Control of lipid droplet fusion and growth by CIDE family proteins

Gao, Guangang; Chen, Feng‐Jung; Zhou, Linkang; Su, Lü; Xu, Duanyi; Xu, Li; Li, Peng

doi:10.1016/j.bbalip.2017.06.009

Cited by 94 publications

(96 citation statements)

References 85 publications

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“…The data demonstrate decreased lipid export, gluconeogenesis, and de novo lipogenesis, as well as a pronounced increase of lipid particle formation and fusion genes in macrosteatotic hepatocytes. In agreement with the current understanding (Gao et al, ; Gong et al, ; Kang et al, ; Xu et al, ), our comprehensive LCM‐based analysis supports a close relationship between microvesicular and macrovesicular LD development. Overall, the data suggest microvesicular steatosis to be an intermediate between nonsteatotic and macrovesicular compartments, and to be relatively benign.…”

Section: Resultssupporting

confidence: 91%

Molecular Characterization of Microvesicular and Macrovesicular Steatosis Shows Widespread Differences in Metabolic Pathways

Kristiansen

Veidal

Christoffersen

et al. 2019

Lipids

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Simple steatosis is the hallmark of nonalcoholic fatty liver disease, with lipid accumulating as either microvesicular or macrovesicular lipid droplets within hepatocytes. The present study used a combination of laser capture microdissection and RNAseq to characterize murine gene expression in nonsteatotic, microsteatotic, and macrosteatotic compartments collected from the same liver. The data indicate that microvesicular steatosis is intermediate to macrovesicular steatosis, showing a widespread and pronounced metabolic gene regulation of lipid export, gluconeogenesis, and de novo lipogenesis. Key enzymes, such as fatty acid synthase and fructose 1,6‐bisphosphatase as well as apolipoprotein C‐III, were identified to show clear expression differences between the compartments. Furthermore, increased expression of lipid particle formation genes provided a molecular description of the fusion of microsteatotic lipid compartments to produce macrosteatotic cells with a single enlarged lipid droplet.

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Section: Resultssupporting

confidence: 91%

Molecular Characterization of Microvesicular and Macrovesicular Steatosis Shows Widespread Differences in Metabolic Pathways

Kristiansen

Veidal

Christoffersen

et al. 2019

Lipids

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“…Accordingly, we identified a number of protein expression changes that may contribute to elevated placental lipid from obese sows. Cell death‐inducing DFF45‐like effector A (CIDEA), which plays crucial roles in regulating lipid storage and lipid droplet fusion and growth (Gao et al.,), was increased in placenta from obese sows. In addition, maternal obesity was associated with elevated FASN, ACACA, and lipoprotein lipase (LPL) and decreased angiopoietin‐like protein 4 (ANGPTL4), which has been shown to inhibit LPL activity (Lafferty, Bradford, Erie, & Neher,), suggesting augmented lipid uptake and lipogenesis in placenta of obese sows.…”

Section: Discussionmentioning

confidence: 99%

Maternal obesity stimulates lipotoxicity and up‐regulates inflammatory signaling pathways in the full‐term swine placenta

Liang

Jinglong

Dong

et al. 2018

Animal Science Journal

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This study aimed to investigate the effects of back-fat thickness (BF), at mating of sows, on placental lipotoxicity, oxidative stress, and inflammation. We performed iTRAQ labeling-based proteomic analysis on term placentas obtained by vaginal delivery from BFI (15-20 mm, control) and BFII (21-27 mm, obese) sows formed according to BF at mating. Proteomic analysis revealed 413 proteins to be significantly different in placenta from BFII sows by ≥1.2-fold. Gene ontology (GO) analysis identified proteins related to lipid metabolism and inflammatory response to be altered in placenta from obese sows. Indicative of a lipotoxic placental environment, increased placental lipid, and up-regulated mRNA expression of lipogenic genes, including ADRP (p = .06), PPARD, FASN, ACACA, DGAT1, and LIPIN3, were associated with decreased AMPK and increased activation of WNT signaling in placenta from BFII group (p < .05). Furthermore, we observed a 18% decrease in total antioxidant capacity (TAC), increased mRNA content of pro-inflammatory cytokines IL-6, IL-18, and TNF-α, and increased activation of inflammatory NF-κB and JNK signaling in placenta from BFII sows that was significantly associated with macrophage accumulation (p < .05). These findings suggest that maternal obesity aggravates a lipotoxic environment in pig term placenta that may be associated with placental dysfunction and impaired fetal growth.

