Microenvironmental and Metabolic Health Sciences

Lipids serve as the largest energy source, cell membrane components, and bioactive mediators. Lipids are major environmental substances supplied as nutrients and spatiotemporally regulate a variety of biological responses in response to given microenvironmental cues within tissues. Our research focuses on the regulation of biological networks driven by lipids and their metabolites. By taking advantages of an array of gene-manipulated mice for lipid-metabolizing enzymes and receptors, we aim to clarify novel lipid-orchestrated mechanisms underlying various diseases such as metabolic and immune disorders. Knowledges obtained from these approaches will be translated to humans toward discovery of new biomarkers or druggable targets.

Team Murakami

1. Inazumi T, Yamada K, Shirata N, Sato H, Taketomi Y, Morita K, Hohjoh H, Tsuchiya S, Oniki K, Watanabe T, Sasaki Y, Oike Y, Ogata Y, Saruwatari J,Murakami M, Sugimoto Y.Prostaglandin E₂-EP4 axis promotes lipolysis and fibrosis in adipose tissue leading to ectopic fat deposition and insulin resistance. Cell Rep. 33, 108265, 2020.
2. Watanabe K, Taketomi Y, Miki Y, Kugiyama K, Murakami M. Group V secreted phospholipase A₂ plays a protective role against aortic dissection. J. Biol. Chem. 295, 10092-10111, 2020. [Editors’ Picks]
3. Sato H, Taketomi Y, Miki Y, Murase R, Yamamoto K, Murakami M. Secreted phospholipase PLA2G2D contributes to metabolic health by mobilizing omega-3 polyunsaturated fatty acids in white adipose tissue. Cell Rep. 31, 107579, 2020.
4. Murakami M, Sato H, Taketomi Y. Updating phospholipase A2 biology. Biomolecules. 10, E1457, 2020 (review)
5. Mori A, Hatano T, Inoshita T, Shiba-Fukushima K, Koinuma T, Meng H, Kubo SI, Spratt S, Cui C, Yamashita C, Miki Y, Yamamoto K, Hirabayashi T,Murakami M, Takahashi Y, Shindou H, Nonaka T, Hasegawa M, Okuzumi A, Imai Y, Hattori N. Parkinson’s disease-assocaitaed iPLA₂-VIA/PLA2G6 regulates neuronal functions and a-synuclein stability through membrane remodeling. Natl. Acad. Sci. U S A. 116, 20689-20699, 2019.
6. Murakami M. Novel functions of phospholipase A₂s: Overview. Biochim. Biophys. Acta 1864, 763-765, 2019 (review)
7. Shimanaka Y, Kono N, Taketomi Y, Arita M, Okayama Y, Tanaka Y, Nishito Y, Mochizuki T, Kusuhara H, Adibekian A, Cravatt BF, Murakami M, Arai H. ω3 fatty acid epoxides are autocrine mediators that control the magnitude of IgE-mediated mast cell activation. Nat. Med. 23, 1287-1297, 2017
8. Murase R, Taketomi Y, Miki Y, Nishito Y, Saito M, Fukami K, Yamamoto K, Murakami M. Group III phospholipase A₂ promotes colitis and colorectal cancer. Sci. Rep. 7, 12261, 2017.
9. Irie A, Yamamoto K, Miki Y, Murakami M. Phosphatidylethanolamine dynamics are required for osteoclast fusion. Sci Rep. 7, 46715, 2017
10. Hirabayashi T, Anjo T, Kaneko A, Senoo Y, Shibata A, Takama H, Yokoyama K, Nishito Y, Ono T, Taya C, Muramatsu K, Fukami K, Muñoz-Garcia A, Brash AR, Ikeda K, Arita M, Akiyama A, Murakami M. PNPLA1 has a crucial role in skin barrier function by directing acylceramide biosynthesis. Nat. Commun. 8, 14609, 2017.
