Closer association of mitochondria with lipid droplets in hepatocytes and activation of Kupffer cells in resveratrol-treated senescence-accelerated mice

Abstract

Resveratrol has been extensively investigated because of its beneficial effects in delaying age-related diseases, thus extending the lifespan, possibly by mimicking calorie restriction. For this study, cell biological techniques were used to examine how resveratrol influenced hepatocytes in a senescence-accelerated mouse P10 (SAMP10), treated from 35 to 55 weeks of age, with special emphasis on the relationship between mitochondria and lipid droplets. Survival ratio, body weight and food intake of SAMP10 did not differ significantly between the control and resveratrol-treated groups. Compared with the control, the treated livers were altered significantly, as follows. Lipid droplets were reduced and mitochondria were increased in number in hepatocytes. Phosphorylation of acetyl-CoA carboxylase and the expression of both the mitochondrial ATP synthase β subunit and Mn superoxide dismutase (SOD2) were increased. Mitochondria, expressing more SOD2, were more tightly associated with lipid droplets, suggesting the enhancement of lipolysis through the activation of mitochondrial functions. Cathepsin D expression was less in hepatocytes but enhanced in Kupffer cells, which were increased in number and size with more numerous lysosome-related profiles. Together, resveratrol may activate mitochondria resulting in consuming lipids, and may also activate Kupffer cells by which a beneficial milieu for hepatocytes may be created. Both might be related to improvement in the functioning of the liver, which is the organ that is central to metabolic regulation.

Ultrastructural changes in the rabbit liver induced by carbamate insecticide bendiocarb

“…They were surrounded by mitochondria, particularly on day 3. Ohsaki et al [33] and Shiozaki et al [34] also observed lipid droplets associated with mitochondria and peroxisomes and assumed that this arrangement is probably related to the provision of lipids for b-oxidation in mitochondria and peroxisomes.…”

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

“…Conversely, CR has been reported to induce a significant increase in the number of mitochondria per cell (López-Lluch et al, 2006). Resveratrol, a partial CR mimetic, had the same effect in middle-aged mice fed with a high diet (Baur et al, 2006) as well as in senescence-accelerated mice (Shiozaki et al, 2011). Consistent with these results, we found significant increases in mitochondrial mass and in the mean number of mitochondria per hepatocyte in all CR groups regardless of dietary fat when compared with AL controls.…”

Hepatic ATGL mediates PPAR-α signaling and fatty acid channeling through an L-FABP independent mechanism

“…ATGL knockdown resulted in a downregulation of all PPAR-␣ target genes examined, with skeletal muscle ( 38 ). When lipolysis is activated with resveratrol in hepatocytes, more mitochondria are observed to directly attach to LDs than those treated with vehicle ( 39 ). Notably, perilipin 5, a LD protein commonly found in oxidative tissues, plays an important role in linking LDs to mitochondria in cardiomyocytes and muscle tissues ( 40,41 ).…”