scholarly journals Dietary fatty acids promote lipid droplet diversity through seipin enrichment in an ER subdomain

2018 ◽  
Author(s):  
Zhe Cao ◽  
Yan Hao ◽  
Yiu Yiu Lee ◽  
Pengfei Wang ◽  
Xuesong Li ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Polyunsaturated Fatty Acids ◽  
Lipid Droplet ◽  
Mammalian Cells ◽  
Dietary Fatty Acids ◽  
Fat Storage ◽  
Over Expression ◽  
C Elegans ◽  
Cyclopropane Fatty Acids ◽  
Host Metabolism

AbstractExogenous metabolites from microbial and dietary origins have profound effects on host metabolism. Here, we report that a sub-population of lipid droplets (LDs), which are conserved organelles for fat storage, is defined by metabolites-driven targeting of theC. elegansseipin ortholog, SEIP-1. Loss of SEIP-1 function reduced the size of a subset of LDs while over-expression of SEIP-1 had the opposite effect. Ultrastructural analysis revealed SEIP-1 enrichment in an endoplasmic reticulum (ER) subdomain, which co-purified with LDs. Analyses ofC. elegansand bacterial genetic mutants indicated a requirement of polyunsaturated fatty acids (PUFAs) and microbial cyclopropane fatty acids (CFAs) for SEIP-1 enrichment, as confirmed by dietary supplementation experiments. In mammalian cells, heterologous expression of SEIP-1 promoted lipid droplet expansion from ER subdomains in a conserved manner. Our results suggest that microbial and polyunsaturated fatty acids serve unexpected roles in regulating cellular fat storage by enforcing LD diversity.

scholarly journals The endoplasmic reticulum-resident protein TMEM-120/TMEM120A promotes fat storage in C. elegans and mammalian cells

2021 ◽  
Author(s):  
Yan Li ◽  
Siwei Huang ◽  
Xuesong Li ◽  
Xingyu Yang ◽  
Ningyi Xu ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Endoplasmic Reticulum ◽  
Mammalian Cells ◽  
Lipid Droplets ◽  
Stimulated Raman Scattering ◽  
Transmembrane Helices ◽  
Fat Storage ◽  
Over Expression ◽  
C Elegans

The synthesis of triacylglycerol (TAG) is essential for the storage of excess fatty acids, which can subsequently be used for energy or cell growth. A series of enzymes act in the endoplasmic reticulum (ER) to synthesize TAG, prior to its transfer to lipid droplets (LDs), which are conserved organelles for fat storage. Here, we report that the deficiency of TMEM-120/TMEM120A, a protein with 6-transmembrane helices, retards TAG synthesis and LD expansion in C. elegans. GFP fusion proteins of TMEM-120, expressed at the endogenous level in live worms, were observed throughout the ER network. Using Stimulated Raman Scattering, we demonstrated the specific requirement of TMEM-120 in the storage of exogenous fatty acids in LDs. Knockdown of TMEM120A impedes adipogenesis of pre-adipocytes in vitro, while its over-expression is sufficient to promote LD expansion in mammalian cells. Our results suggest that TMEM-120/TMEM120A plays a conserved role in increasing the efficiency of TAG synthesis.

scholarly journals Membrane fluidity is regulated by the C. elegans transmembrane protein FLD-1 and its human homologs TLCD1/2

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Mario Ruiz ◽  
Rakesh Bodhicharla ◽  
Emma Svensk ◽  
Ranjan Devkota ◽  
Kiran Busayavalasa ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Polyunsaturated Fatty Acids ◽  
Membrane Fluidity ◽  
Polyunsaturated Fatty Acid ◽  
Dietary Fatty Acids ◽  
Editorial Note ◽  
Membrane Phospholipids ◽  
C Elegans ◽  
Long Chain

Dietary fatty acids are the main building blocks for cell membranes in animals, and mechanisms must therefore exist that compensate for dietary variations. We isolated C. elegans mutants that improved tolerance to dietary saturated fat in a sensitized genetic background, including eight alleles of the novel gene fld-1 that encodes a homolog of the human TLCD1 and TLCD2 transmembrane proteins. FLD-1 is localized on plasma membranes and acts by limiting the levels of highly membrane-fluidizing long-chain polyunsaturated fatty acid-containing phospholipids. Human TLCD1/2 also regulate membrane fluidity by limiting the levels of polyunsaturated fatty acid-containing membrane phospholipids. FLD-1 and TLCD1/2 do not regulate the synthesis of long-chain polyunsaturated fatty acids but rather limit their incorporation into phospholipids. We conclude that inhibition of FLD-1 or TLCD1/2 prevents lipotoxicity by allowing increased levels of membrane phospholipids that contain fluidizing long-chain polyunsaturated fatty acids.Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (<xref ref-type="decision-letter" rid="SA1">see decision letter</xref>).

