Dysregulation of lipid homeostasis leads to the development of metabolic disorders including obesity, diabetes, cardiovascular disease and cancer. Lipid droplets (LDs) are subcellular organelles ...vital in the maintenance of lipid homeostasis by coordinating lipid synthesis, lipid storage, lipid secretion and lipolysis. Under fed condition, free fatty acids (FFAs) are remodeled and esterified into neutral lipids by lipogenesis and stored in the LDs. The lipid storage capacity of LDs is controlled by its growth via local lipid synthesis or by LD fusion. During fasting, neutral lipids are hydrolyzed by lipolysis, released as FFAs and secreted to meet energy demand. Cell death‐inducing DNA fragmentation factor alpha (DFFA)‐like effector (CIDE) family proteins composed of Cidea, Cideb and Cidec/Fsp27 are ER‐ and LD‐associated proteins and have emerged as important regulators of lipid homeostasis. Notably, when localized on the LDs, CIDE proteins enrich at the LD‐LD contact sites (LDCSs) and control LD fusion and growth. Here, we summarize these recent advances made on the role of CIDE proteins in the regulation of lipid metabolism with a particular focus on the molecular mechanisms underlying CIDE‐mediated LD fusion and growth.
CIDE proteins are important regulators of lipid homeostasis by coordinating various cellular lipid metabolic pathways including lipid storage, secretion and synthesis.
The cell death‐inducing DFF45‐like effector (CIDE) proteins, including Cidea, Cideb, and Cidec/Fsp27, regulate various aspects of lipid homeostasis, including lipid storage, lipolysis, and lipid ...secretion. This review focuses on the physiological roles of CIDE proteins based on studies on knockout mouse models and human patients bearing CIDE mutations. The primary cellular function of CIDE proteins is to localize to lipid droplets (LDs) and to control LD fusion and growth across different cell types. We propose a four‐step process of LD fusion, characterized by (a) the recruitment of CIDE proteins to the LD surface and CIDE movement, (b) the enrichment and condensate formation of CIDE proteins to form LD fusion plates at LD–LD contact sites, (c) lipid transfer through lipid‐permeable passageways within the fusion plates, and (d) the completion of LD fusion. Lastly, we outline CIDE‐interacting proteins as regulatory factors, as well as their contribution in LD fusion.
Three members of CIDE proteins play important roles in several aspects of lipid metabolism through different tissue distribution, cellular localization, and interacting proteins. We review the molecular and cellular mechanisms of CIDE proteins in controlling lipid droplet fusion and lipid storage, promoting lipid secretion, and regulating activities of transcriptional factors.
Abstract Statement of problem Limited evidence is available for the marginal and internal fit of fixed dental restorations fabricated with digital impressions compared with those fabricated with ...conventional impressions. Purpose The purpose of this systematic review was to compare marginal and internal fit of fixed dental restorations fabricated with digital techniques to those fabricated using conventional impression techniques and to determine the effect of different variables on the accuracy of fit. Material and methods Medline, Cochrane, and EMBASE databases were electronically searched and enriched by hand searches. Studies evaluating the fit of fixed dental restorations fabricated with digital and conventional impression techniques were identified. Pooled data were statistically analyzed, and factors affecting the accuracy of fit were identified, and their impact on accuracy of fit outcomes were assessed. Results Dental restorations fabricated with digital impression techniques exhibited similar marginal misfit to those fabricated with conventional impression techniques (P>.05). Both marginal and internal gaps were greater for stone die casts, whereas digital dies produced restorations with the smallest gaps ( P <.05). When a digital impression was used to generate stereolithographic (SLA)/polyurethane dies, misfit values were intermediate. The fabrication technique, the type of restoration, and the impression material had no effect on misfit values ( P >.05), whereas die and restoration materials were statistically associated ( P <.05). Conclusions Although conclusions were based mainly on in vitro studies, the digital impression technique provided better marginal and internal fit of fixed restorations than conventional techniques did.
