title: Autocrine inhibition of leptin production by tumor necrosis factor-alpha (TNF-alpha) through TNF-alpha type-I receptor in vitro.
abstract: The aim of this study was to find factors which regulate m-leptin secretion during pregnancy. Mouse parametrial adipocytes from day 13 of pregnancy were cultured with or without mouse placental lactogen (mPL)-I, mPL-II, or mouse tumor necrosis factor-alpha (mTNF-alpha) and mouse-leptin (m-leptin) concentration in the medium was assessed by RIA. Up to four days of mPL-I or mPL-II treatment did not affect m-leptin secretion. However, mTNF-alpha, which is produced by adipocytes, significantly inhibited m-leptin secretion in a dose- and time-dependent manner. Antibody to mTNF-alpha completely blocked the inhibitory effect of mTNF-alpha on m-leptin secretion. mTNF-alpha significantly inhibited the expression of m-leptin messenger RNA. Agonistic polyclonal antibody directed against the mTNF-type-I receptor (mTNF-RI) significantly inhibited m-leptin secretion, but the anti-mTNF-RII antibody did not change m-leptin secretion. Moreover, human TNF-alpha (h-TNF-alpha) also inhibited human-leptin (h-leptin) secretion by cultured human adipocytes collected from the subcutaneous fat of pregnant women. These results suggest that TNF-alpha, which is secreted by adipocytes, inhibits m-leptin secretion through mTNF-RI and suggest the presence of an autocrine or paracrine regulation of leptin secretion in human and mouse adipose tissue in vivo.
authors.affiliation: Department of Obstetrics and Gynecology, Osaka University Medical School, Suita, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Yamaguchi
authors.forename: T
authors.initials: T
authors.lastname: Murakami
authors.forename: T
authors.initials: T
authors.lastname: Tomimatsu
authors.forename: Y
authors.initials: Y
authors.lastname: Nishio
authors.forename: N
authors.initials: N
authors.lastname: Mitsuda
authors.forename: T
authors.initials: T
authors.lastname: Kanzaki
authors.forename: H
authors.initials: H
authors.lastname: Kurachi
authors.forename: K
authors.initials: K
authors.lastname: Shima
authors.forename: T
authors.initials: T
authors.lastname: Aono
authors.forename: Y
authors.initials: Y
authors.lastname: Murata
mesh_terms: D017667:Adipocytes; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D015703:Antigens, CD / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D020738:Leptin; D051379:Mice; D008813:Mice, Inbred ICR; D010926:Placental Hormones / Q000502:physiology; D011247:Pregnancy; D014176:Protein Biosynthesis; D011506:Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D054411:Receptors, Leptin; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology*; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000502:physiology*
chemical_list: D015703:Antigens, CD; C515448:LEPR protein, human; D020738:Leptin; D010926:Placental Hormones; D011506:Proteins; D012333:RNA, Messenger; D054411:Receptors, Leptin; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha; C515447:leptin receptor, mouse