Hexacosenoyl-CoA is the most abundant very long-chain acyl-CoA in ATP binding cassette transporter D1-deficient cells [Patient-Oriented and Epidemiological Research]
In this study, we profiled the acyl-CoA species in fibroblasts from X-ALD patients and in ABCD1-deficient HeLa cells. We found that hexacosenoyl (26:1)-CoA, but not hexacosanoyl (26:0)-CoA, was the most abundantly concentrated among the VLCFA-CoA species in these cells. We also show that 26:1-CoA is mainly synthesized from oleoyl-CoA, and the metabolic turnover rate of 26:1-CoA was almost identical to that of oleoyl-CoA in both WT and ABCD1-deficient HeLa cells. The findings of our study provide precise quantitative and metabolic information of each acyl-CoA species in living cells. Our results suggest that VLCFA is endoge...
Source: The Journal of Lipid Research - March 31, 2020 Category: Lipidology Authors: Hama, K., Fujiwara, Y., Takashima, S., Hayashi, Y., Yamashita, A., Shimozawa, N., Yokoyama, K. Tags: Patient-Oriented and Epidemiological Research Source Type: research
Dynamics of sphingolipids and the serine palmitoyltransferase complex in rat oligodendrocytes during myelination [Research Articles]
Myelin is a unique lipid-rich membrane structure that accelerates neurotransmission and supports neuronal function. Sphingolipids are critical myelin components. Yet sphingolipid content and synthesis have not been well characterized in oligodendrocytes, the myelin-producing cells of the CNS. Here, using quantitative real-time PCR, LC-MS/MS-based lipid analysis, and biochemical assays, we examined sphingolipid synthesis during the peak period of myelination in the postnatal rat brain. Importantly, we characterized sphingolipid production in isolated oligodendrocytes. We analyzed sphingolipid distribution and levels of crit...
Source: The Journal of Lipid Research - March 31, 2020 Category: Lipidology Authors: Davis, D. L., Mahawar, U., Pope, V. S., Allegood, J., Sato-Bigbee, C., Wattenberg, B. W. Tags: Research Articles Source Type: research
HDL inhibits endoplasmic reticulum stress-induced apoptosis of pancreatic {beta}-cells in vitro by activation of Smoothened [Research Articles]
In conclusion, the protective effect of HDL to counter ER stress and β-cell death involves the transport, generation, and mobilization of oxysterols for activation of the Hh signaling receptor SMO (Source: The Journal of Lipid Research)
Source: The Journal of Lipid Research - March 31, 2020 Category: Lipidology Authors: Yalcinkaya, M., Kerksiek, A., Gebert, K., Annema, W., Sibler, R., Radosavljevic, S., Lütjohann, D., Rohrer, L., von Eckardstein, A. Tags: Research Articles Source Type: research
Of mice and men: murine bile acids explain species differences in the regulation of bile acid and cholesterol metabolism [Research Articles]
In conclusion, the presence of MCAs is critical for many of the known metabolic differences between mice and humans. The Cyp2c70-KO mouse should be useful in studies exploring potential therapeutic targets for human disease. (Source: The Journal of Lipid Research)
Source: The Journal of Lipid Research - March 31, 2020 Category: Lipidology Authors: Straniero, S., Laskar, A., Savva, C., Härdfeldt, J., Angelin, B., Rudling, M. Tags: Research Articles Source Type: research
Alcohol effects on hepatic lipid metabolism [Reviews]
Alcoholic liver disease (ALD) is the most prevalent type of chronic liver disease with significant morbidity and mortality worldwide. ALD begins with simple hepatic steatosis and progresses to alcoholic steatohepatitis, fibrosis, and cirrhosis. The severity of hepatic steatosis is highly associated with the development of later stages of ALD. This review explores the disturbances of alcohol-induced hepatic lipid metabolism through altered hepatic lipid uptake, de novo lipid synthesis, fatty acid oxidation, hepatic lipid export, and lipid droplet formation and catabolism. In addition, we review emerging data on the contribu...
