LipidsPub Date : 2022-01-24DOI: 10.1002/lipd.12336
Giulia Cisbani, Alex Koppel, Adam H. Metherel, Mackenzie E. Smith, Kankana N. Aji, Ana C. Andreazza, Romina Mizrahi, Richard P. Bazinet
{"title":"Serum lipid analysis and isotopic enrichment is suggestive of greater lipogenesis in young long-term cannabis users: A secondary analysis of a case–control study","authors":"Giulia Cisbani, Alex Koppel, Adam H. Metherel, Mackenzie E. Smith, Kankana N. Aji, Ana C. Andreazza, Romina Mizrahi, Richard P. Bazinet","doi":"10.1002/lipd.12336","DOIUrl":"10.1002/lipd.12336","url":null,"abstract":"<p>Cannabis is now legal in many countries and while numerous studies have reported on its impact on cognition and appetite regulation, none have examined fatty acid metabolism in young cannabis users. We conducted an exploratory analysis to evaluate cannabis impact on fatty acid metabolism in cannabis users (<i>n</i> = 21) and non-cannabis users (<i>n</i> = 16). Serum levels of some saturated and monounsaturated fatty acids, including palmitic, palmitoleic, and oleic acids were higher in cannabis users compared to nonusers. As palmitic acid can be derived from diet or lipogenesis from sugars, we evaluated lipogenesis using a de novo lipogenesis index (palmitate/linoleic acid) and carbon-specific isotope analysis, which allows for the determination of fatty acid <sup>13</sup>C signature. The significantly higher de novo lipogenesis index in the cannabis users group along with a more enriched <sup>13</sup>C signature of palmitic acid suggested an increase in lipogenesis. In addition, while serum glucose concentration did not differ between groups, pyruvate and lactate were lower in the cannabis user group, with pyruvate negatively correlating with palmitic acid. Furthermore, the endocannabinoid 2-arachidonoylglycerol was elevated in cannabis users and could contribute to lipogenesis by activating the cannabinoid receptor 1. Because palmitic acid has been suggested to increase inflammation, we measured peripheral cytokines and observed no changes in inflammatory cytokines. Finally, an anti-inflammatory metabolite of palmitic acid, palmitoylethanolamide was elevated in cannabis users. Our results suggest that lipogenic activity is increased in cannabis users; however, future studies, including prospective studies that control dietary intake are required.</p>","PeriodicalId":18086,"journal":{"name":"Lipids","volume":"57 2","pages":"125-140"},"PeriodicalIF":1.9,"publicationDate":"2022-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10808168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
LipidsPub Date : 2022-01-20DOI: 10.1002/lipd.12337
Behnam Tajik, Ari Voutilainen, Jussi Kauhanen, Moshen Mazidi, Gregory Y. H. Lip, Tomi-Pekka Tuomainen, Masoud Isanejad
{"title":"Lipid profile, lipid ratios, apolipoproteins, and risk of cardiometabolic multimorbidity in men: The Kuopio Ischaemic Heart Disease Risk Factor Study","authors":"Behnam Tajik, Ari Voutilainen, Jussi Kauhanen, Moshen Mazidi, Gregory Y. H. Lip, Tomi-Pekka Tuomainen, Masoud Isanejad","doi":"10.1002/lipd.12337","DOIUrl":"10.1002/lipd.12337","url":null,"abstract":"<p>The blood level of lipids, apolipoproteins, and lipid ratios are important predictors of some chronic diseases. However, their association with cardiometabolic multimorbidity (CMM) is less known. We evaluated a wide range of lipid profiles and lipid ratios, including low-density lipoprotein-cholesterol (LDL-C), very-low-density lipoprotein-cholesterol (VLDL-C), high-density lipoprotein-cholesterol (HDL-C), and apoA1 and B, as well triglyceride and total cholesterol with risk of incident CMM. In 1728 men aged 52.5 ± 5.2 years from the Kuopio Ischaemic Heart Disease were included in this study. We defined CMM as coexisting of two or more of stroke, type 2 diabetes mellitus (T2D), coronary heart disease (CHD). A Cox proportional hazard regression method was applied to evaluate the risk of CMM against the exposures. During the mean follow-up of 22.4 years, 335 men suffered from CMM conditions. Higher serum triglyceride and VLDL