scholarly journals A Genetic Titration of Membrane Composition in C. elegans Reveals its Importance for Multiple Cellular and Physiological Traits

Genetics ◽  
2021 ◽  
Author(s):  
Ranjan Devkota ◽  
Delaney Kaper ◽  
Rakesh Bodhicharla ◽  
Marcus Henricsson ◽  
Jan Borén ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fluorescence Recovery After Photobleaching ◽  
Saturated Fatty Acids ◽  
Physiological Traits ◽  
Membrane Composition ◽  
Wild Type ◽  
Biophysical Properties ◽  
C Elegans ◽  
Different Temperatures ◽  
Proper Functions

Abstract The composition and biophysical properties of cellular membranes must be tightly regulated to maintain the proper functions of myriad processes within cells. To better understand the importance of membrane homeostasis, we assembled a panel of five C. elegans strains that show a wide span of membrane composition and properties, ranging from excessively rich in saturated fatty acids (SFAs) and rigid to excessively rich in polyunsaturated fatty acids (PUFAs) and fluid. The genotypes of the five strain are, from most rigid to most fluid: paqr-1(tm3262);paqr-2(tm3410), paqr-2(tm3410), N2 (wild-type), mdt-15(et14);nhr-49(et8), and mdt-15(et14);nhr-49(et8);acs-13(et54). We confirmed the excess SFA/rigidity-to-excess PUFA/fluid gradient using the methods of fluorescence recovery after photobleaching (FRAP) and lipidomics analysis. The five strains were then studied for a variety of cellular and physiological traits and found to exhibit defects in: permeability, lipid peroxidation, growth at different temperatures, tolerance to SFA-rich diets, lifespan, brood size, vitellogenin trafficking, oogenesis and autophagy during starvation. The excessively rigid strains often exhibited defects in opposite directions compared to the excessively fluid strains. We conclude that deviation from wild-type membrane homeostasis is pleiotropically deleterious for numerous cellular/physiological traits. The strains introduced here should prove useful to further study the cellular and physiological consequences of impaired membrane homeostasis.

scholarly journals Evolutionarily conserved long-chain Acyl-CoA synthetases regulate membrane composition and fluidity

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Mario Ruiz ◽  
Rakesh Bodhicharla ◽  
Marcus Ståhlman ◽  
Emma Svensk ◽  
Kiran Busayavalasa ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Membrane Fluidity ◽  
Saturated Fatty Acids ◽  
Phospholipid Composition ◽  
Membrane Composition ◽  
C Elegans ◽  
Evolutionarily Conserved ◽  
Chain Acyl ◽  
Dye Staining

The human AdipoR1 and AdipoR2 proteins, as well as their C. elegans homolog PAQR-2, protect against cell membrane rigidification by exogenous saturated fatty acids by regulating phospholipid composition. Here, we show that mutations in the C. elegans gene acs-13 help to suppress the phenotypes of paqr-2 mutant worms, including their characteristic membrane fluidity defects. acs-13 encodes a homolog of the human acyl-CoA synthetase ACSL1, and localizes to the mitochondrial membrane where it likely activates long chains fatty acids for import and degradation. Using siRNA combined with lipidomics and membrane fluidity assays (FRAP and Laurdan dye staining) we further show that the human ACSL1 potentiates lipotoxicity by the saturated fatty acid palmitate: silencing ACSL1 protects against the membrane rigidifying effects of palmitate and acts as a suppressor of AdipoR2 knockdown, thus echoing the C. elegans findings. We conclude that acs-13 mutations in C. elegans and ACSL1 knockdown in human cells prevent lipotoxicity by promoting increased levels of polyunsaturated fatty acid-containing phospholipids.

scholarly journals The H4K20 demethylase DPY-21 regulates the dynamics of condensin DC binding

2021 ◽  
Author(s):  
Laura Breimann ◽  
Ana Karina Morao ◽  
Jun Kim ◽  
David Sebastian Jimenez ◽  
Nina Maryn ◽  
...  
Keyword(s):  
X Chromosome ◽  
Dosage Compensation ◽  
Transcriptional Repression ◽  
Fluorescence Recovery After Photobleaching ◽  
Null Mutant ◽  
Wild Type ◽  
X Chromosomes ◽  
C Elegans ◽  
Catalytic Role ◽  
Mobile Fraction

