Gene expression data from clones of FAO cells with different glucose production capability

In response to energy and nutrient shortage, the liver triggers several catabolic processes to promote survival. Despite recent progresses, the precise molecular mechanisms regulating the hepatic adaptation to fasting remain incompletely characterized. Here, we report the identification of Hydroxysteroid dehydrogenase-like 2 (HSDL2) as a mitochondrial protein highly induced by fasting. We show that activation of PGC1a-PPARa and inhibition of the PI3K- mTORC1 axis stimulate HSDL2 expression in hepatocytes. We found that HSDL2 depletion decreases cholesterol conversion to bile acids (BAs) and impairs FXR activity. HSDL2 knockdown also reduces mitochondrial respiration, fatty acid oxidation, and TCA cycle activity. Bioinformatics analyses revealed that hepatic Hsdl2 expression positively associates with the postprandial excursion of various BA species in mice. Here, we show that liver-specific HSDL2 depletion impacts BA metabolism and decreases circulating cholesterol levels upon refeeding. Overall, our report identifies HSDL2 as a fasting-induced mitochondrial protein that links nutritional signals to BAs and cholesterol homeostasis.

Methods
Single cells were isolated and amplified from a parental culture of FAO cells. The clones were expanded and glucose production was measured in each lines. Using this approach, we have identified Low and High glucose producers. We have then selected 6 Low and 6 High lines and we have performed microarrays to identify the genes differentially expressed.