concentrations were associated with a higher risk of coexisting T2D-CHD (HRs 1.99 (95% CI, 1.12–3.53) and HRs 1.79 (95% CI, 1.04–3.11), respectively. Whereas higher HDL was associated with lower incident [HRs 0.49 (95% CI, 0.40–1.00)]. The HRs for coexisting T2D-CHD was 2.02 (95% CI, 1.01–3.07) for total cholesterol/HDL-C, 1.85 (95% CI, 1.04–3.29) for triglyceride/HDL-C, 1.69 (95% CI, 1.01–2.31) for Non-HDL-C/HDL-C, and 1.89 (95% CI, 1.03–2.46) for apoB/apoA1. In contrast, serum LDL-C/apoB ratios were inversely associated with the risk of coexisting T2D-CHD [HRs 0.50 (95% CI, 0.28–0.90)]. No associations were observed between our exposures and other CMM conditions. In conclusion, elevated triglyceride, VLDL-C, total cholesterol/HDL-C, TG/HDL-C, apoB/apoA1 as well as lower LDL-C/apoB were independently associated with the higher risk of T2D-CHD coexistence.</p>","PeriodicalId":18086,"journal":{"name":"Lipids","volume":"57 2","pages":"141-149"},"PeriodicalIF":1.9,"publicationDate":"2022-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9305561/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39711982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
LipidsPub Date : 2022-01-03DOI: 10.1002/lipd.12335
Hyunsin (Hedy) Sung, Andrew J. Sinclair, Xiao Q Su
{"title":"Enrichment of n-3 containing ether phospholipids in plasma after 30 days of krill oil compared with fish oil supplementation","authors":"Hyunsin (Hedy) Sung, Andrew J. Sinclair, Xiao Q Su","doi":"10.1002/lipd.12335","DOIUrl":"10.1002/lipd.12335","url":null,"abstract":"<p>There are conflicting findings over the bioavailability of long-chain n-3 polyunsaturated fatty acids (n-3 PUFA) from krill oil (KO) compared with fish oil (FO) in short- and long-term studies. The aim of this study was to compare the effects of KO versus FO on the enrichment of molecular species of plasma phospholipids in young women following a 30-day consumption of the n-3 oils. Eleven healthy women aged 18–45 years consumed seven capsules of KO per day (containing a total of 1.27 g n-3 PUFA) or five capsules of FO per day (total of 1.44 g n-3 PUFA) for 30 days in a randomized crossover study, separated by at least a 30-day washout period. Fasting blood samples were collected at day zero (baseline), day 15 and day 30 and analyzed by HPLC-MS/MS for molecular species of phospholipids. Supplementation increased n-3 PUFA in main phospholipids classes in both groups. After 30 days of supplementation, 35 out of 70 molecular species containing eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and docosapentaenoic acid (DPAn-3) had a significantly greater concentration in KO group compared with the FO treated group. The majority (89%) of the differentiated molecular species were choline and ethanolamine ether-phospholipids. These data reveal that analysis of plasma phospholipids following 30 days of consumption of KO (a marine oil rich in phospholipids, including ether phospholipids) resulted in an enrichment of n-3 PUFA in molecular species of ether-phospholipids compared with FO (a triacylglycerol-rich marine oil).</p>","PeriodicalId":18086,"journal":{"name":"Lipids","volume":"57 2","pages":"115-124"},"PeriodicalIF":1.9,"publicationDate":"2022-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://aocs.onlinelibrary.wiley.com/doi/epdf/10.1002/lipd.12335","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39896401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
LipidsPub Date : 2021-12-19DOI: 10.1002/lipd.12334
José Ángel Cahua-Pablo, Jaime Héctor Gómez-Zamudio, Carlos Alberto Reséndiz-Abarca, Vianet Argelia Tello-Flores, Yesica Eulogio-Metodio, Marco Antonio Ramírez-Vargas, Miguel Cruz, Luz del Carmen Alarcón-Romero, Inés Matia-García, Linda Anahí Marino-Ortega, Ma. Isabel Zubillaga-Guerrero, Eugenia Flores-Alfaro
