Beneficial effects of murtilla extract and madecassic acid on insulin sensitivity and endothelial function in a model of diet-induced obesity

Abstract

Infusions of murtilla leaves exhibit antioxidant, analgesic, and anti-inflammatory properties. Several compounds that are structurally similar to madecassic acid (MA), a component of murtilla leaf extract (ethyl acetate extract, EAE), have been shown to inhibit protein tyrosine phosphatase 1B (PTP1P). The aim of this study was to evaluate if EAE and two compounds identified in EAE (MA and myricetin [MYR]) could have a beneficial effect on systemic and vascular insulin sensitivity and endothelial function in a model of diet-induced obesity. Experiments were performed in 5-week-old male C57BL6J mice fed with a standard (LF) or a very high-fat diet (HF) for 4 weeks and treated with EAE, MA, MYR, or the vehicle as control (C). EAE significantly inhibited PTP1B. EAE and MA, but not MYR, significantly improved systemic insulin sensitivity in HF mice and vascular relaxation to Ach in aorta segments, due to a significant increase of eNOS phosphorylation and enhanced nitric oxide availability. EAE, MA, and MYR also accounted for increased relaxant responses to insulin in HF mice, thus evidencing that the treatments significantly improved aortic insulin sensitivity. This study shows for the first time that EAE and MA could constitute interesting candidates for treating insulin resistance and endothelial dysfunction associated with obesity.

Differential Deleterious Impact of Highly Saturated Versus Monounsaturated Fat Intake on Vascular Function, Structure, and Mechanics in Mice

“…One of the major findings of this study is that UOLF, and not only SOLF and HF diet, impairs endothelial function after 8 weeks of diet. This result supports other studies showing a deleterious effect of SFA-enriched diets [37], manufactured either from animal (mainly lard) [3,26,27] or vegetable sources [13], on endothelial function. However, endothelial dysfunction displayed by UOLF animals was surprising, since a beneficial effect of olive oil-enriched diets has been reported by Herrera et al [15].…”

“…Another interesting finding in the current study is the significant reduction of contractile responses to Phe detected in SOLF, UOLF, and HF mice, which has been previously described in mice fed a 62% fat HF diet for only 4 weeks [ 26 ]. This could be due to alterations in alpha-1 receptor function, as suggested by Juarez et al [ 41 ], though further studies are required to better address this matter.…”

“…Numerous studies performed in mice/rat models of diet-induced obesity (DIO) [ 3 , 26 , 27 , 28 ] as well as in humans with obesity [ 29 , 30 , 31 ] have demonstrated a link between excessive energy intake and the development of endothelial dysfunction and arterial stiffness [ 7 , 32 , 33 , 34 , 35 , 36 ]. However, though most of these alterations have been generally attributed to an excessive intake of SFA [ 11 , 13 , 37 , 38 ], the net contribution of different fatty acid types to obesity-derived vascular alterations remains to be clarified.…”

C21 preserves endothelial function in the thoracic aorta from DIO mice: role for AT2, Mas and B2 receptors

“…Pathological conditions shared in the etiology of these diseases are vascular alterations including endothelial dysfunction, decreased vascular compliance and reduced blood flow, among others 2 . In this context, our group and others have demonstrated the deleterious effects of HFD intake and human morbid obesity on vascular disorders such as arterial stiffness and endothelial dysfunction associated with a reduced NO availability and AMPK activity together with an increase in oxidative stress [3][4][5][6][7] .…”

Ursolic Acid and Related Analogues: Triterpenoids with Broad Health Benefits

“…Daily i.p. injections of MA (20 mg/kg, daily) in 5-week-old male C57BL6J mice fed a HFD for 4 weeks, significantly improved systemic insulin sensitivity [ 147 ]. MA also restored vascular relaxation and increased NO bioavailability in these mice through AKT and eNOS phosphorylation.…”