scholarly journals Polyunsaturated Fatty Acids Mediated Regulation of Membrane Biochemistry and Tumor Cell Membrane Integrity

Membranes ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 479
Author(s):  
Souvik Mukerjee ◽  
Abdulaziz S. Saeedan ◽  
Mohd. Nazam Ansari ◽  
Manjari Singh
Keyword(s):  
Fatty Acids ◽  
Polyunsaturated Fatty Acids ◽  
Human Health ◽  
Biological Membrane ◽  
Membrane Integrity ◽  
Dietary Fatty Acids ◽  
Body System ◽  
Omega 3 ◽  
Membrane Composition ◽  
Tumor Cell Membrane

Particular dramatic macromolecule proteins are responsible for various cellular events in our body system. Lipids have recently recognized a lot more attention of scientists for understanding the relationship between lipid and cellular function and human health However, a biological membrane is formed with a lipid bilayer, which is called a P–L–P design. Our body system is balanced through various communicative signaling pathways derived from biological membrane proteins and lipids. In the case of any fatal disease such as cancer, the biological membrane compositions are altered. To repair the biological membrane composition and prevent cancer, dietary fatty acids, such as omega-3 polyunsaturated fatty acids, are essential in human health but are not directly synthesized in our body system. In this review, we will discuss the alteration of the biological membrane composition in breast cancer. We will highlight the role of dietary fatty acids in altering cellular composition in the P–L–P bilayer. We will also address the importance of omega-3 polyunsaturated fatty acids to regulate the membrane fluidity of cancer cells.

scholarly journals Deuterated Polyunsaturated Fatty Acids Reduce Oxidative Stress and Extend the Lifespan of C. elegans

2019 ◽  
Vol 10 ◽  
Author(s):  
Caroline Beaudoin-Chabot ◽  
Lei Wang ◽  
Alexey V. Smarun ◽  
Dragoslav Vidović ◽  
Mikhail S. Shchepinov ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Fatty Acids ◽  
Polyunsaturated Fatty Acids ◽  
C Elegans

Functional analysis of rat liver citrate carrier promoter: differential responsiveness to polyunsaturated fatty acids

2008 ◽  
Vol 417 (2) ◽  
pp. 561-571 ◽  
Author(s):  
Fabrizio Damiano ◽  
Gabriele V. Gnoni ◽  
Luisa Siculella
Keyword(s):  
Fatty Acids ◽  
Arachidonic Acid ◽  
Docosahexaenoic Acid ◽  
Polyunsaturated Fatty Acids ◽  
Dietary Fatty Acids ◽  
Luciferase Reporter ◽  
H4iie Cells ◽  
E Box ◽  
Citrate Carrier ◽  
Response Region

CiC (citrate carrier), a mitochondrial membrane protein, plays an important metabolic role by transporting acetyl-CoA into the cytosol for fatty acid and cholesterol synthesis. Several studies showed that CiC activity and expression is regulated by dietary fatty acids. In the present study we report data on the structural and functional characterization of the 5′-flanking region of the rat Cic gene. By transient transfection assays in H4IIE rat hepatoma cells, a PUFA (polyunsaturated fatty acids) response region has been identified within the CiC promoter. A cluster of putative binding sites for several transcription factors, composed of a NF-Y (nuclear factor-Y) site, an E-box-like site, a SRE1 (sterol regulatory element 1)-like site and four Sp1 (stimulatory protein 1) sites, was localized in the promoter region. Luciferase reporter gene and gel mobility shift assays indicated that a functional E-box-like, essential to the basal CiC promoter activity, confers responsiveness to activation by SREBP (SRE-binding protein)-1c. This study provides evidence for SREBP-1c as a principal target for PUFA regulation of CiC transcription. In H4IIE cells, overexpression of nSREBP (nuclear SREBP)-1c over-rides arachidonic acid (C20:4, n-6) suppression, but does not prevent the repression by docosahexaenoic acid (C22:6, n-3). ChIP (chromatin immunoprecipitation) assays in H4IIE cells showed that docosahexaenoic acid affects the binding of NF-Y, Sp1 and SREBP-1 to the PUFA response region of CiC promoter, whereas arachidonic acid alters only the binding of SREBP-1. Our data show that PUFA inhibition of hepatic Cic gene transcription is mediated not only by the nuclear level of SREBP-1c, but also might involve a reduction in Sp1 and NF-Y DNA binding, suggesting differential mechanisms in the Cic gene regulation by different PUFA.

scholarly journals Impact of oral lipid and glucose tolerance tests on the postprandial concentrations of angiopoietin-like proteins (Angptl) 3 and 4

