Table 3.
Gene expression of targets of lipid and glucose regulation in muscle, liver, subcutaneous and visceral adipose tissue of Tfm mice
| Fat Metabolism | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Muscle | Liver | Subcutaneous Fat | Visceral Fat | ||||||||||
| Gene | Symbol | XY-P | Tfm-P | Tfm-S100 | XY-P | Tfm-P | Tfm-S100 | XY-P | Tfm-P | Tfm-S100 | XY-P | Tfm-P | Tfm-S100 |
| Acetyl CoA carboxylase alpha | ACACA | 1.28 ± 0.27 | 1.65 ± 0.46 | 0.77 ± 0.14 | 1.09 ± 0.13 | 2.49 ± 0.64* | 1.30 ± 0.29 | 1.22 ± 0.28 | 1.15 ± 0.36 | 1.89 ± 0.62 | 1.07 ± 0.16 | 1.02 ± 0.27 | 0.95 ± 0.35 |
| Fatty acid synthase | FASN | 1.52 ± 0.43 | 1.48 ± 0.56 | 0.56 ± 0.14 | 1.15 ± 0.17 | 11.42 ± 4.93* | 2.99 ± 0.88 | 1.20 ± 0.28 | 2.89 ± 1.49 | 4.76 ± 1.90 | 1.12 ± 0.23 | 1.35 ± 0.36 | 0.87 ± 0.30 |
| Stearoyl-CoA desaturase-1 | SCD1 | 1.06 ± 0.11 | 1.30 ± 0.24 | 1.37 ± 0.29 | 1.04 ± 0.14 | 2.45 ± 1.15 | 1.38 ± 0.15 | 1.2 ± 0.29 | 3.05 ± 1.37 | 0.70 ± 0.15 | 1.10 ± 0.23 | 4.99 ± 1.64* | 0.94 ± 0.15 † |
| Lipoprotein lipase | LPL | 1.24 ± 0.31 | 0.90 ± 0.30 | 0.83 ± 0.20 | 1.07 ± 0.13 | 1.26 ± 0.45 | 0.90 ± 0.26 | 1.03 ± 0.08 | 0.70 ± 0.09* | 0.81 ± 0.22 | 1.08 ± 0.13 | 0.99 ± 0.20 | 2.18 ± 0.36 † |
| Hormone sensitive lipase | Lipe | 1.20 ± 0.46 | 1.25 ± 0.24 | 1.18 ± 0.49 | 1.03 ± 0.08 | 1.24 ± 0.16 | 0.85 ± 0.10 | 1.17 ± 0.17 | 1.49 ± 0.29 | 1.14 ± 0.20 | 1.05 ± 0.14 | 1.10 ± 0.27 | 0.82 ± 0.21 |
| Cholesterol Homeostasis | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Muscle | Liver | Subcutaneous Fat | Visceral Fat | ||||||||||
| Gene | Symbol | XY-P | Tfm-P | Tfm-S100 | XY-P | Tfm-P | Tfm-S100 | XY-P | Tfm-P | Tfm-S100 | XY-P | Tfm-P | Tfm-S100 |
| 3-hydroxy-3-methyl-glutaryl-CoA reductase | HMGCoAr | _ | _ | _ | 1.06 ± 0.11 | 3.19 ± 2.09 | 1.15 ± 0.18 | 1.12 ± 0.19 | 0.88 ± 0.16 | 1.33 ± 0.37 | _ | _ | _ |
| Sterol Regulatory Element-Binding Protein | SREBPf1 | 1.29 ± 0.26 | 0.74 ± 0.21 | 1.47 ± 0.39 | 1.13 ± 0.16 | 1.01 ± 0.19 | 1.32 ± 0.29 | 1.07 ± 0.17 | 0.36 ± 0.09** | 0.86 ± 0.16 † | 0.81 ± 0.13 | 0.59 ± 0.25 | 0.78 ± 0.13 |
| Sterol Regulatory Element-Binding Protein | SREBPf2 | 1.17 ± 0.21 | 0.80 ± 0.28 | 1.99 ± 0.62 | 1.08 ± 0.13 | 1.44 ± 0.22 | 1.17 ± 0.16 | 1.07 ± 0.17 | 0.42 ± 0.08** | 1.12 ± 0.33 c | 0.80 ± 0.14 | 0.56 ± 0.21 | 0.79 ± 0.13 |
| Apolipoprotein E | ApoE | _ | _ | _ | 1.07 ± 0.05 | 0.77 ± 0.09** | 1.14 ± 0.11 † | 1.02 ± 0.08 | 0.59 ± 0.13* | 1.14 ± 0.16 † | 1.03 ± 0.10 | 0.75 ± 0.16 | 0.87 ± 0.06 |
| ATP-binding cassette transporter A1 | ABCA1 | _ | _ | _ | 1.05 ± 0.04 | 0.71 ± 0.09** | 1.10 ± 0.13 † | 1.07 ± 0.14 | 0.77 ± 0.12 | 0.63 ± 0.11 | 1.14 ± 0.24 | 0.98 ± 0.20 | 1.19 ± 0.32 |
| ATP-binding cassette transporter G5 | ABCG5 | _ | _ | _ | 1.01 ± 0.06 | 0.81 ± 0.15 | 1.01 ± 0.08 | _ | _ | _ | _ | _ | _ |
| Carbohydrate Metabolism | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Muscle | Liver | Subcutaneous Fat | Visceral Fat | ||||||||||
