Myeloid Krüppel-like factor 2 is a critical regulator of metabolic inflammation.

Nature Communications
David R SweetMukesh K Jain

Abstract

Substantial evidence implicates crosstalk between metabolic tissues and the immune system in the inception and progression of obesity. However, molecular regulators that orchestrate metaflammation both centrally and peripherally remains incompletely understood. Here, we identify myeloid Krüppel-like factor 2 (KLF2) as an essential regulator of obesity and its sequelae. In mice and humans, consumption of a fatty diet downregulates myeloid KLF2 levels. Under basal conditions, myeloid-specific KLF2 knockout mice (K2KO) exhibit increased feeding and weight gain. High-fat diet (HFD) feeding further exacerbates the K2KO metabolic disease phenotype. Mechanistically, loss of myeloid KLF2 increases metaflammation in peripheral and central tissues. A combination of pair-feeding, bone marrow-transplant, and microglial ablation implicate central and peripheral contributions to K2KO-induced metabolic dysfunction observed. Finally, overexpression of myeloid KLF2 protects mice from HFD-induced obesity and insulin resistance. Together, these data establish myeloid KLF2 as a nodal regulator of central and peripheral metabolic inflammation in homeostasis and disease.

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Citations

Jun 4, 2021·Frontiers in Cardiovascular Medicine·David R SweetMukesh K Jain
May 11, 2021·American Journal of Respiratory Cell and Molecular Biology·David WuYun Fang

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Methods Mentioned

BETA
transgenic
ELISA
PCR
dissection

Software Mentioned

iDEP
Cufflinks
Adobe Photoshop
GenePattern
ImageJ
Illustrator
Graphpad Prism
TopHat2
Excel
Gene Set Enrichment Analysis ( GSEA ) toolset

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