Table 2.
Comparison of glucose and lipid metabolism responses in different models of PGC-1α ablation and overexpression
| PGC-1α-Null |
Large (600–2,000%) PGC-1α Overexpression |
Modest (25%) Muscle-Specific PGC-1α Overexpression |
||||
|---|---|---|---|---|---|---|
| Metabolic Parameter | Whole body, Refs. 111, 117* | Muscle specific, Ref. 71** | Whole body (1,000–2,000%), Refs. 109, 133 | Muscle specific (600%), Ref. 39 | Healthy muscle (25%), Ref. 15 | Zucker obese muscle (25%), Ref. 14 |
| Glucose metabolism | ||||||
| Insulin sensitivity | †Improveda | No difference | †Reduced | †Reduceda | ||
| Glucose tolerance | †Improveda | †Intoleranta | †Intolerant | |||
| Peripheral glucose flux | Improved | †Reduceda | ||||
| Muscle glucose transport | †Reduceda | √Increased | √Increased | |||
| Protein expression | ||||||
| Muscle GLUT4 | √Reduced | †Reduced | √Increased | √Increased | ||
| Muscle IRS-1 | No difference | |||||
| Muscle PI 3-kinase | No difference | |||||
| Muscle Akt2 protein | No difference | No difference | ||||
| Muscle AS160 protein | No difference | No difference | ||||
| Insulin signaling | ||||||
| Muscle p-IRS-1 | No difference | Reduced | ||||
| Muscle p-Akt or activity | Increased | Increased | Increased | Increased | ||
| Muscle p-AS160 | Increased | Increased | ||||
| Lipid metabolism | ||||||
| Fatty acid oxidation | Increased | √Increasedc | √Increasedc | |||
| Intramuscular lipids | †No difference | †Increased | √Decreased | √Decreased | ||
| Lipid metabolism gene | ||||||
| AMPKα2 protein | Increased | |||||
| p-AMPKα2 or activity | No difference | |||||
| CD36 mRNA/protein | √Large increasec | √Increased | √Increased | |||
| CPT I mRNA, protein or activity | √Increasedc | √Increasedd,e, | √Increasede | |||
| ACC2 protein | √Increased | |||||
| mtGPAT mRNA | Increased | |||||
| DGAT1 mRNA | Increased | |||||
| Diet-induced obesity | †No (Ref. 117) | †No | †Severely (Ref.109) | No difference | ||
| √Yes (Ref. 111)*** | ||||||
| Fat mass | †Reduced | No difference | ||||
IRS-1, insulin receptor substrate-1; PI, phosphatidylinositol; ACC2, acetyl-CoA carboxylase-2; mtGPAT, mitochondrial glycerol-3-phosphate acyltransferase-1; DGAT1, diacylglycerol acyltransferase 1. Comparisons are relative to wild-type mice or muscles not transfected with PGC-1α.
Response observed is the expected response in the PGC-1α model.
Response observed is contrary to the expected response in the PGC-1α model.
PGC-1α-null mice in Ref. 117 are hyperactive and exhibit neurological disorders characteristic of Huntington's disease.
PGC-1α muscle-specific null mice in Ref. 71 are hypoactive.
Results are observed primarily in female mice.
Observations after a period of high-fat feeding;
fatty acid oxidation was improved in subsarcolemma mitochondria only, not in intramyofibrillar mitochondria;
mRNA;
protein;
activity.