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The Hepatic Mitochondrial Alterations Exacerbate Meta-Inflammation in Autism Spectrum Disorders

2022; Multidisciplinary Digital Publishing Institute; Volume: 11; Issue: 10 Linguagem: Inglês

10.3390/antiox11101990

2076-3921

Giovanna Trinchese, Fabiano Cimmino, Gina Cavaliere, Angela Catapano, Chiara Fogliano, Adriano Lama, Claudio Pirozzi, Claudia Cristiano, Roberto Russo, Lidia Petrella, Rosaria Meli, Giuseppina Mattace Raso, Marianna Crispino, Bice Avallone, Maria Pina Mollica,

Child Nutrition and Feeding Issues

The role of the liver in autism spectrum disorders (ASD), developmental disabilities characterized by impairments in social interactions and repetitive behavioral patterns, has been poorly investigated. In ASD, it has been shown a dysregulation of gut-brain crosstalk, a communication system able to influence metabolic homeostasis, as well as brain development, mood and cognitive functions. The liver, with its key role in inflammatory and metabolic states, represents the crucial metabolic organ in this crosstalk. Indeed, through the portal vein, the liver receives not only nutrients but also numerous factors derived from the gut and visceral adipose tissue, which modulate metabolism and hepatic mitochondrial functions. Here, we investigated, in an animal model of ASD (BTBR mice), the involvement of hepatic mitochondria in the regulation of inflammatory state and liver damage. We observed increased inflammation and oxidative stress linked to hepatic mitochondrial dysfunction, steatotic hepatocytes, and marked mitochondrial fission in BTBR mice. Our preliminary study provides a better understanding of the pathophysiology of ASD and could open the way to identifying hepatic mitochondria as targets for innovative therapeutic strategies for the disease.