PLoS Biology · 18 authors, 9 centres
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This study used a gene knockout mouse model to show that deficiency of the transcriptional coactivator PGC-1α causes a multi-system energy metabolic phenotype, including reduced muscle mitochondrial capacity, impaired thermogenesis, hepatic fat accumulation during fasting, and abnormal weight gain.
Researchers created PGC-1α knockout mice to investigate its role in energy metabolism. Phenotypic analysis revealed that PGC-1α is not essential for embryonic development but is necessary for postnatal adaptation to metabolic stressors. Key findings include blunted growth of mitochondria-rich tissues (heart and slow-twitch skeletal muscle), reduced mitochondrial number and respiratory capacity in muscle, leading to diminished exercise capacity. Female mice exhibited age-related increases in body fat. Following short-term starvation, knockout mice developed hepatic steatosis due to reduced mitochondrial respiration and increased lipogenic gene expression. They also showed impaired core body temperature maintenance during cold exposure. Surprisingly, female knockout mice were more glucose-tolerant and insulin-sensitive on a high-fat diet. Vacuolar lesions were observed in the central nervous system.