2021 ◽  
Author(s):  
Andreas Schmid ◽  
Hannah Belikan ◽  
Alexandra Höpfinger ◽  
Andreas Schäffler ◽  
Thomas Karrasch
Keyword(s):  
Fatty Acids ◽  
Glucose Tolerance ◽  
Polyunsaturated Fatty Acids ◽  
Venous Blood ◽  
Tolerance Test ◽  
Dietary Fatty Acids ◽  
Enzyme Linked Immunosorbent Assay ◽  
Oral Glucose ◽  
Mrna Levels ◽  
Omega 3

Abstract Background The postprandial regulation of angiopoietin-like proteins (Angptls) and their expression in adipocytes is poorly characterized. Objective Circulating Angptl3 and 4 were analyzed in healthy individuals undergoing either an oral lipid tolerance test (OLTT; n = 98) or an oral glucose tolerance test (OGTT; n = 99). Venous blood was drawn after 0, 2, 4, and 6 h during OLTT and after 0, 1, and 2 h during OGTT. Anthropometric and laboratory parameters were assessed and concentrations of Angptls were quantified by enzyme-linked immunosorbent assay. Angptl gene expression in 3T3-L1 adipocytes and in murine adipose tissues and cellular fractions was analyzed by quantitative real-time PCR. Results Angptl3 concentrations significantly decreased while Angptl4 levels continuously increased during OLTT. Both proteins remained unaffected during OGTT. Angptl3 and Angptl4 were expressed in murine subcutaneous and visceral AT with higher mRNA levels in mature adipocytes when compared to the stroma-vascular cell fraction. Both proteins were strongly induced during 3T3-L1 adipocyte differentiation and they were unresponsive to glucose in mature fat cells. Adipocyte Angptl3 (but not Angptl4) mRNA expression was inhibited by the polyunsaturated fatty acids arachidonic acid and docosahexaenoic acid, whereas nine types of dietary fatty acids remained without any effect. Conclusions There is evidence of short-time regulation of Angptl3/4 levels upon metabolic stress. Angptl4 expression is high and Angptl3 expression is low in AT and restricted mainly to mature adipocytes without any differences concerning fat compartments. Whereas dietary fatty acids and glucose are without any effect, omega-3/-6-polyunsaturated fatty acids inhibited Anptl3 expression in adipocytes.

scholarly journals Dietary and Pharmacological Fatty Acids and Cardiovascular Health

2019 ◽  
Vol 105 (4) ◽  
pp. 1030-1045 ◽  
Author(s):  
Huaizhu Wu ◽  
Lu Xu ◽  
Christie M Ballantyne
Keyword(s):  
Fatty Acids ◽  
Clinical Trials ◽  
Polyunsaturated Fatty Acids ◽  
Cardiovascular Health ◽  
Evidence Synthesis ◽  
Saturated Fatty Acids ◽  
Saturated Fat ◽  
Dietary Fatty Acids ◽  
Atherosclerotic Cardiovascular Disease ◽  
Omega 3

Abstract Context The effects of dietary intake of different fatty acids and pharmacological use of fatty acids, specifically long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFAs), on cardiovascular health and atherosclerotic cardiovascular disease (ASCVD) prevention have been examined in a large number of observational studies and clinical trials. This review summarizes recent data and discusses potential mechanisms. Evidence acquisition The review is based on the authors’ knowledge of the field supplemented by a PubMed search using the terms seafood, fish oil, saturated fatty acids, omega-3 fatty acids, eicosapentaenoic acid, docosahexaenoic acid, polyunsaturated fatty acids, monounsaturated fatty acids, and ASCVD. Evidence synthesis We mainly discuss the recent clinical trials that examine the effects of different types of dietary fatty acids and pharmacological use of n-3 PUFA products on ASCVD prevention and the potential mechanisms. Conclusions While replacement of dietary saturated fat with unsaturated fat, polyunsaturated fat in particular, or intake of LC n-3 PUFA–rich seafood has generally shown benefit for ASCVD prevention and is recommended for cardiovascular benefits, data on effects of n-3 PUFA products on ASCVD health are inconsistent. However, recent clinical trials support benefits of prescription EPA in ASCVD prevention. n-3 PUFAs may contribute to ASCVD prevention through multiple mechanisms, including lowering plasma triglyceride levels, anti-inflammatory effects, antithrombotic effects, and effects on endothelial function.

A Lipid Droplet-Associated GFP Reporter-Based Screen Identifies New Fat Storage Regulators in C. elegans

2014 ◽  
Vol 41 (5) ◽  
pp. 305-313 ◽  
Author(s):  
Zhenglong Liu ◽  
Xia Li ◽  
Qinlan Ge ◽  
Mei Ding ◽  
Xun Huang
Keyword(s):  
Lipid Droplet ◽  
Fat Storage ◽  
C Elegans ◽  
Gfp Reporter
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