Mitochondrial ultrastructure and markers of dynamics in hepatocytes from aged, calorie restricted mice fed with different dietary fats

Abstract

In this paper we analyzed changes in hepatocyte mitochondrial mass and ultrastructure as well as in mitochondrial markers of fission/fusion and biogenesis in mice subjected to 40% calorie restriction (CR) for 18 months versus ad libitum-fed controls. Animals subjected to CR were separated into three groups with different dietary fats: soybean oil (also in controls),fish oil and lard. Therefore, the effect of the dietary fat under CR was studied as well. Our results show that CR induced changes in hepatocyte and mitochondrial size, in the volume fraction occupied by mitochondria, and in the number of mitochondria per hepatocyte. Also, mean number of mitochondrial cristae and lengths were significantly higher in all CR groups compared with controls. Finally, CR had no remarkable effects on the expression levels of fission and fusion protein markers. However, considerable differences in many of these parameters were found when comparing the CR groups, supporting the idea that dietary fat plays a relevant role in the modulation of CR effects in aged mice.

Dietary fat composition influences glomerular and proximal convoluted tubule cell structure and autophagic processes in kidneys from calorie-restricted mice

“…Thus, lard extended longevity compared to soy and fish oils (López‐Domínguez et al ., 2015a) pointing to a role of specific dietary components in determining lifespan of mice fed CR diets. To assess the precise effects of this nutritional intervention at a tissue level, we analyzed the impact of dietary fat in different organs and tissues from animals fed these same diets (see Khraiwesh et al ., 2013 and Khraiwesh et al ., 2014 and López‐Domínguez et al ., 2013, 2015b). In this paper, we studied kidney structure and biology in an attempt to determine the possible role this organ plays in health and aging in CR mice fed diets that differ in fat composition.…”

“…These results together with those concerning cellular and nuclear size, likely indicate differential adaptation mechanisms to the conditions imposed by CR. Interestingly, the response of PCT cells (in terms of cell and nuclear size and mitochondrial mass) to the different dietary fats under CR described here was similar to that found in mice hepatocytes (Khraiwesh et al ., 2013, 2014). …”

Effects of Sex, Strain, and Energy Intake on Hallmarks of Aging in Mice

“…In mouse hepatocytes we have shown that aging induces a decrease in mitochondrial mass together with reduction in individual mitochondria size and changes in the expression pattern of proteins related to fusion/fission dynamics (Khraiwesh et al, 2014; Khraiwesh et al, 2013; Lopez-Lluch et al, 2006). However, 40% CR alleviated most of these effects by inducing increases in individual mitochondria size and volume fraction occupied by mitochondria.…”

The influence of dietary fat source on liver and skeletal muscle mitochondrial modifications and lifespan changes in calorie-restricted mice

“…Mitochondrial shape also varied with CR in old mice, with more spherical mitochondria being found in all the CR groups regardless of dietary fat. Mean number of cristae per mitochondria and mean crista length were also increased when comparing CR animals with controls and this change was also affected by dietary fat, since a sequential increase in cristal length was found with CR-Soy > CR-Lard > CR-Fish > control (Khraiwesh et al, 2014). These results contrast with those reported in young mice subjected to 6 months of CR where mitochondria of increased size were found only in the CR-Lard group (Khraiwesh et al, 2013).…”

“…Interestingly, the effect of CR on fission proteins was exacerbated by lard and diminished by fish oil, even while liver mitochondria were the largest in CR-Lard compared with the other dietary groups (Khraiwesh et al, 2013). However, these dietary fat-induced differences in markers of mitochondrial dynamics were attenuated by aging (Khraiwesh et al, 2014). …”