Kruppel-like Factor 15 Is a Critical Regulator of Cardiac Lipid Metabolism

Prosdocimo, Domenick A.; Anand, Priti; Liao, Xudong; Zhu, Han; Shelkay, Shamanthika; Artero-Calderon, Pedro; Zhang, Lilei; Kirsh, Jacob; Moore, D'Vesharronne V.; Roșca, Mariana G.; Vazquez, Edwin J.; Kerner, János; Akat, Kemal M.; Williams, Zev; Zhao, Jihe; Fujioka, Hisashi; Tuschl, Thomas; Bai, Xiaodong; Schulze, P. Christian; Hoppel, Charles L.; Jain, Mukesh K.; Haldar, Saptarsi M.

doi:10.1074/jbc.m113.531384

Cited by 103 publications

(124 citation statements)

References 60 publications

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“…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). However, a role for any member of this gene family as a central regulator of mitochondrial biology has not yet been reported, and thus, the current work serves as an important advance in this field.…”

Section: Discussionmentioning

confidence: 91%

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

Liao

Zhang

Lü

et al. 2015

Journal of Clinical Investigation

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105

113

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Section: Discussionmentioning

confidence: 91%

“…The use of human samples was approved by the institutional review boards of Columbia University and Case Western Reserve University (IRB-AAAE7393). Human heart samples were obtained as described previously (57,66).…”

Section: Methodsmentioning

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

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105

113

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“…The transcription factor KLF15, a direct GR-inducible target in multiple cell types (21,22), is an attractive candidate for mediating important ergogenic effects of GCs in muscle. Studies from our group using systemic KLF15-deficient mice have demonstrated KLF15 to be an important transcriptional regulator of a gene program governing stress-dependent metabolic adaptation in muscle (23,24). KLF15-deficient mice have impaired ability to catabolize muscle branched-chain amino acids as fuel for gluconeogenic flux during fasting (25,26).…”

Section: Significancementioning

confidence: 99%

Glucocorticoids enhance muscle endurance and ameliorate Duchenne muscular dystrophy through a defined metabolic program

Morrison‐Nozik

Anand

Zhu

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Classic physiology studies dating to the 1930s demonstrate that moderate or transient glucocorticoid (GC) exposure improves muscle performance. The ergogenic properties of GCs are further evidenced by their surreptitious use as doping agents by endurance athletes and poorly understood efficacy in Duchenne muscular dystrophy (DMD), a genetic muscle-wasting disease. A defined molecular basis underlying these performance-enhancing properties of GCs in skeletal muscle remains obscure. Here, we demonstrate that ergogenic effects of GCs are mediated by direct induction of the metabolic transcription factor KLF15, defining a downstream pathway distinct from that resulting in GC-related muscle atrophy. Furthermore, we establish that KLF15 deficiency exacerbates dystrophic severity and muscle GC-KLF15 signaling mediates salutary therapeutic effects in the mdx mouse model of DMD. Thus, although glucocorticoid receptor (GR)-mediated transactivation is often associated with muscle atrophy and other adverse effects of pharmacologic GC administration, our data define a distinct GR-induced gene regulatory pathway that contributes to therapeutic effects of GCs in DMD through proergogenic metabolic programming.skeletal muscle metabolism | glucocorticoid | exercise | Duchenne muscular dystrophy | steroid hormone nuclear receptor

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“…In addition, recent findings have revealed that KLF15 inhibits vascular smooth muscle activation by inhibiting NF-κB activity (Lu et al, 2013). Finally, recent studies demonstrate that KLF15 is a key regulator of cardiac lipid metabolism (Prosdocimo et al, 2014) and circadian mediated arrhythmogenesis (Jeyaraj et al, 2012 …”

Section: Klfs In Hematopoietic Disordersmentioning

confidence: 99%

Krüppel-like factors in mammalian stem cells and development

2017

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Krüppel-like factors (KLFs) are a family of zinc-finger transcription factors that are found in many species. Recent studies have shown that KLFs play a fundamental role in regulating diverse biological processes such as cell proliferation, differentiation, development and regeneration. Of note, several KLFs are also crucial for maintaining pluripotency and, hence, have been linked to reprogramming and regenerative medicine approaches. Here, we review the crucial functions of KLFs in mammalian embryogenesis, stem cell biology and regeneration, as revealed by studies of animal models. We also highlight how KLFs have been implicated in human diseases and outline potential avenues for future research.

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Kruppel-like Factor 15 Is a Critical Regulator of Cardiac Lipid Metabolism

Cited by 103 publications

References 60 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

Glucocorticoids enhance muscle endurance and ameliorate Duchenne muscular dystrophy through a defined metabolic program

Krüppel-like factors in mammalian stem cells and development

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