cytochrome-c-t and dibutyryl-cyclic-3--5--cytidine-monophosphate

Mitochondria play an essential role in the ability of brown fat to generate heat, and the PGC-1 coactivators control several aspects of mitochondrial biogenesis. To investigate their specific roles in brown fat cells, we generated immortal preadipocyte lines from the brown adipose tissue of mice lacking PGC-1alpha. We could then efficiently knockdown PGC-1beta expression by shRNA expression. Loss of PGC-1alpha did not alter brown fat differentiation but severely reduced the induction of thermogenic genes. Cells deficient in either PGC-1alpha or PGC-1beta coactivators showed a small decrease in the differentiation-dependant program of mitochondrial biogenesis and respiration; however, this increase in mitochondrial number and function was totally abolished during brown fat differentiation when both PGC-1alpha and PGC-1beta were deficient. These data show that PGC-1alpha is essential for brown fat thermogenesis but not brown fat differentiation, and the PGC-1 coactivators play an absolutely essential but complementary function in differentiation-induced mitochondrial biogenesis.

Topics: Adipocytes; Adipose Tissue, Brown; Animals; CCAAT-Enhancer-Binding Protein-beta; Cell Differentiation; Cell Line; Cell Respiration; Cyclic CMP; Cytochromes c; Gene Expression Profiling; Gene Expression Regulation; Ion Channels; Mice; Mice, Knockout; Mitochondria; Mitochondrial Proteins; Oligonucleotide Array Sequence Analysis; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; RNA Interference; RNA, Messenger; Thermogenesis; Trans-Activators; Transcription Factors; Uncoupling Protein 1