CREB3 mediates the transcriptional regulation of PGC ‐1α, a master regulator of energy homeostasis and mitochondrial biogenesis

CREB3 is an endoplasmic reticulum stress-associated transcription factor that has recently been implicated in metabolic regulation due to the altered lipid accumulation phenotypes seen in CREB3-deficient mice. PGC-1 α is a master metabolic regulator of energy homeostasis and mitochondrial biogenesis. Here, we show that CREB3 regulates the expression ofPPARGC1A, which encodes PGC-1 α. The findings underline the potential role of CREB3 in energy metabolism. Lipid metabolism hinges on a balance between lipogenesis and fatty acid oxidation (FAO). Disruptions in this balance can induce endoplasmic reticulum (ER) stress triggering the unfolded protein response (UPR) and contribute to metabolic diseases. The UPR protein, Luman or CREB3, has recently been implicated in metabolic regulation –CREB3 knockout mice exhibit resistance to diet-induced obesity and altered insulin sensitivity. Here, we show that CREB3 activatedPPARGC1A transcription from a 1  kb promoter region. An increase in CREB3 expression correlated inversely with endogenousPPARGC1A mRNA levels and genes involved in FAO. As PGC-1 α encoded byPPARGC1A is a master regulator of mitochondrial biogenesis and energy homeostasis, these findings demonstrate that CREB3 is a transcriptional regulator of PGC-1 α, underlining the potential role of CREB3 in energy metabolism.
Source: FEBS Letters - Category: Biochemistry Authors: Tags: Research Letter Source Type: research