Regulation of lipid droplet-associated proteins by peroxisome proliferator-activated receptors

Rodriguez, Montserrat A. de la Rosa; Kersten, Sander

doi:10.1016/j.bbalip.2017.07.007

Cited by 67 publications

(51 citation statements)

References 108 publications

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“…Our results indicated that NEAT1 also mediates lipolysis in HCC cells, indicating that NEAT1 may be a central regulator in lipid metabolism. Other genes play similar central roles in lipid metabolism, including those encoding mTOR, PPARs (peroxisome proliferator-activated receptors), TNF-alpha and SIRT1 [ 34 – 37 ]. Further studies are needed to identify the effect of crosstalk between NEAT1 and these genes.…”

Section: Discussionmentioning

confidence: 99%

Long non-coding RNA NEAT1-modulated abnormal lipolysis via ATGL drives hepatocellular carcinoma proliferation

et al. 2018

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BackgroundAbnormal metabolism, including abnormal lipid metabolism, is a hallmark of cancer cells. Some studies have demonstrated that the lipogenic pathway might promote the development of hepatocellular carcinoma (HCC). However, the role of the lipolytic pathway in HCC has not been elucidated.MethodsWe compared levels of adipose triglyceride lipase (ATGL) in human HCC and healthy liver tissues by real time PCR, western blot and immunohistochemistry. We measured diacylglycerol(DAG) and free fatty acid (FFA) levels in HCC cells driven by the NEAT1-ATGL axis and in HCC tissues. We also assessed the effects of ATGL, DAG, FFA, and NEAT1 on HCC cells proliferation in vitro and in an orthotopic xenograft HCC mouse model. We also performed a luciferase reporter assay to investigate the interaction between NEAT1/ATGL and miR-124-3p.ResultsWe found that the lipolytic enzyme, ATGL is highly expressed in human HCC tissues and predicts poor prognosis. We also found that high levels of DAG and FFA are present in HCC tissues. Furthermore, the lncRNA-NEAT1 was found to modulate ATGL expression and disrupt lipolysis in HCC cells via ATGL. Notably, ATGL and its products, DAG and FFA, were shown to be responsible for NEAT1-mediated HCC cell growth. NEAT1 regulated ATGL expression by binding miR-124-3p. Additionally, NEAT1 knockdown attenuated HCC cell growth through miR-124-3p/ATGL/DAG+FFA/PPARα signaling.ConclusionOur results reveal that NEAT1-modulates abnormal lipolysis via ATGL to drive HCC proliferation.Electronic supplementary materialThe online version of this article (10.1186/s12943-018-0838-5) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Long non-coding RNA NEAT1-modulated abnormal lipolysis via ATGL drives hepatocellular carcinoma proliferation

et al. 2018

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“…SLC27A6 is a ubiquitously expressed fatty acid transporter specific to long-chain fats 35 , has been linked to lipid handling in the setting of high dietary fat intake 36 , and is hypothesized to contribute to obesity-related pathophysiology although this has not been established 35 , 37 . FITM2 is an evolutionarily conserved gene required for adipocyte lipid storage and lipid droplet accumulation 38 , and is affected directly by peroxisome proliferator-activated receptors, master regulators of lipid metabolism 39 . These data are suggestive of altered lipid partitioning, favoring storage over catabolic oxidation in RPG infants.…”

Section: Discussionmentioning

confidence: 99%

Altered gene expression and metabolism in fetal umbilical cord mesenchymal stem cells correspond with differences in 5-month-old infant adiposity gain

Baker

Patinkin

Shapiro

et al. 2017

Sci Rep

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The intrauterine period is a critical time wherein developmental exposure can influence risk for chronic disease including childhood obesity. Using umbilical cord-derived mesenchymal stem cells (uMSC) from offspring born to normal-weight and obese mothers, we tested the hypothesis that changes in infant body composition over the first 5 months of life correspond with differences in cellular metabolism and transcriptomic profiles at birth. Higher long-chain acylcarnitine concentrations, lipid transport gene expression, and indicators of oxidative stress in uMSC-adipocytes were related to higher adiposity at 5 months of age. In uMSC-myocytes, lower amino acid concentrations and global differential gene expression for myocyte growth, amino acid biosynthesis, and oxidative stress were related to lower infant percent fat-free mass at 5 months of age, particularly in offspring of obese mothers. This is the first evidence of human infant adipocyte- or myocyte-related alterations in cellular metabolic pathways that correspond with increased adiposity and lower fat-free mass in early infancy. These pathways might reflect the effects of an adverse maternal metabolic environment on the fetal metabolome and genome. Our findings suggest that programmed differences in infant stem cell metabolism correspond with differences in body composition in early life, a known contributor to obesity risk.

