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PGC1α -1 Nucleosome Position and Splice Variant Expression and Cardiovascular Disease Risk in Overweight and Obese Individuals.

Henagan TM, Stewart LK, Forney LA, Sparks LM, Johannsen N, Church TS - PPAR Res (2014)

Bottom Line: We report in this paper that skeletal muscle PGC1α  -1 nucleosome (-1N) position is associated with splice variant NTPGC1α but not FLPGC1α expression.UP showed an increase in body fat percentage and serum total and LDL cholesterol.These findings suggest that the -1N may be a potential epigenetic regulator of NTPGC1α splice variant expression, and -1N position and NTPGC1α variant expression in skeletal muscle are linked to CVD risk.

View Article: PubMed Central - PubMed

Affiliation: Department of Nutrition Science, Purdue University, 700 W. State Street, West Lafayette, IN 47907, USA.

ABSTRACT
PGC1α, a transcriptional coactivator, interacts with PPARs and others to regulate skeletal muscle metabolism. PGC1α undergoes splicing to produce several mRNA variants, with the NTPGC1α variant having a similar biological function to the full length PGC1α (FLPGC1α). CVD is associated with obesity and T2D and a lower percentage of type 1 oxidative fibers and impaired mitochondrial function in skeletal muscle, characteristics determined by PGC1α expression. PGC1α expression is epigenetically regulated in skeletal muscle to determine mitochondrial adaptations, and epigenetic modifications may regulate mRNA splicing. We report in this paper that skeletal muscle PGC1α  -1 nucleosome (-1N) position is associated with splice variant NTPGC1α but not FLPGC1α expression. Division of participants based on the -1N position revealed that those individuals with a -1N phased further upstream from the transcriptional start site (UP) expressed lower levels of NTPGC1α than those with the -1N more proximal to TSS (DN). UP showed an increase in body fat percentage and serum total and LDL cholesterol. These findings suggest that the -1N may be a potential epigenetic regulator of NTPGC1α splice variant expression, and -1N position and NTPGC1α variant expression in skeletal muscle are linked to CVD risk. This trial is registered with clinicaltrials.gov, identifier NCT00458133.

No MeSH data available.


Related in: MedlinePlus

Anthropometric measures in individuals with alternate −1 nucleosome positioning within the PGC1α promoter. Individuals were divided into upstream (UP, black) and downstream (DN, white) groups and (a) body weight, body mass index (BMI), and percent body fat and lean mass, (b) systolic (SBP) and diastolic blood pressure (DBP), (c) total, high density lipoprotein (HDL), and low density lipoprotein (LDL) cholesterol, and (d) plasma triglycerides, free fatty acids (FFA), glucose, and insulin were analyzed by Student's t-test and are shown as mean ± SEM. ∗ indicates significance difference between groups with P < 0.05.
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fig3: Anthropometric measures in individuals with alternate −1 nucleosome positioning within the PGC1α promoter. Individuals were divided into upstream (UP, black) and downstream (DN, white) groups and (a) body weight, body mass index (BMI), and percent body fat and lean mass, (b) systolic (SBP) and diastolic blood pressure (DBP), (c) total, high density lipoprotein (HDL), and low density lipoprotein (LDL) cholesterol, and (d) plasma triglycerides, free fatty acids (FFA), glucose, and insulin were analyzed by Student's t-test and are shown as mean ± SEM. ∗ indicates significance difference between groups with P < 0.05.

Mentions: CVD risk is associated with obesity and T2D and individuals with lower expression of skeletal muscle PGC1α exhibit higher disease risk [20]. When subjects were divided into groups based on −1N position in PGC1α, no differences in body weight (Figure 3(a)) or age (UP 52.78 ± 2.91 y; DN 55.83 ± 3.05 y) existed between UP and DN. Interestingly, percent body fat was lower in UP compared with DN (P = 0.0455), although percentage of lean mass was not different (Figure 3(a)). BMI was not statistically significant between groups (Figure 3(a)). No significant differences in systolic (SBP) or diastolic blood pressure (DBP) were evident (Figure 3(b)). In UP, total serum cholesterol (P < 0.04) and low density lipoprotein (LDL; P < 0.04) cholesterol were lower, and there was no difference in high density lipoprotein (HDL) cholesterol between groups (Figure 3(c)). Serum triglycerides, free fatty acids (FFA), fasting blood glucose, and insulin levels were not different between groups (Figure 3(d)). These data show that individuals with a −1N positioned proximal to the TSS in the PGC1α promoter and with higher levels of NTPGC1α exhibit increased CVD risk as assessed by adiposity, total cholesterol, and LDL cholesterol.


