title: Involvement of IL-1 in the Maintenance of Masseter Muscle Activity and Glucose Homeostasis.
abstract: Physical exercise reportedly stimulates IL-1 production within working skeletal muscles, but its physiological significance remains unknown due to the existence of two distinct IL-1 isoforms, IL-1α and IL-1β. The regulatory complexities of these two isoforms, in terms of which cells in muscles produce them and their distinct/redundant biological actions, have yet to be elucidated. Taking advantage of our masticatory behavior (Restrained/Gnawing) model, we herein show that IL-1α/1β-double-knockout (IL-1-KO) mice exhibit compromised masseter muscle (MM) activity which is at least partially attributable to abnormalities of glucose handling (rapid glycogen depletion along with impaired glucose uptake) and dysfunction of IL-6 upregulation in working MMs. In wild-type mice, masticatory behavior clearly increased IL-1β mRNA expression but no incremental protein abundance was detectable in whole MM homogenates, whereas immunohistochemical staining analysis revealed that both IL-1α- and IL-1β-immunopositive cells were recruited around blood vessels in the perimysium of MMs after masticatory behavior. In addition to the aforementioned phenotype of IL-1-KO mice, we found the IL-6 mRNA and protein levels in MMs after masticatory behavior to be significantly lower in IL-1-KO than in WT. Thus, our findings confirm that the locally-increased IL-1 elicited by masticatory behavior, although present small in amounts, contributes to supporting MM activity by maintaining normal glucose homeostasis in these muscles. Our data also underscore the importance of IL-1-mediated local interplay between autocrine myokines including IL-6 and paracrine cytokines in active skeletal muscles. This interplay is directly involved in MM performance and fatigability, perhaps mediated through maintaining muscular glucose homeostasis.
authors.affiliation: Division of Aging and Geriatric Dentistry, Tohoku University Graduate School of Dentistry, Sendai, Japan.|Division of Oral Molecular Regulation, Tohoku University Graduate School of Dentistry, Sendai, Japan.
authors.forename: Ko
authors.initials: K
authors.lastname: Chiba
authors.affiliation: Kansei Fukushi Research Institute, Tohoku Fukushi University, Sendai, Japan.|Division of Oral Diagnosis, Tohoku University Graduate School of Dentistry, Sendai, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tsuchiya
authors.affiliation: Department of Orthopaedic Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Koide
authors.affiliation: Department of Orthopaedic Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Hagiwara
authors.affiliation: Division of Advanced Prosthetic Dentistry, Tohoku University Graduate School of Dentistry, Sendai, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Sasaki
authors.affiliation: Division of Aging and Geriatric Dentistry, Tohoku University Graduate School of Dentistry, Sendai, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Hattori
authors.affiliation: Division of Aging and Geriatric Dentistry, Tohoku University Graduate School of Dentistry, Sendai, Japan.|Kansei Fukushi Research Institute, Tohoku Fukushi University, Sendai, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Division of Oral Molecular Regulation, Tohoku University Graduate School of Dentistry, Sendai, Japan.
authors.forename: Shunji
authors.initials: S
authors.lastname: Sugawara
authors.affiliation: Tohoku University Graduate School of Biomedical Engineering, Sendai, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Kanzaki
authors.affiliation: Division of Oral Molecular Regulation, Tohoku University Graduate School of Dentistry, Sendai, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Endo
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D006003:Glycogen / Q000378:metabolism; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism*; D053582:Interleukin-1alpha / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008297:Male; D008406:Masseter Muscle / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout
chemical_list: D001786:Blood Glucose; D007375:Interleukin-1; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D015850:Interleukin-6; D006003:Glycogen