11. Yamamoto, K., Miki, Y., Sato, H., Nishito, Y., Gelb, M.H., Taketomi, Y., Murakami, M. Expression and function of group IIE phospholipase A₂ in mouse skin. J. Biol. Chem. 291, 15602-15613, 2016.
12. Miki Y, Kidoguchi Y, Sato M, Taketomi Y, Taya C, Muramatsu K, Gelb MH, Yamamoto K, Murakami M. Dual roles of group IID phospholipase A₂ in inflammation and cancer. J Biol Chem. 291, 15588-15601, 2016.
13. Murakami M, Yamamoto K, Miki Y, Murase R, Sato H, Taketomi Y. The roles of the secreted phospholipase A₂ (sPLA₂) gene family in immunology. Adv. Immunol. 132, 91-134, 2016 (review)
14. Murase R, Sato H, Yamamoto K, Ushida A, Nishito Y, Ikeda K, Kobayashi T, Yamamoto T, Taketomi Y, Murakami M. Group X secreted phospholipase A₂ releases ω-3 polyunsaturated fatty acids, suppresses colitis and promotes sperm fertility. J. Biol. Chem. 291, 6895-6911, 2016
15. Yamamoto K, Miki Y, Sato M, Taketomi Y, Nishito Y, Taya C, Muramatsu K, Ikeda K, Nakanishi H, Taguchi R, Kambe N, Kabashima K, Lambeau G, Gelb MH, Murakami M. The role of group IIF secreted phospholipase A₂ in epidermal homeostasis and hyperplasia. J. Exp. Med. 212, 1901-1919, 2015
16. Vijay R, Gelb MH, Miki Y, Yamamoto K, Murakami M, Perlman S. Critical role for secreted phospholipase A₂ group IID in age-related susceptibility to infection with the severe acute respiratory syndrome coronavirus. J. Exp. Med. 212,1851-1868, 2015
17. Sato H, Taketomi Y, Ushida A, Isogai Y, Kojima T, Hirabayashi T, Miki Y, Yamamoto K, Nishito Y, Kobayashi T, Ikeda K, Taguchi R, Hara S, Ida S, Miyamoto Y, Watanabe M, Baba H, Miyata K, Oike Y, Gelb MH, Murakami M. The adipocyte-inducible secreted phospholipases PLA2G5 and PLA2G2E play distinct roles in obesity. Cell Metab. 20, 119-132, 2014
18. Taketomi Y, Ueno N, Kojima T, Sato H, Murase R, Yamamoto K, Tanaka S, Sakanaka M, Nakamura M, Nishito Y, Kawana M, Kambe N, Ikeda K, Taguchi R, Nakamizo S, Kabashima K, Gelb MH, Arita M, Yokomizo T, Nakamura M, Watanabe K, Hirai H, Nakamura M, Okayama Y, Ra C, Aritake K, Urade Y, Morimoto K, Sugimoto Y, Shimizu T, Narumiya S, Hara S, Murakami M. Mast cell maturation is driven via a group III phospholipase A₂-prostaglandin D₂-DP1 receptor paracrine axis. Nat. Immunol. 14, 554-563, 2013
19. Miki Y, Yamamoto K, Taketomi Y, Sato H, Shimo K, Kobayashi T, Ishikawa Y, Ishii T, Nakanishi H, Ikeda K, Taguchi R, Kabashima K, Arita M, Arai H, Lambeau G, Bollinger JM, Hara S, Gelb MH, Murakami M. Lymphoid tissue phospholipase A₂ group IID resolves contact hypersensitivity by driving anti-inflammatory lipid mediators. J. Exp. Med. 210, 1217-1234, 2013
20. Sato H, Isogai Y, Masuda S, Taketomi Y, Miki Y, Kamei D, Hara S, Kobayashi T, Ishikawa Y, Ishii T, Ikeda K, Taguchi R, Ishimoto Y, Suzuki N, Yokota Y, Hanasaki K, Suzuki-Yamamoto T, Yamamoto K, Murakami M. Physiological roles of group X secreted phospholipase A₂ in reproduction, gastrointestinal phospholipid digestion, and neuronal function. J. Biol. Chem. 286, 11616-11631, 2011
21. Sato H, Taketomi T, Isogai Y, Miki Y, Yamamoto K, Masuda S, Hosono T, Arata S, Ishikawa Y, Ishii T, Kobayashi T, Nakanishi H, Ikeda K, Taguchi R, Hara S, Kudo I, Murakami M. Group III secreted phospholipase A₂ regulates epididymal sperm maturation and fertility in mice. J. Clin. Invest. 120, 1400-1414, 2011

