The Krüppel-Like Factors and Control of Energy Homeostasis

Hsieh, Paishiun N.; Fan, Liyan; Sweet, David R; Jain, Mukesh K.

doi:10.1210/er.2018-00151

Cited by 59 publications

(57 citation statements)

References 138 publications

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“…It was also reported that KLF1 regulates genes involved in autophagy, cell cycle and mitosis (Magor et al, 2015). Klf7 acts as a negative regulator of adipocyte development and inhibits expression of adiponectin and insulin (Hsieh et al, 2019), Klf7 overexpression suppresses hematopoietic stem and progenitor cell function (Schuettpelz et al, 2012). Egr1 (Early growth response 1) is an immediate early transcriptional factor which acts as a coordinator of the complex response to stress, Egr1 controls the expression of a wide range of genes involved in metabolism, cell proliferation, and inflammation (Magee and Zhang, 2017).…”

Section: Discussionmentioning

confidence: 97%

Inhibition of Embryonic HSP 90 Function Promotes Variation of Cold Tolerance in Zebrafish

et al. 2020

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Accumulating evidence indicates that heat shock protein 90 (HSP90) plays essential roles in modulation of phenotypic plasticity in vertebrate development, however, the roles of HSP90 in modulation of cold tolerance capacity in fish are still unclear. In the present study, we showed that transient inhibition of embryonic HSP90 function by a chemical inhibitor or low conductivity stress promoted variation of cold tolerance capacity in adult zebrafish. Further work showed that embryonic HSP90 inhibition enhanced cold tolerance in adult zebrafish could be transmitted to their offspring. RNA-seq data showed that embryonic HSP90 inhibition enhanced cold tolerance involves variation of gene expression related to proteasome, lysosome, autophagy, and ribosome. Experiments with zebrafish ZF4 cells showed that two differentially expressed genes atg9b and psmd12 were up-regulated by radicicol treatment and provided protective roles for cells under cold stress, indicating that up-regulation of autophagy and proteasome function contributes to enhanced cold tolerance. The present work sheds a light on the roles of HSP90 in regulation of phenotypic plasticity associated with thermal adaptation in fish.

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Section: Discussionmentioning

confidence: 97%

Inhibition of Embryonic HSP 90 Function Promotes Variation of Cold Tolerance in Zebrafish

et al. 2020

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“…KLFs are well-documented to be key effectors of both metabolism and inflammation 19,20 . That this diverse family of transcription factors appear to have evolved, in part, to be central in the immunometabolic crosstalk seen in metabolic disease further underscores the interconnectedness of these two fundamental processes.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2020

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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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“…There is newfound appreciation of KLFs as transcriptional regulators of energy metabolism (Hsieh et al, 2019). This role is underscored by the identification and KLF variants involved in cardiometabolic disorders (Oishi and Manabe, 2018).…”

Section: Discussionmentioning

confidence: 99%

“…Krüppel-like factors (KLFs) form another family of transcription regulators, a majority of which has been involved the physiology of metabolic organs including the liver (Hsieh et al, 2019). Many of these KLFs are also clock-controlled genes in mouse liver (Ceglia et al, 2018;Yoshitane et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

KLF10 integrates circadian timing and sugar signaling to coordinate hepatic metabolism

Ruberto

Gréchez-Cassiau

Guérin

et al. 2020

Preprint

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The mammalian circadian timing system and metabolism are highly interconnected, and disruption of this coupling is associated with negative health outcomes. Krüppel-like factors (KLFs) are transcription factors that govern metabolic homeostasis in various organs. Many KLFs show a circadian expression in the liver. Here, we show that the loss of the clock-controlled KLF10 in hepatocytes results in extensive reprogramming of the mouse liver circadian transcriptome, which in turn, alters the temporal coordination of pathways associated with energy metabolism. We also show that glucose and fructose induce Klf10, which helps mitigate glucose intolerance and hepatic steatosis in mice challenged with a sugar beverage. Functional genomics further reveal that KLF10 target genes are primarily involved in central carbon metabolism. Together, these findings show that in the liver, KLF10 integrates circadian timing and sugar metabolism related signaling, and serves as a transcriptional brake that protects against the deleterious effects of increased sugar consumption.

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The Krüppel-Like Factors and Control of Energy Homeostasis

Cited by 59 publications

References 138 publications

Inhibition of Embryonic HSP 90 Function Promotes Variation of Cold Tolerance in Zebrafish

Inhibition of Embryonic HSP 90 Function Promotes Variation of Cold Tolerance in Zebrafish

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

KLF10 integrates circadian timing and sugar signaling to coordinate hepatic metabolism

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