Beneficial Effect of a Multistrain Synbiotic Prodefen ® Plus on the Systemic and Vascular Alterations Associated with Metabolic Syndrome in Rats : The Role of the Neuronal Nitric Oxide Synthase and Protein Kinase A

Abstract

This research was funded by Italfarmaco, S.A (L.O.U. 83; 0138/2018), CiberCV (Grant number: CB16/11/00286), the European Regional Development Grant (FEDER) (Comunidad de Madrid, Grant number B2017/BMD-3676), and R + D projects for young researchers, Universidad Autónoma de Madrid (Comunidad de Madrid (SI1-PJI-2019-00321). R.R.-D. received a fellowship from Juan de la Cierva Program (IJCI-2017-31399).

Altres ajuts: FEDER/B2017/BMD-3676

Altres ajuts: UAM/SI1-PJI-2019-00321

Altres ajuts: JCP/IJCI-2017-31399

A high fat diet (HFD) intake is crucial for the development and progression of metabolic syndrome (MtS). Increasing evidence links gut dysbiosis with the metabolic and vascular alterations associated with MtS. Here we studied the use of a combination of various probiotic strains together with a prebiotic (synbiotic) in a commercially available Prodefen ® Plus. MtS was induced by HFD (45%) in male Wistar rats. Half of the MtS animals received Prodefen ® Plus for 4 weeks. At 12 weeks, we observed an increase in body weight, together with the presence of insulin resistance, liver steatosis, hypertriglyceridemia and hypertension in MtS rats. Prodefen ® Plus supplementation did not affect the body weight gain but ameliorated all the MtS-related symptoms. Moreover, the hypertension induced by HFD is caused by a diminished both nitric oxide (NO) functional role and release probably due to a diminished neuronal nitric oxide synthase (nNOS) activation by protein kinase A (PKA) pathway. Prodefen ® Plus supplementation for 4 weeks recovered the NO function and release and the systolic blood pressure was returned to normotensive values as a result. Overall, supplementation with Prodefen ® Plus could be considered an interesting non-pharmacological approach in MtS.