{"title":"Genetic variants in SLC22A1 are related to serum lipid levels in Mexican women","authors":"José Ángel Cahua-Pablo, Jaime Héctor Gómez-Zamudio, Carlos Alberto Reséndiz-Abarca, Vianet Argelia Tello-Flores, Yesica Eulogio-Metodio, Marco Antonio Ramírez-Vargas, Miguel Cruz, Luz del Carmen Alarcón-Romero, Inés Matia-García, Linda Anahí Marino-Ortega, Ma. Isabel Zubillaga-Guerrero, Eugenia Flores-Alfaro","doi":"10.1002/lipd.12334","DOIUrl":"10.1002/lipd.12334","url":null,"abstract":"<p>Dyslipidemia is the main risk factor for coronary artery disease and is characterized by alterations in concentrations of lipids, including low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), and triacylglycerols. The participation of several genes in the development of dyslipidemia has been evidenced. Genetic variants in <i>SLC22A1</i> have been associated with elevated cholesterol and LDL-c levels. The aim of this study was to evaluate the association between single-nucleotide polymorphisms (SNPs) in the <i>SLC22A1</i> gene with atherogenic risk lipid levels in Mexican women. Anthropometric and biochemical measurements were performed, and four SNPs in <i>SLC22A1</i> were genotyped by real-time polymerase chain reaction. The Hardy–Weinberg equilibrium was verified, and haplotype frequencies were calculated. We found significant differences between the allele frequencies of the SNPs analyzed with those reported in Mexico and in the world, which could be due to differences in the historical admixture of the women studied. Generalized linear models were evaluated to determine the association between genotypes and haplotypes with lipids levels. We identified a significant increase in total cholesterol and LDL-c levels in women who were carriers of the GA and AG genotypes of the polymorphisms rs628031 and rs594709, respectively, significant effect that is also shown in a dominant inheritance model. Interestingly, we identified an important relationship of the AGC-GAT haplotype with the elevation in LDL-c levels and AGA-GAT haplotype with the elevation in HDL-c levels. On the other hand, we found a strong linkage disequilibrium between the polymorphisms studied. Our results show that variants in the <i>SLC22A1</i> gene influence serum levels of atherogenic risk lipids, suggesting that these variants probably affect the function of organic cation transporter-1 and therefore, on the regulation of lipid metabolism.</p>","PeriodicalId":18086,"journal":{"name":"Lipids","volume":"57 2","pages":"105-114"},"PeriodicalIF":1.9,"publicationDate":"2021-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39617417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
LipidsPub Date : 2021-12-13DOI: 10.1002/lipd.12333
Arnis Kuksis, Waldemar Pruzanski
{"title":"Destruction of polyunsaturated alkyl/acyl and alkenyl/acyl glycerophosphocholine of plasma lipoproteins during incubation with group V and X secretory phospholipase A2s","authors":"Arnis Kuksis, Waldemar Pruzanski","doi":"10.1002/lipd.12333","DOIUrl":"10.1002/lipd.12333","url":null,"abstract":"<p>Plasma lipoproteins are carriers of various glycerophospholipids including diacyl, alkenyl/acyl, and alkyl/acyl glycerophosphocholines (GPCs), which become distributed among cells and tissues during metabolism. For metabolic function, these phospholipids require hydrolysis by phospholipases, but the responsible enzymes have not been identified. We had previously shown that after complete digestion of lipoprotein diacyl- and oxo-diacyl-GPCs, degradation of residual alkyl/acyl and alkenyl/acyl GPCs continues, despite the fact that ether lipids are resistant to hydrolysis by Ca<sup>2+</sup>-activated secretory PLA<sub>2</sub>s and require the presence of the Ca<sup>2+</sup>-independent PLA<sub>2</sub>. In the course of further investigation, we came across a report by Khaselev and Murphy in which the autoxidative degradation of plasmalogens in the presence of 2,2′-azobis(2-amidinopropane) dihydrochloride (AAPH) proceeded beyond the formation of dihydroperoxides, hydroxides and epoxides, and led to an attack on the enyl bond of the plasmalogen, resulting in formation of 1-OH/2-20:4-GPC and 1-formyl/2-20:4-GPC. Our preliminary investigation indicated that lipoprotein 16:0p/20:4ω6-GPC yielded the same autoxidation products as those reported for synthetic 16:0p/20:4ω6-GPC in the presence of AAPH. Such autoxidative degradation of lipoprotein plasmalogens had not been previously reported with or without AAPH. Subsequent study led to the conclusion that this reaction was not limited to arachidonates, but extended to other polyunsaturated eicosanoids, docosanoids, and tetracosanoids, as well as oligounsaturated octadecanoids. These observations led to a hypothesis that the autoxidative cleavage of the lipoprotein plasmalogens proceeded under the influence of apo-protein-derived free radicals as intermediates of oxidative processes.