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1
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Palmer MA, Benatzy Y, Brüne B. Murine Alox8 versus the human ALOX15B ortholog: differences and similarities. Pflugers Arch 2024; 476:1817-1832. [PMID: 38637408 PMCID: PMC11582214 DOI: 10.1007/s00424-024-02961-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2024] [Revised: 03/30/2024] [Accepted: 04/03/2024] [Indexed: 04/20/2024]
Abstract
Human arachidonate 15-lipoxygenase type B is a lipoxygenase that catalyzes the peroxidation of arachidonic acid at carbon-15. The corresponding murine ortholog however has 8-lipoxygenase activity. Both enzymes oxygenate polyunsaturated fatty acids in S-chirality with singular reaction specificity, although they generate a different product pattern. Furthermore, while both enzymes utilize both esterified fatty acids and fatty acid hydro(pero)xides as substrates, they differ with respect to the orientation of the fatty acid in their substrate-binding pocket. While ALOX15B accepts the fatty acid "tail-first," Alox8 oxygenates the free fatty acid with its "head-first." These differences in substrate orientation and thus in regio- and stereospecificity are thought to be determined by distinct amino acid residues. Towards their biological function, both enzymes share a commonality in regulating cholesterol homeostasis in macrophages, and Alox8 knockdown is associated with reduced atherosclerosis in mice. Additional roles have been linked to lung inflammation along with tumor suppressor activity. This review focuses on the current knowledge of the enzymatic activity of human ALOX15B and murine Alox8, along with their association with diseases.
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Affiliation(s)
- Megan A Palmer
- Institute of Biochemistry I, Faculty of Medicine, Goethe University Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt, Germany.
| | - Yvonne Benatzy
- Institute of Biochemistry I, Faculty of Medicine, Goethe University Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt, Germany.
| | - Bernhard Brüne
- Institute of Biochemistry I, Faculty of Medicine, Goethe University Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt, Germany
- Frankfurt Cancer Institute, Goethe University Frankfurt, Frankfurt, Germany
- Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Frankfurt, Germany
- German Cancer Consortium (DKTK), Partner Site Frankfurt, Frankfurt, Germany
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2
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Du L, Wang J, Qiu X, Wang Q, Peng H, Huang J, Yang F, Liu Z, Qi R. Clostridium sporogenes increases fat accumulation in mice by enhancing energy absorption and adipogenesis. Microbiol Spectr 2024; 12:e0411623. [PMID: 38916334 PMCID: PMC11302664 DOI: 10.1128/spectrum.04116-23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2023] [Accepted: 05/09/2024] [Indexed: 06/26/2024] Open
Abstract
Gut bacteria belonging to the Clostridium family play a pivotal role in regulating host energy balance and metabolic homeostasis. As a commensal bacterium, Clostridium sporogenes has been implicated in modulating host energy homeostasis, albeit the underlying mechanism remains elusive. Therefore, this study aimed to investigate the impact of C. sporogenes supplementation on various physiological parameters, intestinal morphology, particularly adipose tissue accumulation, and glucolipid metabolism in mice. The findings reveal that mice supplemented with C. sporogenes for 6 weeks exhibited a notable increase in body weight, fat mass, adipocyte size, and serum triglyceride (TG) levels. Notably, the increased fat accumulation is observed despite consistent feed intake in treated mice. Mechanistically, C. sporogenes supplementation significantly improved the structure integrity of intestinal villi and enhanced energy absorption efficiency while reducing excretion of carbohydrates and fatty acids in feces. This was accompanied by upregulation of glucose and fatty acid transporter expression. Furthermore, supplementation with C. sporogenes promoted adipogenesis in both liver and adipose tissues, as evidenced by increased levels of hepatic pyruvate, acetyl-CoA, and TG, along with elevated expression levels of genes associated with lipid synthesis. Regarding the microbiological aspect, C. sporogenes supplementation correlated with an increased abundance of Clostridium genus bacteria and enhanced carbohydrate enzyme activity. In summary, C. sporogenes supplementation significantly promotes fat accumulation in mice by augmenting energy absorption and adipogenesis, possibly mediated by the expansion of Clostridium bacteria population with robust glycolipid metabolic ability. IMPORTANCE The Clostridia clusters have been implicated in energy metabolism, the specific species and underlying mechanisms remain unclear. This present study is the first to report Clostridium sporogenes is able to affect fat accumulation and glycolipid metabolism. We indicated that gavage of C. sporogenes promoted the adipogenesis and fat accumulation in mice by not only increasing the abundance of Clostridium bacteria but by also enhancing the metabolic absorption of carbohydrates and fatty acids significantly. Obviously, changes of gut microbiota caused by the C. sporogenes, especially the significant increase of Clostridium bacteria, contributed to the fat accumulation of mice. In addition, the enhancement of Clostridium genus bacteria remarkably improved the synthesis of hepatic pyruvate, acetyl-CoA, and triglyceride levels, as well as reduced the excretion of fecal carbohydrates, short-chain fatty acids, and free fatty acids remarkably. These findings will help us to understand the relationship of specific bacteria and host energy homeostasis.
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Affiliation(s)
- Lei Du
- Chongqing Academy of Animal Science, Chongqing, China
- Zhejiang Engineering Research Center for Tissue Repair Materials, Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang, China
| | - Jing Wang
- Chongqing Academy of Animal Science, Chongqing, China
| | - Xiaoyu Qiu
- Chongqing Academy of Animal Science, Chongqing, China
| | - Qi Wang
- Chongqing Academy of Animal Science, Chongqing, China
| | - Han Peng
- Sichuan Animal Science Academy, Chengdu, China
| | - Jinxiu Huang
- Chongqing Academy of Animal Science, Chongqing, China
| | - Feiyun Yang
- Chongqing Academy of Animal Science, Chongqing, China
- National Pig Technology Innovation Center, Chongqing, China
| | - Zuohua Liu
- Chongqing Academy of Animal Science, Chongqing, China
- National Pig Technology Innovation Center, Chongqing, China
| | - Renli Qi
- Chongqing Academy of Animal Science, Chongqing, China
- National Pig Technology Innovation Center, Chongqing, China
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Komiya Y, Sakazaki Y, Goto T, Kawabata F, Suzuki T, Sato Y, Sawano S, Nakamura M, Tatsumi R, Ikeuchi Y, Arihara K, Mizunoya W. Eicosapentaenoic acid increases proportion of type 1 muscle fibers through PPARδ and AMPK pathways in rats. iScience 2024; 27:109816. [PMID: 38779480 PMCID: PMC11108975 DOI: 10.1016/j.isci.2024.109816] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Revised: 03/07/2024] [Accepted: 04/24/2024] [Indexed: 05/25/2024] Open
Abstract
Muscle fiber type composition (% slow-twitch and % fast-twitch fibers) is associated with metabolism, with increased slow-twitch fibers alleviating metabolic disorders. Previously, we reported that dietary fish oil intake induced a muscle fiber-type transition in a slower direction in rats. The aim of this study was to determine the functionality of eicosapentaenoic acid (EPA), a unique fatty acid in fish oil, to skeletal muscle fiber type and metabolism in rats. Here, we showed that dietary EPA promotes whole-body oxidative metabolism and improves muscle function by increasing proportion of slow-twitch type 1 fibers in rats. Transcriptomic and metabolomic analyses revealed that EPA supplementation activated the peroxisome proliferator-activated receptor δ (PPARδ) and AMP-activated protein kinase (AMPK) pathways in L6 myotube cultures, which potentially increasing slow-twitch fiber share. This highlights the role of EPA as an exercise-mimetic dietary component that improves metabolism and muscle function, with potential benefits for health and athletic performance.
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Affiliation(s)
- Yusuke Komiya
- Department of Animal Science, School of Veterinary Medicine, Kitasato University, Towada, Japan
| | - Yuka Sakazaki
- Department of Animal and Marine Bioresource Sciences, Faculty of Agriculture, Graduate School of Agriculture, Kyushu University, Fukuoka, Japan
| | - Tsuyoshi Goto
- Division of Food Science & Biotechnology, Kyoto University, Kyoto, Japan
| | - Fuminori Kawabata
- Faculty of Agriculture and Life Science, Hirosaki University, Hirosaki, Japan
| | - Takahiro Suzuki
- Department of Animal and Marine Bioresource Sciences, Faculty of Agriculture, Graduate School of Agriculture, Kyushu University, Fukuoka, Japan
| | - Yusuke Sato
- Department of Animal Science, School of Agriculture, Tokai University, Kumamoto, Japan
| | - Shoko Sawano
- Department of Food and Life Science, School of Life and Environmental Science, Azabu University, Sagamihara, Japan
| | - Mako Nakamura
- Department of Animal and Marine Bioresource Sciences, Faculty of Agriculture, Graduate School of Agriculture, Kyushu University, Fukuoka, Japan
| | - Ryuichi Tatsumi
- Department of Animal and Marine Bioresource Sciences, Faculty of Agriculture, Graduate School of Agriculture, Kyushu University, Fukuoka, Japan
| | - Yoshihide Ikeuchi
- Department of Animal and Marine Bioresource Sciences, Faculty of Agriculture, Graduate School of Agriculture, Kyushu University, Fukuoka, Japan
| | - Keizo Arihara
- Department of Animal Science, School of Veterinary Medicine, Kitasato University, Towada, Japan
| | - Wataru Mizunoya
- Department of Animal Science and Biotechnology, School of Veterinary Medicine, Azabu University, Sagamihara, Japan
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Yamada H, Miyasaka R, Hamada H. Euphausia pacifica emulsified oil powder improves sleep quality in partially sleep-restricted healthy volunteers. Biosci Biotechnol Biochem 2024; 88:561-570. [PMID: 38305100 DOI: 10.1093/bbb/zbae012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2023] [Accepted: 01/27/2024] [Indexed: 02/03/2024]
Abstract
Although it is known that adequate sleep is crucial for maintaining a healthy lifestyle, approximately 30% of the general population has experienced insomnia. Thus, a better understanding of the relationship between food components and sleep quality is needed. North Pacific krill, Euphausia pacifica, is rich in marine n-3 polyunsaturated fatty acids in phospholipid form as well as 8R-hydroxy-eicosapentanoic acid. Here, emulsified oil powder derived from this krill was used in a trial involving 64 participants to assess its potential to enhance sleep quality. Consumption of the powdered emulsified oil was found to reduce drowsiness upon waking and enhance fatigue recovery, and for participants aged 40 and above, an improvement in sleep cycle was observed. In conclusion, consumption of krill emulsified oil powder was effective in enhancing sleep quality for individuals with partial sleep restrictions.
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Affiliation(s)
- Hidetoshi Yamada
- Faculty of Life & Environmental Science, Teikyo University of Science, Tokyo, Japan
| | - Raimu Miyasaka
- Faculty of Life & Environmental Science, Teikyo University of Science, Tokyo, Japan
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5
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Ziqubu K, Dludla PV, Mabhida SE, Jack BU, Keipert S, Jastroch M, Mazibuko-Mbeje SE. Brown adipose tissue-derived metabolites and their role in regulating metabolism. Metabolism 2024; 150:155709. [PMID: 37866810 DOI: 10.1016/j.metabol.2023.155709] [Citation(s) in RCA: 9] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2023] [Revised: 09/28/2023] [Accepted: 10/14/2023] [Indexed: 10/24/2023]
Abstract
The discovery and rejuvenation of metabolically active brown adipose tissue (BAT) in adult humans have offered a new approach to treat obesity and metabolic diseases. Beyond its accomplished role in adaptive thermogenesis, BAT secretes signaling molecules known as "batokines", which are instrumental in regulating whole-body metabolism via autocrine, paracrine, and endocrine action. In addition to the intrinsic BAT metabolite-oxidizing activity, the endocrine functions of these molecules may help to explain the association between BAT activity and a healthy systemic metabolic profile. Herein, we review the evidence that underscores the significance of BAT-derived metabolites, especially highlighting their role in controlling physiological and metabolic processes involving thermogenesis, substrate metabolism, and other essential biological processes. The conversation extends to their capacity to enhance energy expenditure and mitigate features of obesity and its related metabolic complications. Thus, metabolites derived from BAT may provide new avenues for the discovery of metabolic health-promoting drugs with far-reaching impacts. This review aims to dissect the complexities of the secretory role of BAT in modulating local and systemic metabolism in metabolic health and disease.
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Affiliation(s)
- Khanyisani Ziqubu
- Department of Biochemistry, North-West University, Mmabatho 2745, South Africa
| | - Phiwayinkosi V Dludla
- Cochrane South Africa, South African Medical Research Council, Tygerberg 7505, South Africa; Department of Biochemistry and Microbiology, Faculty of Science and Agriculture, University of Zululand, KwaDlangezwa 3886, South Africa
| | - Sihle E Mabhida
- Non-Communicable Diseases Research Unit, South African Medical Research Council, Tygerberg 7505, South Africa
| | - Babalwa U Jack
- Biomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg 7505, South Africa
| | - Susanne Keipert
- Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, SE-106 91 Stockholm, Sweden
| | - Martin Jastroch
- Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, SE-106 91 Stockholm, Sweden
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Guo X, Liang K, Xia L, Zhang X, Liu J, Wang C, Li J, Li X, Hou X, Chen L. Mof plays distinct roles in hepatic lipid metabolism under healthy or non-alcoholic fatty liver conditions. iScience 2023; 26:108446. [PMID: 38034359 PMCID: PMC10687339 DOI: 10.1016/j.isci.2023.108446] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2023] [Revised: 09/11/2023] [Accepted: 11/09/2023] [Indexed: 12/02/2023] Open
Abstract
The disturbance of hepatic lipid metabolism has a strong association with non-alcoholic fatty liver disease (NAFLD) and diabetes. Mof, an acetyltransferase involved in obesity and carbon metabolism, has not been thoroughly examined in its connection to hepatic metabolism. We aimed to explore the impact of Mof on hepatic lipid metabolism. The alteration of Mof expression was found in both obese mice and NAFLD human liver. The genes regulated by Mof were closely associated with lipid metabolism. In normal mice or hepatic cells, the down-regulation or inhibition of Mof resulted in increased lipid accumulation due to decreased PPARα expression. Conversely, in diet-induced obesity (DIO) mice or hepatic cells treated with palmitic acid, the inhibition of Mof led to improved lipid metabolism, attributed to the reduction in p-mTOR/mTOR levels. In summary, Mof exhibited distinct roles in lipid metabolism under different conditions. The inhibition of Mof may hold potential as a therapeutic target for hepatic lipid metabolism disturbances.