Source: The Journal of Lipid Research - March 31, 2020 Category: Lipidology Authors: Jeon, S., Carr, R. Tags: Reviews Source Type: research
HDL and pancreatic {beta} cells: a SMO-king gun? [Commentary]
(Source: The Journal of Lipid Research)
Source: The Journal of Lipid Research - March 31, 2020 Category: Lipidology Authors: Brunham, L. R. Tags: Commentary Source Type: research
In Memoriam: Lina M. Obeid (1957-2019) [Tribute]
(Source: The Journal of Lipid Research)
Source: The Journal of Lipid Research - March 31, 2020 Category: Lipidology Authors: Snider, A. J., Cowart, L. A., Luberto, C., Siskind, L. J. Tags: Tribute Source Type: research
The data must be accessible to all [Editorials]
(Source: The Journal of Lipid Research)
Source: The Journal of Lipid Research - March 31, 2020 Category: Lipidology Authors: Gierasch, L. M., Davidson, N. O., Rye, K.-A., Burlingame, A. L. Tags: Editorials Source Type: research
Separation of postprandial lipoproteins: improved purification of chylomicrons using an ApoB100 immunoaffinity method [Methods]
Elevated levels of triglyceride-rich lipoproteins (TRLs), both fasting and postprandial, are associated with increased risk for atherosclerosis. However, guidelines for treatment are defined solely by fasting lipid levels, even though postprandial lipids may be more informative. In the postprandial state, circulating lipids consist of dietary fat transported from the intestine in chylomicrons (CMs; containing ApoB48) and fat transported from the liver in VLDL (containing ApoB100). Research into the roles of endogenous versus dietary fat has been hindered because of the difficulty in separating these particles by ultracentr...
Source: The Journal of Lipid Research - February 29, 2020 Category: Lipidology Authors: Jones, G. M., Caccavello, R., Palii, S. P., Pullinger, C. R., Kane, J. P., Mulligan, K., Gugliucci, A., Schwarz, J.-M. Tags: Methods Source Type: research
High density lipoprotein and its apolipoprotein-defined subspecies and risk of dementia [Patient-Oriented and Epidemiological Research]
Whether HDL is associated with dementia risk is unclear. In addition to apoA1, other apolipoproteins are found in HDL, creating subspecies of HDL that may have distinct metabolic properties. We measured apoA1, apoC3, and apoJ levels in plasma and apoA1 levels in HDL that contains or lacks apoE, apoJ, or apoC3 using a modified sandwich ELISA in a case-cohort study nested within the Ginkgo Evaluation of Memory Study. We included 995 randomly selected participants and 521 participants who developed dementia during a mean of 5.1 years of follow-up. The level of total apoA1 was not significantly related to dementia risk, regard...
Source: The Journal of Lipid Research - February 29, 2020 Category: Lipidology Authors: Koch, M., DeKosky, S. T., Goodman, M., Sun, J., Furtado, J. D., Fitzpatrick, A. L., Mackey, R. H., Cai, T., Lopez, O. L., Kuller, L. H., Mukamal, K. J., Jensen, M. K. Tags: Patient-Oriented and Epidemiological Research Source Type: research
Nonsynonymous SNPs in LPA homologous to plasminogen deficiency mutants represent novel null apo(a) alleles [Patient-Oriented and Epidemiological Research]
Plasma lipoprotein (a) [Lp(a)] levels are largely determined by variation in the LPA gene, which codes for apo(a). Genome-wide association studies (GWASs) have identified nonsynonymous variants in LPA that associate with low Lp(a) levels, although their effect on apo(a) function is unknown. We investigated two such variants, R990Q and R1771C, which were present in four null Lp(a) individuals, for structural and functional effects. Sequence alignments showed the R990 and R1771 residues to be highly conserved and homologous to each other and to residues associated with plasminogen deficiency. Structural modeling showed both ...