An extended Kalman-based interacting multiple model (EK-IMM) smoother is proposed for mobile location estimation with the data fusion of the time of arrival (TOA) and the received signal strength ...(RSS) measurements in a rough wireless environment. The extended Kalman filter is used for nonlinear estimation. The IMM is employed as a switch between the line-of-sight (LOS) and non-LOS (NLOS) states, which are considered to be a Markov process with two interactive modes. Combining extended Kalman filtering with the IMM scheme for accurately smooth range estimation between the corresponding base station (BS) and mobile station (MS) in the rough wireless environment, the proposed robust mobile location estimator, in association with data fusion, can efficiently mitigate the NLOS effects on the measurement range error. Simulation results illustrate that the performance of the proposed method has been significantly improved in the LOS/NLOS transition case. Moreover, the performance of the EK-IMM smoother with data fusion is also better than that with a single measurement used alone.
Control of lipid droplet fusion and growth by CIDE family proteins Gao, Guangang; Chen, Feng-Jung; Zhou, Linkang ...
Biochimica et biophysica acta. Molecular and cell biology of lipids,
October 2017, 2017-Oct, 2017-10-00, 20171001, Volume:
1862, Issue:
10
Journal Article
Peer reviewed
Cell death-inducing DFF45-like effector (CIDE) family proteins including Cidea, Cideb and Cidec/Fsp27 are expressed in many different tissues and are known as lipid droplet (LD)-and ER-associated ...proteins. Systematic analyses using genetically modified animal models have demonstrated that CIDE proteins play important roles in regulating various aspects of lipid homeostasis, including lipid storage, lipolysis and lipid secretion. Recent research in ours and other laboratories has revealed that CIDE proteins are crucial regulators of LD fusion and growth in the adipose tissue, liver, skin and mammary glands. CIDE-mediated LD fusion and growth is different from other membrane fusions in that it requires CIDE proteins to be enriched and clustered at the LD-LD contact sites (LDCS). The enriched CIDE proteins then allow the recruitment of other proteins to the LDCS and the formation of potential fusion pores. Neutral lipids in the smaller LDs of the contacted pair are transferred to the larger LDs, owing to the internal pressure difference, thus resulting in the fusion and growth of the LDs. This review summarizes the physiological roles of CIDE proteins in controlling lipid homeostasis, insulin sensitivity and the development of metabolic diseases including obesity, diabetes and fatty liver, with a particular focus on the role of CIDE proteins in controlling LD fusion and growth. This article is part of a Special Issue entitled: Recent Advances in Lipid Droplet Biology edited by Rosalind Coleman and Matthijs Hesselink.
•CIDEs control lipid storage and regulate insulin sensitivity.•CIDEs control LD fusion and growth.•Transcriptional and post-translational regulation of CIDEs.
SREBPs are master regulators of lipid homeostasis and undergo sterol‐regulated export from ER to Golgi apparatus for processing and activation via COPII‐coated vesicles. While COPII recognizes SREBP ...through its escort protein SCAP, factor(s) specifically promoting SREBP/SCAP loading to the COPII machinery remains unknown. Here, we show that the ER/lipid droplet‐associated protein Cideb selectively promotes the loading of SREBP/SCAP into COPII vesicles. Sterol deprivation releases SCAP from Insig and enhances ER export of SREBP/SCAP by inducing SCAP‐Cideb interaction, thereby modulating sterol sensitivity. Moreover, Cideb binds to the guanine nucleotide exchange factor Sec12 to enrich SCAP/SREBP at ER exit sites, where assembling of COPII complex initiates. Loss of Cideb inhibits the cargo loading of SREBP/SCAP, reduces SREBP activation, and alleviates diet‐induced hepatic steatosis. Our data point to a linchpin role of Cideb in regulated ER export of SREBP and lipid homeostasis.
Synopsis
Factors that mediate sterol‐regulated targeting of SREBP/SCAP to COPII vesicles for lipid homeostasis are unknown. Cideb is an ER/lipid droplet‐localized protein that binds escort factor SCAP and SAR21 GTPase to promote ER‐to‐Golgi transport of SREBBP/SCAP on COPII vesicles.
Cideb deficiency abrogates COPII‐mediated SREBP activation in mouse liver.
Sterol‐controlled Cideb/SCAP interaction regulates SREBP processing and sterol sensitivity.
Cideb transfers SCAP/SREBP to the active budding machinery by interacting with Sec12.
Loss of Cideb inhibits the cargo loading of SREBP/SCAP, reduces SREBP activation, and protects mice from diet‐induced non‐alcoholic fatty liver disease.
The ER/lipid droplet‐localized protein Cideb binds escort factor SCAP and SAR21 GTPase to promote ER‐to‐Golgi transport of SREBP/SCAP on COPII vesicles.