PGC1α -1 Nucleosome Position and Splice Variant Expression and Cardiovascular Disease Risk in Overweight and Obese Individuals.

Henagan TM, Stewart LK, Forney LA, Sparks LM, Johannsen N, Church TS - PPAR Res (2014)

Anthropometric measures in individuals with alternate −1 nucleosome positioning within the PGC1α promoter. Individuals were divided into upstream (UP, black) and downstream (DN, white) groups and (a) body weight, body mass index (BMI), and percent body fat and lean mass, (b) systolic (SBP) and diastolic blood pressure (DBP), (c) total, high density lipoprotein (HDL), and low density lipoprotein (LDL) cholesterol, and (d) plasma triglycerides, free fatty acids (FFA), glucose, and insulin were analyzed by Student's t-test and are shown as mean ± SEM. ∗ indicates significance difference between groups with P < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig3: Anthropometric measures in individuals with alternate −1 nucleosome positioning within the PGC1α promoter. Individuals were divided into upstream (UP, black) and downstream (DN, white) groups and (a) body weight, body mass index (BMI), and percent body fat and lean mass, (b) systolic (SBP) and diastolic blood pressure (DBP), (c) total, high density lipoprotein (HDL), and low density lipoprotein (LDL) cholesterol, and (d) plasma triglycerides, free fatty acids (FFA), glucose, and insulin were analyzed by Student's t-test and are shown as mean ± SEM. ∗ indicates significance difference between groups with P < 0.05.
Mentions: CVD risk is associated with obesity and T2D and individuals with lower expression of skeletal muscle PGC1α exhibit higher disease risk [20]. When subjects were divided into groups based on −1N position in PGC1α, no differences in body weight (Figure 3(a)) or age (UP 52.78 ± 2.91 y; DN 55.83 ± 3.05 y) existed between UP and DN. Interestingly, percent body fat was lower in UP compared with DN (P = 0.0455), although percentage of lean mass was not different (Figure 3(a)). BMI was not statistically significant between groups (Figure 3(a)). No significant differences in systolic (SBP) or diastolic blood pressure (DBP) were evident (Figure 3(b)). In UP, total serum cholesterol (P < 0.04) and low density lipoprotein (LDL; P < 0.04) cholesterol were lower, and there was no difference in high density lipoprotein (HDL) cholesterol between groups (Figure 3(c)). Serum triglycerides, free fatty acids (FFA), fasting blood glucose, and insulin levels were not different between groups (Figure 3(d)). These data show that individuals with a −1N positioned proximal to the TSS in the PGC1α promoter and with higher levels of NTPGC1α exhibit increased CVD risk as assessed by adiposity, total cholesterol, and LDL cholesterol.

Bottom Line: We report in this paper that skeletal muscle PGC1α  -1 nucleosome (-1N) position is associated with splice variant NTPGC1α but not FLPGC1α expression.UP showed an increase in body fat percentage and serum total and LDL cholesterol.These findings suggest that the -1N may be a potential epigenetic regulator of NTPGC1α splice variant expression, and -1N position and NTPGC1α variant expression in skeletal muscle are linked to CVD risk.

View Article: PubMed Central - PubMed

Affiliation: Department of Nutrition Science, Purdue University, 700 W. State Street, West Lafayette, IN 47907, USA.

ABSTRACT
PGC1α, a transcriptional coactivator, interacts with PPARs and others to regulate skeletal muscle metabolism. PGC1α undergoes splicing to produce several mRNA variants, with the NTPGC1α variant having a similar biological function to the full length PGC1α (FLPGC1α). CVD is associated with obesity and T2D and a lower percentage of type 1 oxidative fibers and impaired mitochondrial function in skeletal muscle, characteristics determined by PGC1α expression. PGC1α expression is epigenetically regulated in skeletal muscle to determine mitochondrial adaptations, and epigenetic modifications may regulate mRNA splicing. We report in this paper that skeletal muscle PGC1α  -1 nucleosome (-1N) position is associated with splice variant NTPGC1α but not FLPGC1α expression. Division of participants based on the -1N position revealed that those individuals with a -1N phased further upstream from the transcriptional start site (UP) expressed lower levels of NTPGC1α than those with the -1N more proximal to TSS (DN). UP showed an increase in body fat percentage and serum total and LDL cholesterol. These findings suggest that the -1N may be a potential epigenetic regulator of NTPGC1α splice variant expression, and -1N position and NTPGC1α variant expression in skeletal muscle are linked to CVD risk. This trial is registered with clinicaltrials.gov, identifier NCT00458133.

No MeSH data available.


Related in: MedlinePlus