Transcriptional response of hepatocytes lacking KLF10 to a high sugar challenge

The mammalian circadian timing system and metabolism are highly interconnected, and disruption of this coupling is associated with negative health outcomes. Krüppel-like transcription factors (KLFs) govern metabolic homeostasis in various organs and many members show a circadian expression. We previously showed that the transcription factor Kru¨ppel-like factor 10 (KLF10) is a clock-controlled and a glucose responsive gene in liver. We now show that Klf10 is also induced by fructose and that effects of glucose and fructose are additive. To understand the role of KLF10 in the response of hepatocytes to a high sugar challenge, primary hepatocytes lacking KLF10 were treated with 25 mM glucose and 5 mM fructose for 12 h. The transcriptional response of these cells to the high sugar challenge was analyzed using RNA-sequencing and compared to that of hepatocytes expressing KLF10. Results show that hepatocytes lacking KLF10 display an altered metabolic response. KLF10 negatively regulates genes involved in amino acid degradation, fatty acid oxidation, carbohydrate metabolism and de novo lipogenesis.