Résumé
Abstract only Obesity is tightly associated with insulin resistance (IR) and endothelial dysfunction. It is suggested that hepatic IR is sufficient to promote progression to cardiovascular disease. We showed recently that specific deletion of liver PTP1B (L‐PTP1B), a negative regulator of insulin receptor, improves whole body glucose and lipid homeostasis. Thus, we propose to investigate the impact of these improvements in L‐PTP1B −/− mice, on cardiovascular function in the context of diet‐induced obesity. We analyzed glucose tolerance, blood pressure, cardiac and vascular function, in L‐PTP1B −/− and control mice, fed a chow or high fat diet (HFD). Compared to control littermates, L‐PTP1B −/− mice had improved glucose and lipid homeostasis without changes in body mass. HFD feeding increased systolic blood pressure in both mouse groups; however, it was lower in L‐PTP1B −/− mice. Structure and function analysis of the left ventricle showed that HFD‐feeding decreased cardiac index in control mice, while L‐PTP1B −/− mice were fully protected. HFD feeding significantly impaired endothelium‐dependent relaxation in response to acetylcholine in aortas taken from control mice compared to chow diet‐fed mice, while L‐PTP1B −/− mice were protected. Altogether, these data indicate that targeting L‐PTP1B may be useful to reduce obesity‐associated cardiovascular risk in addition to diabetes.