Raspberry seed flour attenuates high-sucrose diet-mediated hepatic stress and adipose tissue inflammation.
Study Goal
The researchers aimed to determine whether ellagic acid (EA) supplementation could mitigate high-sucrose diet-induced hepatic toxicity and metabolic dysregulation.
Results Summary
EA supplementation improved dyslipidemia, restored glucose homeostasis, reduced hepatic ER stress and oxidative damage, and decreased visceral adipocyte hypertrophy and adipose tissue inflammation.
Population
C57BL/6 male mice and human hepatoma cells.
Effective Dosage
Equivalent to 0.03% of EA from raspberry seed flour.
Duration
12 weeks.
Interactions
None mentioned.
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
Chronic intake of high sucrose (HS) diet | increase | high-fat (HF) diet-induced obesity and its associated metabolic complications | - | - | exacerbates | #1 |
ellagic acid (EA) | decrease | lipid levels | hepatocytes and adipocytes | - | exerts distinct lipid-lowering characteristics | #2 |
EA supplementation | decrease | HS diet-mediated hepatic toxicity and its accompanied metabolic dysregulation | - | - | inhibits | #3 |
EA from RSF | decrease | HFHS diet-mediated dyslipidemia | C57BL/6 male mice | - | significantly improved | #4 |
EA from RSF | increase | glucose homeostasis levels | C57BL/6 male mice | similar to the HF diet-fed mice | restored | #5 |
EA | decrease | activation of endoplasmic reticulum (ER) stress and oxidative damage triggered by HFHS diet in the liver | C57BL/6 male mice | - | substantially reversed | #6 |
EA | decrease | ER stress and reactive oxygen species (ROS) production | human hepatoma cells | - | reducing | #7 |
HFHS-R diet | decrease | visceral adipocyte hypertrophy and adipose tissue inflammation | C57BL/6 male mice | - | significantly decreased | #8 |
HFHS-R diet | decrease | proinflammatory gene expression and macrophage infiltration | C57BL/6 male mice | - | reduced | #9 |
EA supplementation from RSF | decrease | HFHS diet-mediated metabolic complication | - | - | effective in reducing | #10 |
EA supplementation from RSF | decrease | hepatic ER and oxidative stresses as well as adipocyte inflammation | - | - | attenuating | #11 |
inclusion of EA in diets | decrease | metabolic insults triggered by HS consumption | - | - | may normalize | #12 |
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.