Source: The Journal of Lipid Research - February 29, 2020 Category: Lipidology Authors: Morgan, B. M., Brown, A. N., Deo, N., Harrop, T. W. R., Taiaroa, G., Mace, P. D., Wilbanks, S. M., Merriman, T. R., Williams, M. J. A., McCormick, S. P. A. Tags: Patient-Oriented and Epidemiological Research Source Type: research
Exon 9-deleted CETP inhibits full length-CETP synthesis and promotes cellular triglyceride storage [Research Articles]
We reported previously that reducing both CETP isoforms or overexpressing FL-CETP impairs cellular triglyceride (TG) storage. To investigate this further, E9-deleted CETP was expressed in SW872 cells that naturally synthesize CETP and in mouse 3T3-L1 cells that do not. E9-deleted CETP overexpression stimulated SW872 triglyceride synthesis and increased stored TG 2-fold. Expression of E9-deleted CETP in mouse 3T3-L1 cells produced a similar lipid phenotype. In vitro, FL-CETP promotes the transfer of TG from ER-enriched membranes to lipid droplets. E9-deleted CETP also promoted this transfer, although less effectively, and i...
Source: The Journal of Lipid Research - February 29, 2020 Category: Lipidology Authors: Izem, L., Liu, Y., Morton, R. E. Tags: Research Articles Source Type: research
Deficiency in ZMPSTE24 and resulting farnesyl-prelamin A accumulation only modestly affect mouse adipose tissue stores [Research Articles]
Zinc metallopeptidase STE24 (ZMPSTE24) is essential for the conversion of farnesyl–prelamin A to mature lamin A, a key component of the nuclear lamina. In the absence of ZMPSTE24, farnesyl–prelamin A accumulates in the nucleus and exerts toxicity, causing a variety of disease phenotypes. By ~4 months of age, both male and female Zmpste24–/– mice manifest a near-complete loss of adipose tissue, but it has never been clear whether this phenotype is a direct consequence of farnesyl–prelamin A toxicity in adipocytes. To address this question, we generated a conditional knockout Zmpste24 allele and...
Source: The Journal of Lipid Research - February 29, 2020 Category: Lipidology Authors: Heizer, P. J., Yang, Y., Tu, Y., Kim, P. H., Chen, N. Y., Hu, Y., Yoshinaga, Y., de Jong, P. J., Vergnes, L., Morales, J. E., Li, R. L., Jackson, N., Reue, K., Young, S. G., Fong, L. G. Tags: Research Articles Source Type: research
Monitoring the itinerary of lysosomal cholesterol in Niemann-Pick Type C1-deficient cells after cyclodextrin treatment [Research Articles]
Niemann-Pick disease type C (NPC) disease is a lipid-storage disorder that is caused by mutations in the genes encoding NPC proteins and results in lysosomal cholesterol accumulation. 2-Hydroxypropyl-β-cyclodextrin (CD) has been shown to reduce lysosomal cholesterol levels and enhance sterol homeostatic responses, but CD’s mechanism of action remains unknown. Recent work provides evidence that CD stimulates lysosomal exocytosis, raising the possibility that lysosomal cholesterol is released in exosomes. However, therapeutic concentrations of CD do not alter total cellular cholesterol, and cholesterol homeostatic...
Source: The Journal of Lipid Research - February 29, 2020 Category: Lipidology Authors: Feltes, M., Gale, S. E., Moores, S., Ory, D. S., Schaffer, J. E. Tags: Research Articles Source Type: research
The citrus flavonoid nobiletin confers protection from metabolic dysregulation in high-fat-fed mice independent of AMPK [Research Articles]
Obesity, dyslipidemia, and insulin resistance, the increasingly common metabolic syndrome, are risk factors for CVD and type 2 diabetes that warrant novel therapeutic interventions. The flavonoid nobiletin displays potent lipid-lowering and insulin-sensitizing properties in mice with metabolic dysfunction. However, the mechanisms by which nobiletin mediates metabolic protection are not clearly established. The central role of AMP-activated protein kinase (AMPK) as an energy sensor suggests that AMPK is a target of nobiletin. We tested the hypothesis that metabolic protection by nobiletin required phosphorylation of AMPK an...
Source: The Journal of Lipid Research - February 29, 2020 Category: Lipidology Authors: Morrow, N. M., Burke, A. C., Samsoondar, J. P., Seigel, K. E., Wang, A., Telford, D. E., Sutherland, B. G., ODwyer, C., Steinberg, G. R., Fullerton, M. D., Huff, M. W. Tags: Research Articles Source Type: research