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Affiliation(s)
- Xinghong Guo
- Department of Endocrinology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China
- Institute of Endocrine and Metabolic Diseases of Shandong University, Jinan, Shandong 250012, China
- Key Laboratory of Endocrine and Metabolic Diseases, Shandong Province Medicine & Health, Jinan, Shandong 250012, China
- Jinan Clinical Research Center for Endocrine and Metabolic Disease, Jinan, Shandong 250012, China
| | - Kai Liang
- Department of Endocrinology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China
- Institute of Endocrine and Metabolic Diseases of Shandong University, Jinan, Shandong 250012, China
- Key Laboratory of Endocrine and Metabolic Diseases, Shandong Province Medicine & Health, Jinan, Shandong 250012, China
- Jinan Clinical Research Center for Endocrine and Metabolic Disease, Jinan, Shandong 250012, China
| | - Longqing Xia
- Department of Endocrinology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China
| | - Xu Zhang
- Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, Life Science School of Shandong University, Qingdao, Shandong 266237, China
| | - Jinbo Liu
- Department of Endocrinology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China
- Institute of Endocrine and Metabolic Diseases of Shandong University, Jinan, Shandong 250012, China
- Key Laboratory of Endocrine and Metabolic Diseases, Shandong Province Medicine & Health, Jinan, Shandong 250012, China
- Jinan Clinical Research Center for Endocrine and Metabolic Disease, Jinan, Shandong 250012, China
| | - Chuan Wang
- Department of Endocrinology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China
- Institute of Endocrine and Metabolic Diseases of Shandong University, Jinan, Shandong 250012, China
- Key Laboratory of Endocrine and Metabolic Diseases, Shandong Province Medicine & Health, Jinan, Shandong 250012, China
- Jinan Clinical Research Center for Endocrine and Metabolic Disease, Jinan, Shandong 250012, China
| | - Jinquan Li
- Department of Endocrinology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China
- Institute of Endocrine and Metabolic Diseases of Shandong University, Jinan, Shandong 250012, China
- Key Laboratory of Endocrine and Metabolic Diseases, Shandong Province Medicine & Health, Jinan, Shandong 250012, China
- Jinan Clinical Research Center for Endocrine and Metabolic Disease, Jinan, Shandong 250012, China
| | - Xiangzhi Li
- Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, Life Science School of Shandong University, Qingdao, Shandong 266237, China
| | - Xinguo Hou
- Department of Endocrinology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China
- Institute of Endocrine and Metabolic Diseases of Shandong University, Jinan, Shandong 250012, China
- Key Laboratory of Endocrine and Metabolic Diseases, Shandong Province Medicine & Health, Jinan, Shandong 250012, China
- Jinan Clinical Research Center for Endocrine and Metabolic Disease, Jinan, Shandong 250012, China
| | - Li Chen
- Department of Endocrinology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China
- Institute of Endocrine and Metabolic Diseases of Shandong University, Jinan, Shandong 250012, China
- Key Laboratory of Endocrine and Metabolic Diseases, Shandong Province Medicine & Health, Jinan, Shandong 250012, China
- Jinan Clinical Research Center for Endocrine and Metabolic Disease, Jinan, Shandong 250012, China
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7
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Antarctic krill extracts enhance muscle regeneration and muscle function via mammalian target of rapamycin regulation. J Funct Foods 2023. [DOI: 10.1016/j.jff.2023.105483] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/19/2023] Open
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8
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Fuller H, Race AD, Fenton H, Burke L, Downing A, Williams EA, Rees CJ, Brown LC, Loadman PM, Hull MA. Plasma and rectal mucosal oxylipin levels during aspirin and eicosapentaenoic acid treatment in the seAFOod polyp prevention trial. Prostaglandins Leukot Essent Fatty Acids 2023; 192:102570. [PMID: 37003144 DOI: 10.1016/j.plefa.2023.102570] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Revised: 03/20/2023] [Accepted: 03/21/2023] [Indexed: 04/03/2023]
Abstract
BACKGROUND Aspirin and eicosapentaenoic acid (EPA) have colorectal polyp prevention activity, alone and in combination. This study measured levels of plasma and rectal mucosal oxylipins in participants of the seAFOod 2 × 2 factorial, randomised, placebo-controlled trial, who received aspirin 300 mg daily and EPA 2000 mg free fatty acid, alone and in combination, for 12 months. METHODS Resolvin (Rv) E1, 15-epi-lipoxin (LX) A4 and respective precursors 18-HEPE and 15-HETE (with chiral separation) were measured by ultra-high performance liquid chromatography-tandem mass spectrometry in plasma taken at baseline, 6 months and 12 months, as well as rectal mucosa obtained at trial exit colonoscopy at 12 months, in 401 trial participants. RESULTS Despite detection of S- and R- enantiomers of 18-HEPE and 15-HETE in ng/ml concentrations, RvE1 or 15‑epi-LXA4 were not detected above a limit of detection of 20 pg/ml in plasma or rectal mucosa, even in individuals randomised to both aspirin and EPA. We have confirmed in a large clinical trial cohort that prolonged (12 months) treatment with EPA is associated with increased plasma 18-HEPE concentrations (median [inter-quartile range] total 18-HEPE 0.51 [0.21-1.95] ng/ml at baseline versus 0.95 [0.46-4.06] ng/ml at 6 months [P<0.0001] in those randomised to EPA alone), which correlate strongly with respective rectal mucosal 18-HEPE levels (r = 0.82; P<0.001), but which do not predict polyp prevention efficacy by EPA or aspirin. CONCLUSION Analysis of seAFOod trial plasma and rectal mucosal samples has not provided evidence of synthesis of the EPA-derived specialised pro-resolving mediator RvE1 or aspirin-trigged lipoxin 15‑epi-LXA4. We cannot rule out degradation of individual oxylipins during sample collection and storage but readily measurable precursor oxylipins argues against widespread degradation.
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Affiliation(s)
- H Fuller
- Leeds Institute of Medical Research, University of Leeds, UK
| | - A D Race
- Institute of Cancer Therapeutics, University of Bradford, UK
| | - H Fenton
- Leeds Institute of Medical Research, University of Leeds, UK
| | - L Burke
- Institute of Cancer Therapeutics, University of Bradford, UK
| | - A Downing
- Leeds Institute of Medical Research, University of Leeds, UK
| | - E A Williams
- Department of Oncology and Metabolism, University of Sheffield, UK
| | - C J Rees
- Population Health Science Institute, Newcastle University, UK
| | - L C Brown
- MRC Clinical Trials Unit at University College, London, UK
| | - P M Loadman
- Institute of Cancer Therapeutics, University of Bradford, UK
| | - M A Hull
- Leeds Institute of Medical Research, University of Leeds, UK.
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Shaikh SR, Virk R, Van Dyke TE. Potential Mechanisms by Which Hydroxyeicosapentaenoic Acids Regulate Glucose Homeostasis in Obesity. Adv Nutr 2022; 13:2316-2328. [PMID: 35709423 PMCID: PMC9776734 DOI: 10.1093/advances/nmac073] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2022] [Revised: 02/16/2022] [Accepted: 06/13/2022] [Indexed: 01/29/2023] Open
Abstract
Dysregulation of glucose metabolism in response to diet-induced obesity contributes toward numerous complications, such as insulin resistance and hepatic steatosis. Therefore, there is a need to develop effective strategies to improve glucose homeostasis. In this review, we first discuss emerging evidence from epidemiological studies and rodent experiments that increased consumption of EPA (either as oily fish, or dietary/pharmacological supplements) may have a role in preventing impairments in insulin and glucose homeostasis. We then review the current evidence on how EPA-derived metabolites known as hydroxyeicosapentaenoic acids (HEPEs) may be a major mode of action by which EPA exerts its beneficial effects on glucose and lipid metabolism. Notably, cell culture and rodent studies show that HEPEs prevent fat accumulation in metabolic tissues through peroxisome proliferator activated receptor (PPAR)-mediated mechanisms. In addition, activation of the resolvin E1 pathway, either by administration of EPA in the diet or via intraperitoneal administration of resolvin E1, improves hyperglycemia, hyperinsulinemia, and liver steatosis through multiple mechanisms. These mechanisms include shifting immune cell phenotypes toward resolution of inflammation and preventing dysbiosis of the gut microbiome. Finally, we present the next steps for this line of research that will drive future precision randomized clinical trials with EPA and its downstream metabolites. These include dissecting the variables that drive heterogeneity in the response to EPA, such as the baseline microbiome profile and fatty acid status, circadian rhythm, genetic variation, sex, and age. In addition, there is a critical need to further investigate mechanisms of action for HEPEs and to establish the concentration of HEPEs in differing tissues, particularly in response to consumption of oily fish and EPA-enriched supplements.
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Affiliation(s)
- Saame Raza Shaikh
- Department of Nutrition, Gillings School of Global Public Health and School
of Medicine, The University of North Carolina at Chapel Hill, Chapel
Hill, NC, USA
| | - Rafia Virk
- Department of Nutrition, Gillings School of Global Public Health and School
of Medicine, The University of North Carolina at Chapel Hill, Chapel
Hill, NC, USA
| | - Thomas E Van Dyke
- Center for Clinical and Translational Research, The Forsyth
Institute, Cambridge, MA, USA
- Department of Oral Medicine, Infection, and Immunity, Harvard School of
Dental Medicine, Harvard Medical School, Boston, MA, USA
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10
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da Silva Batista E, Nakandakari SCBR, Ramos da Silva AS, Pauli JR, Pereira de Moura L, Ropelle ER, Camargo EA, Cintra DE. Omega-3 pleiad: The multipoint anti-inflammatory strategy. Crit Rev Food Sci Nutr 2022; 64:4817-4832. [PMID: 36382659 DOI: 10.1080/10408398.2022.2146044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Omega 3 (ω3) fatty acids have been described since the 1980s as promising anti-inflammatory substances. Prostaglandin and leukotriene modulation were exhaustively explored as the main reason for ω3 beneficial outcomes. However, during the early 2000s, after the human genome decoding advent, the nutrigenomic approaches exhibited an impressive plethora of ω3 targets, now under the molecular point of view. Different G protein-coupled receptors (GPCRs) recognizing ω3 and its derivatives appear to be responsible for blocking inflammation and insulin-sensitizing effects. A new class of ω3-derived substances, such as maresins, resolvins, and protectins, increases ω3 actions. Inflammasome disruption, the presence of GPR120 on immune cell surfaces, and intracellular crosstalk signaling mediated by PPARγ compose the last discoveries regarding the multipoint anti-inflammatory targets for this nutrient. This review shows a detailed mechanistic proposal to understand ω3 fatty acid action over the inflammatory environment in the background of several chronic diseases.
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Affiliation(s)
- Ellencristina da Silva Batista
- Graduate Program of Health Sciences (PPGCS), Federal University of Sergipe, Aracaju, Sergipe, Brazil
- Nutritional Genomics Laboratory, LabGeN, School of Applied Sciences, UNICAMP, São Paulo, Brazil
- Nutrigenomics and Lipids Research Center, CELN, School of Applied Sciences, UNICAMP, São Paulo, Brazil
- Nutrition Department, Federal University of Sergipe, Lagarto, Sergipe, Brazil
| | - Susana Castelo Branco Ramos Nakandakari
- Nutritional Genomics Laboratory, LabGeN, School of Applied Sciences, UNICAMP, São Paulo, Brazil
- Nutrigenomics and Lipids Research Center, CELN, School of Applied Sciences, UNICAMP, São Paulo, Brazil
| | | | - José Rodrigo Pauli
- Nutrigenomics and Lipids Research Center, CELN, School of Applied Sciences, UNICAMP, São Paulo, Brazil
- Laboratory of Molecular Biology of Exercise, School of Applied Sciences, UNICAMP, São Paulo, Brazil
| | - Leandro Pereira de Moura
- Laboratory of Molecular Biology of Exercise, School of Applied Sciences, UNICAMP, São Paulo, Brazil
| | - Eduardo Rochete Ropelle
- Nutrigenomics and Lipids Research Center, CELN, School of Applied Sciences, UNICAMP, São Paulo, Brazil
- Laboratory of Molecular Biology of Exercise, School of Applied Sciences, UNICAMP, São Paulo, Brazil
| | - Enilton A Camargo
- Graduate Program of Health Sciences (PPGCS), Federal University of Sergipe, Aracaju, Sergipe, Brazil
- Department of Physiology, Federal University of Sergipe, São Cristóvão, Sergipe, Brazil
| | - Dennys Esper Cintra
- Nutritional Genomics Laboratory, LabGeN, School of Applied Sciences, UNICAMP, São Paulo, Brazil
- Nutrigenomics and Lipids Research Center, CELN, School of Applied Sciences, UNICAMP, São Paulo, Brazil
- OCRC - Obesity and Comorbidities Research Center, UNICAMP, São Paulo, Brazil
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11
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Naganuma T, Fujinami N, Arita M. Polyunsaturated Fatty Acid-Derived Lipid Mediators That Regulate Epithelial Homeostasis. Biol Pharm Bull 2022; 45:998-1007. [DOI: 10.1248/bpb.b22-00252] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Affiliation(s)
- Tatsuro Naganuma
- Division of Physiological Chemistry and Metabolism, Keio University Faculty of Pharmacy
| | - Nodoka Fujinami
- Division of Physiological Chemistry and Metabolism, Keio University Faculty of Pharmacy
| | - Makoto Arita
- Cellular and Molecular Epigenetics Laboratory, Graduate School of Medical Life Science, Yokohama-City University
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12
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Misheva M, Kotzamanis K, Davies LC, Tyrrell VJ, Rodrigues PRS, Benavides GA, Hinz C, Murphy RC, Kennedy P, Taylor PR, Rosas M, Jones SA, McLaren JE, Deshpande S, Andrews R, Schebb NH, Czubala MA, Gurney M, Aldrovandi M, Meckelmann SW, Ghazal P, Darley-Usmar V, White DA, O'Donnell VB. Oxylipin metabolism is controlled by mitochondrial β-oxidation during bacterial inflammation. Nat Commun 2022; 13:139. [PMID: 35013270 PMCID: PMC8748967 DOI: 10.1038/s41467-021-27766-8] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2020] [Accepted: 12/12/2021] [Indexed: 12/19/2022] Open
Abstract
Oxylipins are potent biological mediators requiring strict control, but how they are removed en masse during infection and inflammation is unknown. Here we show that lipopolysaccharide (LPS) dynamically enhances oxylipin removal via mitochondrial β-oxidation. Specifically, genetic or pharmacological targeting of carnitine palmitoyl transferase 1 (CPT1), a mitochondrial importer of fatty acids, reveal that many oxylipins are removed by this protein during inflammation in vitro and in vivo. Using stable isotope-tracing lipidomics, we find secretion-reuptake recycling for 12-HETE and its intermediate metabolites. Meanwhile, oxylipin β-oxidation is uncoupled from oxidative phosphorylation, thus not contributing to energy generation. Testing for genetic control checkpoints, transcriptional interrogation of human neonatal sepsis finds upregulation of many genes involved in mitochondrial removal of long-chain fatty acyls, such as ACSL1,3,4, ACADVL, CPT1B, CPT2 and HADHB. Also, ACSL1/Acsl1 upregulation is consistently observed following the treatment of human/murine macrophages with LPS and IFN-γ. Last, dampening oxylipin levels by β-oxidation is suggested to impact on their regulation of leukocyte functions. In summary, we propose mitochondrial β-oxidation as a regulatory metabolic checkpoint for oxylipins during inflammation.
