Mouse KLF11 regulates hepatic lipid metabolism

Zhang, Huabing; Chen, Qi; Yang, Min; Zhu, Bin; Cui, Ying; Xue, Yan; Gong, Ning; Cui, Anfang; Wang, Min; Shen, Lian; Zhang, Shutian; Fang, Fude; Chang, Yongsheng

doi:10.1016/j.jhep.2012.11.024

Cited by 56 publications

(56 citation statements)

References 27 publications

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“…Since then, 8 additional members of this gene family have been shown to regulate adipogenesis both in mammals and worms (52,53). Several KLF factors (e.g., KLF10, KLF11, KLF15) have been shown to regulate hepatic metabolism (22,(54)(55)(56). KLF15 has also been shown to control lipid flux and metabolism in cardiac and skeletal muscles (57,58).…”

Section: Discussionmentioning

confidence: 99%

Kruppel-like factor 4 is critical for transcriptional control of cardiac mitochondrial homeostasis

Liao

Zhang

Lü

et al. 2015

Journal of Clinical Investigation

110

113

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Section: Discussionmentioning

confidence: 99%

Kruppel-like factor 4 is critical for transcriptional control of cardiac mitochondrial homeostasis

Liao

Zhang

Lü

et al. 2015

Journal of Clinical Investigation

110

113

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“…Here we selected KLF11, which is a member of the SP1/KLF family of transcription factors, for further analyses. KLFs constitute an interesting family of transcription factors involved in the regulation of diverse metabolic networks (Neve et al 2005;Lomberk et al 2013;Zhang et al 2013). Several KLF family members, including KLF2, KLF3, KLF4, KLF5, KLF6, KLF7, KLF9, and KLF15, have been implicated in different stages of adipogenesis (Wu and Wang 2013), but a role of KLF11 in adipogenesis has not been described.…”

Section: Discussionmentioning

confidence: 99%

Browning of human adipocytes requires KLF11 and reprogramming of PPARγ superenhancers

et al. 2014

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Long-term exposure to peroxisome proliferator-activated receptor g (PPARg) agonists such as rosiglitazone induces browning of rodent and human adipocytes; however, the transcriptional mechanisms governing this phenotypic switch in adipocytes are largely unknown. Here we show that rosiglitazone-induced browning of human adipocytes activates a comprehensive gene program that leads to increased mitochondrial oxidative capacity. Once induced, this gene program and oxidative capacity are maintained independently of rosiglitazone, suggesting that additional browning factors are activated. Browning triggers reprogramming of PPARg binding, leading to the formation of PPARg ''superenhancers'' that are selective for brown-in-white (brite) adipocytes. These are highly associated with key brite-selective genes. Based on such an association, we identified an evolutionarily conserved metabolic regulator, Kruppel-like factor 11 (KLF11), as a novel browning transcription factor in human adipocytes that is required for rosiglitazone-induced browning, including the increase in mitochondrial oxidative capacity. KLF11 is directly induced by PPARg and appears to cooperate with PPARg in a feed-forward manner to activate and maintain the brite-selective gene program.

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“…Quantitative PCR (qPCR) was performed as previously described [25]. mRNA levels for specific genes were normalised to β-actin mRNA levels and expressed relative to their mRNA levels from control samples.…”

Section: Preparation Of Expression Plasmids and Recombinant Adenovirusesmentioning

confidence: 99%

“…Western blot analysis Western blot assays were performed as previously described [25] using antibodies specific for rabbit anti-PGC-1α (1:2000), rabbit anti-G6Pase (1:1000), mouse anti-Flag (1:2000), mouse anti-c-Myc (1:5000), rabbit anti-FOXO1 (1:2000) and mouse anti-β-actin (1:2000). A polyclonal antibody against FOXQ1 (1:700) was generated in our laboratory by immunising rats with glutathione S-transferase (GST)-full-length FOXQ1 fusion protein.…”

Section: Preparation Of Expression Plasmids and Recombinant Adenovirusesmentioning

confidence: 99%

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The hepatic FOXQ1 transcription factor regulates glucose metabolism in mice

et al. 2016

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Aim/hypothesis Hepatic forkhead box q1 (FOXQ1) expression levels are regulated by nutritional and pathophysiological status. In this study we investigated the role of FOXQ1 in the regulation of hepatic gluconeogenesis. Methods We used multiple mouse and cell models to study the role of FOXQ1 in regulating expression of gluconeogenic genes, and cellular and hepatic glucose production. Results Expression of hepatic FOXQ1 was regulated by fasting in normal mice and was dysregulated in diabetic mice. Overexpression of FOXQ1 in primary hepatocytes inhibited expression of gluconeogenic genes and decreased cellular glucose output. Hepatic FOXQ1 rescue in db/db and high-fat diet-induced obese mice markedly decreased blood glucose level and improved glucose intolerance. In contrast, wildtype C57 mice with hepatic FOXQ1 deficiency displayed increased blood glucose levels and impaired glucose tolerance. Interestingly, studies into molecular mechanisms indicated that FOXQ1 interacts with FOXO1, thereby blocking FOXO1 activity on hepatic gluconeogenesis, preventing it from directly binding to insulin response elements mapped in the promoter region of gluconeogenic genes. Conclusions/interpretation FOXQ1 is a novel factor involved in regulating hepatic gluconeogenesis, and the decreased FOXQ1 expression in liver may contribute to the development of type 2 diabetes.

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Mouse KLF11 regulates hepatic lipid metabolism

Cited by 56 publications

References 27 publications

Kruppel-like factor 4 is critical for transcriptional control of cardiac mitochondrial homeostasis

Kruppel-like factor 4 is critical for transcriptional control of cardiac mitochondrial homeostasis

Browning of human adipocytes requires KLF11 and reprogramming of PPARγ superenhancers

The hepatic FOXQ1 transcription factor regulates glucose metabolism in mice

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