</p>","PeriodicalId":18086,"journal":{"name":"Lipids","volume":"57 2","pages":"91-104"},"PeriodicalIF":1.9,"publicationDate":"2021-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39722703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Lipopolysaccharide and tyloxapol accelerate the development of atherosclerosis in mice","authors":"Meiyu Jin, Di Zhang, Lianwen Zheng, Yunfei Wei, Siru Yan, Haiyan Qin, Qi Wang, Lilei Zhao, Haihua Feng","doi":"10.1002/lipd.12331","DOIUrl":"10.1002/lipd.12331","url":null,"abstract":"<p>The occurrence of atherosclerosis is closely related to inflammation and lipid metabolism disorder. It has been found that lipopolysaccharide (LPS) could induce inflammation, and tyloxapol (Ty) could induce hyperlipidemia. However, the effects of LPS and Ty on the development and mechanism of atherosclerosis have not been investigated thoroughly. To answer this question, we used assay kits to detect total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL) content to evaluate dyslipidemia. We used hematoxylin and eosin staining to evaluate the pathological structure of the aorta and liver, and then used Oil Red O staining to access lipid accumulation in the aortic wall. Subsequently, we used the alanine transaminase (ALT) kit to examine the liver injury. Finally, we used the Western blot experiment to measure proteins that regulate lipid metabolism. We found that the LPS + Ty group could increase the levels of TC, TG, and LDL in the serum and promote lipid accumulation in the aortic wall in mice. Moreover, our study showed that the LPS + Ty group induced pathological changes in hepatocytes and increased ALT content in mice. Significantly, we found that the LPS + Ty group could activate acetyl-CoA carboxylase, sterol regulatory element-binding protein-1c, and inhibit peroxisome proliferator-activated receptors α in mice. Therefore, we suppose that LPS and Ty aggravated the development of atherosclerosis by promoting hyperlipidemia and the disorder of lipid metabolism in mice. These findings are significant for the study of the pathogenesis of atherosclerosis and the selection of animal models.</p>","PeriodicalId":18086,"journal":{"name":"Lipids","volume":"57 2","pages":"83-90"},"PeriodicalIF":1.9,"publicationDate":"2021-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39789568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
LipidsPub Date : 2021-12-05DOI: 10.1002/lipd.12330
Yan Liu, Daniel Mihna, Lahoucine Izem, Richard E. Morton
{"title":"Both full length-cholesteryl ester transfer protein and exon 9-deleted cholesteryl ester transfer protein promote triacylglycerol storage in cultured hepatocytes","authors":"Yan Liu, Daniel Mihna, Lahoucine Izem, Richard E. Morton","doi":"10.1002/lipd.12330","DOIUrl":"10.1002/lipd.12330","url":null,"abstract":"<p>We previously reported that overexpression of full-length cholesteryl ester transfer protein (FL-CETP), but not its exon 9-deleted variant (∆E9-CETP), in an adipose cell line reduces their triacylglycerol (TAG) content. This provided mechanistic insight into several in vivo studies where FL-CETP levels are inversely correlated with adiposity. However, increased FL-CETP is also associated with elevated hepatic lipids, suggesting that the effect of CETP on cellular lipid metabolism may be tissue-specific. Here, we directly investigated the role of FL-CETP and ∆E9-CETP in hepatic lipid metabolism. FL- or ∆E9-CETP was overexpressed in HepG2-C3A by adenovirus transduction. Overexpression of either FL or ∆E9-CETP in hepatocytes