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Affiliation(s)
- Mariya Misheva
- Systems Immunity Research Institute and Division of Infection and Immunity, and School of Medicine, Cardiff University, CF14 4XN, Cardiff, UK
| | - Konstantinos Kotzamanis
- Systems Immunity Research Institute and Division of Infection and Immunity, and School of Medicine, Cardiff University, CF14 4XN, Cardiff, UK
| | - Luke C Davies
- Systems Immunity Research Institute and Division of Infection and Immunity, and School of Medicine, Cardiff University, CF14 4XN, Cardiff, UK
| | - Victoria J Tyrrell
- Systems Immunity Research Institute and Division of Infection and Immunity, and School of Medicine, Cardiff University, CF14 4XN, Cardiff, UK
| | - Patricia R S Rodrigues
- Systems Immunity Research Institute and Division of Infection and Immunity, and School of Medicine, Cardiff University, CF14 4XN, Cardiff, UK
| | - Gloria A Benavides
- Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, 35294, USA
| | - Christine Hinz
- Systems Immunity Research Institute and Division of Infection and Immunity, and School of Medicine, Cardiff University, CF14 4XN, Cardiff, UK
| | - Robert C Murphy
- Department of Pharmacology, University of Colorado Denver, Aurora, CO, 80045, USA
| | - Paul Kennedy
- Cayman Chemical, 1180 E Ellsworth Rd, Ann Arbor, MI, 48108, USA
| | - Philip R Taylor
- Systems Immunity Research Institute and Division of Infection and Immunity, and School of Medicine, Cardiff University, CF14 4XN, Cardiff, UK
- UK Dementia Research Institute at Cardiff, Cardiff University, CF14 4XN, Cardiff, UK
| | - Marcela Rosas
- Systems Immunity Research Institute and Division of Infection and Immunity, and School of Medicine, Cardiff University, CF14 4XN, Cardiff, UK
| | - Simon A Jones
- Systems Immunity Research Institute and Division of Infection and Immunity, and School of Medicine, Cardiff University, CF14 4XN, Cardiff, UK
| | - James E McLaren
- Systems Immunity Research Institute and Division of Infection and Immunity, and School of Medicine, Cardiff University, CF14 4XN, Cardiff, UK
| | - Sumukh Deshpande
- Systems Immunity Research Institute and Division of Infection and Immunity, and School of Medicine, Cardiff University, CF14 4XN, Cardiff, UK
| | - Robert Andrews
- Systems Immunity Research Institute and Division of Infection and Immunity, and School of Medicine, Cardiff University, CF14 4XN, Cardiff, UK
| | - Nils Helge Schebb
- Chair of Food Chemistry, Faculty of Mathematics and Natural Sciences, University of Wuppertal, Gausstraße 20, 42119, Wuppertal, Germany
| | - Magdalena A Czubala
- Systems Immunity Research Institute and Division of Infection and Immunity, and School of Medicine, Cardiff University, CF14 4XN, Cardiff, UK
| | - Mark Gurney
- Systems Immunity Research Institute and Division of Infection and Immunity, and School of Medicine, Cardiff University, CF14 4XN, Cardiff, UK
| | - Maceler Aldrovandi
- Systems Immunity Research Institute and Division of Infection and Immunity, and School of Medicine, Cardiff University, CF14 4XN, Cardiff, UK
| | - Sven W Meckelmann
- Systems Immunity Research Institute and Division of Infection and Immunity, and School of Medicine, Cardiff University, CF14 4XN, Cardiff, UK
| | - Peter Ghazal
- Systems Immunity Research Institute and Division of Infection and Immunity, and School of Medicine, Cardiff University, CF14 4XN, Cardiff, UK
| | - Victor Darley-Usmar
- Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, 35294, USA
| | - Daniel A White
- Systems Immunity Research Institute and Division of Infection and Immunity, and School of Medicine, Cardiff University, CF14 4XN, Cardiff, UK.
| | - Valerie B O'Donnell
- Systems Immunity Research Institute and Division of Infection and Immunity, and School of Medicine, Cardiff University, CF14 4XN, Cardiff, UK.
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13
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Penner AL, Waytt V, Winter T, Leng S, Duhamel TA, Aukema HM. Oxylipin profiles and levels vary by skeletal muscle type, dietary fat and sex in young rats. Appl Physiol Nutr Metab 2021; 46:1378-1388. [PMID: 34115947 DOI: 10.1139/apnm-2021-0161] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Polyunsaturated fatty acids (PUFA)-derived bioactive lipid mediators called oxylipins have been shown to influence muscle growth, inflammation and repair in select muscles. Since individual oxylipins have varying effects and potencies, broad profiling in differing muscle types is required to further understand their overall effects. In addition, diet and sex are key determinants of oxylipin levels. Therefore, to provide comprehensive data on oxylipin profiles in rat soleus (SO), red gastrocnemius (RG), and white gastrocnemius (WG) muscles, female and male weanling Sprague-Dawley rats were provided control or experimental diets enriched in n-3 (ω-3) or n-6 (ω-6) PUFA for 6 weeks. Free oxylipin analysis by HPLC/MS/MS revealed that SO muscle had 25% more oxylipins and 4-13 times greater oxylipin mass than WG muscle. Dietary n-3 PUFA (α-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid) each increased n-3 oxylipins derived directly from their precursors and several that were not direct precursors, while reducing arachidonic acid derived oxylipins. Dietary linoleic acid had few effects on oxylipins. Oxylipins with a sex effect were higher in females in SO and RG. Oxylipins generally reflected the effects of diet and sex on PUFA, but there were exceptions. These fundamental oxylipin profile data provide groundwork knowledge and context for future research on muscle oxylipin functions. Novelty: Rat SO compared with RG and WG muscles have a higher number and greater mass of oxylipins. Oxylipins generally reflect diet effects on PUFA in all muscles, but there are notable exceptions. Oxylipins in SO and RG are higher in females.
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Affiliation(s)
- Avery L Penner
- Department of Food and Human Nutritional Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
- Canadian Centre for Agri-Food Research in Health and Medicine, Winnipeg, Manitoba, Canada
| | - Victoria Waytt
- Department of Food and Human Nutritional Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
- Canadian Centre for Agri-Food Research in Health and Medicine, Winnipeg, Manitoba, Canada
| | - Tanja Winter
- Department of Food and Human Nutritional Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
- Canadian Centre for Agri-Food Research in Health and Medicine, Winnipeg, Manitoba, Canada
| | - Shan Leng
- Department of Food and Human Nutritional Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
- Canadian Centre for Agri-Food Research in Health and Medicine, Winnipeg, Manitoba, Canada
| | - Todd A Duhamel
- Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, Manitoba, Canada
- Faculty of Kinesiology and Recreation Management, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Harold M Aukema
- Department of Food and Human Nutritional Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
- Canadian Centre for Agri-Food Research in Health and Medicine, Winnipeg, Manitoba, Canada
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14
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Ishida N, Yamada H, Hirose M. Euphausia pacifica (North Pacific Krill): Review of Chemical Features and Potential Benefits of 8-HEPE against Metabolic Syndrome, Dyslipidemia, NAFLD, and Atherosclerosis. Nutrients 2021; 13:nu13113765. [PMID: 34836021 PMCID: PMC8618228 DOI: 10.3390/nu13113765] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2021] [Revised: 10/22/2021] [Accepted: 10/22/2021] [Indexed: 11/16/2022] Open
Abstract
Marine n-3 fatty acids are well known to have health benefits. Recently, krill oil, which contains phospholipids, has been in the spotlight as an n-3 PUFA-containing oil. Euphausia pacifica (E. pacifica), also called North Pacific krill, is a small, red crustacean similar to shrimp that flourishes in the North Pacific Ocean. E. pacifica oil contains 8-hydroxyeicosapentaenoic acid (8-HEPE) at a level more than 10 times higher than Euphausia superba oil. 8-HEPE can activate the transcription of peroxisome proliferator-activated receptor alpha (PPARα), PPARγ, and PPARδ to levels 10, 5, and 3 times greater than eicosapentaenoic acid, respectively. 8-HEPE has beneficial effects against metabolic syndrome (reduction in body weight gain, visceral fat area, amount of gonadal white adipose tissue, and gonadal adipocyte cell size), dyslipidemia (reduction in serum triacylglycerol and low-density lipoprotein cholesterol and induction of serum high-density lipoprotein cholesterol), atherosclerosis, and nonalcoholic fatty liver disease (reduction in triglyceride accumulation and hepatic steatosis in the liver) in mice. Further studies should focus on the beneficial effects of North Pacific krill oil products and 8-HEPE on human health.
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Affiliation(s)
- Nanae Ishida
- Department of Pathophysiology and Pharmacology, School of Pharmaceutical Sciences, Iwate Medical University, Iwate 028-3694, Japan;
| | - Hidetoshi Yamada
- Faculty of Life & Environmental Science, Teikyo University of Science, Tokyo 120-0045, Japan;
| | - Masamichi Hirose
- Department of Pathophysiology and Pharmacology, School of Pharmaceutical Sciences, Iwate Medical University, Iwate 028-3694, Japan;
- Correspondence: ; Tel.: +81-19-651-5110
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15
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Saleh RNM, West AL, Ostermann AI, Schebb NH, Calder PC, Minihane AM. APOE Genotype Modifies the Plasma Oxylipin Response to Omega-3 Polyunsaturated Fatty Acid Supplementation in Healthy Individuals. Front Nutr 2021; 8:723813. [PMID: 34604280 PMCID: PMC8484638 DOI: 10.3389/fnut.2021.723813] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2021] [Accepted: 08/17/2021] [Indexed: 01/10/2023] Open
Abstract
The omega-3 polyunsaturated fatty acids (n-3 PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), mediate inflammation in large part by affecting pro-inflammatory and anti-inflammatory/pro-resolving oxylipin concentrations. Common gene variants are thought to underlie the large inter-individual variation in oxylipin levels in response to n-3 PUFA supplementation, which in turn is likely to contribute to the overall heterogeneity in response to n-3 PUFA intervention. Given its known role in inflammation and as a modulator of the physiological response to EPA and DHA, here we explore, for the first time, the differential response of plasma hydroxy-, epoxy- and dihydroxy-arachidonic acid, EPA and DHA oxylipins according to apolipoprotein E (APOE) genotype using samples from a dose-response parallel design RCT. Healthy participants were given doses of EPA+DHA equivalent to intakes of 1, 2, and 4 portions of oily fish per week for 12 months. There was no difference in the plasma levels of EPA, DHA or ARA between the wildtype APOE3/E3 and APOE4 carrier groups after 3 or 12 months of n-3 PUFA supplementation. At 12 months, hydroxy EPAs (HEPEs) and hydroxy-DHAs (HDHAs) were higher in APOE4 carriers, with the difference most evident at the highest EPA+DHA intake. A significant APOE*n-3 PUFA dose effect was observed for the CYP-ω hydroxylase products 19-HEPE (p = 0.027) and 20-HEPE (p = 0.011). 8-HEPE, which, along with several other plasma oxylipins, is an activator of peroxisome proliferator activated receptors (PPARs), showed the highest fold change in APOE4 carriers (14-fold) compared to APOE3/E3 (4-fold) (p = 0.014). Low basal plasma EPA levels (EPA < 0.85% of total fatty acids) were associated with a greater change in 5-HEPE, 9-HEPE, 11-HEPE, and 20-HEPE compared to high basal EPA levels (EPA > 1.22% of total fatty acids). In conclusion, APOE genotype modulated the plasma oxylipin response to increased EPA+DHA intake, with APOE4 carriers presenting with the greatest increases following high dose n-3 PUFA supplementation for 12 months.
