Abstract：
:Mutations in the genes coding for patatin-like phospholipase domain-containing 1 (PNPLA1) and α/β-hydrolase domain-containing 5 (ABHD5), also known as comparative gene identification 58, are causative for ichthyosis, a severe skin barrier disorder. Individuals with mutations in either of these genes show a defect in epidermal ω-O-acylceramide (AcylCer) biosynthesis, suggesting that PNPLA1 and ABHD5 act in the same metabolic pathway. In this report, we identified ABHD5 as a coactivator of PNPLA1 that stimulates the esterification of ω-hydroxy ceramides with linoleic acid for AcylCer biosynthesis. ABHD5 interacts with PNPLA1 and recruits the enzyme to its putative triacylglycerol substrate onto cytosolic lipid droplets. Conversely, alleles of ABHD5 carrying point mutations associated with ichthyosis in humans failed to accelerate PNPLA1-mediated AcylCer biosynthesis. Our findings establish an important biochemical function of ABHD5 in interacting with PNPLA1 to synthesize crucial epidermal lipids, emphasizing the significance of these proteins in the formation of a functional skin permeability barrier.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
Kien B,Grond S,Haemmerle G,Lass A,Eichmann TO,Radner FPWdoi
10.1194/jlr.M089771subject
Has Abstractpub_date
2018-12-01 00:00:00pages
2360-2367issue
12eissn
0022-2275issn
1539-7262pii
jlr.M089771journal_volume
59pub_type
杂志文章abstract：:Ketone bodies (KBs), acetoacetate and β-hydroxybutyrate (βHB), were considered harmful metabolic by-products when discovered in the mid-19th century in the urine of patients with diabetic ketoacidosis. It took physicians many years to realize that KBs are normal metabolites synthesized by the liver and exported into t...
journal_title：Journal of lipid research
pub_type： 杂志文章,评审
doi：10.1194/jlr.R046599
更新日期：2014-09-01 00:00:00
abstract：:We have recently reported that the human apolipoprotein A-I (apoA-I) and apolipoprotein C-III (apoC-III) genes are physically linked and that the presence of a DNA insertion in the apoA-I gene is correlated with apoA-I-apoC-III deficiency in patients with premature atherosclerosis. In addition, the presence of a polym...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1985-04-01 00:00:00
abstract：:In human serum, polymorphism of apoA-II predominantly in HDL3 could be demonstrated. HDL3-apoA-II was composed of four isoproteins, each with a molecular weight of 8600 (reduced form) and identical immunological properties. The isoproteins are designated apoA-II-1 (pI 5.16), apoA-II-2 (pI 4.89) corresponding to the al...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1983-08-01 00:00:00
abstract：:X-linked adrenoleukodystrophy (X-ALD) is a peroxisomal disorder caused by impaired degradation of very long-chain fatty acids (VLCFAs) due to mutations in the ABCD1 gene responsible for VLCFA transport into peroxisomes. Lorenzo's oil, a 4:1 mixture of glyceryl trioleate and glyceryl trierucate, has been used to reduce...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M044586
更新日期：2014-03-01 00:00:00
abstract：:Human apolipoprotein E (apoE) is a constituent of plasma very low density and high density lipoproteins and is important in modulating the catabolism of remnants of triglyceride-rich lipoproteins. There are three common isoforms of apoE, designated apoE-2, E-3, and E-4, which are coded by three separate alleles (epsil...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1984-11-01 00:00:00
abstract：:We describe a method for estimating the total activity of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase (EC 1.1.1.34) in the small intestine of rats. An homogenate of the whole small intestine is prepared rapidly and assayed directly to maximize the yield of enzyme and to minimize opportunity for uncontrolled cha...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1982-02-01 00:00:00
abstract：:The extent to which the heart can convert alpha-linolenic acid (alpha-LNA, 18:3n-3) to longer chain n-3 PUFAs is not known. Conversion rates can be measured in vivo using radiolabeled alpha-LNA and a kinetic fatty acid model. [1-(14)C]alpha-LNA was infused intravenously for 5 min in unanesthetized rats that had been f...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M800093-JLR200
更新日期：2008-08-01 00:00:00
abstract：:The central region of apolipoprotein A-I (apoA-I), spanning residues 143--165, has been implicated in lecithin:cholesterol acyltransferase (LCAT) activation and also in high density lipoprotein (HDL) structural rearrangements. To examine the role of individual amino acids in these functions, we constructed, overexpres...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：2001-03-01 00:00:00