Condensin is a multi-subunit SMC complex that binds to and compacts chromosomes. Here we addressed the regulation of condensin binding dynamics using C. elegans condensin DC, which represses X chromosomes in hermaphrodites for dosage compensation. We established fluorescence recovery after photobleaching (FRAP) using the SMC4 homolog DPY-27 and showed that a well-characterized ATPase mutation abolishes its binding. Next, we performed FRAP in the background of several chromatin modifier mutants that cause varying degrees of X-chromosome derepression. The greatest effect was in a null mutant of the H4K20me2 demethylase DPY-21, where the mobile fraction of condensin DC reduced from ∼30% to 10%. In contrast, a catalytic mutant of dpy-21 did not regulate condensin DC mobility. Hi-C data in the dpy-21 null mutant showed little change compared to wild type, uncoupling Hi-C measured long-range DNA contacts from transcriptional repression of the X chromosomes. Together, our results indicate that DPY-21 has a non-catalytic role in regulating the dynamics of condensin DC binding, which is important for transcription repression.

scholarly journals Saturated fatty acid-induced cardiomyopathy with diastolic dysfunction can be ameliorated by changing the quality of fatty acids to monounsaturated fatty acid

2021 ◽  
Author(s):  
Tsunehisa Yamamoto ◽  
Jin Endo ◽  
Masaharu Kataoka ◽  
Yoshinori Katsumata ◽  
Kohsuke Shirakawa ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Er Stress ◽  
Diastolic Dysfunction ◽  
Knockout Mice ◽  
Saturated Fatty Acids ◽  
Monounsaturated Fatty Acids ◽  
Control Group ◽  
Wild Type

IntroductionLipotoxicity due to obesity is known to lead to cardiac dysfunction. In an earlier study, we found that an increase in the ratio of saturated fatty acids (SFA) to monounsaturated fatty acids (MUFA) in the membrane of cardiomyocytes causes endoplasmic reticulum (ER) stress. Such stress is hypothesized to be involved in development of SFA-related cardiomyopathy. Another factor affecting the membrane SFA/MUFA ratio is suppression by SFA of SIRT1-mediated stearoyl-CoA desaturase-1 (SCD1), which is involved in converting SFA to MUFA. Therefore, we evaluated whether increasing dietary intake of MUFA can improve the membrane SFA/MUFA ratio.Material and methodsWild-type mice (n = 30) and cardiomyocyte-specific SIRT1 knockout mice (n = 30) were randomly divided into 3 groups and assigned to 16 weeks of a standard mouse diet, 16 weeks of an SFA-rich high-lard diet (HLD), or 8 weeks of a HLD followed by 8 weeks of a MUFA-rich high olive oil diet (HOD switch).ResultsCompared with the control group, the wild-type mice on the HOD diet showed normalized SIRT1-mediated SCD1 signaling, increased membrane SFA/MUFA ratio, decreased ER stress, and improved cardiomyopathy variables. The HLD-fed SIRT1 knockout mice showed greater changes in the SFA/MUFA ratio, ER stress, and cardiomyopathy variables than the wild-type mice. Switching from HLD to HOD ameliorated these phenotypes, although it did not restore the reduced expression of SCD1.ConclusionsThe MUFA-rich diet was found to have a therapeutic effect on SFA-induced cardiomyopathy with diastolic dysfunction by directly rebalancing membrane fatty acid oversaturation and indirectly through the de-inhibition of SIRT1/SCD1 signaling.

scholarly journals Sequential dynamics of Stearoyl-CoA Desaturase-1(SCD1) /ligand binding and unbinding mechanism: A computational study

2020 ◽  
Author(s):  
Anna B. Petroff ◽  
Rebecca L. Weir ◽  
Charles R. Yates ◽  
Joseph D. Ng ◽  
Jerome Baudry
Keyword(s):  
Molecular Dynamics ◽  
Fatty Acids ◽  
Computational Study ◽  
Saturated Fatty Acids ◽  
Monounsaturated Fatty Acids ◽  
Membrane Composition ◽  
Endoplasmic Reticulum Protein ◽  
Metabolic Protein ◽  
Stearoyl Coa Desaturase ◽  
Dynamic Series

AbstractStearoyl-CoA desaturase-1 (SCD1 or delta-9 desaturase, D9D) is a key metabolic protein that modulates cellular inflammation and stress, but overactivity of SCD1 is associated with diseases including cancer and metabolic syndrome. This transmembrane endoplasmic reticulum protein converts saturated fatty acids into monounsaturated fatty acids, primarily stearoyl-CoA into oleoyl-CoA, which are critical products for energy metabolism and membrane composition. The present computational molecular dynamics study characterizes the molecular dynamics of SCD1 with substrate, product, and as apoprotein. The modeling of SCD1:fatty acid interactions suggests that 1) SCD1:CoA moiety interactions open the substrate binding tunnel, 2) SCD1 stabilizes a substrate conformation favorable for desaturation, and 3) SCD1:product interactions result in an opening of the tunnel, possibly allowing product exit into the surrounding membrane. Together, these results describe a highly dynamic series of SCD1 conformations resulting from the enzyme:cofactor:substrate interplay that inform drug-discovery efforts.