Team Osako

1. Aiba T, Saito T, Hayashi A, Sato S, Yunokawa H, Fukami M, Hayashi Y, Mizuno K, Sato Y, Kojima Y, Ohsako S. Exploring disease-specific methylated CpGs in human male genital abnormalities by using MSD-AFLP. J Reprod 65, 491-497, 2019
2. Sarma SN, Nagano R, Ohsako S. Tyroxine hydroxylase-positive neuronal cell population is increased by temporal dioxin exposure at early stage of differentiation from human embryonic stem cells. Int J Mol Sci 20, E2687, 2019
3. Aiba T, Saito T, Hayashi A, Sato S, Yunokawa H, Maruyama R, Fujibuchi W, Ohsako S. Does the prenatal bisphenol A exposure alter DNA methylation levels in the mouse hippocampus?: Analysis using a high-sensitivity methylome technique. Genes Environ 40, 12, 2018
4. Kurita H, Aiba T, Saito T, Ohsako S. Detection of dioxin-induced demethylation of mouse Cyp1a1 gene promoter by a new labeling method for short DNA fragments possessing 5′-methylcytosine at the end. Genes Environ 40, 1, 2018
5. Ohsako S, Aiba T, Miyado M, Fukami M, Ogata T, Hayashi Y, Mizuno K, Kojima Y. Expression of xenobiotic biomarkers CYP1-Family in preputial tissue of patients with hypospadias and phimosis and its association with DNA methylation level of SRD5A2 minimal promoter. Arch Environ Contam Toxicol 74, 240-247, 2018
6. Aiba T, Saito T, Hayashi A, Sato S, Yunokawa H, Maruyama T, Fujibuchi W, Kurita H, Tohyama C, Ohsako S. Methylated site display (MSD)-AFLP, a sensitive and affordable method for analysis of CpG methylation profiles. BMC Mol Biol 18, 7, 2017
7. Amenya HZ, Tohyama C, Ohsako S. Dioxin induces Ahr-dependent robust DNA demethylation of the Cyp1a1 promoter via Tdg in the mouse liver. Sci Rep 6, 34989, 2016
8. Ohsako S. Perinatal exposure to environmental chemicals induces epigenomic changes in offspring. Genes Environ 33, 43-49, 2011 (review)
9. Ohsako S, Fukuzawa N, Ishimura R, Kawakami T, Wu Q, Nagano R, Zaha H, Sone H, Yonemoto J, Tohyama C. Comparative contribution of the aryl hydrocarbon receptor gene to perinatal stage development and dioxin-induced toxicity between the urogenital complex and testis in the mouse. Biol Reprod 82, 636-643, 2010
10. Wu Q, Suzuki JS, Zaha H, Lin TM, Peterson RE, Tohyama C, Ohsako S. Differences in gene expression and benzo[a]pyrene-induced DNA adduct formation in the liver of three strains of female mice with identical AhRb2 genotype treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin and/or benzo[a]pyrene. J Appl Toxicol 28, 724-733, 2008
11. Sakata Y, Yoshioka W, Tohyama C, Ohsako S. Internal genomic sequence of human CYP1A1 gene is involved in superinduction of dioxin-induced CYP1A1 transcription by cycloheximide. Biochem Biophys Res Comm 355, 687-692, 2007
12. Ohsako S, Tohyama C. Comparison of study controls. Environ Health Perspect 113: A582; author reply, 2005
13. Ohsako S, Kubota K, Kurosawa S, Takeda K, Wu Q, Ishimura R, Tohyama C. Alterations of gene expression in adult male rat testis and pituitary shortly after subacute administration of the antiandrogen flutamide. J Reprod Dev 49, 275-290, 2003
14. Sakaue M, Ohsako S, Ishimura R, Kurosawa S, Kurohmaru M, Hayashi Y, Aoki Y, Yonemoto J, Tohyama C. Bisphenol-A affects spermatogenesis in the mature rat even at a low dose. J Occupational Health 43, 185-190, 2001
15. Ohsako S, Miyabara Y, Nishimura N, Kurosawa S, Sakaue M, Ishimura R, Sato M, Aoki Y, Sone H, Tohyama C, and Yonemoto J. Maternal exposure to a low dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) suppressed the development of reproductive organs of male rats: dose-dependent increase of mRNA levels of 5α-reductase type 2 in contrast to decrease of androgen receptor in the pubertal ventral prostate. Toxicol Sci 60, 132-143, 2001