A High-Fat Diet Coordinately Downregulates Genes Required for Mitochondrial Oxidative Phosphorylation in Skeletal Muscle
Article Figures & Tables
Figures
- FIG. 1.
HFD decreases mRNA for genes involved in OXPHOS in healthy young men and mice. A: Effect of a 3-day isoenergetic HFD (50% fat vs. 35% fat) in a cohort of healthy insulin-sensitive males (n = 10) at baseline and after intervention on the expression of genes in complex I (NDUFB3, NDUFB5, NDUFV1, and NDUFS1), complex II (SDHB), complex III (CYC1), complex IV (SURF1), and a mitochondrial carrier protein (SLC25A12). mRNA was quantified by quantitative RT-PCR. Data are shown as means ± SE and corrected for the expression of 18S and RPLP0. NDUFB3, NADH dehydrogenase (ubiquinone) one β subcomplex, 3; NDUFB5, NADH dehydrogenase (ubiquinone) one β subcomplex, 5; NDUFV1, NADH dehydrogenase (ubiquinone) flavoprotein 1; NDUFS1, NADH dehydrogenase (ubiquinone) Fe-S protein 1); SDHB, succinate dehydrogenase complex, subunit B; SLC25A12, solute carrier family 25 (mitochondrial carrier); CYC1, cytochrome c-1; SURF1, surfeit 1. B: Effect of a 21-day HFD (45% fat vs. 10% fat) in a cohort of C57Bl/6J mice (control, n = 6; HFD, n = 7) on genes in complex I (NDUFB3 AND NDUFB5), complex II (SDHB), complex III (CYC1), complex IV (SURF1), and a mitochondrial carrier protein (SLC25A12). Data are shown as means ± SE and corrected for the expression of cyclophilin B.
- FIG. 2.
HFD decreases expression of transcriptional cofactors involved in the regulation of OXPHOS expression and mitochondrial biogenesis in healthy young men and mice. A: Effect of a 3-day isoenergetic HFD (50% fat vs. 35% fat) in a cohort of healthy insulin-sensitive males (n = 10) at baseline and after intervention on the expression of genes involved in mitochondrial biogenesis. Data are shown as means ± SE and corrected for the expression of ribosomal protein, large, P0. NRF1, nuclear respiratory factor-1. B: Effect of a 21-day HFD (45% fat vs. 10% fat) in a cohort of C57Bl/6J mice (control, n = 6; HFD, n = 7) on genes involved in mitochondrial biogenesis and function and mtDNA copy number per nuclear DNA copy number. Data are shown as means ± SE and corrected for the expression of cyclophilin B for mRNA and glyceraldehyde-3-phosphate dehydrogenase for protein.
Tables
- TABLE 1
Characteristics of the study population before the high-fat diet
Age (years) 23.0 ± 3.1 Height (cm) 179.7 ± 6.3 Weight (kg) 78.9 ± 13.2 BMI (kg/m2) 24.3 ± 3.0 Vo2max (ml · kg−1 · min−1) 48.8 ± 3.3 Waist-to-hip ratio (AU) 0.88 ± 0.1 RQ–metabolic cart (AU) 0.87 ± 0.1 Fasting glucose (ml/dl) 78.4 ± 4.7 Fasting insulin (μl/ml) 4.6 ± 1.4 GDR (mg · kg FFM−1 · min−1) 14.7 ± 4.1 Free fatty acids (mmol) 0.4 ± 0.1 Body fat (%) 16.2 ± 3.2 Fat cell size (μl) 0.93 ± 0.2 Data are means ± SD. GDR, glucose disposal rate; RQ, respiratory quotient.
- TABLE 2
Change in overnight fasting blood parameters after a 50% high-fat diet at energy balance and fixed activity level
Variable BL1 BL2 HFD day 1 HFD day 2 HFD day 3 Glucose (mg/dl) 88.60 ± 7.38 89.77 ± 8.74 89.00 ± 9.76 89.40 ± 7.29 90.40 ± 9.03 Insulin (mIU/ml) 6.81 ± 3.02 6.98 ± 2.86 6.65 ± 3.00 6.07 ± 2.98* 6.89 ± 2.67 Free fatty acids (mmol) 0.26 ± 0.08 0.28 ± 0.10 0.22 ± 0.08 0.25 ± 0.08 0.27 ± 0.10 Data are means ± SE. The HFD contained 50% fat. Repeated-measures ANOVA was used to test for time effects; P = 0.847, 0.130, and 0.047 for glucose, insulin, and free fatty acids, respectively.
- *
* Post hoc comparisons of each HFD day versus average of the two baseline (BL) values were significant (P < 0.05; Dunnett’s adjustment).
- TABLE 3
Microarray hits: oxidative phosphorylation
Gene Fold change Baseline value (%) P NDUFB3 ↓ 1.4 71.4 <0.01 NDUFB5 ↓ 1.9 52.6 <0.01 SDHB ↓ 2.4 41.6 <0.01 SLC25A12 ↓ 1.8 55.5 <0.01 NDUFV1 ↓ 1.9 52.6 <0.01 NDUFS1 ↓ 2.4 41.6 <0.01 By microarray analysis, 297 genes were up- or downregulated after a HFD. Of those 297, 6 are known to be involved in oxidative phosphorylation or mitochondrial function. NDUFB3, NADH dehydrogenase (ubiquinone) 1β subcomplex, 3; NDUFB5, NADH dehydrogenase (ubiquinone) 1βsubcomplex, 5; NDUFV1, NADH dehydrogenase (ubiquinone) flavoprotein 1; NDUFS1, NADH dehydrogenase (ubiquinone) Fe-S protein 1; SDHB, succinate dehydrogenase complex, subunit B; SLC25A12, solute carrier family 25 (mitochondrial carrier).
In this Issue