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Affiliation(s)
- Rasha N M Saleh
- Nutrition and Preventive Medicine Group, Norwich Medical School, University of East Anglia, Norwich, United Kingdom.,Department of Clinical and Chemical Pathology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Annette L West
- School of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, United Kingdom
| | - Annika I Ostermann
- Chair of Food Chemistry, Faculty of Mathematics and Natural Sciences, University of Wuppertal, Wuppertal, Germany
| | - Nils Helge Schebb
- Chair of Food Chemistry, Faculty of Mathematics and Natural Sciences, University of Wuppertal, Wuppertal, Germany
| | - Philip C Calder
- School of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.,National Institute for Health Research (NIHR) Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton, United Kingdom
| | - Anne Marie Minihane
- Nutrition and Preventive Medicine Group, Norwich Medical School, University of East Anglia, Norwich, United Kingdom
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16
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Stability of eicosapentaenoic acid and docosahexaenoic acid in spray-dried powder of emulsified krill oil. FUTURE FOODS 2021. [DOI: 10.1016/j.fufo.2020.100009] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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17
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Pinto C, Ibáñez MR, Loyola G, León L, Salvatore Y, González C, Barraza V, Castañeda F, Aldunate R, Contreras-Porcia L, Fuenzalida K, Bronfman FC. Characterization of an Agarophyton chilense Oleoresin Containing PPARγ Natural Ligands with Insulin-Sensitizing Effects in a C57Bl/6J Mouse Model of Diet-Induced Obesity and Antioxidant Activity in Caenorhabditis elegans. Nutrients 2021; 13:1828. [PMID: 34071972 PMCID: PMC8227508 DOI: 10.3390/nu13061828] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 05/19/2021] [Accepted: 05/20/2021] [Indexed: 12/27/2022] Open
Abstract
The biomedical potential of the edible red seaweed Agarophyton chilense (formerly Gracilaria chilensis) has not been explored. Red seaweeds are enriched in polyunsaturated fatty acids and eicosanoids, which are known natural ligands of the PPARγ nuclear receptor. PPARγ is the molecular target of thiazolidinediones (TZDs), drugs used as insulin sensitizers to treat type 2 diabetes mellitus. Medical use of TZDs is limited due to undesired side effects, a problem that has triggered the search for selective PPARγ modulators (SPPARMs) without the TZD side effects. We produced Agarophyton chilense oleoresin (Gracilex®), which induces PPARγ activation without inducing adipocyte differentiation, similar to SPPARMs. In a diet-induced obesity model of male mice, we showed that treatment with Gracilex® improves insulin sensitivity by normalizing altered glucose and insulin parameters. Gracilex® is enriched in palmitic acid, arachidonic acid, oleic acid, and lipophilic antioxidants such as tocopherols and β-carotene. Accordingly, Gracilex® possesses antioxidant activity in vitro and increased antioxidant capacity in vivo in Caenorhabditis elegans. These findings support the idea that Gracilex® represents a good source of natural PPARγ ligands and antioxidants with the potential to mitigate metabolic disorders. Thus, its nutraceutical value in humans warrants further investigation.
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Affiliation(s)
- Claudio Pinto
- Postgraduate Department, Faculty of Veterinary Sciences, Universidad Austral de Chile, Valdivia 5110566, Chile;
- Center for Aging and Regeneration (CARE), Department of Cellular and Molecular Biology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago 8320000, Chile
| | - María Raquel Ibáñez
- Department of Physiology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago 8320000, Chile; (M.R.I.); (G.L.); (L.L.); (Y.S.); (C.G.); (V.B.)
- Institute of Biomedical Sciences (ICB), Faculty of Medicine, Universidad Andres Bello, Santiago 8320000, Chile
| | - Gloria Loyola
- Department of Physiology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago 8320000, Chile; (M.R.I.); (G.L.); (L.L.); (Y.S.); (C.G.); (V.B.)
- Institute of Biomedical Sciences (ICB), Faculty of Medicine, Universidad Andres Bello, Santiago 8320000, Chile
| | - Luisa León
- Department of Physiology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago 8320000, Chile; (M.R.I.); (G.L.); (L.L.); (Y.S.); (C.G.); (V.B.)
| | - Yasmin Salvatore
- Department of Physiology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago 8320000, Chile; (M.R.I.); (G.L.); (L.L.); (Y.S.); (C.G.); (V.B.)
| | - Carla González
- Department of Physiology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago 8320000, Chile; (M.R.I.); (G.L.); (L.L.); (Y.S.); (C.G.); (V.B.)
| | - Víctor Barraza
- Department of Physiology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago 8320000, Chile; (M.R.I.); (G.L.); (L.L.); (Y.S.); (C.G.); (V.B.)
| | - Francisco Castañeda
- Department of Ecology and Biodiversity, Faculty of Life Sciences, Universidad Andres Bello, Santiago 8320000, Chile; (F.C.); (L.C.-P.)
- Quintay Marine Research Center (CIMARQ), Faculty of Life Sciences, Universidad Andres Bello, Valparaiso, Quintay 2480000, Chile
- Center of Applied Ecology and Sustainability (CAPES), Santiago 8331150, Chile
- Instituto Milenio en Socio-Ecología Costera (SECOS), Santiago 8370251, Chile
| | - Rebeca Aldunate
- Faculty of Sciences, School of Biotechnology, Universidad Santo Tomas, Santiago 8320000, Chile;
| | - Loretto Contreras-Porcia
- Department of Ecology and Biodiversity, Faculty of Life Sciences, Universidad Andres Bello, Santiago 8320000, Chile; (F.C.); (L.C.-P.)
- Quintay Marine Research Center (CIMARQ), Faculty of Life Sciences, Universidad Andres Bello, Valparaiso, Quintay 2480000, Chile
- Center of Applied Ecology and Sustainability (CAPES), Santiago 8331150, Chile
- Instituto Milenio en Socio-Ecología Costera (SECOS), Santiago 8370251, Chile
| | - Karen Fuenzalida
- Department of Physiology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago 8320000, Chile; (M.R.I.); (G.L.); (L.L.); (Y.S.); (C.G.); (V.B.)
- Institute of Biomedical Sciences (ICB), Faculty of Medicine, Universidad Andres Bello, Santiago 8320000, Chile
| | - Francisca C. Bronfman
- Department of Physiology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago 8320000, Chile; (M.R.I.); (G.L.); (L.L.); (Y.S.); (C.G.); (V.B.)
- Institute of Biomedical Sciences (ICB), Faculty of Medicine, Universidad Andres Bello, Santiago 8320000, Chile
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18
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Duan J, Song Y, Zhang X, Wang C. Effect of ω-3 Polyunsaturated Fatty Acids-Derived Bioactive Lipids on Metabolic Disorders. Front Physiol 2021; 12:646491. [PMID: 34113260 PMCID: PMC8185290 DOI: 10.3389/fphys.2021.646491] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2020] [Accepted: 04/26/2021] [Indexed: 12/23/2022] Open
Abstract
Arachidonic acid (ARA) is an important ω-6 polyunsaturated fatty acid (PUFA), and docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) and n-3 docosapentaenoic acid (n-3 DPA) are three well-known ω-3 PUFAs. These fatty acids can be metabolized into a number of bioactive lipids. Eicosanoids derived from ARA have drawn great attention because of their important and complex biofunctions. Although EPA, DHA and n-3 DPA have also shown powerful biofunctions, we have fewer studies of metabolites derived from them than those from ARA. Recently, growing research has focused on the bioaction of ω-3 PUFA-derived metabolites, which indicates their great potential for treating metabolic disorders. Most of the functional studies of these bioactive lipids focused on their anti-inflammatory effects. However, several studies elucidated their direct effects on pancreatic β cells, hepatocytes, adipocytes, skeletal muscle cells, and endothelial cells. These researches revealed the importance of studying the functions of metabolites derived from ω-3 polyunsaturated fatty acids other than themselves. The current review summarizes research into the effects of ω-3 PUFA-derived oxylipins on metabolic disorders, including diabetes, non-alcoholic fatty liver disease, adipose tissue dysfunction, and atherosclerosis.
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Affiliation(s)
- Jinjie Duan
- Department of Physiology and Pathophysiology, The Province and Ministry Co-Sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Medical University, Tianjin, China.,Tianjin Key Laboratory of Medical Epigenetics, Tianjin Medical University, Tianjin, China
| | - Yayue Song
- Department of Physiology and Pathophysiology, The Province and Ministry Co-Sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Medical University, Tianjin, China.,Tianjin Key Laboratory of Medical Epigenetics, Tianjin Medical University, Tianjin, China
| | - Xu Zhang
- Department of Physiology and Pathophysiology, The Province and Ministry Co-Sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Medical University, Tianjin, China
| | - Chunjiong Wang
- Department of Physiology and Pathophysiology, The Province and Ministry Co-Sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Medical University, Tianjin, China.,Tianjin Key Laboratory of Medical Epigenetics, Tianjin Medical University, Tianjin, China
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19
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12-Hydroxyeicosapentaenoic acid inhibits foam cell formation and ameliorates high-fat diet-induced pathology of atherosclerosis in mice. Sci Rep 2021; 11:10426. [PMID: 34001916 PMCID: PMC8129127 DOI: 10.1038/s41598-021-89707-1] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2020] [Accepted: 04/26/2021] [Indexed: 02/02/2023] Open
Abstract
Atherosclerosis is a chronic inflammatory disease associated with macrophage aggregate and transformation into foam cells. In this study, we sought to investigate the impact of dietary intake of ω3 fatty acid on the development of atherosclerosis, and demonstrate the mechanism of action by identifying anti-inflammatory lipid metabolite. Mice were exposed to a high-fat diet (HFD) supplemented with either conventional soybean oil or α-linolenic acid-rich linseed oil. We found that as mice became obese they also showed increased pulsatility and resistive indexes in the common carotid artery. In sharp contrast, the addition of linseed oil to the HFD improved pulsatility and resistive indexes without affecting weight gain. Histological analysis revealed that dietary linseed oil inhibited foam cell formation in the aortic valve. Lipidomic analysis demonstrated a particularly marked increase in the eicosapentaenoic acid-derived metabolite 12-hydroxyeicosapentaenoic acid (12-HEPE) in the serum from mice fed with linseed oil. When we gave 12-HEPE to mice with HFD, the pulsatility and resistive indexes was improved. Indeed, 12-HEPE inhibited the foamy transformation of macrophages in a peroxisome proliferator-activated receptor (PPAR)γ-dependent manner. These results demonstrate that the 12-HEPE-PPARγ axis ameliorates the pathogenesis of atherosclerosis by inhibiting foam cell formation.
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20
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Kamboj P, Sarkar S, Gupta SK, Bisht N, Kumari D, Alam MJ, Barge S, Kashyap B, Deka B, Bharadwaj S, Rahman S, Dutta PP, Borah JC, Talukdar NC, Banerjee SK, Kumar Y. Methanolic Extract of Lysimachia Candida Lindl. Prevents High-Fat High-Fructose-Induced Fatty Liver in Rats: Understanding the Molecular Mechanism Through Untargeted Metabolomics Study. Front Pharmacol 2021; 12:653872. [PMID: 33935766 PMCID: PMC8082144 DOI: 10.3389/fphar.2021.653872] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2021] [Accepted: 03/10/2021] [Indexed: 12/12/2022] Open
Abstract
Fatty liver is one of the most common metabolic syndrome affecting the global population. Presently, limited treatment modalities with symptomatic approach are available for alleviating fatty liver. Traditional and herbal treatment modalities have shown evidence to improve the disease pathology. In the present research work, evaluation of a selected medicinal plant Lysimachia candida Lindl. was carried out to investigate its beneficial effects on fatty liver disease in rats. Male Sprague Dawley (SD) rats were fed with high-fat high-fructose diet to induce fatty liver phenotypes. After induction for 15 weeks, methanolic extract of Lysimachia candida Lindl. (250 mg/kg b. w. p. o.) was administrated to the rats daily for the next 17 weeks. Blood samples were collected at different time points to analyze fasting blood glucose levels and relevant biochemical parameters important for the assessment of metabolic disease phenotypes. Liquid chromatography-mass spectrometry (LC-MS) based metabolomics was done to study the dynamics of metabolic changes in the serum during disease progression and how the medicinally important plant extract treatment reversed the metabolic diseases. Multivariate data analysis approaches have been employed to understand the metabolome changes and disease pathology. This study has identified the interplay of some metabolic pathways that alter the disease progression and their reversal after administration of the plant extract. Different group of metabolites mainly bile acids, fatty acids, carnitines, and their derivatives were found to be altered in the diseased rats. However, all the metabolites identified between control and disease groups are mainly related to lipid metabolism. The results depict that the treatment with the above-mentioned plant extract improves the regulation of aberrant lipid metabolism, and reverses the metabolic syndrome phenotype. Therefore, the present study reveals the potential mechanism of the herbal extract to prevent metabolic syndrome in rats.
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Affiliation(s)
- Parul Kamboj
- Non-communicable Disease Group, Translational Health Science and Technology Institute (THSTI), Faridabad, India
| | - Soumalya Sarkar
- Non-communicable Disease Group, Translational Health Science and Technology Institute (THSTI), Faridabad, India
| | - Sonu Kumar Gupta
- Non-communicable Disease Group, Translational Health Science and Technology Institute (THSTI), Faridabad, India
| | - Neema Bisht
- Non-communicable Disease Group, Translational Health Science and Technology Institute (THSTI), Faridabad, India
| | - Deepika Kumari
- Non-communicable Disease Group, Translational Health Science and Technology Institute (THSTI), Faridabad, India
| | - Md Jahangir Alam
- Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, India
| | - Sagar Barge
- Institute of Advanced Study in Science and Technology (IASST), Guwahati, India
| | - Bhaswati Kashyap
- Institute of Advanced Study in Science and Technology (IASST), Guwahati, India
| | - Barsha Deka
- Institute of Advanced Study in Science and Technology (IASST), Guwahati, India
| | - Simanta Bharadwaj
- Institute of Advanced Study in Science and Technology (IASST), Guwahati, India
| | - Seydur Rahman
- Institute of Advanced Study in Science and Technology (IASST), Guwahati, India
| | - Partha Pratim Dutta
- Institute of Advanced Study in Science and Technology (IASST), Guwahati, India.,Assam Down Town University, Guwahati, India
| | - Jagat C Borah
- Institute of Advanced Study in Science and Technology (IASST), Guwahati, India
| | - Narayan Chandra Talukdar
- Institute of Advanced Study in Science and Technology (IASST), Guwahati, India.,Assam Down Town University, Guwahati, India
| | - Sanjay K Banerjee
- Non-communicable Disease Group, Translational Health Science and Technology Institute (THSTI), Faridabad, India.,Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, India
| | - Yashwant Kumar
- Non-communicable Disease Group, Translational Health Science and Technology Institute (THSTI), Faridabad, India
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21
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Saito M, Ishida N, Yamada H, Ibi M, Hirose M. 8-HEPE-Concentrated Materials from Pacific Krill Improve Plasma Cholesterol Levels and Hepatic Steatosis in High Cholesterol Diet-Fed Low-Density Lipoprotein (LDL) Receptor-Deficient Mice. Biol Pharm Bull 2021; 43:919-924. [PMID: 32475913 DOI: 10.1248/bpb.b20-00162] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Eicosapentaenoic acid (EPA), one of the N-3 polyunsaturated fatty acids (n-3 PUFAs), is a major active ingredient of fish that contributes to improve dyslipidemia. Recently, we demonstrated that 8-hydroxyeicosapentaenoic acid (8-HEPE) had a more positive effect on metabolic syndrome than EPA, and that 8-HEPE induced peroxisome proliferator-activated receptor (PPAR)α activation in the liver. We investigated the effects of 8-HEPE-concentrated materials from Pacific krill on dyslipidemia and hepatic steatosis in low-density lipoprotein (LDL) receptor-deficient (LDLR-KO) mice. Eight-week-old male LDLR-KO mice were fed a Western diet (0.15% cholesterol, WD), WD supplemented with 8-HEPE-concentrated materials from Pacific krill (8-HEPE included; WD +8-HEPE), or a standard diet (SD) for eighteen weeks, respectively. Murine J774.1 macrophages were incubated in the absence or presence of 8-HEPE (50 µM) or EPA (50 µM). 8-HEPE-concentrated materials significantly increased the plasma high-density lipoprotein (HDL)-cholesterol level, and decreased the plasma LDL-cholesterol and hepatic triglyceride levels in WD-fed LDLR-KO mice. Moreover, the rate of Oil Red O-positive staining was higher in the liver of WD-fed LDLR-KO mice than in that of 8-HEPE + WD-fed LDLR-KO mice. 8-HEPE but not EPA significantly increased gene expression levels of ABCA1, CD36, and interleukin 6 (IL-6) in murine J774.1 macrophages compared with those in the control. These results suggest that 8-HEPE-concentrated materials improve dyslipidemia and hepatic steatosis increasing ABCA1, CD36, and IL-6 gene expressions in macrophages.
