TG2014Bhaskar and Mohanty [78]
ImidaclopridNeonicotinoidInsecticideNo affinity to PPARγ
ParaquatDipiridileHerbicideMale Wistar ratsAtorvastatin reduces the inflammation produced by pesticide, via PPARγ2014Malekinejad et al. [131]
PronamideBenzamideHerbicideMale CD-1 miceThe MoA of hepatocarcinogenesis although to PPARγ and CAR2014LeBaron et al. [100]
NitrofenDiphenyl etherHerbicidePregnant rats and their fetusDown-regulated PPARγ and altered late gestation possibly due to impair lung development and maturation2012Gosemann et al. [132]
ParaquatDipiridileHerbicidePPARγ heterozygous mice (PPARclox/lox/aP2-Cre)Reduce expression of PPARγ, improve insulin sensitivity, and increased resistance to paraquat-induce oxidative stress2008Luo et al. [105]
TBTOrganotionAntifoulingPregnant C57BL/6J mice and their pupsIncrease the number of adipocytes and lipid accumulation through RXR and PPARγ2006Grün et al. [130]
PPARα PPARγImidaclopridNeonicotinoidsInsecticideZebrafish (Danio rerio)Inhibit the growth of zebrafish and alters the levels of glycolipid metabolism and oxidative stress; reduce the expression of PPARα and PPARγ2021Luo et al. [96]
Endosulfan sulfateOrganochlorineInsecticidePregnant CD-1 mice and their male pupsIn high and low-fat diet, PPARα and its target gene Cpt1a are increased, but not modify PPARγ2021Yan et al. [87]
ChlorpyrifosOrganophosphateInsecticideMale zebrafish (Danio rerio)Decrease PPARα and PPARγ, due to lipid metabolism disorders that are associated with gut oxidative stress and microbiota dysbiosis2019Wang et al. [86]
AtrazineTriazineHerbicideMale Kunming miceInduce nephrotoxicity via modulating CYP450, PPARα, PPARγ, AhR, CAR, and PXR2018Xia et al. [108]
Lambda cyhalothrinPyrethroidInsecticideMale albino ratsUp-regulate mRNA expression levels of PPARα, PPARγ, TNF-α FAS, and SREBP-1C2016Moustafa and Hussein [81]
TriphenyltinOrganotionAntifoulingWood frog (Lithobates sylvaticus)In chronic exposure, increase the expression of PPARα, PPARγ, FAS, and LPL2013Higley et al. [75]
PPARα PPARγ PPARβ/δGlyphosateOrganophosphateHerbicideTilapia (Oreochromis niloticus)Increase lipid content, alter redox status in liver, the genes involved in ion transport, lipid metabolism, and PPAR signaling pathway2022Jia et al. [74]
AllethrinPyrethroidsInsecticideMale Sprague Dawley ratsNo activation of nuclear receptor in liver2019Fujino et al. [30]
Bioresmethrin
Cis-permetryn
Cypermethrin
Deltamethrin
Fenvalerate
Trans-permetryn
Phenothrin
DifenoconazoleTriazoleFungicideMarine medaka (Oryzias melastigma)Increase the expression of receptor PPARα, PPARβ/δ, PPARγ, and increase lipid levels in muscle but not in liver2016Dong et al. [73]
PaclobutrazolTriazoleFungicideMale rockfish (Sebasticus marmoratus)Increase total lipid, TG, TC, free fatty acid and up-regulate PPARα, PPARβ/δ, PPARγ, AR, FAS, FABP4, ACC2013Sun et al. [72]
AtrazineTriazineHerbicideCFI miceNo interact with the receptors α, β/δ, or γ2003Devos et al. [104]
DiclofopAriloxiphenoxypropionateHerbicideMale Wistar rats (Pzh:WIS)Increase the number of peroxisome and are a rodent PP2001Palut et al. [101]
OxadiazonOxadiazolHerbicideMale SD ratsPeroxisome proliferation only occurred in rats and mice maybe to PPARs activation1996Richert 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.