Novel elasticity measurement techniques reveal that the C. elegans cuticle is required for physical integrity with age

2021 ◽  
Author(s):  
Mohammad Rahimi ◽  
Salman Sohrabi ◽  
Coleen T. Murphy
Keyword(s):  
Insulin Signaling ◽  
Osmotic Shock ◽  
Measurement Techniques ◽  
Biomechanical Properties ◽  
Mammalian Tissue ◽  
Wild Type ◽  
Biophysical Properties ◽  
Mechanical Loads ◽  
C Elegans ◽  
Elasticity Measurement

AbstractChanges in biomechanical properties have profound impacts on human health. C. elegans might serve as a model for studying the molecular genetics of mammalian tissue decline. Previously, we found that collagens are required for insulin signaling mutants’ long lifespan and that overexpression of specific collagens extends wild-type lifespan. However, whether these effects on lifespan are due to mechanical changes during aging has not yet been established. Here, we have developed two novel methods to study the cuticle: we measure mechanical properties of live animals using osmotic shock (OS), and we directly perform the tensile test (TT) on isolated cuticles using microfluidic technology. Using these tools, we find that cuticle, not the muscle, is responsible for changes in ‘stretchiness’ of C. elegans, and that cuticle stiffness is highly non-linear and anisotropic. We also found that collagen mutations alter integrity of the cuticle by significantly altering elasticity. Additionally, aging stiffens the cuticle under mechanical loads beyond the cuticle’s healthy stretched state. Measurements of elasticity showed that long-lived daf-2 mutants were considerably better at preventing progressive mechanical changes with age. These tests of C. elegans biophysical properties suggest that the cuticle is responsible for their resilience.

scholarly journals Effect of postharvest storage temperatures on the quality parameters of pistachio nuts

2013 ◽  
Vol 31 (No. 5) ◽  
pp. 467-473 ◽  
Author(s):  
E. Arena ◽  
G. Ballistreri ◽  
B. Fallico
Keyword(s):  
Fatty Acids ◽  
Peroxide Value ◽  
Storage Time ◽  
Saturated Fatty Acids ◽  
Quality Parameters ◽  
Peroxide Values ◽  
Pistachio Nuts ◽  
Different Temperatures ◽  
Pistachio Oil ◽  
Storage Temperatures

Pistachios from Italy and Turkey were stored at different temperatures (10, 20, and 30°C) and the moisture of the pistachios, the free fatty acids (FFA) content, the peroxide value, and triacylglycerols (TGs) composition of the extracted oils were evaluated. The content of FFA decreased during storage at 10°C and increased at 20 and 30°C. No differences between the peroxide values were found during storage at 10°C. A significant increase in the peroxide values was observed after 20 days at 20°C and 5 days at 30°C in both the Italian and Turkish samples. The main TGs found in the pistachio oil of both origins were OLO, OLL, OLP, LLL, LLP, OOP, OLLn, and OOO; these accounted for approximately 85% of the total TGs content. A decrease was observed in the amounts of TGs esterified with polyunsaturated fatty acids, such as LLP, OLP, LLL and OLL, and an increase of the relative amounts of TGs with monounsaturated and saturated fatty acids, such as OOO and OOP, with the increasing storage time and temperatures in both samples.

scholarly journals The differential effects of fatty acids on enterocytic abundance of amyloid-beta

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Susan Galloway ◽  
Ryusuke Takechi ◽  
Michael Nesbit ◽  
Menuka M. Pallebage-Gamarallage ◽  
Virginie Lam ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Plasma Concentration ◽  
Plasma Levels ◽  
Saturated Fatty Acids ◽  
Amyloid Β ◽  
Causal Mechanism ◽  
Wild Type ◽  
Pufa Diet ◽  
Chronic Ingestion ◽  
Aβ Production

Abstract Background Consumption of a Western-styled diet enriched in saturated fatty acids (SFA) relative to polyunsaturated fatty acids is positively associated with risk for Alzheimer’s disease. Whilst potential causal mechanism are unclear, there is increasing evidence that chronic ingestion of SFA enriched diets promote increase the plasma levels of lipoprotein-associated amyloid-β (Aβ). However, the effects of dietary mono- and poly-unsaturated fats (MUFA/PUFA) on nascent lipoprotein Aβ abundance have not been previously reported. Methods Wild-type C57BL/6 J mice were maintained on low-fat control chow (LF) or diets enriched in either SFA, MUFA, or PUFA for 9 months. Enterocytic abundance of Aβ was determined with quantitative immunofluorescent microscopy and plasma Aβ was measured by ELISA. Results The chronic ingestion of SFA-enriched diet increased the enterocytic abundance and plasma concentration of Aβ compared to LF control mice. The mice maintained on MUFA or PUFA diet showed comparable enterocytic and plasma Aβ levels to the LF control mice. Conclusions The data indicates that a diet enriched in SFA significantly increases the enterocytic Aβ production and secretion into the circulation, whilst MUFA and PUFA enriched diet do not exert such effects.