abstract：:Decreased HDL-cholesterol (HDL-C) and familial combined hyperlipidemia (FCHL) are the two most common familial dyslipidemias predisposing to premature coronary heart disease (CHD). These dyslipidemias share many phenotypic features, suggesting a partially overlapping molecular pathogenesis. This was supported by our p...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M400141-JLR200
更新日期：2004-10-01 00:00:00
abstract：:Nucleoredoxin (NRX) is a member of the thioredoxin family of proteins that controls redox homeostasis in cell. Redox homeostasis is a well-known regulator of cell differentiation into various tissue types. We found that NRX expression levels were higher in white adipose tissue of obese ob/ob mice and increased in the ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M054056
更新日期：2015-02-01 00:00:00
abstract：:ATP-citrate lyase (ACL) is a key lipogenic enzyme that converts citrate in the cytoplasm to acetyl-CoA, the initial precursor that yields malonyl-CoA for fatty acid biosynthesis. As cytosolic citrate is derived from the tricarboxylic acid cycle in the mitochondrion, ACL catalyzes a critical reaction linking cellular g...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M003335
更新日期：2010-09-01 00:00:00
abstract：:The major net flux of cholesterol in the intact animal or human is from the peripheral organs to the liver. This flux is made up of cholesterol that is either synthesized in these peripheral tissues or taken up as lipoprotein cholesterol. This study investigates whether it is the concentration of apolipoprotein (apo) ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1998-11-01 00:00:00
abstract：:The oxidation of the side chain of 3 alpha, 7 alpha-dihydroxy-5 beta-cholestanoic acid (DHCA) into chenodeoxycholic acid has been studied in subcellular fractions of rat liver. The product was separated from the substrate by high pressure liquid chromatography and identified by gas-liquid chromatography-mass spectrome...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1986-06-01 00:00:00
abstract：:Distinct isoforms of long-chain acyl-CoA synthetases (ACSLs) may partition fatty acids toward specific metabolic cellular pathways. For each of the five members of the rat ACSL family, we analyzed tissue mRNA distributions, and we correlated the mRNA, protein, and activity of ACSL1 and ACSL4 after fasting and refeedin...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M600150-JLR200
更新日期：2006-09-01 00:00:00
abstract：:The skin surface represents our interface with the external environment, and as such, is our first line of defense against microbial colonization and infection. Lipids at the skin surface are thought to underlie at least part of an antimicrobial barrier. Some of these lipids are synthesized in the epidermis and are ca...
journal_title：Journal of lipid research
pub_type： 杂志文章,评审
doi：10.1194/jlr.R700016-JLR200
更新日期：2008-01-01 00:00:00
abstract：:We have previously observed that the Ya subunit-containing glutathione (GSH) S-transferases from rat liver exhibit a common high affinity binding site for lithocholic acid, bilirubin, and sulfobromophthalein (BSP) (1984. J. Lipid Res. 25: 1177-1183). Subsequently we found that cholic acid and its amidates bound to a s...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1988-03-01 00:00:00
abstract：:Lipoprotein lipase (LPL) and hepatic lipase (HL) mediate the hydrolysis of triglycerides and phospholipids present in circulating lipoprotein particles and are essential for normal lipid metabolism. Both enzymes have a similar primary amino acid structure and share requirements for intact catalytic, lipid binding, and...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1993-08-01 00:00:00
abstract：:Apolipoproteins, such as apolipoprotein A-I (apoA-I), can stimulate cholesterol efflux from cells expressing the ATP binding cassette transporter A1 (ABCA1). The nature of the molecular interaction between these cholesterol acceptors and ABCA1 is controversial, and models suggesting a direct protein-protein interactio...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M300355-JLR200
更新日期：2004-02-01 00:00:00
abstract：:Proprotein convertase, subtilisin/kexin type 9 (PCSK9), a key regulator of plasma LDL-cholesterol (LDL-c) and cardiovascular risk, is produced in liver and secreted into plasma where it binds hepatic LDL receptors (LDLR), leading to their degradation. PCSK9 is transcriptionally activated by sterol response element-bin...
