Whole life exposure to low dose cadmium alters diet-induced NAFLD.
Toxicol Appl Pharmacol
; 436: 115855, 2022 02 01.
Article
en En
| MEDLINE
| ID: mdl-34990729
ABSTRACT
Nonalcoholic fatty liver disease (NAFLD) is a major global public health concern affecting more than 25% of the world's population. Although obesity and diabetes are major risk factors for NAFLD, they cannot account for all cases, indicating the importance of other factors such as environmental exposures. Cadmium (Cd) exposure is implicated in the development of NAFLD; however, the influence of early life, in utero Cd exposure on the development of diet-induced NAFLD is poorly understood. Therefore, we developed an in vivo, multiple-hit model to study the effect of whole-life, low dose Cd exposure on high fat diet (HFD)-induced NAFLD. Adult male and female C57BL/6 J mice fed normal diets (ND) were exposed to 0, 0.5 or 5 ppm Cd-containing drinking water for 14 weeks before breeding. At weaning, offspring were fed ND or HFD and continued on the same drinking water regimen as their parents for 24 weeks. Cd exposure at different concentrations differentially altered HFD-associated adverse health effects, including liver injury. HFD-induced increased body weight, decreased glucose tolerance. Liver injury and lipid deposition were exacerbated by 5 ppm Cd exposure but attenuated by 0.5 ppm Cd exposure. Further, HFD blunted the response of metallothionein, a major Cd detoxification protein, in mice exposed to 5 ppm Cd but enhanced the response in mice exposed to 0.5 ppm Cd, suggesting a possible mechanism for Cd alteration of HFD-induced NAFLD. These results confirm the multi-hit nature of NAFLD and show whole life, low dose Cd exposure alters HFD-induced NAFLD with outcomes dependent on Cd concentration.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Cadmio
/
Enfermedad del Hígado Graso no Alcohólico
/
Hígado
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
Toxicol Appl Pharmacol
Año:
2022
Tipo del documento:
Article