Closer association of mitochondria with lipid droplets in hepatocytes and activation of Kupffer cells in resveratrol-treated senescence-accelerated mice |
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Authors: | Motoko Shiozaki Naoya Hayakawa Masahiro Shibata Masato Koike Yasuo Uchiyama Takahiro Gotow |
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Institution: | (1) Laboratory of Cell Biology, College of Nutrition, Koshien University, Takarazuka, Hyogo 665-0006, Japan;(2) Division of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan;(3) Department of Molecular Pathology, Osaka University Graduate School of Medicine and Health Science, Suita, Osaka 565-0871, Japan;(4) Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8122, Japan;(5) Department of Cell Biology and Neuroscience, Juntendo University School of Medicine, Tokyo 113-8421, Japan; |
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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. |
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