title: 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.
authors.affiliation: Department of Nutrition and Health Sciences at the University of Nebraska-Lincoln, Lincoln, NE, USA.
authors.forename: Inhae
authors.initials: I
authors.lastname: Kang
authors.affiliation: Department of Food Science and Technology, CEBAS-CSIC, Murcia, Spain.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Espín
authors.affiliation: Department of Nutrition and Health Sciences at the University of Nebraska-Lincoln, Lincoln, NE, USA.
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Carr
authors.affiliation: Department of Food Science and Technology, CEBAS-CSIC, Murcia, Spain.
authors.forename: Francisco A
authors.initials: FA
authors.lastname: Tomás-Barberán
authors.affiliation: Department of Nutrition and Health Sciences at the University of Nebraska-Lincoln, Lincoln, NE, USA. Electronic address: schung4@unl.edu.
authors.forename: Soonkyu
authors.initials: S
authors.lastname: Chung
mesh_terms: D050154:Adiposity; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000032:analysis / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D000975:Antioxidants / Q000032:analysis / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D045744:Cell Line, Tumor; D000070601:Diet, Carbohydrate Loading / Q000009:adverse effects; D059305:Diet, High-Fat / Q000009:adverse effects; D019422:Dietary Sucrose / Q000009:adverse effects; D019587:Dietary Supplements / Q000032:analysis; D004610:Ellagic Acid / Q000032:analysis / Q000378:metabolism / Q000627:therapeutic use; D059865:Endoplasmic Reticulum Stress; D006801:Humans; D050152:Intra-Abdominal Fat / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000209:etiology / Q000503:physiopathology; D018384:Oxidative Stress; D015434:Panniculitis / Q000178:diet therapy* / Q000209:etiology / Q000276:immunology / Q000378:metabolism; D011897:Random Allocation; D065856:Rubus / Q000737:chemistry*; D012639:Seeds / Q000737:chemistry; D013047:Specific Pathogen-Free Organisms
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D015415:Biomarkers; D019422:Dietary Sucrose; D004610:Ellagic Acid
keywords: Adipose inflammation; Ellagic acid; Hepatic stress; Obesity; Raspberry seed flour