journal_title：Journal of lipid research
pub_type： 临床试验,杂志文章
doi：10.1194/jlr.P009860
更新日期：2010-11-01 00:00:00
abstract：:We have reported the use of a retroviral vector to introduce the low density lipoprotein (LDL) receptor gene into receptor-deficient Watanabe heritable hyperlipidemic (WHHL) rabbit fibroblasts (Miyanohara, A., M. F. Sharkey, D. Steinberg, J. L. Witztum, and T. Friedmann. 1988. Proc. Natl. Acad. Sci. USA. 85: 6538-6542...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1990-12-01 00:00:00
abstract：:Effects of serum cholesterol on cholesterol content in the retina are currently unknown. It is also unclear how cholesterol levels are controlled in the retina. High-cholesterol diet and oral administrations of simvastatin were used to modulate serum cholesterol in mice. These treatments only modestly affected cholest...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M053439
更新日期：2015-01-01 00:00:00
abstract：:Recent findings described the role of CD36-mediated signaling in regulating cellular calcium and the release of various bioactive molecules, including the prostaglandins, neurotransmitters, cholecystokinin, and secretin. Here we document the role of CD36 in the secretion of hepatic VLDL. CD36 deletion resulted in 60% ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M037812
更新日期：2013-11-01 00:00:00
abstract：:Agonist-induced lipolysis of adipose fat is robustly inhibited by insulin or by feedback inhibition by the long-chain fatty acids (LCFA) produced during lipolysis. However, the mode of action of LCFA in suppressing adipose lipolysis is not clear. β,β'-Tetramethyl hexadecanedioic acid (Mββ/ EDICA16) is a synthetic LCFA...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M022673
更新日期：2012-05-01 00:00:00
abstract：:Protein palmitoylation refers to the posttranslational addition of a 16 carbon fatty acid to the side chain of cysteine, forming a thioester linkage. This acyl modification is readily reversible, providing a potential regulatory mechanism to mediate protein-membrane interactions and subcellular trafficking of proteins...
journal_title：Journal of lipid research
pub_type： 杂志文章,评审
doi：10.1194/jlr.R600007-JLR200
更新日期：2006-06-01 00:00:00
abstract：:The accumulation of phosphatidylcholine hydroperoxide (PCOOH), a primary oxidation product of phosphatidylcholine (PC), in blood plasma and tissues has been observed in various pathological conditions, including atherosclerosis. However, the biological roles of PCOOH in these conditions remain unknown. To estimate the...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M800582-JLR200
更新日期：2009-05-01 00:00:00
abstract：:The relative rates of hydrolysis of the secondary ester in glycerol 1,3-benzylidene 2-oleate and in glycerol 1,3-dihexadecyl ether 2-oleate, and of the primary and secondary esters in triolein were determined. Both unaltered and selectively inactivated rat pancreatic juice were used as sources of enzyme. It was found ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1968-01-01 00:00:00
abstract：:Cardiac triacylglycerol (TG) catabolism critically depends on the TG hydrolytic activity of adipose triglyceride lipase (ATGL). Perilipin 5 (Plin5) is expressed in cardiac muscle (CM) and has been shown to interact with ATGL and its coactivator comparative gene identification-58 (CGI-58). Furthermore, ectopic Plin5 ex...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M034710
更新日期：2013-04-01 00:00:00
abstract：:An enzyme-coupled, colorimetric method for the assay of acyl-CoA synthetase is described. Acyl-CoA formed from fatty acid and CoA by acyl-CoA synthetase was dehydrogenated by acyl-CoA oxidase. Hydrogen peroxide produced was then converted into formaldehyde in the presence of methanol by catalase. The formaldehyde reac...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1991-10-01 00:00:00
abstract：:Cholesterol 7α-hydroxylase (CYP7A1) is the first and rate-limiting enzyme in the conversion of cholesterol to bile acids in the liver. In addition to absorption and digestion of nutrients, bile acids play a critical role in the regulation of lipid, glucose, and energy homeostasis. We have backcrossed Cyp7a1(-/-) mice ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M064709
更新日期：2016-07-01 00:00:00
abstract：:The activity of lipoprotein lipase isolated from rat postheparin plasma has been determined with synthetic lipids, in the presence and absence of apoprotein of the natural substrate very low density lipoprotein, as a function of medium ion-pair concentration of a number of different inorganic salts. The several kineti...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1976-05-01 00:00:00