This review summarizes the anti-diabetic effects of Ganoderma lucidum. Four types of molecules, proteins, proteoglycans, polysaccharides and triterpenoids were shown to regulate multiple pathways in ...the performance of anti-diabetic activities. Display omitted
•Polysaccharides inhibit glycogenolysis and gluconeogenesis.•Proteoglycans inhibit PTP1B activity, glucose transported 2 and 4 expression.•Triterpenoids inhibit aldose reductase and α-glucosidase.•Ling Zhi-8 stimulates expansion of FOXP3+ regulatory T-cells (FOXP3+ Treg).
Ganoderma lucidum is a white rot fungus widely used as a tonic for the promotion of longevity and health. Extracts of G. lucidum have been recognized as an alternative adjuvant treatment for diabetes. Among the many biologically active constituents of G. lucidum, polysaccharides, proteoglycans, proteins and triterpenoids have been shown to have hypoglycemic effects. G. lucidum polysaccharides have been reported to have hypoglycemic activity by increasing plasma insulin levels and decreasing plasma sugar levels in mice. Protein tyrosine phosphatase 1B is a promising therapeutic target in diabetes, and G. lucidum proteoglycan can inhibit this enzyme in vitro. Moreover, G. lucidum triterpenoids were shown to have inhibitory activity on aldose reductase and α-glucosidase that can suppress postprandial hyperglycemia. In addition, a protein Ling Zhi-8 extracted from G. lucidum significantly decreased lymphocyte infiltration and increased the antibody detection of insulin in diabetic mice. This review summarizes most of the research about the hypoglycemic action effects of polysaccharides, proteoglycans, proteins and tritrerpenoids from G. lucidum as a guide for future research.
This Special Issue, entitled “Food Processing and Food Analysis: Principles, Techniques, and Applications”, explores perspectives and latest advances in the field of food science ...
How amphipathic phospholipids are shuttled between the membrane bilayer remains an essential but elusive process, particularly at the endoplasmic reticulum (ER). One prominent phospholipid shuttling ...process concerns the biogenesis of APOB-containing lipoproteins within the ER lumen, which may require bulk trans-bilayer movement of phospholipids from the cytoplasmic leaflet of the ER bilayer. Here, we show that TMEM41B, present in the lipoprotein export machinery, encodes a previously conceptualized ER lipid scramblase mediating trans-bilayer shuttling of bulk phospholipids. Loss of hepatic TMEM41B eliminates plasma lipids, due to complete absence of mature lipoproteins within the ER, but paradoxically also activates lipid production. Mechanistically, scramblase deficiency triggers unique ER morphological changes and unsuppressed activation of SREBPs, which potently promotes lipid synthesis despite stalled secretion. Together, this response induces full-blown nonalcoholic hepatosteatosis in the TMEM41B-deficient mice within weeks. Collectively, our data uncovered a fundamental mechanism safe-guarding ER function and integrity, dysfunction of which disrupts lipid homeostasis.
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•TMEM41B associates with lipoproteins and encodes an ER lipid scramblase•Hepatic TMEM41B is required for lipoprotein biogenesis and lipid homeostasis•TMEM41B deficiency triggers drastic morphological changes of the ER membrane•TMEM41B deficiency causes unsuppressed SREBP activation and full-blown NASH
Chen and colleagues showed that TMEM41B encodes an ER lipid scramblase and executes a produce-and-protect mechanism for ER function and integrity. Deficiency of TMEM41B triggers severe metabolic defects independent of the canonical ER stress pathway and potently promotes lipid synthesis.
A Kalman-based interacting multiple model (IMM) smoother is proposed for mobile location estimation with the time of arrival (TOA) measurement data in cellular networks to meet the Federal ...Communications Commission (FCC) requirement for phase 2. In this study, the line-of-sight (LOS) and non-line-of-sight (NLOS) conditions in cellular networks are considered as a Markov process with two interactive modes. Then we propose a Kalman-based IMM smoother to accurately estimate smooth range between the corresponding base station (BS) and mobile station (MS) in cellular networks. It is shown that the proposed mobile location estimator can efficiently mitigate the NLOS effects of the measurement range error even when the corresponding BS changes the condition between LOS and NLOS. Simulation results demonstrate that the performance of the proposed Kalman-based IMM smoother is improved significantly over the FCC target in both fixed LOS/NLOS and LOS/NLOS transition conditions
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