| Gene | Symbol | XY-P | Tfm-P | Tfm-S100 | XY-P | Tfm-P | Tfm-S100 | XY-P | Tfm-P | Tfm-S100 | XY-P | Tfm-P | Tfm-S100 |
| Insulin receptor substrate 1 | IRS1 | 1.34 ± 0.32 | 1.37 ± 0.59 | 1.85 ± 0.94 | 1.08 ± 0.17 | 1.74 ± 0.54 | 1.13 ± 0.29 | _ | _ | _ | _ | _ | _ |
| Hexokinase 2 | HK2 | 1.18 ± 0.19 | 0.50 ± 0.16* | 0.54 ± 0.10 | _ | _ | _ | 1.32 ± 0.36 | 0.24 ± 0.05** | 0.61 ± 0.19 † | 0.97 ± 0.23 | 1.00 ± 0.21 | 1.57 ± 0.54 |
| Hexokinase 4 (Glucokinase) | GCK | _ | _ | _ | 1.07 ± 0.10 | 0.47 ± 0.14** | 0.97 ± 0.13 † | _ | _ | _ | _ | _ | _ |
| Phosphofructokinase | PFK | 1.28 ± 0.23 | 0.64 ± 0.16* | 0.62 ± 0.10 | 1.19 ± 0.11 | 0.79 ± 0.15* | 0.77 ± 0.06 | 1.76 ± 0.68 | 0.16 ± 0.05* | 0.54 ± 0.31 | _ | _ | _ |
| mitogen-activated protein kinase kinase 1 | MAP2K1 | 1.22 ± 0.22 | 0.65 ± 0.19 a | 1.09 ± 0.21 | 1.09 ± 0.14 | 1.01 ± 0.14 | 1.62 ± 0.21 † | _ | _ | _ | _ | _ | _ |
| Carbohydrate regulatory element binding protein | ChREBP | 1.25 ± 0.24 | 2.16 ± 1.02 | 1.16 ± 0.22 | 1.05 ± 0.12 | 1.17 ± 0.13 | 1.11 ± 0.13 | 1.00 ± 0.19 | 1.76 ± 0.47 | 1.53 ± 0.38 | 1.33 ± 0.38 | 1.96 ± 0.7 | 1.76 ± 0.37 |
| Glucose transporter 4 | GLUT4 | 1.20 ± 0.19 | 0.59 ± 0.14* | 0.71 ± 0.13 | _ | _ | _ | 1.31 ± 0.32 | 0.37 ± 0.12* | 0.73 ± 0.29 | 1.03 ± 0.10 | 1.24 ± 0.26 | 0.83 ± 0.16 |
| glucose-6-phosphate 1-dehydrogenase X | G6PDx | 1.13 ± 0.19 | 1.72 ± 0.38 | 0.92 ± 0.12 | 1.03 ± 0.07 | 1.99 ± 0.20*** | 1.45 ± 0.18 b | 1.06 ± 0.23 | 2.67 ± 1.36 | 1.09 ± 0.16 | 1.57 ± 0.59 | 2.53 ± 0.87 | 1.69 ± 0.4 |
| Glycogen synthase | Gys1 | 1.14 ± 0.15 | 1.01 ± 0.31 | 1.82 ± 0.72 | 1.18 ± 0.18 | 2.13 ± 0.65 | 1.56 ± 0.22 | _ | _ | _ | _ | _ | _ |
| Master Regulators | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Muscle | Liver | Subcutaneous Fat | Visceral Fat | ||||||||||
| Gene | Symbol | XY-P | Tfm-P | Tfm-S100 | XY-P | Tfm-P | Tfm-S100 | XY-P | Tfm-P | Tfm-S100 | XY-P | Tfm-P | Tfm-S100 |
| Liver X receptor | LXR | 1.35 ± 0.29 | 0.62 ± 0.12* | 1.50 ± 0.27 †† | 1.05 ± 0.09 | 0.66 ± 0.08** | 1.28 ± 0.24 † | 1.07 ± 0.14 | 0.42 ± 0.13** | 1.15 ± 0.28 † | 1.27 ± 0.35 | 1.00 ± 0.30 | 1.44 ± 0.48 |
| Peroxisome proliferator-activated receptor alpha | PPARa | 1.16 ± 0.20 | 1.65 ± 0.78 | 0.94 ± 0.21 | 1.02 ± 0.07 | 1.84 ± 0.55 | 0.93 ± 0.14 | 1.13 ± 0.23 | 0.41 ± 0.11 | 0.69 ± 0.22 | 1.09 ± 0.20 | 0.92 ± 0.32 | 0.98 ± 0.22 |
| Peroxisome proliferator-activated receptor gamma | PPARg | 1.29 ± 0.31 | 1.29 ± 0.62 | 0.63 ± 0.17 | 1.09 ± 0.14 | 0.99 ± 0.19 | 1.29 ± 0.23 | 1.06 ± 0.14 | 0.67 ± 0.06 | 0.82 ± 0.12 | 1.05 ± 0.11 | 0.49 ± 0.08*** | 0.66 ± 0.10 |
Relative tissue-specific qPCR end-point analysis of selected genes of (a) fat metabolism, (b) cholesterol homeostasis, (c) carbohydrate metabolism and (d) master regulators between Tfm placebo-treated versus XY littermates placebo-treated, and Tfm placebo-treated versus Tfm testosterone-treated. N=11. *p < 0.05, **p < 0.01, ***p < 0.001 versus XY placebo, †p < 0.05, ††p < 0.01 versus Tfm placebo, ap = 0.053, bp = 0.058, cp = 0.056.