4.5 Article

Aggravation of hepatic lipidosis in red-footed tortoise Chelonoidis carbonaria with age is associated with alterations in liver mitochondria

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1016/j.cbpb.2022.110731

Keywords

Non-alcoholic fatty liver disease; Mitochondrial dysfunction; Permeability transition pore; Melanin; Melanomacrophage; Captive reptiles; Turtles

Funding

  1. Sao Paulo Research Foundation (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo, FAPESP) [2017/05487-6, 2019/20855-7]
  2. FAPESP [2017/17728-8]

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Hepatic lipidosis is common in captive reptiles, leading to NAFLD-like liver diseases. This study found that adult captive red-footed tortoises exhibited higher levels of lipids, histopathological alterations, and compromised mitochondrial function compared to juveniles, indicating the progression to NASH. These findings highlight the importance of mitochondria in liver disease progression in reptiles.
The occurrence of hepatic lipidosis is commonly reported in different reptilian species, especially in animals under captivity. Liver accumulation of fat is associated with disorders, better described in mammals as non-alcoholic fatty liver diseases (NAFLD), ranging from simple steatosis, to non-alcoholic steatohepatitis (NASH), and to more severe lesions of cirrhosis and hepatocellular carcinoma. Mitochondria play a central role in NAFLD pathogenesis, therefore in this study we characterized livers of ad libitum fed captive red-footed tortoise Chelo-noidis carbonaria through histological and mitochondrial function evaluations of juvenile and adult individuals. Livers from adult tortoises exhibited higher levels of lipids, melanomacrophages centers and melanin than ju-veniles. The observed high score levels of histopathological alterations in adult tortoises, such as microvesicular steatosis, inflammation and fibrosis, indicated the progression to a NASH condition. Mitochondrial oxygen consumption at different respiratory states and with different substrates was 30 to 58% lower in adult when compared to juvenile tortoises. Despite citrate synthase activity was also lower in adults, cardiolipin content was similar to juveniles, indicating that mitochondrial mass was unaffected by age. Mitochondrial Ca2+ retention capacity was reduced by 70% in adult tortoises. Overall, we found that aggravation of NAFLD in ad libitum fed captive tortoises is associated with compromised mitochondrial function, indicating a critical role of the organelle in liver disease progression in reptiles.

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