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Long-Term Aspartame Administration Leads to Fibrosis, Inflammasome Activation, and Gluconeogenesis Impairment in the Liver of Mice.


ABSTRACT:

Background

Aspartame is an artificial sweetener used in foods and beverages worldwide. However, it is linked to oxidative stress, inflammation, and liver damage through mechanisms that are not fully elucidated yet. This work aimed to investigate the effects of long-term administration of aspartame on the oxidative and inflammatory mechanisms associated with liver fibrosis progression in mice.

Methods

Mice were divided into two groups with six animals each: control and aspartame. Aspartame (80 mg/kg, via oral) or vehicle was administrated for 12 weeks.

Results

Aspartame caused liver damage and elevated serum transaminase levels. Aspartame also generated liver fibrosis, as evidenced by histology analysis, and pro-fibrotic markers' upregulation, including transforming growth factor ? 1, collagen type I alpha 1, and alpha-smooth muscle actin. Furthermore, aspartame reduced nuclear factor erythroid 2-related factor 2 (Nrf2) activation and enzymatic antioxidant activity and increased lipid peroxidation, which triggered NOD-like receptor containing protein 3 (NLRP3) inflammasome activation and p53 induction. Furthermore, aspartame reduced peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1?) levels, possibly through p53 activation. This PGC-1? deficiency could be responsible for the changes in lipid profile in serum, total lipid accumulation, and gluconeogenesis impairment in liver, evidenced by the gluconeogenic enzymes' downregulation, thus causing hypoglycemia.

Conclusions

This work provides new insights to understand the mechanisms related to the adverse effects of aspartame on liver tissue.

SUBMITTER: Finamor IA 

PROVIDER: S-EPMC7911935 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Publications

Long-Term Aspartame Administration Leads to Fibrosis, Inflammasome Activation, and Gluconeogenesis Impairment in the Liver of Mice.

Finamor Isabela A IA   Bressan Caroline A CA   Torres-Cuevas Isabel I   Rius-Pérez Sergio S   da Veiga Marcelo M   Rocha Maria I MI   Pavanato Maria A MA   Pérez Salvador S  

Biology 20210122 2


<h4>Background</h4>Aspartame is an artificial sweetener used in foods and beverages worldwide. However, it is linked to oxidative stress, inflammation, and liver damage through mechanisms that are not fully elucidated yet. This work aimed to investigate the effects of long-term administration of aspartame on the oxidative and inflammatory mechanisms associated with liver fibrosis progression in mice.<h4>Methods</h4>Mice were divided into two groups with six animals each: control and aspartame. A  ...[more]

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