Abstract
Raspberry ketone [4-(4-hydroxyphenyl)-2-butanone] is a natural aromatic compound found in raspberries and other fruits. Raspberry ketone (RK) is synthetically produced for use as a commercial flavoring agent. In the United States and other markets, it is sold as a dietary supplement for weight control. The potential of RK to reduce or prevent excessive weight gain is unclear and could be a convergence of several different actions. This study sought to determine whether acute RK can immediately delay carbohydrate hyperglycemia and reduce gastrointestinal emptying. In addition, we explored the metabolic signature of chronic RK to prevent or remedy the metabolic effects of diet-induced weight gain. In high-fat diet (HFD; 45% fat)-fed male mice, acute oral gavage of RK (200 mg/kg) reduced hyperglycemia from oral sucrose load (4 g/kg) at 15 min. In HFD-fed female mice, acute oral RK resulted in an increase in blood glucose at 30 min. Chronic daily oral gavage of RK (200 mg/kg) commencing with HFD access (HFD_RK) for 11 weeks resulted in less body weight gain and reduced fat mass compared with vehicle treated (HFD_Veh) and chronic RK starting 4 weeks after HFD access (HFD_RKw4) groups. Compared with a control group fed a low-fat diet (LFD; 10% fat) and dosed with vehicle (LFD_Veh), glucose AUC of an oral glucose tolerance test was increased with HFD_Veh, but not in HFD_RK or HFD_RKw4. Apelin (Apln) gene expression in epididymal white adipose tissue was increased in HFD_Veh, but reduced to LFD_Veh levels in the HFD_RK group. Peroxisome proliferator activated receptor alpha (Ppara) gene expression was increased in the hepatic tissue of HFD_RK and HFD_RKw4 groups. Overall, our findings suggest that long term daily use of RK prevents diet-induced weight gain, normalizes high-fat diet-induced adipose Apln, and increases hepatic Ppara expression.
Highlights
Raspberry ketone {RK; [4-(4-hydroxyphenyl)-2-butanone]} is a natural phenolic compound derived from red raspberries (Borejsza-Wysocki et al, 1992; Borejsza-Wysocki and Hrazdina, 1994)
To determine the weight gain prevention potential, we investigated the expression of genes related to inflammation, metabolism, and body weight homeostasis to determine the metabolic signature of RK for management of high-fat diet (HFD)-induced weight gain
Post hoc testing revealed that blood glucose in Acar was lower than in vehicle at 15 min (p < 0.05), and that RK dosing elevated blood glucose at 30 min compared with Acar and vehicle (p < 0.05 for both) (Figure 1C)
Summary
Raspberry ketone {RK; [4-(4-hydroxyphenyl)-2-butanone]} is a natural phenolic compound derived from red raspberries (Borejsza-Wysocki et al, 1992; Borejsza-Wysocki and Hrazdina, 1994). The notion that RK acts directly on white adipose tissue is supported by its rapid absorption (Tmax ∼ 15 min) and distribution into white adipose tissue following an acute oral gavage of RK (200 mg/kg) (Zhao D. et al, 2020). Another possible weight control mechanism for RK could be from actions on α-glucosidase. The potential effects of RK could be from several integrative actions to promote body weight control
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