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Affiliation(s)
- Maki Saito
- Department of Patophysiology and Pharmacology, Iwate Medical University School of Pharmaceutical Sciences
| | - Nanae Ishida
- Department of Patophysiology and Pharmacology, Iwate Medical University School of Pharmaceutical Sciences
| | | | - Miho Ibi
- Department of Pathology, Iwate Medical University School of Dentistry
| | - Masamichi Hirose
- Department of Patophysiology and Pharmacology, Iwate Medical University School of Pharmaceutical Sciences
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22
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Yamada H, Kumagai K, Uemura A, Yuki S. Euphausia pacifica as a source of 8( R)-hydroxy-eicosapentaenoic acid (8 R-HEPE), 8( R)-hydroxy-eicosatetraenoic acid (8 R-HETE) and 10( R)-hydroxy-docosahexaenoic acid (10 R-HDHA). Biosci Biotechnol Biochem 2019; 84:455-462. [PMID: 31738665 DOI: 10.1080/09168451.2019.1691912] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
Although not fully investigated, 8-HEPE, 8-HETE, and 10-HDHA have potentially beneficial effects for human health. Euphausia pacifica (North Pacific krill) is unique in containing several ppm level of 8R-HEPE, and sub-ppm levels of 8R-HETE and 10R-HDHA. Obtaining sufficient quantities of these compounds is a major bottleneck for conducting in vivo experiments to evaluate their biological activities. In this study, we examined an efficient way of obtaining 8R-HEPE, 8R-HETE, and 10R-HDHA by enzymatic production in E. pacifica. We devised a novel method to purify 199.4 mg of 8R-HEPE, 2.1 mg of 8R-HETE and 5.6 mg of 10R-HDHA from 1 kg of E. pacifica. We identified the stereochemistry of the hydroxy group at C-8 of HEPE and HETE and C-10 of HDHA as the R configuration by chiral column chromatography analysis using LC/QTOFMS.Abbreviations: 8-HEPE: 8-hydroxy-eicosapentaenoic acid; 8-HETE: 8-hydroxy-eicosatetraenoic acid; 10-HDHA: 10-hydroxy-docosahexaenoic acid; EPA: eicosapentaenoic acid; TLC-FID, thin layer chromatograph-Flame Ionization Detector; LC/QTOFMS: liquid chromatography/hybrid quadrupole time of flight mass spectrometry.
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Affiliation(s)
| | | | - Aiko Uemura
- Iwate Biotechnology Research Center, Kitakami, Japan
| | - Sayaka Yuki
- Iwate Biotechnology Research Center, Kitakami, Japan
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23
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Komiya Y, Nakamura T, Ishii M, Shimizu K, Hiraki E, Kawabata F, Nakamura M, Tatsumi R, Ikeuchi Y, Mizunoya W. Increase in muscle endurance in mice by dietary Yamabushitake mushroom (Hericium erinaceus) possibly via activation of PPARδ. Anim Sci J 2019; 90:781-789. [PMID: 30938015 PMCID: PMC6594082 DOI: 10.1111/asj.13199] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2019] [Revised: 02/18/2019] [Accepted: 02/28/2019] [Indexed: 12/18/2022]
Abstract
Skeletal muscle fiber is largely classified into two types: type 1 (slow‐twitch) and type 2 (fast‐twitch) fibers. Meat quality and composition of fiber types are thought to be closely related. Previous research showed that overexpression of constitutively active peroxisome proliferator‐activated receptor (PPAR)δ, a nuclear receptor present in skeletal muscle, increased type 1 fibers in mice. In this study, we found that hexane extracts of Yamabushitake mushroom (Hericium erinaceus) showed PPARδ agonistic activity in vitro. Eight‐week‐old C57BL/6J mice were fed a diet supplemented with 5% (w/w) freeze‐dried Yamabushitake mushroom for 24 hr. After the treatment period, the extensor digitorum longus (EDL) muscles were excised. The Yamabushitake‐supplemented diet up‐regulated the PPARδ target genes Pdk4 and Ucp3 in mouse skeletal muscles in vivo. Furthermore, feeding the Yamabushitake‐supplemented diet to mice for 8 weeks resulted in a significant increase in muscle endurance. These results indicate that Yamabushitake mushroom contains PPARδ agonistic ligands and that dietary intake of Yamabushitake mushroom could activate PPARδ in skeletal muscle of mice. Unexpectedly, we observed no significant alterations in composition of muscle fiber types between the mice fed control and Yamabushitake‐supplemented diets.
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Affiliation(s)
- Yusuke Komiya
- Department of Animal Science, School of Veterinary Medicine, Kitasato University, Towada, Japan.,Department of Bioresource Sciences, Faculty of Agriculture, Kyushu University, Fukuoka, Japan
| | - Toshiya Nakamura
- Department of Bioresource Sciences, Faculty of Agriculture, Kyushu University, Fukuoka, Japan
| | - Momoko Ishii
- Department of Bioresource Sciences, Faculty of Agriculture, Kyushu University, Fukuoka, Japan
| | - Kuniyoshi Shimizu
- Department of Bioresource Sciences, Faculty of Agriculture, Kyushu University, Fukuoka, Japan
| | - Eri Hiraki
- Department of Bioresource Sciences, Faculty of Agriculture, Kyushu University, Fukuoka, Japan
| | - Fuminori Kawabata
- Department of Bioresource Sciences, Faculty of Agriculture, Kyushu University, Fukuoka, Japan.,Faculty of Agriculture and Life Science, Hirosaki University, Hirosaki, Japan
| | - Mako Nakamura
- Department of Bioresource Sciences, Faculty of Agriculture, Kyushu University, Fukuoka, Japan
| | - Ryuichi Tatsumi
- Department of Bioresource Sciences, Faculty of Agriculture, Kyushu University, Fukuoka, Japan
| | - Yoshihide Ikeuchi
- Department of Bioresource Sciences, Faculty of Agriculture, Kyushu University, Fukuoka, Japan
| | - Wataru Mizunoya
- Department of Bioresource Sciences, Faculty of Agriculture, Kyushu University, Fukuoka, Japan
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24
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Uchida T, Koshino H, Abe J, Hakozaki M, Yamada H, Kimura KI. Isolation of yeast Ca 2+ signal transduction inhibitors from the Early Cretaceous Burmese amber. Fitoterapia 2019; 134:422-428. [PMID: 30858047 DOI: 10.1016/j.fitote.2019.02.018] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2019] [Revised: 02/20/2019] [Accepted: 02/20/2019] [Indexed: 11/25/2022]
Abstract
Two kinds of biologically active compounds were isolated from the MeOH extract of the Early Cretaceous Burmese amber [99 million years ago (Ma)], which is older than the K-Pg boundary (65 Ma). These compounds had inhibitory activity against the hypersensitive mutant yeast strain (zds1∆ erg3∆ pdr1∆ pdr3∆) with respect to Ca2+ signal transduction. They were identified as 16,17-bisnordehydroabietic acid (1) and 16,17-bisnorcallitrisic acid (2), respectively, on the basis of spectral analyses including HREIMS, 1D, and 2D NMR. Both have faint growth restoring activities around the clear inhibition zone against the mutant yeast on the 0.31-0.16 μg/spot. This is the first report of direct structural elucidation of 1 and 2 and the biologically active compounds derived from Burmese amber.
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Affiliation(s)
- Takeshi Uchida
- Graduate School of Agriculture, Iwate University, Morioka, Iwate 020-8550, Japan
| | - Hiroyuki Koshino
- RIKEN Center for Sustainable Resource Science, Wako, Saitama 351-0198, Japan
| | - Junpei Abe
- Graduate School of Agriculture, Iwate University, Morioka, Iwate 020-8550, Japan
| | - Mayuka Hakozaki
- Iwate Biotechnology Research Center, Kitakami, Iwate 024-0003, Japan
| | - Hidetoshi Yamada
- Iwate Biotechnology Research Center, Kitakami, Iwate 024-0003, Japan
| | - Ken-Ichi Kimura
- Graduate School of Agriculture, Iwate University, Morioka, Iwate 020-8550, Japan.
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25
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Chocholoušková M, Jirásko R, Vrána D, Gatěk J, Melichar B, Holčapek M. Reversed phase UHPLC/ESI-MS determination of oxylipins in human plasma: a case study of female breast cancer. Anal Bioanal Chem 2019; 411:1239-1251. [PMID: 30617406 DOI: 10.1007/s00216-018-1556-y] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2018] [Revised: 12/04/2018] [Accepted: 12/18/2018] [Indexed: 01/08/2023]
Abstract
The ultrahigh-performance liquid chromatography-mass spectrometry (UHPLC/MS) method was optimized and validated for the determination of oxylipins in human plasma using the targeted approach with selected reaction monitoring (SRM) in the negative-ion electrospray ionization (ESI) mode. Reversed phase UHPLC separation on an octadecylsilica column enabled the analysis of 63 oxylipins including numerous isomeric species within 12-min run time. The method was validated (calibration curve, linearity, limit of detection, limit of quantification, carry-over, precision, accuracy, recovery rate, and matrix effect) and applied to 40 human female plasma samples from breast cancer patients and age-matched healthy volunteers (control). Thirty-six oxylipins were detected in human plasma with concentrations above the limit of detection, and 21 of them were quantified with concentrations above the limit of quantitation. The concentrations determined in healthy controls are in a good agreement with previously reported data on human plasma. Quantitative data were statistically evaluated by multivariate data analysis (MDA) methods including principal component analysis (PCA) and orthogonal partial least square discriminant analysis (OPLS-DA). S-plot and box plots showed that 13-HODE, 9-HODE, 13-HOTrE, 9-HOTrE, and 12-HHTrE were the most upregulated oxylipin species in plasma of breast cancer patients.
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Affiliation(s)
- Michaela Chocholoušková
- Faculty of Chemical Technology, Department of Analytical Chemistry, University of Pardubice, Studentská 573, 532 10, Pardubice, Czech Republic
| | - Robert Jirásko
- Faculty of Chemical Technology, Department of Analytical Chemistry, University of Pardubice, Studentská 573, 532 10, Pardubice, Czech Republic
| | - David Vrána
- Medical School and Teaching Hospital, Department of Oncology, Palacký University, I.P. Pavlova 6, 775 20, Olomouc, Czech Republic
| | - Jiří Gatěk
- Atlas Hospital, Department of Surgery, Tomáš Baťa University in Zlín, nám. T.G. Masaryka 5555, 760 01, Zlín, Czech Republic
| | - Bohuslav Melichar
- Medical School and Teaching Hospital, Department of Oncology, Palacký University, I.P. Pavlova 6, 775 20, Olomouc, Czech Republic
| | - Michal Holčapek
- Faculty of Chemical Technology, Department of Analytical Chemistry, University of Pardubice, Studentská 573, 532 10, Pardubice, Czech Republic.
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26
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Halade GV, Black LM, Verma MK. Paradigm shift - Metabolic transformation of docosahexaenoic and eicosapentaenoic acids to bioactives exemplify the promise of fatty acid drug discovery. Biotechnol Adv 2018; 36:935-953. [PMID: 29499340 PMCID: PMC5971137 DOI: 10.1016/j.biotechadv.2018.02.014] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2017] [Revised: 02/01/2018] [Accepted: 02/25/2018] [Indexed: 02/06/2023]
Abstract
Fatty acid drug discovery (FADD) is defined as the identification of novel, specialized bioactive mediators that are derived from fatty acids and have precise pharmacological/therapeutic potential. A number of reports indicate that dietary intake of omega-3 fatty acids and limited intake of omega-6 promotes overall health benefits. In 1929, Burr and Burr indicated the significant role of essential fatty acids for survival and functional health of many organs. In reference to specific dietary benefits of differential omega-3 fatty acids, docosahexaenoic and eicosapentaenoic acids (DHA and EPA) are transformed to monohydroxy, dihydroxy, trihydroxy, and other complex mediators during infection, injury, and exercise to resolve inflammation. The presented FADD approach describes the metabolic transformation of DHA and EPA in response to injury, infection, and exercise to govern uncontrolled inflammation. Metabolic transformation of DHA and EPA into a number of pro-resolving molecules exemplifies a novel, inexpensive approach compared to traditional, expensive drug discovery. DHA and EPA have been recommended for prevention of cardiovascular disease since 1970. Therefore, the FADD approach is relevant to cardiovascular disease and resolution of inflammation in many injury models. Future research demands identification of novel action targets, receptors for biomolecules, mechanism(s), and drug-interactions with resolvins in order to maintain homeostasis.
