Raspberry seed flour attenuates high-sucrose diet-mediated hepatic stress and adipose tissue inflammation

Abstract

Chronic intake of high sucrose (HS) diet exacerbates high-fat (HF) diet-induced obesity and its associated metabolic complications. Previously, we have demonstrated that ellagic acid (EA), an abundant polyphenol found in some fruits and nuts, exerts distinct lipid-lowering characteristics in hepatocytes and adipocytes. In this study, we hypothesized that EA supplementation inhibits HS diet-mediated hepatic toxicity and its accompanied metabolic dysregulation. To test this hypothesis, C57BL/6 male mice were randomly assigned to three isocaloric HF diets (41% calories from fat) containing either no-sucrose (HF), high-sucrose (HFHS), or high-sucrose plus EA (HFHS-R) from raspberry seed flour (RSF, equivalent to 0.03% of EA), and fed for 12weeks. The inclusion of EA from RSF significantly improved HFHS diet-mediated dyslipidemia and restored glucose homeostasis levels similar to the HF diet-fed mice. Despite marginal difference in hepatic triglyceride content, the addition of EA substantially reversed the activation of endoplasmic reticulum (ER) stress and oxidative damage triggered by HFHS diet in the liver. These effects of EA were further confirmed in human hepatoma cells by reducing ER stress and reactive oxygen species (ROS) production. Moreover, HFHS-R diet significantly decreased visceral adipocyte hypertrophy and adipose tissue inflammation evidenced by reduced proinflammatory gene expression and macrophage infiltration. In summary, EA supplementation from RSF was effective in reducing HFHS diet-mediated metabolic complication by attenuating hepatic ER and oxidative stresses as well as adipocyte inflammation. Our results suggest that the inclusion of EA in diets may normalize metabolic insults triggered by HS consumption.

Raspberry Supplementation Improves Insulin Signaling and Promotes Brown‐Like Adipocyte Development in White Adipose Tissue of Obese Mice

“…WAT of obese subjects are in a state of chronic inflammation characterized by increased macrophage infiltration and enhanced cytokine production . RB seed flour supplementation reduced inflammatory response in WAT of high fat and sugar fed mice . Consistently, HFD enhanced macrophage infiltration, Mcp1 mRNA level and inflammatory response in IngWAT, which were restored by RB supplementation, which might be related to improved insulin sensitivity …”

Macronutrient Intake and Risk of Crohn’s Disease: Systematic Review and Dose–Response Meta-Analysis of Epidemiological Studies

“…In animal models, high consumption of dietary sucrose could induce the inflammation of multiple tissues [36,37,38]. Secondly, high intake of dietary sucrose could trigger endoplasmic reticulum (ER) stress which was also associated with the pathogenesis of Crohn’s disease [39,40].…”

Toxicological evaluation of Lafoensia pacari A. St.-Hil. (Lythraceae) stem bark extract: Acute and subchronic studies in mice

“…Furthermore, no change was observed in the expression of the Ki-67 cell proliferation indicator in the kidney or liver tissues, which suggests that LPE did not promote changes in the proliferative activity of these organs. Several studies have reported the protective effects of ellagic acid, the main active compound responsible for the biological effects of LPE, and of other Lythraceae family species on liver (Baravalia, Chanda, 2011;García-Niño, Zazueta, 2015;Kang et al, 2016;Salem et al, 2016) and kidney (Priya, Sabu, Jolly, 2007;Basha, Saumya, 2013; El-Garhy et al, 2014; Ayhanci et al, 2015) injuries triggered by xenobiotic-induced oxidative stress.…”