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Biochim Biophys Acta. 2017 Sep 26. pii: S0925-4439(17)30336-8. doi: 10.1016/j.bbadis.2017.09.021. [Epub ahead of print]

Germline deletion of Krüppel-like factor 14 does not increase risk of diet induced metabolic syndrome in male C57BL/6 mice.

Author information

1
Department of Genetics and Genomic Sciences, Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, NY, New York, USA.
2
Center for Comparative Medicine and Surgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
3
Department of Medicine, Diabetes, Obesity, and Metabolism Institute, Icahn School of Medicine at Mount Sinai, NY, New York, USA.
4
Department of Genetics and Genomic Sciences, Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, NY, New York, USA. Electronic address: sander.houten@mssm.edu.

Abstract

OBJECTIVE:

The transcription factor Krüppel-like factor 14 (KLF14) has been associated with type 2 diabetes and high-density lipoprotein-cholesterol (HDL-C) through genome-wide association studies. The mechanistic underpinnings of KLF14's control of metabolic processes remain largely unknown. We studied the physiological roles of KLF14 in a knockout (KO) mouse model.

METHODS:

Male whole body Klf14 KO mice were fed a chow or high fat diet (HFD) and diet induced phenotypes were analyzed. Additionally, tissue-specific expression of Klf14 was determined using RT-PCR, RNA sequencing, immunoblotting and whole mount lacZ staining. Finally, the consequences of KLF14 loss-of-function were studied using RNA sequencing in tissues with relatively high Klf14 expression levels.

RESULTS:

KLF14 loss-of-function did not affect HFD-induced weight gain or insulin resistance. Fasting plasma concentrations of glucose, insulin, cholesterol, HDL-C and ApoA-I were also comparable between Klf14+/+ and Klf14-/- mice on chow and HFD. We found that in mice expression of Klf14 was the highest in the anterior pituitary (adenohypophysis), lower but detectable in white adipose tissue and undetectable in liver. Loss of KLF14 function impacted on the pituitary transcriptome with extracellular matrix organization as the primary affected pathway and a predicted link to glucocorticoid receptor signaling.

CONCLUSIONS:

Whole body loss of KLF14 function in male mice does not result in metabolic abnormalities as assessed under chow and HFD conditions. Mostly likely there is redundancy for the role of KLF14 in the mouse and a diverging function in humans.

KEYWORDS:

Adenohypophysis; Genome-wide association studies; Krüppel-like factor; Mouse model

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