Bcl-2 and Bax are involved in the sympathetic protection of brown adipocytes from obesity-linked apoptosis.
Obesity is linked to functional brown adipose tissue (BAT) atrophy, partially due to adipocyte apoptosis. The brown adipocytes of obese rats have lower Bcl-2/Bax mRNA and protein ratios than those of their lean littermates. Exposure to a low temperature for three days markedly increased the Bcl-2/Bax ratio, by increasing the noradrenergic output to BAT, which has previously been shown to reduce apoptotic cell death. This effect could be mimicked in vitro by the addition of noradrenaline (NA) to brown adipocytes differentiated in culture. Micromolar NA concentrations increased the Bcl-2/Bax mRNA and protein ratios, and protected against serum deprivation-induced apoptosis. We conclude that NA acts by modulating bcl-2 and bax gene expression.
Center for Study and Research on Obesity, Department of Pharmacology, L.I.T.A. Vialba, School of Medicine, University of Milan, Italy.
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Briscini
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Tonello
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Carruba
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Nisoli
D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D005786:Gene Expression Regulation; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D009765:Obesity / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011924:Rats, Zucker; D013696:Temperature; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D051028:bcl-2-Associated X Protein
C494828:Bax protein, rat; D016895:Culture Media, Serum-Free; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein; D009638:Norepinephrine