Acidity, Proteolysis and Lipolysis Changes in Rapid-Cured Fermented Sausage Dried at Different Temperatures

2001 ◽  
Vol 7 (3) ◽  
pp. 269-276 ◽  
Author(s):  
T. Bolumar ◽  
P. Nieto ◽  
J. Flores
Keyword(s):  
Fatty Acids ◽  
Sensory Analysis ◽  
Saturated Fatty Acids ◽  
Monounsaturated Fatty Acids ◽  
Pilot Scale ◽  
Total Acidity ◽  
Fermented Sausage ◽  
Drying Temperature ◽  
Different Temperatures ◽  
The Difference

Two batches of dry-cured fermented sausage were made by industrial methods at pilot scale. The difference between them was the drying temperature applied (5 or 12 °C) for a period of time extending from the moment when pH = 5 was attained until a weight loss of 20% was achieved. The other conditions were the same for the two processes. Changes in pH, total acidity, D and L-lactic acids, acetic acid, total volatile basic nitrogen (TVBN), free amino acids (FAA) and free fatty acids (FFA) were studied, and a discriminatory sensory analysis of the ready-to-eat product was carried out. Only L-lactic acid and total acidity within the acidity parameters showed substantial differences halfway through the drying process. No significant differences were found in any of the acidity variables at the end of the process. The drying temperature encouraged the production of TVBN, but no direct relationship was established between it and the quantity of FAA. The three fractions of FFA [SFA (saturated fatty acids), MUFA (monounsaturated fatty acids) and PUFA (polyunsaturated fatty acids)] increased during the curing period, always higher at 12 °C than at 5 °C throughout the process. No differences between the two processes were detected by the discriminatory sensory analysis.

scholarly journals Reducing Effect of Farnesylquinone on Lipid Mass in C. elegans by Modulating Lipid Metabolism

Marine Drugs ◽  
2019 ◽  
Vol 17 (6) ◽  
pp. 336 ◽  
Author(s):  
Xihua Jia ◽  
Manglin Xu ◽  
Aigang Yang ◽  
Yan Zhao ◽  
Dong Liu ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fermentation Broth ◽  
Saturated Fatty Acids ◽  
Monounsaturated Fatty Acids ◽  
Lipid Lowering ◽  
Transcriptional Level ◽  
C Elegans ◽  
Etoac Fraction ◽  
Worm Model

Bioassay-guided fractionation of marine-derived fungi revealed that the EtOAc fraction from the fermentation broth of a mutated fungal strain Streptomyces nitrosporeus YBH10-5 had lipid-lowering effects in HepG2 cells. Chromatographic separation of the EtOAc fraction resulted in the isolation of 11 PKS-based derivatives, including a structurally unique meroterpenoid namely nitrosporeunol H (1). The structure of compound 1 was determined by the analysis of spectroscopic data. Further bioassay resulted in farnesylquinone (2) and its analogues to exert in vivo fat-reducing effects in C. elegans worm model. The underlying mode of action of compound 2 in the context of live worms was investigated, uncovering that compound 2 enhanced the mitochondrial β-oxidation rate and changed the transcriptional level of energy metabolism genes. Additional experiments revealed that compound 2 exerted its effects in C. elegans partially through repressing FAT-5, an isoform of stearoyl-CoA desaturase (SCD) which catalyzes the conversion of saturated fatty acids to monounsaturated fatty acids, thereafter leading to the modification of the fatty acid profile. Thus, compound 2 was suggested to be a promising lead for further optimization to treat obesity.

scholarly journals Paradigm shift: the primary function of the “Adiponectin Receptors” is to regulate cell membrane composition

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Marc Pilon
Keyword(s):  
Fatty Acids ◽  
Paradigm Shift ◽  
Phospholipid Composition ◽  
Experimental Models ◽  
Cell Models ◽  
Membrane Composition ◽  
Adiponectin Receptors ◽  
Membrane Phospholipids ◽  
C Elegans ◽  
Evolutionarily Conserved

AbstractThe ADIPOR1 and ADIPOR2 proteins (ADIPORs) are generally considered as adiponectin receptors with anti-diabetic properties. However, studies on the yeast and C. elegans homologs of the mammalian ADIPORs, and of the ADIPORs themselves in various mammalian cell models, support an updated/different view. Based on findings in these experimental models, the ADIPORs are now emerging as evolutionarily conserved regulators of membrane homeostasis that do not require adiponectin to act as membrane fluidity sensors and regulate phospholipid composition. More specifically, membrane rigidification activates ADIPOR signaling to promote fatty acid desaturation and incorporation of polyunsaturated fatty acids into membrane phospholipids until fluidity is restored. The present review summarizes the evidence supporting this new view of the ADIPORs, and briefly examines physiological consequences.

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