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

Carmen A. Argmann, Sara Violante, Tetyana Dodatko, Mariana P. Amaro, Jacob Hagen, Virginia L. Gillespie, Christoph Buettner, Eric E. Schadt, Sander M. Houten

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)3277-3285
Number of pages9
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1863
Issue number12
DOIs
StatePublished - Dec 2017
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology

Keywords

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

Fingerprint

Dive into the research topics of 'Germline deletion of Krüppel-like factor 14 does not increase risk of diet induced metabolic syndrome in male C57BL/6 mice'. Together they form a unique fingerprint.

Cite this