Tatyana
11-01-2009, 09:48 PM
http://www.cell.com/cell-metabolism/abstract/S1550-4131(09)00229-0
Non-CpG Methylation of the PGC-1α Promoter through DNMT3B Controls Mitochondrial Density
Romain Barrès1 (http://www.cell.com/cell-metabolism/abstract/S1550-4131(09)00229-0#aff1), Megan E. Osler1 (http://www.cell.com/cell-metabolism/abstract/S1550-4131(09)00229-0#aff1), Jie Yan1 (http://www.cell.com/cell-metabolism/abstract/S1550-4131(09)00229-0#aff1), Anna Rune1 (http://www.cell.com/cell-metabolism/abstract/S1550-4131(09)00229-0#aff1), Tomas Fritz3 (http://www.cell.com/cell-metabolism/abstract/S1550-4131(09)00229-0#aff3), Kenneth Caidahl2 (http://www.cell.com/cell-metabolism/abstract/S1550-4131(09)00229-0#aff2), Anna Krook1 (http://www.cell.com/cell-metabolism/abstract/S1550-4131(09)00229-0#aff1), 4 (http://www.cell.com/cell-metabolism/abstract/S1550-4131(09)00229-0#aff4) and Juleen R. Zierath1 (http://www.cell.com/cell-metabolism/abstract/S1550-4131(09)00229-0#aff1), 4 (http://www.cell.com/cell-metabolism/abstract/S1550-4131(09)00229-0#aff4), http://www.cell.com/images/REcor.gif (http://www.cell.com/cell-metabolism/abstract/S1550-4131(09)00229-0#cor1), http://www.cell.com/images/REemail.gif ([email protected])
1 Department of Molecular Medicine and Surgery, Section for Integrative Physiology, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
2 Department of Molecular Medicine and Surgery, Section for Clinical Physiology, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
3 Centre of Family Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
4 Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
http://www.cell.com/images/REcor.gif (http://www.cell.com/cell-metabolism/abstract/S1550-4131(09)00229-0#bcor1)Corresponding author
Summary
Epigenetic modification through DNA methylation is implicated in metabolic disease.
Using whole-genome promoter methylation analysis of skeletal muscle from normal glucose-tolerant and type 2 diabetic subjects, we identified cytosine hypermethylation of peroxisome proliferator-activated receptor γ (PPARγ) coactivator-1 α (PGC-1α) in diabetic subjects.
Methylation levels were negatively correlated with PGC-1α mRNA and mitochondrial DNA (mtDNA). Bisulfite sequencing revealed that the highest proportion of cytosine methylation within PGC-1α was found within non-CpG nucleotides.
Non-CpG methylation was acutely increased in human myotubes by exposure to tumor necrosis factor-α (TNF-α) or free fatty acids, but not insulin or glucose.
Selective silencing of the DNA methyltransferase 3B (DNMT3B), but not DNMT1 or DNMT3A, prevented palmitate-induced non-CpG methylation of PGC-1α and decreased mtDNA and PGC-1α mRNA.
We provide evidence for PGC-1α hypermethylation, concomitant with reduced mitochondrial content in type 2 diabetic patients, and link DNMT3B to the acute fatty-acid-induced non-CpG methylation of PGC-1α promoter.
This is basically saying that healthy muscle cells can become like cells taken from people with diabetes when exposed to fat (palmitate), by permanently shutting off the genes that control fat burning, PGC-1 (DNA can't be transcribed when it is methylated, so hypermethylation is even worse).
It implies that diet changes your DNA, and specifically, that palmitate/palmitic acid/palm oil, shuts off one of your fat burning genes.
Palm oil is in a lot of foods.
Non-CpG Methylation of the PGC-1α Promoter through DNMT3B Controls Mitochondrial Density
Romain Barrès1 (http://www.cell.com/cell-metabolism/abstract/S1550-4131(09)00229-0#aff1), Megan E. Osler1 (http://www.cell.com/cell-metabolism/abstract/S1550-4131(09)00229-0#aff1), Jie Yan1 (http://www.cell.com/cell-metabolism/abstract/S1550-4131(09)00229-0#aff1), Anna Rune1 (http://www.cell.com/cell-metabolism/abstract/S1550-4131(09)00229-0#aff1), Tomas Fritz3 (http://www.cell.com/cell-metabolism/abstract/S1550-4131(09)00229-0#aff3), Kenneth Caidahl2 (http://www.cell.com/cell-metabolism/abstract/S1550-4131(09)00229-0#aff2), Anna Krook1 (http://www.cell.com/cell-metabolism/abstract/S1550-4131(09)00229-0#aff1), 4 (http://www.cell.com/cell-metabolism/abstract/S1550-4131(09)00229-0#aff4) and Juleen R. Zierath1 (http://www.cell.com/cell-metabolism/abstract/S1550-4131(09)00229-0#aff1), 4 (http://www.cell.com/cell-metabolism/abstract/S1550-4131(09)00229-0#aff4), http://www.cell.com/images/REcor.gif (http://www.cell.com/cell-metabolism/abstract/S1550-4131(09)00229-0#cor1), http://www.cell.com/images/REemail.gif ([email protected])
1 Department of Molecular Medicine and Surgery, Section for Integrative Physiology, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
2 Department of Molecular Medicine and Surgery, Section for Clinical Physiology, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
3 Centre of Family Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
4 Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
http://www.cell.com/images/REcor.gif (http://www.cell.com/cell-metabolism/abstract/S1550-4131(09)00229-0#bcor1)Corresponding author
Summary
Epigenetic modification through DNA methylation is implicated in metabolic disease.
Using whole-genome promoter methylation analysis of skeletal muscle from normal glucose-tolerant and type 2 diabetic subjects, we identified cytosine hypermethylation of peroxisome proliferator-activated receptor γ (PPARγ) coactivator-1 α (PGC-1α) in diabetic subjects.
Methylation levels were negatively correlated with PGC-1α mRNA and mitochondrial DNA (mtDNA). Bisulfite sequencing revealed that the highest proportion of cytosine methylation within PGC-1α was found within non-CpG nucleotides.
Non-CpG methylation was acutely increased in human myotubes by exposure to tumor necrosis factor-α (TNF-α) or free fatty acids, but not insulin or glucose.
Selective silencing of the DNA methyltransferase 3B (DNMT3B), but not DNMT1 or DNMT3A, prevented palmitate-induced non-CpG methylation of PGC-1α and decreased mtDNA and PGC-1α mRNA.
We provide evidence for PGC-1α hypermethylation, concomitant with reduced mitochondrial content in type 2 diabetic patients, and link DNMT3B to the acute fatty-acid-induced non-CpG methylation of PGC-1α promoter.
This is basically saying that healthy muscle cells can become like cells taken from people with diabetes when exposed to fat (palmitate), by permanently shutting off the genes that control fat burning, PGC-1 (DNA can't be transcribed when it is methylated, so hypermethylation is even worse).
It implies that diet changes your DNA, and specifically, that palmitate/palmitic acid/palm oil, shuts off one of your fat burning genes.
Palm oil is in a lot of foods.