title: Loss of the TNFα function inhibits Wnt/β-catenin signaling, exacerbates obesity development in adolescent spontaneous obese mice.
abstract: Tumor necrosis factor alpha (TNFα) is an adipokine involved in the regulation of cell differentiation and lipid metabolism, but its specific role has not been clearly understood. We validated a hypothesis that loss of TNFα function would inhibit Wnt/β-catenin signaling and accelerate adipogenesis in adolescent genetic obese mice. Epididymal white adipose tissues (eWAT) from TNFα deficient (TNFα(-/-)), leptin receptor deficient (db/db) and double gene mutant (db/db/TNFα(-/-), DT) male mice were used for comparative analysis of key molecules in Wnt/β-catenin signaling and adipogenic markers by qRT-PCR and western blot techniques. Compared with TNFα(-/-) and WT mice of 28 days old, an obese trait was observed in both db/db and DT mice, while the latter showed more significant body weight gain and eWAT hypertrophy. The mRNA level of key molecules in Wnt/β-catenin pathway was reduced in both obese groups, while the DT group was the lowest. Expression of adipocyte-specific genes was up-regulated during obese development in the two obese groups, while the DT group revealed more correlation than that of db/db group. At the protein level, a down regulation of Wnt10b and β-catenin in obese eWAT showed similar tendency with that of mRNA level. Compared with the lean groups, the levels of adiponectin and PPARγ2 for the obese groups were down-regulated at 21-day-old age, while they were elevated at older age. Our results suggested that deficiency in TNFα inhibited Wnt/β-catenin signaling of the obese eWAT and up-regulated expression of adipokines, and accelerated adipogenesis in genetic obese mice on a chow diet.
authors: Shandong Provincial Key Laboratory of Animal Resistant Biology, College of Life Sciences, Shandong Normal University, #88 East Wenhua Ave., Jinan, 250014, People's Republic of China.
authors: Maolei
authors: M
authors: Gong
authors: Chuanguo
authors: C
authors: Liu
authors: Liang
authors: L
authors: Zhang
authors: Hongbin
authors: H
authors: Zhang
authors: Jie
authors: J
authors: Pan
mesh_terms: D050156:Adipogenesis / Q000235:genetics; D052436:Adipose Tissue, White / Q000473:pathology; D000375:Aging / Q000473:pathology*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D004822:Epididymis / Q000473:pathology; D005786:Gene Expression Regulation; D005838:Genotype; D006706:Homeostasis; D007328:Insulin / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009765:Obesity / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D009929:Organ Size; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000172:deficiency* / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000235:genetics
chemical_list: D001786:Blood Glucose; D007328:Insulin; D008055:Lipids; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha