Dynamic regulation of mitochondrial network and oxidative functions during 3T3-L1 fat cell differentiation

Autor: Mireille Weitheimer, Annie Durand, Mélissa Flamment, Lucie Duluc, Jennifer Rieusset, Mélanie Priou, Gilles Simard, Yves Malthièry, Pierre-Henri Ducluzeau, Raffaela Soleti, Ramaroson Andriantsitohaina, Fransceco Iacobazi
Přispěvatelé: Université d'Angers (UA), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon
Rok vydání: 2011
Předmět:
STRESS
Physiology
[SDV]Life Sciences [q-bio]
Gene Expression
Mitochondrion
Biochemistry
Mice
0302 clinical medicine
Lipid droplet
Adipocytes
TRANSCRIPTION
NRF1
Membrane Potential
Mitochondrial
0303 health sciences
Adipogenesis
Microscopy
Video
Cell Differentiation
General Medicine
Catalase
Mitochondria
ADIPOSE-TISSUE
OBESITY
OXYGEN SPECIES PRODUCTION
Adiponectin
Oxidation-Reduction
BIOGENESIS
Citrate (si)-Synthase
Oxidative phosphorylation
Biology
Nitric Oxide
Electron Transport Complex IV
Mitochondrial Proteins
03 medical and health sciences
Oxygen Consumption
Lipid oxidation
3T3-L1 Cells
Animals
Enzyme Assays
030304 developmental biology
Mitochondrial network
Glutathione Peroxidase
NITRIC-OXIDE
L-Lactate Dehydrogenase
Superoxide Dismutase
TFAM
Fat cell differentiation
DYSFUNCTION
Lipid metabolism
Fatty Acid Synthases
Reactive Oxygen Species
030217 neurology & neurosurgery
Zdroj: Journal of Physiology and Biochemistry
Journal of Physiology and Biochemistry, Springer Verlag (Germany), 2011, 67 (3), pp.285-296. ⟨10.1007/s13105-011-0074-6⟩
ISSN: 1877-8755
1138-7548
Popis: International audience; Mitochondria have been shown to be impaired in insulin resistance-related diseases but have not been extensively studied during the first steps of adipose cell development. This study was designed to determine the sequence of changes of the mitochondrial network and function during the first days of adipogenesis. 3T3-L1 preadipocytes were differentiated into adipocytes without using glitazone compounds. At days 0, 3, 6, 9, and 12, mitochondrial network imaging, mitochondrial oxygen consumption, membrane potential, and oxidative phosphorylation efficiency were assessed in permeabilized cells. Gene and protein expressions related to fatty acid metabolism and mitochondrial network were also determined. Compared to preadipocytes (day 0), new adipocytes (days 6 and 9) displayed profound changes of their mitochondrial network that underwent fragmentation and redistribution around lipid droplets. Drp1 and mitofusin 2 displayed a progressive increase in their gene expression and protein content during the first 9 days of differentiation. In parallel with the mitochondrial network redistribution, mitochondria switched to uncoupled respiration with a tendency towards decreased membrane potential, with no variation of mtTFA and NRF1 gene expression. The expression of PGC1 alpha and NRF2 genes and genes involved in lipid oxidation (UCP2, CD36, and CPT1) was increased. Reactive oxygen species (ROS) production displayed a nadir at day 6 with a concomitant increase in antioxidant enzyme gene expression. This 3T3-L1-based in vitro model of adipogenesis showed that mitochondria adapted to the increased number of lipid droplets by network redistribution and uncoupling respiration. The timing and regulation of lipid oxidation-associated ROS production appeared to play an important role in these changes.
Databáze: OpenAIRE
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