The Role of Mitochondria in Sex-Dependent Differences in Hepatic Steatosis and Oxidative Stress in Response to Cafeteria Diet-Induced Obesity in Mice

Abstract

Female mice fed a cafeteria diet (FCaf) develop higher liver steatosis and oxidative stress than males (MCaf) as a consequence of unresolved ER stress. Here, we investigated whether mitochondria play a role in this sex difference. The isolated mitochondria from FCaf showed more signs of oxidative stress than those of MCaf, correlated with a reduced content of GSH, increased amount of reactive oxygen species (ROS), and lower activities of enzymes involved in ROS neutralisation. Mitochondria from FCaf and MCaf livers exhibited lower rates of succinate-driven state III respiration and reduced ATPase activity in intact coupled mitochondria compared to their controls fed a standard diet (FC and MC), with no differences between the sexes. Fatty acid oxidation in mitochondria and peroxisomes was higher in MCaf and FCaf compared to their respective controls. In the intact perfused liver, there was no difference between sex or diet regarding the fatty acid oxidation rate. These results indicated that cafeteria diet did not affect mitochondrial energy metabolism, even in FCaf livers, which have higher steatosis and cellular oxidative stress. Nevertheless, the increase in mitochondrial ROS generation associated with a decrease in the antioxidant defence capacity, probably contributes to inducing or reinforcing the ER stress in FCaf livers.

The XBP1-MARCH5-MFN2 Axis Confers ER Stress Resistance by Coordinating Mitochondrial Fission and Mitophagy in Melanoma

“…Of note, mitochondrion is the crucial organelle of which the structure and function are highly connected with ER, and is relatively sensitive to pathological stimuli that induce ER stress. The communication between ER and mitochondria is greatly implicated in metabolic diseases like diabetes and obesity with unsolved ER stress and mitochondrial dysfunction [39][40][41][42]. Extending to this, our present study unveiled the role of mitochondrial dynamics and mitophagy in mediating the resistance to ER stress, highlighting the importance of ER-mitochondria crosstalk in cancer pathogenesis.…”

Comportamento doentio em camundongos obesos

“…Trata-se de uma alimentação característica do estilo ocidental, particularmente rica em gordura e carboidratos que normalmente leva à hiperfagia e ganho de peso e é amplamente empregada para induzir a obesidade experimental. Portanto, esse modelo se assemelha à obesidade humana, na qual dietas com alto valor lipídico e sobrecarga de carboidratos são o fator causador do desenvolvimento da obesidade (Scoaris et al, 2010;Maeda Junior et al, 2018;Morais Mewes et al, 2019). O peso do tecido adiposo também é um indicador de obesidade.…”

“…Como citado acima, no presente estudo, a dieta de cafeteria levou ao aumento do peso do tecido adiposo epididimal e retroperitoneal, assim como no estudo desenvolvido por Morais Mewels e colaboradores (2019). Esse aumento está diretamente relacionado à celularidade tecidual, pois uma dieta rica em carboidratos e lipídios promove aumento do tamanho celular e do número de adipócitos (Scoaris et al, 2010, Morais Mewes et al, 2019.…”

Swimming training mitigates the sex‐specific hepatic disruption caused by a high‐calorie diet: The putative modulation of Nrf2/Keap‐1 pathway in male mice

“…Sex differences might contribute to the oxidant action of saturated fat or carbohydrate diets and, consequently, to different vulnerability to hepatic steatosis in male and female mice 5 . Several variations, including metabolism, gene expression, cellular differentiation, anatomical structures, hormonal, and stress responses, are influenced by a sex‐specific manner 6 …”