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“…In the present study, we observed the significant decrease in the size of lipid droplets. Cell death‐inducing DFFA‐like effector proteins have emerged as key regulators of LDs . We evaluated the expression of the Fsp27 gene, which was predominantly expressed in white adipocytes as well as steatotic livers .…”

Section: Discussionmentioning

confidence: 99%

“…Lipid droplets are composed of a central core of neutral lipids surrounded by a phospholipid monolayer and proteins, and can quickly expand or shrink, governed by a special set of LD‐associated proteins . Recent research has revealed cell death‐inducing DFFA‐like effector (CIDE) family proteins are key regulators of LD fusion and growth in the adipose tissue, liver, skin, and mammary glands . The CIDE protein family, including CIDEA, CIDEB, and cell‐death‐inducing DFFA‐like effector c (CIDEC) (FSP27 in mice) has been detected in metabolically active tissues.…”

Section: Introductionmentioning

confidence: 99%

“…The CIDE protein family, including CIDEA, CIDEB, and cell‐death‐inducing DFFA‐like effector c (CIDEC) (FSP27 in mice) has been detected in metabolically active tissues. FSP27 is commonly strongly expressed in white adipocytes and steatotic hepatocytes, but is undetectable in normal liver . FSP27 is present at LD‐LD contact sites and promotes the formation of large LDs .…”

Section: Introductionmentioning

confidence: 99%

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Eicosapentaenoic acid‐enriched phospholipids suppressed lipid accumulation by specific inhibition of lipid droplet‐associated protein FSP27 in mice

et al. 2020

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BACKGROUND Sea cucumber is a rich source of eicosapentaenoic acid in the form of eicosapentaenoic acid‐enriched phospholipids (EPA‐PL). It is known to be efficacious in preventing obesity. However, few studies have focused on the role of EPA‐PL in inhibiting lipid accumulation by lipid droplets (LDs). This study first investigated the effect of EPA‐PL from sea cucumber on the formation of LDs and the underlying mechanism in C57BL/6J mice. The mice were randomly divided into two groups and treated for 8 weeks or 3, 7, and 14 days with either (i) a high‐sucrose diet (model group), (ii) a high‐sucrose diet plus 2% EPA‐PL (EPA‐PL group). RESULTS Eight‐week EPA‐PL supplementation significantly reduced lipid accumulation and LD size in liver and white adipose tissue (WAT), which was accompanied by the decreased expression of LDs‐associated protein FSP27. A 3‐day EPA‐PL treatment suppressed the mRNA expression of Fsp27. The mRNA level of Fsp27 reached its ‘normal level’ after withdrawing EPA‐PL for 7 days, suggesting that EPA‐PL might serve as a rapid regulator of FSP27. Furthermore, EPA‐PL increased the expression of lipolysis genes Hsl and Atgl accompanied by the regulation of Pparγ in WAT. CONCLUSIONS Dietary EPA‐PL from sea cucumber (Cucumaria frondosa) protected against lipid accumulation by regulating LDs‐associated protein FSP27, which might provide novel evidence for the anti‐obesity action of EPA‐PL. © 2020 Society of Chemical Industry

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Control of lipid droplet fusion and growth by CIDE family proteins

Cited by 94 publications

References 85 publications

Molecular Characterization of Microvesicular and Macrovesicular Steatosis Shows Widespread Differences in Metabolic Pathways

Molecular Characterization of Microvesicular and Macrovesicular Steatosis Shows Widespread Differences in Metabolic Pathways

Maternal obesity stimulates lipotoxicity and up‐regulates inflammatory signaling pathways in the full‐term swine placenta

Eicosapentaenoic acid‐enriched phospholipids suppressed lipid accumulation by specific inhibition of lipid droplet‐associated protein FSP27 in mice

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