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Affiliation(s)
- Ganesh V Halade
- Division of Cardiovascular Disease, Department of Medicine, The University of Alabama at Birmingham, AL, United States.
| | - Laurence M Black
- Division of Nephrology, Department of Medicine, The University of Alabama at Birmingham, AL, United States
| | - Mahendra Kumar Verma
- Department of Biological Sciences, Indian Institute of Science Education and Research, Bhopal, Madhya Pradesh, India
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27
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Pauls SD, Rodway LA, Winter T, Taylor CG, Zahradka P, Aukema HM. Anti-inflammatory effects of α-linolenic acid in M1-like macrophages are associated with enhanced production of oxylipins from α-linolenic and linoleic acid. J Nutr Biochem 2018; 57:121-129. [PMID: 29698923 DOI: 10.1016/j.jnutbio.2018.03.020] [Citation(s) in RCA: 67] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2017] [Revised: 03/16/2018] [Accepted: 03/20/2018] [Indexed: 12/19/2022]
Abstract
Chronic inflammation, mediated in large part by proinflammatory macrophage populations, contributes directly to the induction and perpetuation of metabolic diseases, including obesity, insulin resistance and type 2 diabetes. Polyunsaturated fatty acids (PUFAs) can have profound effects on inflammation through the formation of bioactive oxygenated metabolites called oxylipins. The objective of this study was to determine if exposure to the dietary omega-3 PUFA α-linolenic acid (ALA) can dampen the inflammatory properties of classically activated (M1-like) macrophages derived from the human THP-1 cell line and to examine the accompanying alterations in oxylipin secretion. We find that ALA treatment leads to a reduction in lipopolysaccharide (LPS)-induced interleukin (IL)-1β, IL-6 and tumor necrosis factor-α production. Although ALA is known to be converted to longer-chain PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), DHA oxylipins were reduced overall by ALA treatment, as was LPS-induced secretion of EPA oxylipins. In contrast, we observed profound increases in oxylipins directly derived from ALA. Lipoxygenase products of linoleic acid were also dramatically increased, and LPS-induced production of AA oxylipins, particularly prostaglandin D2, was reduced. These results suggest that ALA may act to dampen the inflammatory phenotype of M1-like macrophages by a unique set of mechanisms distinct from those used by the long-chain omega-3 fatty acids EPA and DHA. Thus, there is strong rationale for investigating the functions of ALA oxylipins and lesser-known LA oxylipins since they hold promise as anti-inflammatory agents.
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Affiliation(s)
- Samantha D Pauls
- Department of Food and Human Nutritional Sciences, University of Manitoba, Canada; Canadian Centre for Agri-Food Research in Health and Medicine, Winnipeg, Canada
| | - Lisa A Rodway
- Department of Food and Human Nutritional Sciences, University of Manitoba, Canada; Canadian Centre for Agri-Food Research in Health and Medicine, Winnipeg, Canada
| | - Tanja Winter
- Department of Food and Human Nutritional Sciences, University of Manitoba, Canada; Canadian Centre for Agri-Food Research in Health and Medicine, Winnipeg, Canada
| | - Carla G Taylor
- Department of Food and Human Nutritional Sciences, University of Manitoba, Canada; Canadian Centre for Agri-Food Research in Health and Medicine, Winnipeg, Canada; Department of Physiology and Pathophysiology, University of Manitoba, Canada
| | - Peter Zahradka
- Department of Food and Human Nutritional Sciences, University of Manitoba, Canada; Canadian Centre for Agri-Food Research in Health and Medicine, Winnipeg, Canada; Department of Physiology and Pathophysiology, University of Manitoba, Canada
| | - Harold M Aukema
- Department of Food and Human Nutritional Sciences, University of Manitoba, Canada; Canadian Centre for Agri-Food Research in Health and Medicine, Winnipeg, Canada.
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28
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Mendonça AM, Cayer LGJ, Pauls SD, Winter T, Leng S, Taylor CG, Zahradka P, Aukema HM. Distinct effects of dietary ALA, EPA and DHA on rat adipose oxylipins vary by depot location and sex. Prostaglandins Leukot Essent Fatty Acids 2018; 129:13-24. [PMID: 29482766 DOI: 10.1016/j.plefa.2017.12.004] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2017] [Revised: 12/20/2017] [Accepted: 12/22/2017] [Indexed: 12/22/2022]
Abstract
Dietary EPA and DHA given together alter oxylipins in adipose tissue. To compare the separate effects of individual dietary n-3 PUFA on oxylipins in different adipose depots (gonadal, mesenteric, perirenal, subcutaneous) in males and females, rats were provided diets containing higher levels of α-linolenic acid (ALA), EPA or DHA. Each n-3 PUFA enhanced its respective oxylipins the most, while effects on other n-3 oxylipins varied. For example: in perirenal and subcutaneous depots, more DHA oxylipins were higher with dietary ALA than with EPA; dietary EPA uniquely decreased 14-hydroxy-docosahexaenoic acid, in contrast to increasing many other DHA oxylipins. The n-3 PUFAs also reduced oxylipins from n-6 PUFAs in order of effectiveness: DHA > EPA > ALA. Diet by sex interactions in all depots except the perirenal depot resulted in higher oxylipins in males given DHA, and higher oxylipins in females given the other diets. Diet and sex effects on oxylipins did not necessarily reflect effects on either their tissue phospholipid or neutral lipid PUFA precursors. These varying diet and sex effects on oxylipins in the different adipose sites indicate that they may have distinct effects on adipose function.
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Affiliation(s)
- Anne M Mendonça
- School of Medicine, Federal University of Uberlândia, Brazil; Department of Food and Human Nutritional Sciences, University of Manitoba, Canada
| | - Lucien G J Cayer
- Department of Food and Human Nutritional Sciences, University of Manitoba, Canada
| | - Samantha D Pauls
- Department of Food and Human Nutritional Sciences, University of Manitoba, Canada
| | - Tanja Winter
- Department of Food and Human Nutritional Sciences, University of Manitoba, Canada
| | - Shan Leng
- Department of Food and Human Nutritional Sciences, University of Manitoba, Canada
| | - Carla G Taylor
- Department of Food and Human Nutritional Sciences, University of Manitoba, Canada; Canadian Centre for Research in Agri-Food Research in Health and Medicine, Winnipeg, Canada; Department of Physiology and Pathophysiology, University of Manitoba, Canada
| | - Peter Zahradka
- Department of Food and Human Nutritional Sciences, University of Manitoba, Canada; Canadian Centre for Research in Agri-Food Research in Health and Medicine, Winnipeg, Canada; Department of Physiology and Pathophysiology, University of Manitoba, Canada
| | - Harold M Aukema
- Department of Food and Human Nutritional Sciences, University of Manitoba, Canada; Canadian Centre for Research in Agri-Food Research in Health and Medicine, Winnipeg, Canada.
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29
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Rodriguez-Echevarria R, Macias-Barragan J, Parra-Vargas M, Davila-Rodriguez JR, Amezcua-Galvez E, Armendariz-Borunda J. Diet switch and omega-3 hydroxy-fatty acids display differential hepatoprotective effects in an obesity/nonalcoholic fatty liver disease model in mice. World J Gastroenterol 2018; 24:461-474. [PMID: 29398867 PMCID: PMC5787781 DOI: 10.3748/wjg.v24.i4.461] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2017] [Revised: 11/22/2017] [Accepted: 11/27/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To study the effect of 18-hydroxy-eicosapentaenoic acid (18-HEPE) and 17-hydroxy-docosahexaenoic acid (17-HDHA) in a murine model of obesity/nonalcoholic fatty liver disease.
METHODS C57BL/6 mice were fed with standard chow diet (CD) or high-fat, fructose-enriched diet (HFD) for 16 wk. Then, three groups were treated for 14 d with either, diet switch (HFD for CD), 18-HEPE, or 17-HDHA. Weight and fasting glucose were recorded on a weekly basis. Insulin tolerance test was performed at the end of treatment. Histological analysis (HE and Masson’s trichrome stain) and determination of serum insulin, glucagon, glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide, adiponectin and resistin were carried out as well as liver proteins by western blot.
RESULTS Mice treated with hydroxy-fatty acids 18-HEPE and 17-HDHA displayed no weight loss or improved insulin sensitivity. However, these mice groups showed a significant amelioration on serum GLP-1, adiponectin and resistin levels. Also, a significant reduction on inflammatory infiltrate was observed at both portal and lobular zones. Furthermore, up-regulation of PPARα/γ protein levels was observed in liver tissue and it was associated with decreased levels of NF-κB also determined by western blot analysis. On the other hand, diet switch regimen resulted in a marked improvement in most parameters including: weight loss, increased insulin sensitivity, decreased steatosis, restored levels of insulin, glucagon, leptin, adiponectin and resistin. However, no significant changes were observed regarding inflammatory infiltrate in this last group.
CONCLUSION 18-HEPE and 17-HDHA differentially exert hepatoprotective effects through up-regulation of nuclear receptors PPARα/γ and amelioration of serum adipokines profile.
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Affiliation(s)
- Roberto Rodriguez-Echevarria
- Institute for Molecular Biology and Gene Therapy-CUCS, Department of Molecular Biology and Genomics, University of Guadalajara, Guadalajara 44340, Mexico
| | - Jose Macias-Barragan
- Department of Health Sciences-CUValles, University of Guadalajara, Guadalajara 46600, Mexico
| | - Marcela Parra-Vargas
- Institute for Molecular Biology and Gene Therapy-CUCS, Department of Molecular Biology and Genomics, University of Guadalajara, Guadalajara 44340, Mexico
| | | | | | - Juan Armendariz-Borunda
- Institute for Molecular Biology and Gene Therapy-CUCS, Department of Molecular Biology and Genomics, University of Guadalajara, Guadalajara 44340, Mexico
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30
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Kuda O, Rossmeisl M, Kopecky J. Omega-3 fatty acids and adipose tissue biology. Mol Aspects Med 2018; 64:147-160. [PMID: 29329795 DOI: 10.1016/j.mam.2018.01.004] [Citation(s) in RCA: 67] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2017] [Revised: 01/05/2018] [Accepted: 01/08/2018] [Indexed: 12/16/2022]
Abstract
This review provides evidence for the importance of white and brown adipose tissue (i.e. WAT and BAT) function for the maintenance of healthy metabolic phenotype and its preservation in response to omega-3 polyunsaturated fatty acids (omega-3 PUFA), namely in the context of diseased states linked to aberrant accumulation of body fat, systemic low-grade inflammation, dyslipidemia and insulin resistance. More specifically, the review deals with (i) the concept of immunometabolism, i.e. how adipose-resident immune cells and adipocytes affect each other and define the immune-metabolic interface; and (ii) the characteristic features of "healthy adipocytes" in WAT, which are relatively small fat cells endowed with a high capacity for mitochondrial oxidative phosphorylation, triacylglycerol/fatty acid (TAG/FA) cycling and de novo lipogenesis (DNL). The intrinsic metabolic features of WAT and their flexible regulations, reflecting the presence of "healthy adipocytes", provide beneficial local and systemic effects, including (i) protection against in situ endoplasmic reticulum stress and related inflammatory response during activation of adipocyte lipolysis; (ii) prevention of ectopic fat accumulation and dyslipidemia caused by increased hepatic VLDL synthesis, as well as prevention of lipotoxic damage of insulin signaling in extra-adipose tissues; and also (iii) increased synthesis of anti-inflammatory and insulin-sensitizing lipid mediators with pro-resolving properties, including the branched fatty acid esters of hydroxy fatty acids (FAHFAs), also depending on the activity of DNL in WAT. The "healthy adipocytes" phenotype can be induced in WAT of obese mice in response to various stimuli including dietary omega-3 PUFA, especially when combined with moderate calorie restriction, and possibly also with other life style (e.g. physical activity) or pharmacological (e.g. thiazolidinediones) interventions. While omega-3 PUFA could exert beneficial systemic effects by improving immunometabolism of WAT without a concomitant induction of BAT, it is currently not clear whether the metabolic effects of the combined intervention using omega-3 PUFA and calorie restriction or thiazolidinediones depend also on the activation of BAT function and/or the induction of brite/beige adipocytes in WAT. It remains to be established why omega-3 PUFA intervention in type 2 diabetic subjects does not improve insulin sensitivity and glucose homeostasis despite inducing various anti-inflammatory mediators in WAT, including the recently discovered docosahexaenoyl esters of hydroxy linoleic acid, the lipokines from the FAHFA family, as well as several endocannabinoid-related anti-inflammatory lipids. To answer the question whether and to which extent omega-3 PUFA supplementation could promote the formation of "healthy adipocytes" in WAT of human subjects, namely in the obese insulin-resistant patients, represents a challenging task that is of great importance for the treatment of some serious non-communicable diseases.
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Affiliation(s)
- Ondrej Kuda
- Department of Adipose Tissue Biology, Institute of Physiology of the Czech Academy of Sciences, Videnska, 1083 Prague 4, Czech Republic
| | - Martin Rossmeisl
- Department of Adipose Tissue Biology, Institute of Physiology of the Czech Academy of Sciences, Videnska, 1083 Prague 4, Czech Republic
| | - Jan Kopecky
- Department of Adipose Tissue Biology, Institute of Physiology of the Czech Academy of Sciences, Videnska, 1083 Prague 4, Czech Republic.
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Zhang J, Yang Q, Li J, Zhong Y, Zhang L, Huang Q, Chen B, Mo M, Shen S, Zhong Q, Liu H, Cai C. Distinct differences in serum eicosanoids in healthy, enteritis and colorectal cancer individuals. Metabolomics 2017; 14:4. [PMID: 30830334 DOI: 10.1007/s11306-017-1293-9] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2017] [Accepted: 11/02/2017] [Indexed: 12/14/2022]
Abstract
BACKGROUND Eicosanoids as inflammatory mediators take part in the regulation of disease progression. However, the application of serum eicosanoid in disease progression identification was still uncertain. METHODS Serum from 52 healthy volunteers, 34 enteritis patients and 55 colorectal cancer (CRC) patients were collected. Ultra-high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was used to analyze the change of serum eicosanoids. RESULTS Of 158 eicosanoids, we found that lower levels of anti-inflammatory eicosanoids 13-HOTrE, 9-HOTrE, DHA, 11-HETE and 12-HHT were observed in enteritis and CRC group compared with healthy group, meanwhile the content of 5-iPF2α-VI as oxidative stress mediator in enteritis and CRC group was greater than that in healthy groups. Moreover, 9-HODE, 13-HODE, 12,13-diHOME, 8-HETE and 15-HETE were dramatically decrease in CRC group compared with non-CRC group. Additionally, the change of 5-, 12- and 15-HETE content in serum sample was associated with progression from healthy to enteritis, finally to CRC. No significant difference between serum eicosanoids and the expression of CerbB-2 and Ki67 were observed. CONCLUSION Serum eicosanoids might be used as a possible biomarker for identifying among health, enteritis and CRC.
