Review
Copyright ©The Author(s) 2017.
World J Biol Chem. May 26, 2017; 8(2): 108-119
Published online May 26, 2017. doi: 10.4331/wjbc.v8.i2.108
Table 1 Chemicals, sources and routes of exposure, examples, and some demonstrated metabolic effects
ChemicalsSourcesExamplesSome demonstrated metabolic effects
AlkylphenolsLubricating oil additives; detergents; emulsifiers, pesticides; plastics Exposure occurs via water drinking and food consumption[67]NPEstrogenic activities[68]
DioxinsByproducts of industries from incomplete combustion; release during natural events such as wood burning and volcanic eruption Diet is the main route of exposure[69]TCDDHepatic steatosis[70] and fibrosis[71]; increased adipocyte differentiation (in vitro)[72]
Flame retardantsUsed in electronic equipment, furniture, plastics…and then, present in dust, air and soil Dermal exposure is a significant route of exposure[73]Penta-BDEDecrease in glucose oxidation[74]
Organotin compoundUsed as biocide in anti-fouling paint, heat stabilizer in Poly Vinyl Chloride Exposure mainly by consumption of seafood[75]TBTInduction of adipocyte differentiation[76]; increase of body weight and hepatic steatosis[77]; transgenerational effects on fat depots and hepatic steatosis[39]
Phenolic derivativesPlastic components, cosmetics, disinfectants, thermal paper receipts Food and water drinking are the major routes of exposure[78]BPA, BPSEstrogenic activities[79]; alteration of pancreatic β cell functions and hepatic insulin signaling (BPA)[47]; induction of lipid accumulation and differentiation (in vitro, BPS)[80]
PesticidesDue to their persistence, accumulation in soils and sediments; bioaccumulation throughout the food chainDDT and its metaboliteAlteration of systemic glucose homeostasis and hepatic lipid metabolism[83]; Glucose intolerance, hyperinsulinemia, dyslipidemia and altered bile acid metabolism[84]
Processing of agriculture products (banned in Europe); Dietary sources[81] as well as inhalation and dermal routes of exposure[82]Atrazine (C8H14ClN5)Increased body weight, intra-abdominal fat and insulin resistance[85]
PhthalatesPlastic components, cosmetics, medical equipment; Exposure mainly derives from dietary sources for high molecular weight phthalates (e.g., DEHP) and non-dietary sources for low molecular weight phthalates (e.g., DBP)[86]DBP, DEHPAnti-androgenic effects[87]; Transgenerational inheritance of obesity[88]; Increased adipocyte differentiation[89]
PCBsSynthetic compounds now banned but previously used, in particular, in electrical capacitors; still release in environment due to their persistence Food consumption contributes over 90% of total exposure[90]PCB153 (C12H4Cl6), PCB170 (C12H3Cl7), PCB187 (C12H3Cl7) (non dioxin-like); PCB126 (C12H5Cl5), PCB77 (C12H6Cl4) (dioxin-like)Increased adipocyte differentiation (in vitro); increased body weight, adipocyte hypertrophy[72]; increased hepatic steatosis and visceral adiposity in the context of a lipid-enriched diet[91]
PAHByproducts of incomplete combustion of organic compounds (cigarette smoke, wood burning, overcooked meat…) Contamination primarily through inhalation and consumption of certain foods[92]B[a]PCarcinogenic Alteration of estrogen metabolism in human mammary carcinoma-derived cell lines[93] Inhibition of lipolysis, increased fat accumulation and weight gain[94]
PFAAWater and oil repellent; used for treatments of clothing, insulation and fire-fighting foams Oral and dermal exposure[95]PFOAElevated serum leptin and insulin; overweight after in utero exposure[96]
Table 2 Metabolic characteristics of mice deficient in some nuclear receptors1
Insulin statusObesityNo body weight change
Insulin resistanceERα (-/-) in both males and females[38]
No difference in insulin sensitivityAR (-/-) in males only[97]
Improved insulin sensitivityERβ (-/-) (study on males only)[26]CAR activation (study on males only in HFD context, activation by TOBOBOP)[99]
ERRβ (deletion in neurons; study on males only)[98]AhR (-/-) (studies on males only)[100]
AhR (-/-) (studies on males only, in HFD context)[101]
PPARα (-/-) (studies on males only, in HFD context)[102]
PXR (-/-) (studies on males only, in HFD context)[103]
Table 3 Interactions of some nuclear receptors with endocrine disruptors
Nuclear receptorsInteractions with chemicals
Steroid receptors
ERBPA (Erα[38], GPR30[104])
ARBPA[105]
GRBPA; phthalates[106]
PRBPA[107]
TRBPA[108]; brominated flame retardants, BFR[109]
RXR heterodimers
PPARαPhthalates[110]; polyfluoroalkyl compounds[111]; pyrethrins[112]
PPARγPhthalates[110,113]; organotins[76]; BPA[114]
FXRPyrethroids[115]
CARPhthalates[116,117]
LXRαPhthalates; BPA[118]
PXRPhthalates; BPA[119,120]
Other receptors
AhRDioxines; PCB dioxin-like[72,121,122]