TFE3 Alleviates Hepatic Steatosis through Autophagy-Induced Lipophagy and PGC1α-Mediated Fatty Acid β-Oxidation

Xiong, Jie; Wang, Kezhou; He, Jiangping; Zhang, Guangya; Zhang, Dandan; Chen, Fengling

doi:10.3390/ijms17030387

Cited by 44 publications

(31 citation statements)

References 34 publications

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“…(61) Lentivirus-mediated overexpression of this transcriptional regulator in hepatoma cells results in an increased association of LC3 with LDs and reductions in total cellular lipid content. (62) It is unknown, however, if similar results are observed in vivo. Similarly, knockout of TFEB, another transcriptional regulator of lysosome biogenesis, also resulted in an accumulation of hepatocellular LDs.…”

Section: Regulation Of Hepatic Lipophagymentioning

confidence: 95%

“…Transcriptional regulation of lipophagy may thus be mediated by factors such as the transcription factor TFE3, which binds to promoters key to the process of lysosomal biogenesis . Lentivirus‐mediated overexpression of this transcriptional regulator in hepatoma cells results in an increased association of LC3 with LDs and reductions in total cellular lipid content . It is unknown, however, if similar results are observed in vivo .…”

Section: Regulation Of Hepatic Lipophagymentioning

confidence: 99%

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Hepatic lipophagy: New insights into autophagic catabolism of lipid droplets in the liver

Schulze

Drižytė

Casey

et al. 2017

Hepatology Communications

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The liver is a central fat‐storage organ, making it especially susceptible to steatosis as well as subsequent inflammation and cirrhosis. The mechanisms by which the liver mobilizes stored lipid for energy production, however, remain incompletely defined. The catabolic process of autophagy, a well‐known process of bulk cytoplasmic recycling and cellular self‐regeneration, is a central regulator of lipid metabolism in the liver. In the past decade, numerous studies have examined a selective form of autophagy that specifically targets a unique neutral lipid storage organelle, the lipid droplet, to better understand the function for this process in hepatocellular fatty acid metabolism. In the liver (and other oxidative tissues), this specialized pathway, lipophagy, likely plays as important a role in lipid turnover as conventional lipase‐driven lipolysis. In this review, we highlight several recent studies that have contributed to our understanding about the regulation and effects of hepatic lipophagy. (Hepatology Communications 2017;1:359–369)

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Section: Regulation Of Hepatic Lipophagymentioning

confidence: 95%

Section: Regulation Of Hepatic Lipophagymentioning

confidence: 99%

Hepatic lipophagy: New insights into autophagic catabolism of lipid droplets in the liver

Schulze

Drižytė

Casey

et al. 2017

Hepatology Communications

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“…TFE3 also regulates lipophagy in the liver. Specifically, liver-specific ablation of TFE3 promotes steatosis, and overexpression reduces steatosis via lipophagy [76]. In contrast, adipose-specific overexpression of TFE3 increases adiposity [77], which may be explained by studies showing that autophagy promotes adipocyte differentiation [78–80].…”

Section: Regulation Of Lipophagymentioning

confidence: 99%

Breaking fat: The regulation and mechanisms of lipophagy

Schulze

Sathyanarayan

Mashek

2017

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

189

115

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Lipophagy is defined as the autophagic degradation of intracellular lipid droplets (LDs). While the field of lipophagy research is relatively young, an expansion of research in this area over the past several years has greatly advanced our understanding of lipophagy. Since its original characterization in fasted liver, the contribution of lipophagy is now recognized in various organisms, cell types, metabolic states and disease models. Moreover, recent studies provide exciting new insights into the underlying mechanisms of lipophagy induction as well as the consequences of lipophagy on cell metabolism and signaling. This review summarizes recent work focusing on LDs and lipophagy as well as highlighting challenges and future directions of research as our understanding of lipophagy continues to grow and evolve.

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“…Members of this family including TFEB or TFE3 can both induce lipophagy and reduce hepatic lipid accumulation. In contrast, the absence of either TFEB or TFE3 increases lipid accumulation [38,39]. TFEB/TFE3 also target the peroxisome proliferator-activated receptors (PPAR) and PPAR-gamma coactivator-1 family of transcription factors and coactivators.…”

Section: Regulation Of Lipophagymentioning

confidence: 99%

“…TFEB/TFE3 also target the peroxisome proliferator-activated receptors (PPAR) and PPAR-gamma coactivator-1 family of transcription factors and coactivators. These assist in driving transcription of mitochondrial and fatty acid oxidation genes allowing full utilization of the fatty acid products of lipophagy [38,39]. Two other recent studies identified farnesoid-X receptor (FXR) as a transcriptional repressor of autophagy (Fig.…”

Section: Regulation Of Lipophagymentioning

confidence: 99%

Classical and alternative roles for autophagy in lipid metabolism

Zhang

Evans

Jeong

et al. 2018

Current Opinion in Lipidology

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Purpose of review Intracellular lipid metabolism is a complex interplay of exogenous lipid handling, trafficking, storage, lipolysis, and export. Recent work has implicated the cellular degradative process called autophagy in several aspects of lipid metabolism. We will discuss both the classical and novel roles of autophagy and the autophagic machinery in this setting. Recent findings The delivery of lipid droplets to lysosomes for hydrolysis, named lipophagy, was the first described functional role for autophagy in lipid metabolism. The molecular machinery and regulation of this selective form of macroautophagy is beginning to be discovered and has the potential to shed enormous light on intracellular lipolysis. Yet, the autophagic machinery appears to also be coopted for alternative roles that include interaction with cytosolic lipolysis pathways, supply and expansion of lipid droplets, and lipoprotein trafficking. Additionally, lesser studied forms of autophagy called microautophagy and chaperone-mediated autophagy have distinct roles in lipid handling that also intersect with classical macroautophagy. The integration of current knowledge in these areas into a holistic understanding of intracellular lipid metabolism will be a goal of this review. Summary As the field of autophagy has evolved and expanded to include functional roles in various aspects of cellular degradation, so has its role in intracellular lipid metabolism. Understanding the mechanisms underlying these classical and alternative roles of autophagy will not only enhance our knowledge in lipid biology but also provide new avenues of translation to human lipid disorders.

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TFE3 Alleviates Hepatic Steatosis through Autophagy-Induced Lipophagy and PGC1α-Mediated Fatty Acid β-Oxidation

Cited by 44 publications

References 34 publications

Hepatic lipophagy: New insights into autophagic catabolism of lipid droplets in the liver

Hepatic lipophagy: New insights into autophagic catabolism of lipid droplets in the liver

Breaking fat: The regulation and mechanisms of lipophagy

Classical and alternative roles for autophagy in lipid metabolism

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