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Affiliation(s)
- Junjie Zhang
- Analysis Center, Zhanjiang Scientific Center of Guangdong Medical University, Zhanjiang, Guangdong, 524023, China
| | - Qingjin Yang
- Analysis Center, Zhanjiang Scientific Center of Guangdong Medical University, Zhanjiang, Guangdong, 524023, China
| | - Jian Li
- Analysis Center, Zhanjiang Scientific Center of Guangdong Medical University, Zhanjiang, Guangdong, 524023, China
| | - Yu Zhong
- Analysis Center, Zhanjiang Scientific Center of Guangdong Medical University, Zhanjiang, Guangdong, 524023, China
| | - Lijian Zhang
- Analysis Center, Zhanjiang Scientific Center of Guangdong Medical University, Zhanjiang, Guangdong, 524023, China
| | - Qionglin Huang
- Analysis Center, Zhanjiang Scientific Center of Guangdong Medical University, Zhanjiang, Guangdong, 524023, China
| | - Bin Chen
- Analysis Center, Zhanjiang Scientific Center of Guangdong Medical University, Zhanjiang, Guangdong, 524023, China
| | - Mingming Mo
- Analysis Center, Zhanjiang Scientific Center of Guangdong Medical University, Zhanjiang, Guangdong, 524023, China
| | - Sensen Shen
- Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Institute of Analytical Chemistry, College of Chemistry and Molecular Engineering Peking University, Beijing, 100871, China
| | - Qisheng Zhong
- Shimadzu Global COE for Application and Technical Development, Guangzhou, Guangdong, 510010, China
| | - Huwei Liu
- Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Institute of Analytical Chemistry, College of Chemistry and Molecular Engineering Peking University, Beijing, 100871, China
| | - Chun Cai
- Analysis Center, Zhanjiang Scientific Center of Guangdong Medical University, Zhanjiang, Guangdong, 524023, China.
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Bao Q, Liu Y, Song H, Yang N, Ai D, Zhu Y, Zhang X. Spectrum evaluation-assisted eicosanoid metabolomics for global eicosanoid profiling in human vascular endothelial cells. Clin Exp Pharmacol Physiol 2017; 45:98-108. [DOI: 10.1111/1440-1681.12825] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2017] [Revised: 07/18/2017] [Accepted: 07/19/2017] [Indexed: 01/25/2023]
Affiliation(s)
- Qiankun Bao
- Tianjin Key Laboratory of Metabolic Diseases; Department of Physiology and Pathophysiology; Tianjin Medical University; Tianjin China
| | - Yajin Liu
- Tianjin Key Laboratory of Metabolic Diseases; Department of Physiology and Pathophysiology; Tianjin Medical University; Tianjin China
| | - Hao Song
- Tianjin Key Laboratory of Metabolic Diseases; Department of Physiology and Pathophysiology; Tianjin Medical University; Tianjin China
| | - Nan Yang
- Department of Physiology and Pathophysiology; Peking University Health Science Center; Beijing China
| | - Ding Ai
- Tianjin Key Laboratory of Metabolic Diseases; Department of Physiology and Pathophysiology; Tianjin Medical University; Tianjin China
| | - Yi Zhu
- Tianjin Key Laboratory of Metabolic Diseases; Department of Physiology and Pathophysiology; Tianjin Medical University; Tianjin China
- Collaborative Innovation Center of Tianjin for Medical Epigenetics; Tianjin Medical University; Tianjin China
| | - Xu Zhang
- Tianjin Key Laboratory of Metabolic Diseases; Department of Physiology and Pathophysiology; Tianjin Medical University; Tianjin China
- Collaborative Innovation Center of Tianjin for Medical Epigenetics; Tianjin Medical University; Tianjin China
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Nagahora N, Yamada H, Kikuchi S, Hakozaki M, Yano A. Nrf2 Activation by 5-lipoxygenase Metabolites in Human Umbilical Vascular Endothelial Cells. Nutrients 2017; 9:nu9091001. [PMID: 28892009 PMCID: PMC5622761 DOI: 10.3390/nu9091001] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2017] [Revised: 09/01/2017] [Accepted: 09/07/2017] [Indexed: 12/14/2022] Open
Abstract
5-hydroxyeicosatetraenoic acid (5-HETE) and 5-hydroxyeicosapentaenoic acid (5-HEPE) are major metabolites produced by 5-lipoxygenase (5-LOX) from arachidonic acid (AA) and eicosapentaenoic acid (EPA). Effects of hydroxides on endothelial cells are unclear, although 5-LOX is known to increase at arteriosclerotic lesions. To investigate the effects of hydroxides on human umbilical vein endothelial cells (HUVECs), the cells were treated with 50 μM each of AA, EPA, 5-HETE, and 5-HEPE. Treatment of HUVECs with 5-HETE and 5-HEPE, rather than with AA and EPA, increased the nuclear translocation of NF-E2 related factor 2 (Nrf2) and upregulated the expression of heme oxygenase-1 and cystine/glutamate transporter regulated by Nrf2. Reactive oxygen species (ROS) generation was markedly elevated in HUVECs after treatment with 5-HETE and 5-HEPE, and the pretreatment with α-tocopherol abrogated ROS levels similar to those in the vehicle control. However, ROS generation was independent of Nrf2 activation induced by 5-HETE and 5-HEPE. 5-HETE was converted to 5-oxo-eicosatetraenoic acid (5-oxo-ETE) in HUVECs, and 5-oxo-ETE increased Nrf2 activation. These results suggest that 5-HETE works as an Nrf2 activator through the metabolite 5-oxo-ETE in HUVECs. Similarly, 5-HEPE works in the same way, because 5-HEPE is metabolized to 5-oxo-eicosapentaenoic acid through the same pathway as that for 5-HETE.
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Affiliation(s)
- Nozomi Nagahora
- Iwate Biotechnology Research Center, 22-174-4 Narita, Kitakami, Iwate 024-0003, Japan.
| | - Hidetoshi Yamada
- Iwate Biotechnology Research Center, 22-174-4 Narita, Kitakami, Iwate 024-0003, Japan.
| | - Sayaka Kikuchi
- Iwate Biotechnology Research Center, 22-174-4 Narita, Kitakami, Iwate 024-0003, Japan.
| | - Mayuka Hakozaki
- Iwate Biotechnology Research Center, 22-174-4 Narita, Kitakami, Iwate 024-0003, Japan.
| | - Akira Yano
- Iwate Biotechnology Research Center, 22-174-4 Narita, Kitakami, Iwate 024-0003, Japan.
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Yamada H, Yamazaki Y, Koike S, Hakozaki M, Nagahora N, Yuki S, Yano A, Tsurumi K, Okumura T. Lipids, fatty acids and hydroxy-fatty acids of Euphausia pacifica. Sci Rep 2017; 7:9944. [PMID: 28855640 PMCID: PMC5577276 DOI: 10.1038/s41598-017-09637-9] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2017] [Accepted: 07/27/2017] [Indexed: 11/09/2022] Open
Abstract
Euphausia pacifica is a good candidate for a resource of marine n-3 PUFA. However, few reports exist of the lipid and fatty acid composition of E. pacifica. To examine the potential of E. pacifica as a resource of marine n-3 PUFA, we analyzed E. pacifica oil. We extracted lipids from E. pacifica harvested from the Pacific Ocean near Sanriku, Japan. Lipid classes of E. pacifica oil were analyzed by TLC-FID and the fatty acid composition of the oil was analyzed by GC/MS. Free fatty acids and hydroxy-fatty acids were analyzed by LC/QTOFMS. The lipid content of E. pacifica ranged from 1.30% to 3.57%. The ratios of triacylglycerols, phosphatidylcholine, phosphatidylethanolamine and free fatty acids in E. pacifica lipids were 5.3-23.0%, 32.6-53.4%, 8.5-25.4% and 2.5-7.0%, respectively. The content of n-3 PUFA in E. pacifica lipids was 38.6-46.5%. We also showed that E. pacifica contains unusual fatty acids and derivatives: C16-PUFAs (9,12-hexadecadienoic acid, 6,9,12-hexadecatrienoic acid and 6,9,12,15-hexadecatetraenoic acid) and hydroxy-PUFAs (8-HETE and 10-HDoHE). E. pacifica is a good resource of marine n-3 PUFA. Moreover, E. pacifica can provide C16-PUFA and hydroxy-PUFAs.
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Affiliation(s)
- Hidetoshi Yamada
- Iwate Biotechnology Research Center, 22-174-4 Narita, Kitakami, Iwate, 024-0003, Japan.
| | - Yuya Yamazaki
- Life Science Materials Laboratory, ADEKA Corporation, 7-2-34 Higashiogu, Arakawaku, Tokyo, 116-8553, Japan
| | - Seiji Koike
- Life Science Materials Laboratory, ADEKA Corporation, 7-2-34 Higashiogu, Arakawaku, Tokyo, 116-8553, Japan
| | - Mayuka Hakozaki
- Iwate Biotechnology Research Center, 22-174-4 Narita, Kitakami, Iwate, 024-0003, Japan
| | - Nozomi Nagahora
- Iwate Biotechnology Research Center, 22-174-4 Narita, Kitakami, Iwate, 024-0003, Japan
| | - Sayaka Yuki
- Iwate Biotechnology Research Center, 22-174-4 Narita, Kitakami, Iwate, 024-0003, Japan
| | - Akira Yano
- Iwate Biotechnology Research Center, 22-174-4 Narita, Kitakami, Iwate, 024-0003, Japan
| | - Koichiro Tsurumi
- Hachinohe Gakuin University, 13-98 Mihono, Hachinohe, Aomori, 031-8588, Japan
| | - Takuji Okumura
- National Research Institute of Aquaculture, Japan Fisheries Reseach and Education Agency, 422-1 Nakatsuhamaura, Minami-ise, Mie, 516-0193, Japan
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Wimuttisuk W, Tobwor P, Deenarn P, Intaraudom C, Pruksatrakul T, Nithithanasilp S, Wongtripop S, Phomklad S, Chaitongsakul P, Vichai V. Differential regulation of the lipoxygenase pathway in shrimp hepatopancreases and ovaries during ovarian development in the black tiger shrimp Penaeus monodon. Biochem Biophys Res Commun 2017; 487:396-402. [PMID: 28416387 DOI: 10.1016/j.bbrc.2017.04.073] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2017] [Accepted: 04/13/2017] [Indexed: 11/29/2022]
Abstract
Dietary polyunsaturated fatty acids (PUFAs) are critical to the success of ovarian development in marine crustaceans, especially for domesticated species such as the black tiger shrimp Penaeus monodon. These fatty acids are stored in a midgut gland called the hepatopancreas and subsequently serve as an energy source or are incorporated in yolk during ovarian development. PUFAs are known precursors of hydroxy fatty acids, including hydroxyeicosatetraenoic acid and hydroxyeicosapentaenoic acid (HEPE), which are catalyzed by lipoxygenases (LOX). In previous studies, 8-HEPE has been shown to regulate female reproduction and adipogenesis in marine crustaceans. However, whether the biosynthesis of 8-HEPE in these species is the result of LOX activity has yet to be investigated. In this study, 8-HEPE was identified exclusively in P. monodon hepatopancreases using liquid chromatography-mass spectrometry. Treatment with nordihydroguaiaretic acid resulted in the reduction of 8-HEPE, suggesting the enzyme-dependent catalysis of 8-HEPE in hepatopancreases. Additionally, a full-length P. monodon LOX (PmLOX) was amplified from shrimp ovary cDNA. Sequence analysis revealed that the putative PmLOX contains domains and catalytic residues required for LOX catalytic function. Furthermore, PmLOX expression increased steadily as shrimp ovary maturation progressed, while PmLOX expression and the amount of 8-HEPE decreased in shrimp hepatopancreases. These findings not only suggest differential requirements for hydroxy fatty acid biosynthesis in shrimp ovaries and hepatopancreases during the P. monodon ovarian development, but also provide insights into the LOX pathway in marine crustaceans.
