Physiological Roles of Group X-secreted Phospholipase A2 in Reproduction, Gastrointestinal Phospholipid Digestion, and Neuronal Function

• Published in: The Journal of biological chemistry Vol. 286; no. 13; pp. 11632 - 11648
• Main Authors: Sato, Hiroyasu, Isogai, Yuki, Masuda, Seiko, Taketomi, Yoshitaka, Miki, Yoshimi, Kamei, Daisuke, Hara, Shuntaro, Kobayashi, Tetsuyuki, Ishikawa, Yukio, Ishii, Toshiharu, Ikeda, Kazutaka, Taguchi, Ryo, Ishimoto, Yoshikazu, Suzuki, Noriko, Yokota, Yasunori, Hanasaki, Kohji, Suzuki-Yamamoto, Toshiko, Yamamoto, Kei, Murakami, Makoto
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2011; American Society for Biochemistry and Molecular Biology
• Subjects: Animals; Arachidonic Acid; Digestion - physiology; Eicosanoid; Female; Gastrointestinal Tract - enzymology; Gene Expression Regulation, Enzymologic - physiology; Lipids; Male; Mice; Mice, Knockout; Mouse; Neurons - enzymology; Organ Specificity; Phospholipase A; Phospholipases A2, Secretory - biosynthesis; Phospholipases A2, Secretory - genetics; Phospholipid; Phospholipids - genetics; Phospholipids - metabolism; Reproduction - physiology; Phospholipid; Mouse; Arachidonic Acid; Phospholipase A; Eicosanoid
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M110.206755

Although the secreted phospholipase A2 (sPLA2) family has been generally thought to participate in pathologic events such as inflammation and atherosclerosis, relatively high and constitutive expression of group X sPLA2 (sPLA2-X) in restricted sites such as reproductive organs, the gastrointestinal tract, and peripheral neurons raises a question as to the roles played by this enzyme in the physiology of reproduction, digestion, and the nervous system. Herein we used mice with gene disruption or transgenic overexpression of sPLA2-X to clarify the homeostatic functions of this enzyme at these locations. Our results suggest that sPLA2-X regulates 1) the fertility of spermatozoa, not oocytes, beyond the step of flagellar motility, 2) gastrointestinal phospholipid digestion, perturbation of which is eventually linked to delayed onset of a lean phenotype with reduced adiposity, decreased plasma leptin, and improved muscle insulin tolerance, and 3) neuritogenesis of dorsal root ganglia and the duration of peripheral pain nociception. Thus, besides its inflammatory action proposed previously, sPLA2-X participates in physiologic processes including male fertility, gastrointestinal phospholipid digestion linked to adiposity, and neuronal outgrowth and sensing.