The impact of mitochondrial dysfunction on metabolic and inflammatory profile in an animal model of the autism spectrum disorders (ASD)

In the last decade, research interest has focused on understanding the etiology and pathogenesis of the autism spectrum disorders (ASD), a developmental disability characterized by impairments in social interactions and repetitive behavioral patterns. Inflammation and mitochondrial dysfunctions in the brain and periphery have been identified as causative factors for impaired cellular functions in ASD, along with a dysregulation of gut- brain crosstalk. Indeed, mitochondria are pivotal mediators of environmental-genetic interactions that regulate healthy metabolism. In this complex framework, the liver is a key organ controlling whole-body inflammatory and metabolic homeostasis. Therefore, we investigated in an animal model of ASD (BTBR mice) the involvement of hepatic mitochondria in the regulation of inflammatory state and hepatic damage. C57Bl/6J and BTBR mice were fed with standard diet, monitoring daily body weights and food intake. Energy balance, inflammation, hepatic mitochondrial function, oxidative stress, and liver histological analyses were assessed. BTBR mice showed increased inflammation and oxidative stress linked to hepatic mitochondrial dysfunction, steatotic hepatocytes, marked mitochondrial fission. Our findings, underscoring the involvement of impaired hepatic metabolism in systemic inflammation of BTBR mice, are of great help in understanding the pathophysiology of ASD, and in developing new diagnostic tools and potential treatment for the disease