On 2017 Oct 12, Sander Houten commented:

This paper focuses on the role of KLF14 in the regulation of hepatic ApoA-I expression. The authors show that hepatic KLF14 expression is reduced in dyslipidemia mouse models. They show that overexpression of human KLF14 in liver of mice that were fed a high fat diet, increased HDL-cholesterol, cholesterol efflux and ApoA-I expression. Conversely, they show that liver-specific deletion of Klf14 decreased HDL-cholesterol and ApoA-I expression. The authors offer a mechanistic explanation by demonstrating that the ApoA-I promoter contains one KLF14-binding site. Moreover, perhexiline was identified as a KLF14 activator that raised HDL-cholesterol, ApoA-I and cholesterol efflux in vivo and reduced atherosclerosis development in Apoe^−/− mice (Guo Y, 2015). I would like to point out that there is little evidence to support the hypothesis that KLF14 plays an important role in adult mouse liver biology. We found no evidence for expression of KLF14 in adult mouse liver as we were unable to amplify Klf14 cDNA, did not find Klf14 mapped reads in liver RNA sequencing data and found no specific signal upon immunoblotting (Argmann CA, 2017). Our data on the absence of Klf14 expression in liver are consistent with previously published work by others (Parker-Katiraee L, 2007) and publicly available data sources. We also investigated the physiological functions of KLF14 by studying a whole body KO mouse model and focused on the metabolic role of this transcription factor in mice on chow and high fat diet. Our results do not support a major role of hepatic KLF14 in the regulation of ApoA-I and HDL-cholesterol levels (Argmann CA, 2017).

On 2017 Oct 12, Sander Houten commented:

This paper focuses on the role of KLF14 in the regulation of hepatic ApoA-I expression. The authors show that hepatic KLF14 expression is reduced in dyslipidemia mouse models. They show that overexpression of human KLF14 in liver of mice that were fed a high fat diet, increased HDL-cholesterol, cholesterol efflux and ApoA-I expression. Conversely, they show that liver-specific deletion of Klf14 decreased HDL-cholesterol and ApoA-I expression. The authors offer a mechanistic explanation by demonstrating that the ApoA-I promoter contains one KLF14-binding site. Moreover, perhexiline was identified as a KLF14 activator that raised HDL-cholesterol, ApoA-I and cholesterol efflux in vivo and reduced atherosclerosis development in Apoe^−/− mice (Guo Y, 2015). I would like to point out that there is little evidence to support the hypothesis that KLF14 plays an important role in adult mouse liver biology. We found no evidence for expression of KLF14 in adult mouse liver as we were unable to amplify Klf14 cDNA, did not find Klf14 mapped reads in liver RNA sequencing data and found no specific signal upon immunoblotting (Argmann CA, 2017). Our data on the absence of Klf14 expression in liver are consistent with previously published work by others (Parker-Katiraee L, 2007) and publicly available data sources. We also investigated the physiological functions of KLF14 by studying a whole body KO mouse model and focused on the metabolic role of this transcription factor in mice on chow and high fat diet. Our results do not support a major role of hepatic KLF14 in the regulation of ApoA-I and HDL-cholesterol levels (Argmann CA, 2017).