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“…In the absence of ligands, the PPAR:retinoid X receptor heterodimer is bound with corepressors such as nuclear receptor corepressors, HDAC, and G-protein pathway suppressor 2, which prevent transcription of the target genes. When a ligand binds to PPAR, the corepressors dissociate from the heterodimer, and coactivators such as PPAR-g coactivator-1 (PGC-1), the histone acetyltransferase p300, cAMP response element binding protein binding protein, and steroid receptor coactivator 1 are recruited to assemble an active transcription initiation complex on the promoter of target genes (2,71,90). Thus, PPARs function as factors promoting the expression of specific target genes.…”

Section: Pparsmentioning

confidence: 99%

“…AMPK activation will eventually lead to higher activity of CPT-1, allowing for more fatty acids to undergo oxidation and produce more energy. Initially, this was thought to be the only mechanism, but it was subsequently discovered that AMPK activation increases expression of PPAR-a, leading to increased transcription of genes involved in fatty acid oxidation such as CPT-1 (71,90,(246)(247)(248). Integrating these data, it seems that the absence of the microbiota culminates in an increase in fatty acid oxidation through the AMPK-PPAR-a pathway.…”

Section: Ppar the Gut Microbiota And Musclementioning

confidence: 99%

The PPAR–microbiota–metabolic organ trilogy to fine‐tune physiology

Visvalingam

Wahli

2019

FASEB j.

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The human gut is colonized by commensal microorganisms, predominately bacteria that have coevolved in symbiosis with their host. The gut microbiota has been extensively studied in recent years, and many important findings on how it can regulate host metabolism have been unraveled. In healthy individuals, feeding timing and type of food can influence not only the composition but also the circadian oscillation of the gut microbiota. Host feeding habits thus influence the type of microbe‐derived metabolites produced and their concentrations throughout the day. These microbe‐derived metabolites influence many aspects of host physiology, including energy metabolism and circadian rhythm. Peroxisome proliferator‐activated receptors (PPARs) are a group of ligand‐activated transcription factors that regulate various metabolic processes such as fatty acid metabolism. Similar to the gut microbiota, PPAR expression in various organs oscillates diurnally, and studies have shown that the gut microbiota can influence PPAR activities in various metabolic organs. For example, short‐chain fatty acids, the most abundant type of metabolites produced by anaerobic fermentation of dietary fibers by the gut microbiota, are PPAR agonists. In this review, we highlight how the gut microbiota can regulate PPARs in key metabolic organs, namely, in the intestines, liver, and muscle. Knowing that the gut microbiota impacts metabolism and is altered in individuals with metabolic diseases might allow treatment of these patients using noninvasive procedures such as gut microbiota manipulation.—Oh, H. Y. P., Visvalingam, V., Wahli, W. The PPAR–microbiota–metabolic organ trilogy to fine‐tune physiology. FASEB J. 33, 9706–9730 (2019). http://www.fasebj.org

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Regulation of lipid droplet-associated proteins by peroxisome proliferator-activated receptors

Cited by 67 publications

References 108 publications

Long non-coding RNA NEAT1-modulated abnormal lipolysis via ATGL drives hepatocellular carcinoma proliferation

Long non-coding RNA NEAT1-modulated abnormal lipolysis via ATGL drives hepatocellular carcinoma proliferation

Altered gene expression and metabolism in fetal umbilical cord mesenchymal stem cells correspond with differences in 5-month-old infant adiposity gain

The PPAR–microbiota–metabolic organ trilogy to fine‐tune physiology

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