increased cellular TAG mass by 25% but reduced TAG secretion. This cellular TAG was contained in larger and more numerous lipid droplets. Analysis of TAG synthetic and catabolic pathways showed that this elevated TAG content was due to increased incorporation of fatty acid into TAG (24%), and higher de novo synthesis of fatty acid (50%) and TAG from acetate (40%). siRNA knockdown of CETP had the opposite effect on TAG synthesis and lipogenesis, and decreased cellular TAG. This novel increase in cellular TAG by FL-CETP overexpression was reproduced in Caco-2 intestinal epithelial cells. We conclude that, unlike that seen in adipocyte cells, overexpression of either CETP isoform in lipoprotein-secreting cells promotes the accumulation of TAG. These data suggest that the in vivo correlation between CETP levels and hepatic steatosis can be explained, in part, by a direct effect of CETP on hepatocyte cellular metabolism.</p>","PeriodicalId":18086,"journal":{"name":"Lipids","volume":"57 1","pages":"69-79"},"PeriodicalIF":1.9,"publicationDate":"2021-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9060302/pdf/nihms-1773171.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10456833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
LipidsPub Date : 2021-11-20DOI: 10.1002/lipd.12329
Ahmed S. A. El-Zenary, Khalid M. Gaafar, Reham Abou-Elkhair, Robert G. Elkin, John W. Boney, Kevin J. Harvatine
{"title":"Comparison of Ahiflower oil containing stearidonic acid to a high-alpha-linolenic acid flaxseed oil at two levels on tissue omega-3 enrichment in broilers","authors":"Ahmed S. A. El-Zenary, Khalid M. Gaafar, Reham Abou-Elkhair, Robert G. Elkin, John W. Boney, Kevin J. Harvatine","doi":"10.1002/lipd.12329","DOIUrl":"10.1002/lipd.12329","url":null,"abstract":"Enrichment of broiler meat with very long-chain omega-3 fatty acids (VLCn-3 FA) is of interest because of their beneficial effects on human health. The ability of Ahiflower® (AHI) oil (Buglossoides arvensis), which naturally contains stearidonic acid (SDA), and a high-alpha-linolenic acid (ALA) flaxseed (FLAX) oil to enrich VLCn-3 FA contents in broilers tissues was investigated. Fifty-five Cobb 500 chicks were fed from days 12 to 35 of life either a control (CON) diet that contained 27.9 g/kg soybean oil or AHI or FLAX oils, each individually at 7.5 or 22.5 g/kg of the diet in substitution for soybean oil (all on an as fed basis). Total VLCn-3 FA contents were greater in breast, thigh, liver, adipose tissue, and plasma of all n-3 treatments compared to CON, with the greatest increase observed at the highest level of AHI and FLAX oils (p < 0.001). AHI oil at 7.5 g/kg promoted the most efficient synthesis and deposition of VLCn-3 in broiler tissues measured as deposition of VLCn-3 FA in tissues relative to intake of n3 FA. In conclusion, both ALA and SDA oils increased VLCn-3 FA deposition in tissues, but there were diminishing returns when increasing dietary levels of the oils.","PeriodicalId":18086,"journal":{"name":"Lipids","volume":"57 1","pages":"57-68"},"PeriodicalIF":1.9,"publicationDate":"2021-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://aocs.onlinelibrary.wiley.com/doi/epdf/10.1002/lipd.12329","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39893632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
LipidsPub Date : 2021-11-09DOI: 10.1002/lipd.12326
Rahau S. Shirazi, Mikhail Vyssotski, Kirill Lagutin, Dion Thompson, Christa MacDonald, Vincent Luscombe, Michelle Glass, Kim Parker, Emma K. Gowing, D. Bradley G. Williams, Andrew N. Clarkson
