Phenolic-enriched raspberry fruit extract (Rubus idaeus) resulted in lower weight gain, increased ambulatory activity, and elevated hepatic lipoprotein lipase and heme oxygenase-1 expression in male mice fed a high-fat diet

Nutr Res. 2019 Aug;68:19-33. doi: 10.1016/j.nutres.2019.05.005. Epub 2019 May 23.


Red raspberries (Rubus idaeus) contain numerous phenolic compounds with purported health benefits. Raspberry ketone (4-(4-hydroxyphenyl)-2-butanone) is a primary raspberry flavor phenolic found in raspberries and is designated as a synthetic flavoring agent by the Food and Drug Administration. Synthetic raspberry ketone has been demonstrated to result in weight loss in rodents. We tested whether phenolic-enriched raspberry extracts, compared with raspberry ketone, would be more resilient to the metabolic alterations caused by an obesogenic diet. Male C57BL/6J mice (8 weeks old) received a daily oral dose of vehicle (VEH; 50% propylene glycol, 40% water, and 10% dimethyl sulfoxide), raspberry extract low (REL; 0.2 g/kg), raspberry extract high (REH; 2 g/kg), or raspberry ketone (RK; 0.2 g/kg). Coincident with daily dosing, mice were placed on a high-fat diet (45% fat). After 4 weeks, REH and RK reduced body weight gain (approximately 5%-9%) and white adipose mass (approximately 20%) compared with VEH. Hepatic gene expression of heme oxygenase-1 and lipoprotein lipase was upregulated in REH compared with VEH. Indirect calorimetry indicated that respiratory exchange ratio (CO2 production to O2 consumption) was lower, suggesting increased fat oxidation with all treatments. REH treatment increased total ambulatory behavior. Energy expenditure/lean mass was higher in REH compared with REL treatment. There were no treatment differences in cumulative intake, meal patterns, or hypothalamic feed-related gene expression. Our results suggest that raspberry ketone and a phenolic-enriched raspberry extract both have the capacity to prevent weight gain but differ in the preventative mechanisms for excess fat accumulation following high-fat diet exposure.

Keywords: Adiponectin; Dietary supplements; Ellagitannin; Frambinone; Ghrelin; Phenolic acids; Sanguiin H-6.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Body Composition / drug effects
  • Butanones / administration & dosage
  • Diet, High-Fat / adverse effects
  • Eating
  • Fruit / chemistry*
  • Gene Expression Regulation / drug effects
  • Heme Oxygenase-1 / genetics
  • Heme Oxygenase-1 / metabolism*
  • Lipoprotein Lipase / genetics
  • Lipoprotein Lipase / metabolism*
  • Liver / enzymology
  • Male
  • Mice
  • Oxygen Consumption / drug effects
  • Phenols / administration & dosage*
  • Physical Conditioning, Animal
  • Plant Extracts / administration & dosage
  • Rubus / chemistry*
  • Weight Gain / drug effects*


  • Butanones
  • Phenols
  • Plant Extracts
  • raspberry ketone
  • Heme Oxygenase-1
  • Lipoprotein Lipase