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Affiliation(s)
- Wananit Wimuttisuk
- National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Phaholyothin Road, Khlong Luang, Pathum Thani, 12120, Thailand.
| | - Punsa Tobwor
- National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Phaholyothin Road, Khlong Luang, Pathum Thani, 12120, Thailand
| | - Pacharawan Deenarn
- National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Phaholyothin Road, Khlong Luang, Pathum Thani, 12120, Thailand
| | - Chakapong Intaraudom
- National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Phaholyothin Road, Khlong Luang, Pathum Thani, 12120, Thailand
| | - Thapanee Pruksatrakul
- National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Phaholyothin Road, Khlong Luang, Pathum Thani, 12120, Thailand
| | - Sutichai Nithithanasilp
- National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Phaholyothin Road, Khlong Luang, Pathum Thani, 12120, Thailand
| | - Somjai Wongtripop
- Shrimp Genetic Improvement Center, 333 Moo 5, Poomrieng, Chaiya, Surat Thani, 84110, Thailand
| | - Suwanchai Phomklad
- Shrimp Genetic Improvement Center, 333 Moo 5, Poomrieng, Chaiya, Surat Thani, 84110, Thailand
| | - Panomkorn Chaitongsakul
- Shrimp Genetic Improvement Center, 333 Moo 5, Poomrieng, Chaiya, Surat Thani, 84110, Thailand
| | - Vanicha Vichai
- National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Phaholyothin Road, Khlong Luang, Pathum Thani, 12120, Thailand
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Adkins Y, Belda BJ, Pedersen TL, Fedor DM, Mackey BE, Newman JW, Kelley DS. Dietary Docosahexaenoic Acid and trans-10, cis-12-Conjugated Linoleic Acid Differentially Alter Oxylipin Profiles in Mouse Periuterine Adipose Tissue. Lipids 2017; 52:399-413. [DOI: 10.1007/s11745-017-4252-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2016] [Accepted: 04/04/2017] [Indexed: 02/08/2023]
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Markworth JF, Kaur G, Miller EG, Larsen AE, Sinclair AJ, Maddipati KR, Cameron-Smith D. Divergent shifts in lipid mediator profile following supplementation with n-3 docosapentaenoic acid and eicosapentaenoic acid. FASEB J 2016; 30:3714-3725. [PMID: 27461565 DOI: 10.1096/fj.201600360r] [Citation(s) in RCA: 67] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2016] [Accepted: 07/11/2016] [Indexed: 12/31/2022]
Abstract
In contrast to the well-characterized effects of specialized proresolving lipid mediators (SPMs) derived from eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), little is known about the metabolic fate of the intermediary long-chain (LC) n-3 polyunsaturated fatty acid (PUFA) docosapentaenoic acid (DPA). In this double blind crossover study, shifts in circulating levels of n-3 and n-6 PUFA-derived bioactive lipid mediators were quantified by an unbiased liquid chromatography-tandem mass spectrometry lipidomic approach. Plasma was obtained from human subjects before and after 7 d of supplementation with pure n-3 DPA, n-3 EPA or placebo (olive oil). DPA supplementation increased the SPM resolvin D5n-3DPA (RvD5n-3DPA) and maresin (MaR)-1, the DHA vicinal diol 19,20-dihydroxy-DPA and n-6 PUFA derived 15-keto-PG E2 (15-keto-PGE2). EPA supplementation had no effect on any plasma DPA or DHA derived mediators, but markedly elevated monohydroxy-eicosapentaenoic acids (HEPEs), including the e-series resolvin (RvE) precursor 18-HEPE; effects not observed with DPA supplementation. These data show that dietary n-3 DPA and EPA have highly divergent effects on human lipid mediator profile, with no overlap in PUFA metabolites formed. The recently uncovered biologic activity of n-3 DPA docosanoids and their marked modulation by dietary DPA intake reveals a unique and specific role of n-3 DPA in human physiology.-Markworth, J. F., Kaur, G., Miller, E. G., Larsen, A. E., Sinclair, A. J., Maddipati, K. R., Cameron-Smith, D. Divergent shifts in lipid mediator profile following supplementation with n-3 docosapentaenoic acid and eicosapentaenoic acid.
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Affiliation(s)
| | - Gunveen Kaur
- Centre for Physical Activity and Nutrition Research, School of Exercise and Nutrition Sciences, Deakin University, Melbourne, Victoria, Australia
| | - Eliza G Miller
- Centre for Physical Activity and Nutrition Research, School of Exercise and Nutrition Sciences, Deakin University, Melbourne, Victoria, Australia
| | - Amy E Larsen
- Department of Physiology, Anatomy and Microbiology, La Trobe University Melbourne, Victoria, Australia
| | | | - Krishna Rao Maddipati
- Department of Pathology, Lipidomics Core Facility, Wayne State University, Detroit, Michigan, USA; and.,Karmanos Cancer Institute, Wayne State University, Detroit, Michigan, USA
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Koomyart I, Nagamizu H, Khuwijitjaru P, Kobayashi T, Shiga H, Yoshii H, Adachi S. Using severity factor as a parameter to optimize krill treatment under subcritical water conditions. Biosci Biotechnol Biochem 2016; 80:2192-2197. [PMID: 27379912 DOI: 10.1080/09168451.2016.1204220] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
The aim of this study was to optimize the conditions for subcritical water treatment of krill, as expressed with a single parameter: the severity factor (log R0). Raw krill was treated under subcritical water conditions at various log R0 values (1.54-3.75) by varying the treatment temperatures (120-180 °C) and times (0-10 min) in two different sizes of batch-type vessel (10 and 117 mL). The log R0 value could efficiently describe changes in various properties of the obtained liquid extracts and solid residues. The most desirable shrimp-like flavor intensity and highest sensory preference were obtained for log R0 values of 2.75-3.01. The results also proved that severity factor can be used as a single parameter to control subcritical water treatment conditions in differently sized batch-type vessels to produce shrimp-like flavor extract and residue from krill.
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Affiliation(s)
- Intira Koomyart
- a Department of Food Technology, Faculty of Engineering and Industrial Technology , Silpakorn University , Nakhon Pathom , Thailand
| | - Hironori Nagamizu
- b Division of Food Science and Biotechnology , Graduate School of Agriculture, Kyoto University , Kyoto , Japan
| | - Pramote Khuwijitjaru
- a Department of Food Technology, Faculty of Engineering and Industrial Technology , Silpakorn University , Nakhon Pathom , Thailand
| | - Takashi Kobayashi
- b Division of Food Science and Biotechnology , Graduate School of Agriculture, Kyoto University , Kyoto , Japan
| | - Hirokazu Shiga
- c Department of Agriculture and Food Technology, Faculty of Bio-Environmental Science , Kyoto Gakuen University , Kyoto , Japan
| | - Hidefumi Yoshii
- d Department of Applied Biological Science, Faculty of Agriculture , Kagawa University , Kagawa , Japan
| | - Shuji Adachi
- b Division of Food Science and Biotechnology , Graduate School of Agriculture, Kyoto University , Kyoto , Japan
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8-Hydroxyeicosapentaenoic Acid Decreases Plasma and Hepatic Triglycerides via Activation of Peroxisome Proliferator-Activated Receptor Alpha in High-Fat Diet-Induced Obese Mice. J Lipids 2016; 2016:7498508. [PMID: 27239345 PMCID: PMC4864551 DOI: 10.1155/2016/7498508] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2015] [Revised: 03/16/2016] [Accepted: 03/29/2016] [Indexed: 01/22/2023] Open
Abstract
PPARs regulate the expression of genes involved in lipid homeostasis. PPARs serve as molecular sensors of fatty acids, and their activation can act against obesity and metabolic syndromes. 8-Hydroxyeicosapentaenoic acid (8-HEPE) acts as a PPAR ligand and has higher activity than EPA. However, to date, the PPAR ligand activity of 8-HEPE has only been demonstrated in vitro. Here, we investigated its ligand activity in vivo by examining the effect of 8-HEPE treatment on high fat diet-induced obesity in mice. After the 4-week treatment period, the levels of plasma and hepatic triglycerides in the 8-HEPE-fed mice were significantly lower than those in the HFD-fed mice. The expression of genes regulated by PPARα was significantly increased in 8-HEPE-fed mice compared to those that received only HFD. Additionally, the level of hepatic palmitic acid in 8-HEPE-fed mice was significantly lower than in HFD-fed mice. These results suggested that intake of 8-HEPE induced PPARα activation and increased catabolism of lipids in the liver. We found no significant differences between EPA-fed mice and HFD-fed mice. We demonstrated that 8-HEPE has a larger positive effect on metabolic syndrome than EPA and that 8-HEPE acts by inducing PPARα activation in the liver.
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Ramot Y, Mastrofrancesco A, Camera E, Desreumaux P, Paus R, Picardo M. The role of PPARγ-mediated signalling in skin biology and pathology: new targets and opportunities for clinical dermatology. Exp Dermatol 2016; 24:245-51. [PMID: 25644500 DOI: 10.1111/exd.12647] [Citation(s) in RCA: 66] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/21/2015] [Indexed: 12/19/2022]
Abstract
Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that modulate the expression of multiple different genes involved in the regulation of lipid, glucose and amino acid metabolism. PPARs and cognate ligands also regulate important cellular functions, including cell proliferation and differentiation, as well as inflammatory responses. This includes a role in mediating skin and pilosebaceous unit homoeostasis: PPARs appear to be essential for maintaining skin barrier permeability, inhibit keratinocyte cell growth, promote keratinocyte terminal differentiation and regulate skin inflammation. They also may have protective effects on human hair follicle (HFs) epithelial stem cells, while defects in PPARγ-mediated signalling may promote the death of these stem cells and thus facilitate the development of cicatricial alopecia (lichen planopilaris). Overall, however, selected PPARγ modulators appear to act as hair growth inhibitors that reduce the proliferation and promote apoptosis of hair matrix keratinocytes. The fact that commonly prescribed PPARγ-modulatory drugs of the thiazolidine-2,4-dione class can exhibit a battery of adverse cutaneous effects underscores the importance of distinguishing beneficial from clinically undesired cutaneous activities of PPARγ ligands and to better understand on the molecular level how PPARγ-regulated cutaneous lipid metabolism and PPARγ-mediated signalling impact on human skin physiology and pathology. Surely, the therapeutic potential that endogenous and exogenous PPARγ modulators may possess in selected skin diseases, ranging from chronic inflammatory hyperproliferative dermatoses like psoriasis and atopic dermatitis, via scarring alopecia and acne can only be harnessed if the complexities of PPARγ signalling in human skin and its appendages are systematically dissected.
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Affiliation(s)
- Yuval Ramot
- Department of Dermatology, Hadassah - Hebrew University Medical Center, Jerusalem, Israel
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Gabbs M, Leng S, Devassy JG, Monirujjaman M, Aukema HM. Advances in Our Understanding of Oxylipins Derived from Dietary PUFAs. Adv Nutr 2015; 6:513-40. [PMID: 26374175 PMCID: PMC4561827 DOI: 10.3945/an.114.007732] [Citation(s) in RCA: 506] [Impact Index Per Article: 50.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Oxylipins formed from polyunsaturated fatty acids (PUFAs) are the main mediators of PUFA effects in the body. They are formed via cyclooxygenase, lipoxygenase, and cytochrome P450 pathways, resulting in the formation of prostaglandins, thromboxanes, mono-, di-, and tri-hydroxy fatty acids (FAs), epoxy FAs, lipoxins, eoxins, hepoxilins, resolvins, protectins (also called neuroprotectins in the brain), and maresins. In addition to the well-known eicosanoids derived from arachidonic acid, recent developments in lipidomic methodologies have raised awareness of and interest in the large number of oxylipins formed from other PUFAs, including those from the essential FAs and the longer-chain n-3 (ω-3) PUFAs. Oxylipins have essential roles in normal physiology and function, but can also have detrimental effects. Compared with the oxylipins derived from n-3 PUFAs, oxylipins from n-6 PUFAs generally have greater activity and more inflammatory, vasoconstrictory, and proliferative effects, although there are notable exceptions. Because PUFA composition does not necessarily reflect oxylipin composition, comprehensive analysis of the oxylipin profile is necessary to understand the overall physiologic effects of PUFAs mediated through their oxylipins. These analyses should include oxylipins derived from linoleic and α-linolenic acids, because these largely unexplored bioactive oxylipins constitute more than one-half of oxylipins present in tissues. Because collated information on oxylipins formed from different PUFAs is currently unavailable, this review provides a detailed compilation of the main oxylipins formed from PUFAs and describes their functions. Much remains to be elucidated in this emerging field, including the discovery of more oxylipins, and the understanding of the differing biological potencies, kinetics, and isomer-specific activities of these novel PUFA metabolites.
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Affiliation(s)
| | | | | | | | - Harold M Aukema
- Human Nutritional Sciences, University of Manitoba, Winnipeg, Canada; and Canadian Centre for Agri-Food Research in Health and Medicine, St. Boniface Hospital Research Centre, Winnipeg, Canada
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Masoodi M, Kuda O, Rossmeisl M, Flachs P, Kopecky J. Lipid signaling in adipose tissue: Connecting inflammation & metabolism. Biochim Biophys Acta Mol Cell Biol Lipids 2014; 1851:503-18. [PMID: 25311170 DOI: 10.1016/j.bbalip.2014.09.023] [Citation(s) in RCA: 159] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2014] [Revised: 09/25/2014] [Accepted: 09/28/2014] [Indexed: 02/08/2023]
Abstract
Obesity-associated low-grade inflammation of white adipose tissue (WAT) contributes to development of insulin resistance and other disorders. Accumulation of immune cells, especially macrophages, and macrophage polarization from M2 to M1 state, affect intrinsic WAT signaling, namely anti-inflammatory and proinflammatory cytokines, fatty acids (FA), and lipid mediators derived from both n-6 and n-3 long-chain PUFA such as (i) arachidonic acid (AA)-derived eicosanoids and endocannabinoids, and (ii) specialized pro-resolving lipid mediators including resolvins derived from both eicosapentaenoic (EPA) and docosahexaenoic acid (DHA), lipoxins (AA metabolites), protectins and maresins (DHA metabolites). In this respect, potential differences in modulating adipocyte metabolism by various lipid mediators formed by inflammatory M1 macrophages typical of obese state, and non-inflammatory M2 macrophages typical of lean state remain to be established. Studies in mice suggest that (i) transient accumulation of M2 macrophages could be essential for the control of tissue FA levels during activation of lipolysis, (ii) currently unidentified M2 macrophage-borne signaling molecule(s) could inhibit lipolysis and re-esterification of lipolyzed FA back to triacylglycerols (TAG/FA cycle), and (iii) the egress of M2 macrophages from rebuilt WAT and removal of the negative feedback regulation could allow for a full unmasking of metabolic activities of adipocytes. Thus, M2 macrophages could support remodeling of WAT to a tissue containing metabolically flexible adipocytes endowed with a high capacity of both TAG/FA cycling and oxidative phosphorylation. This situation could be exemplified by a combined intervention using mild calorie restriction and dietary supplementation with EPA/DHA, which enhances the formation of "healthy" adipocytes. This article is part of a Special Issue entitled Oxygenated metabolism of PUFA: analysis and biological relevance."
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Affiliation(s)
- Mojgan Masoodi
- Nestlé Institute of Health Sciences SA, EPFL Innovation Park, bâtiment H, 1015 Lausanne, Switzerland.
| | - Ondrej Kuda
- Department of Adipose Tissue Biology, Institute of Physiology Academy of Sciences of the Czech Republic, v.v.i., Prague, Czech Republic
| | - Martin Rossmeisl
- Department of Adipose Tissue Biology, Institute of Physiology Academy of Sciences of the Czech Republic, v.v.i., Prague, Czech Republic
| | - Pavel Flachs
- Department of Adipose Tissue Biology, Institute of Physiology Academy of Sciences of the Czech Republic, v.v.i., Prague, Czech Republic
| | - Jan Kopecky
- Department of Adipose Tissue Biology, Institute of Physiology Academy of Sciences of the Czech Republic, v.v.i., Prague, Czech Republic.
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