{"title":"Neuroprotective activity of new Δ3-N-acylethanolamines in a focal ischemia stroke model","authors":"Rahau S. Shirazi, Mikhail Vyssotski, Kirill Lagutin, Dion Thompson, Christa MacDonald, Vincent Luscombe, Michelle Glass, Kim Parker, Emma K. Gowing, D. Bradley G. Williams, Andrew N. Clarkson","doi":"10.1002/lipd.12326","DOIUrl":"10.1002/lipd.12326","url":null,"abstract":"<p>N-acylethanolamines (NAE, also called ethanolamides) are significant lipid signaling molecules with anti-inflammatory, pain-relieving, cell-protective, and anticancer properties. Here, we present the use of a hitherto unreported group of Δ3-NAE and also some Δ4- and Δ5-NAE, in in vitro and in vivo assays to gain a better understanding of their structure–bioactivity relationships. We have developed an efficient synthetic method to rapidly produce novel unlabeled and <sup>13</sup>C-labeled Δ3-NAE (NAE-18:5n-3, NAE-18:4n-6) and Δ4-NAE (NAE-22:5n-6). The new NAE with shorter carbon backbone structures confers greater neuroprotection than their longer carbon backbone counterparts, including anandamide (Δ5-NAE-20:4n-6) in a focal ischemia mouse model of stroke. This study highlights structure-dependent protective effects of new NAE following focal ischemia, in which some of the new NAE, administered intranasally, lead to significantly reduced infarct volume and improved recovery of limb use. The relative affinity of the new NAE toward cannabinoid receptors was assessed against anandamide, NAE-22:6n-3 and NAE-20:5n-3, which are known cannabinoid receptor ligands with high-binding constants. Among the newly synthesized NAE, Δ4-NAE-22:5n-6 shows the greatest relative affinity to cannabinoid receptors hCB<sub>1</sub> and hCB<sub>2</sub>, and inhibition of cyclic adenosine monophosphate activity through hCB<sub>2</sub> compared to anandamide.</p>","PeriodicalId":18086,"journal":{"name":"Lipids","volume":"57 1","pages":"17-31"},"PeriodicalIF":1.9,"publicationDate":"2021-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://aocs.onlinelibrary.wiley.com/doi/epdf/10.1002/lipd.12326","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39709345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Astragalus polysaccharide regulates brown adipocytes differentiation by miR-6911 targeting Prdm16","authors":"Shihe Zhang, Pengkang Song, Xiaoyou Chen, Yu Wang, Xuyang Gao, Lin Liang, Junxing Zhao","doi":"10.1002/lipd.12328","DOIUrl":"10.1002/lipd.12328","url":null,"abstract":"<p>Brown adipose tissue (BAT) is a specialized tissue in mammals related to thermogenesis. The <i>Astragalus</i> polysaccharide (APS) is the major natural active component of <i>Astragalus membranaceus</i>, which has been recognized as one of the most popular herbal medicines worldwide. The role and possible mechanisms of APS on brown adipocytes differentiation is not well defined. Here, we explored the effect of APS on the differentiation of brown adipocytes in C3H10T 1/2 cells. The results showed that APS promoted the differentiation of brown adipocytes and improved insulin sensitivity along with significant increases in the expression of brown adipogenic marker proteins (C/EBPα, C/EBPβ, and PPARγ), thermogenesis marker proteins (UCP1, PRDM16, and PGC-1α), and insulin sensitivity marker protein (GLUT4). Meanwhile, the results showed that the amount of the phosphorylation of insulin receptor substrate 1 (p-IRS1) and phospho-AKT (p-AKT) which are critical factors in the insulin signaling pathway was increased without changing the total amount of IRS and AKT. Furthermore, the results of RNA-seq showed that APS altered the expression profiles of various miRNAs, and among which the expression of miR-6911 as a universal regulatory factor was significantly decreased. Importantly, we found that miR-6911 regulated the differentiation of brown adipocytes by targeting <i>PR domain-containing 16</i> (<i>Prdm16</i>). In addition, after transfection of miR-6911 mimics, compared with the control and inhibitor group, PRDM16 protein expression significantly decreased, which was accompanied by the decrease of PPARγ, UCP1, and PGC-1α. Collectively, our results indicated that APS regulated brown adipocytes differentiation in C3H10T 1/2 cells via miRNA-6911 targeting <i>Prdm16</i>.</p>","PeriodicalId":18086,"journal":{"name":"Lipids","volume":"57 1","pages":"45-55"},"PeriodicalIF":1.9,"publicationDate":"2021-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://aocs.onlinelibrary.wiley.com/doi/epdf/10.1002/lipd.12328","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39681440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}