Cellular and Molecular Biology


The origin of lipofuscin in brown adipocytes of hyperinsulinaemic rats: the role of lipid peroxidation and iron

Milica Markelic1, Ksenija Velickovic1, Igor Golic1, Waltraud Klepal2, Vesna Otasevic3, Ana Stancic3, Aleksandra Jankovic3, Milica Vucetic3, Biljana Buzadzic3, Bato Korac3 and Aleksandra Korac1

1Faculty of Biology, Centre for Electron Microscopy, University of Belgrade, Serbia, 2Faculty of Life Sciences, Cell Imaging and Ultrastructure Research Centre, University of Vienna, Austria and 3Institute for Biological Research “Sinisa Stankovic”, University of Belgrade, Serbia.

Offprint requests to: Prof Dr. Aleksandra Korac, Faculty of Biology, Centre for Electron Microscopy, University of Belgrade, Studentski trg 16, 11000 Belgrade, Serbia. e-mail: aleksandra.korac@bio.bg.ac.rs

Summary. The aim of this study was to investigate lipofuscin origin in brown adipocytes of hyper-insulinaemic rats and the possible role of lipid peroxidation and iron in this process. Ultrastructural examination revealed hyperinsulinaemia-induced enhancement in the lipofuscin production, accompanied by an increase of mitochondrial damage in brown adipocytes. Extensive fusions of lipid droplets and mitochondria with lysosomes were also observed. Confocal microscopy showed lipofuscin auto-fluorescence emission in brown adipose tissue (BAT) after excitation at 488 nm and 633 nm, particularly in the insulin-treated groups. The presence and distribution of lipid peroxidation product, 4-hydroxy-2-nonenal (4-HNE), in brown adipocytes was assessed by immunohistochemical examination revealing its higher content after treatment with insulin. The iron content was quantified by electron dispersive X-ray analysis (EDX) showing its higher content in the hyper-insulinaemic groups. The ultrastucture of the majority of lipofuscin granules suggests their mitochondrial origin, which was additionally confirmed by their co-localization with ATP synthase. In conclusion, our results suggest that increased lipofuscinogenesis in the brown adipocytes of hyperinsulinaemic rats is a consequence of lipid peroxidation, mitochondrial damage and iron accumulation
. Histol Histopathol 28, 493-503 (2013)

Key words: Brown adipocyte, Lipofuscin, Hyper-insulinaemia, Iron

DOI: 10.14670/HH-28.493