Beneficial effects of cherry consumption as a dietary intervention for metabolic, hepatic and vascular complications in type 2 diabetic rats

Abstract

BackgroundOxidative stress (OS) plays an important role in type 2 diabetes (T2D) pathogenesis and its complications. New therapies target natural antioxidants as an alternative and/or supplemental strategy to prevent and control them. Our previous chemical and biological studies highlighted the important antioxidant activities of cherries, among other fruits and vegetables, thus we aimed to determine in vivo effects of 2-month long cherry consumption using a high-fat/high-fructose (HFHF) model of diabetic-rats (Lozano et al. in Nutr Metab 13:15, 2016).MethodsAfter 2 months of HFHF, male Wistar rats were divided into: HFHF and HFHF enriched in cherry (nutritional approach) or standard diet ND (lifestyle measures) and ND plus cherry during 2 months. Metabolic, lipidic, oxidative parameters were quantified. Tissues (liver, pancreas and vessels) OS were assessed and hepatic (steatosis, fibrosis, inflammation) and vascular (endothelial dysfunction) complications were characterized.ResultsT2D was induced after 2 months of HFHF diet, characterized by systemic hyperglycaemia, hyperinsulinemia, glucose intolerance, dyslipidaemia, hyperleptinemia, and oxidative stress associated with endothelial dysfunction and hepatic complications. Cherry consumption for 2 months, in addition to lifestyle measures, in T2D-rats decreased and normalized the systemic disturbances, including oxidative stress complications. Moreover, in the vessel, cherry consumption decreased oxidative stress and increased endothelial nitric oxide (NO) synthase levels, thus increasing NO bioavailability, ensuring vascular homeostasis. In the liver, cherry consumption decreased oxidative stress by inhibiting NADPH oxidase subunit p22phox expression, nuclear factor erythroid-2 related factor 2 (Nrf2) degradation and the formation of reactive oxygen species. It inhibited the activation of sterol regulatory element-binding proteins (1c and 2) and carbohydrate-responsive element-binding protein, and thus decreased steatosis as observed in T2D rats. This led to the improvement of metabolic profiles, together with endothelial and hepatic function improvements.ConclusionCherry consumption normalized vascular function and controlled hepatic complications, thus reduced the risk of diabetic metabolic disorders. These results demonstrate that a nutritional intervention with a focus on OS could prevent and/or delay the onset of vascular and hepatic complications related to T2D.Electronic supplementary materialThe online version of this article (10.1186/s12933-018-0744-6) contains supplementary material, which is available to authorized users.

Diet‐induced rodent models of obesity‐related metabolic disorders—A guide to a translational perspective

“…It is generally assumed that the criteria used for rats are closest to those used for humans, namely, FBG > 126 mg/dl (7.0 mmol/L). 158,159 In contrast, the basal levels of FBG in mice are higher than those in rats and humans (ranging between 140 and 220 mg/dl), indicating that according to the aforementioned criteria, all mice would develop diabetes. Hence, FBG values ≥250 mg/dl is the recommended threshold for defining T2DM in mice.…”

Proteomic analysis of liver mitochondria of db/db mice treated with grape seed procyanidin B2

“…Although several pathways of diabetic hepatic lesions have been identified, oxidative stress, and ROS production are still the main cause. Antioxidant therapy might be an effective treatment for ameliorating diabetic hepatic damage (Polce et al., 2018; Simões et al., 2013; Van der Werf et al., 2018).…”

High-Fructose Diet-Induced Metabolic Disorders Were Counteracted by the Intake of Fruit and Leaves of Sweet Cherry in Wistar Rats

“…The addition of fruit and leaves to the HFr diet also caused improvement of the lipid profile in the serum (Table 2). Der Werf et al [13] observed the beneficial effect of consumption of sweet cherry fruit in rats fed with high-fat/high-fructose diet, i.e., decrease in the hepatic lipid accumulation, as well as reduction in cholesterol and triglycerides level in the serum. We suppose that the bioactive compounds contained in fruit and leaves of sweet cherry (dietary fiber, carotenoids, polyphenols) [15,16] can be responsible for this effect.…”

“…Gibert-Ramos et al [37], who assessed the effect of sweet cherry fruit on lipid metabolism and fat accumulation in Fischer rats treated with 1:1 glucose:fructose solution in water, have also observed that intake of fruit downregulated the expression of Fasn and Acaca in the adipose tissue. Der Werf et al [13] have shown that the addition of fruit to high-fat/high-fructose diet caused the reduction in hepatic lipogenic transcription factors: ChREBP ( Mlxipl) and Srebp . We suppose, that anthocyanins contained in fruit may be responsible for this activity.…”

“…The taste, color of the skin, and the content of numerous nutrients and phytochemicals make them attractive to consumers [11]. Literature data have indicated beneficial effect of these fruits on disorders related to non-communicable diseases, among other on lipid metabolism and inflammation [12,13,14]. Our previous studies revealed that not only fruit but also by-product-leaves, unused until now, are a rich source of bioactive compounds and exhibit a high antioxidant activity [15,16].…”