title: Visfatin is involved in TNFα-mediated insulin resistance via an NAD(+)/Sirt1/PTP1B pathway in 3T3-L1 adipocytes.
abstract: Tumor necrosis factor α (TNFα) is a well-known mediator of inflammation in the context of obesity in adipose tissue. Its action appears to be directly linked to perturbations of the insulin pathway, leading to the development of insulin resistance. Visfatin has been suspected to be linked to insulin sensitivity, but the mechanism involved is still partly unknown. The aim of this study was to evaluate the role of visfatin in the impairment of the insulin pathway by TNFα activity in 3T3-L1 adipocytes and to unveil the mechanisms involved in such impairment. We demonstrated in 3T3-L1 adipocytes that visfatin was involved in TNFα-mediated insulin resistance in adipocytes. Indeed, after TNFα treatment in 3T3-L1 cells, visfatin was downregulated, leading to decreased nicotinamide adenine dinucleotide (NAD(+)) concentrations in cells. This decrease was followed by a decrease in Sirt1 activity, which was linked to an increase in PTP1B expression. The modulation of PTP1B by visfatin was likely responsible for the observed decreases in glucose uptake and Akt phosphorylation in 3T3-L1 adipocytes. Here, we demonstrated a complete pathway involving visfatin, NAD(+), Sirt1, and PTP1B that led to the perturbation of insulin signaling by TNFα in 3T3-L1 adipocytes.
authors: INRA; UMR1260; Marseille, France ; INSERM; UMR1062; "Nutrition, Obesity and Risk of Thrombosis"; Marseille, France ; Faculté de Médecine; Aix-Marseille University; Marseille, France.
authors: Erwan
authors: E
authors: Gouranton
authors: INRA; UMR1260; Marseille, France ; INSERM; UMR1062; "Nutrition, Obesity and Risk of Thrombosis"; Marseille, France ; Faculté de Médecine; Aix-Marseille University; Marseille, France.
authors: Béatrice
authors: B
authors: Romier
authors: INRA; UMR1260; Marseille, France ; INSERM; UMR1062; "Nutrition, Obesity and Risk of Thrombosis"; Marseille, France ; Faculté de Médecine; Aix-Marseille University; Marseille, France.
authors: Julie
authors: J
authors: Marcotorchino
authors: INRA; UMR1260; Marseille, France ; INSERM; UMR1062; "Nutrition, Obesity and Risk of Thrombosis"; Marseille, France ; Faculté de Médecine; Aix-Marseille University; Marseille, France.
authors: Franck
authors: F
authors: Tourniaire
authors: INRA; UMR1260; Marseille, France ; INSERM; UMR1062; "Nutrition, Obesity and Risk of Thrombosis"; Marseille, France ; Faculté de Médecine; Aix-Marseille University; Marseille, France.
authors: Julien
authors: J
authors: Astier
authors: INRA; UMR1260; Marseille, France ; INSERM; UMR1062; "Nutrition, Obesity and Risk of Thrombosis"; Marseille, France ; Faculté de Médecine; Aix-Marseille University; Marseille, France.
authors: Franck
authors: F
authors: Peiretti
authors: INRA; UMR1260; Marseille, France ; INSERM; UMR1062; "Nutrition, Obesity and Risk of Thrombosis"; Marseille, France ; Faculté de Médecine; Aix-Marseille University; Marseille, France.
authors: Jean-François
authors: JF
authors: Landrier
keywords: NAD; TNF; adipocytes; insulin resistance; sirtuin; visfatin