Raspberry Ketone [4-(4-Hydroxyphenyl)-2-Butanone] Differentially Effects Meal Patterns and Cardiovascular Parameters in Mice

Abstract

Raspberry ketone (RK; [4-(4-hydroxyphenyl)-2-butanone]) is a popular nutraceutical used for weight management and appetite control. We sought to determine the physiological benefits of RK on the meal patterns and cardiovascular changes associated with an obesogenic diet. In addition, we explored whether the physiological benefits of RK promoted anxiety-related behaviors. Male and female C57BL/6J mice were administered a daily oral gavage of RK 200 mg/kg, RK 400 mg/kg, or vehicle for 14 days. Commencing with dosing, mice were placed on a high-fat diet (45% fat) or low-fat diet (10% fat). Our results indicated that RK 200 mg/kg had a differential influence on meal patterns in males and females. In contrast, RK 400 mg/kg reduced body weight gain, open-field total distance travelled, hemodynamic measures (i.e., reduced systolic blood pressure (BP), diastolic BP and mean BP), and increased nocturnal satiety ratios in males and females. In addition, RK 400 mg/kg increased neural activation in the nucleus of the solitary tract, compared with vehicle. RK actions were not influenced by diet, nor resulted in an anxiety-like phenotype. Our findings suggest that RK has dose-differential feeding and cardiovascular actions, which needs consideration as it is used as a nutraceutical for weight control for obesity.

Reduced Body Fat and Epididymal Adipose Apelin Expression Associated With Raspberry Ketone [4-(4-Hydroxyphenyl)-2-Butanone] Weight Gain Prevention in High-Fat-Diet Fed Mice

“…A generalized interpretation of our study is limited, because our long-term dosing experiments were performed in male mice only. Previous short-term (14 days) studies demonstrate reduced HFD-induced weight gain with oral RK (400 mg/kg) in males but not in females ( Kshatriya et al, 2020 ). In addition, there was a dose-dependent sex difference of RK on meal patterns and sex-dependent difference in bioavailability following oral RK administration ( Kshatriya et al, 2020 ; Zhao D. et al, 2020 ).…”

“…Previous short-term (14 days) studies demonstrate reduced HFD-induced weight gain with oral RK (400 mg/kg) in males but not in females (Kshatriya et al, 2020). In addition, there was a dose-dependent sex difference of RK on meal patterns and sex-dependent difference in bioavailability following oral RK administration (Kshatriya et al, 2020;Zhao D. et al, 2020). Nonetheless, the sex-dependent effects of the long-term oral administration of RK on weight gain prevention and treatment remains to be determined.…”

“…This study was designed to evaluate the in vivo potential of RK for prevention and treatment of HFD-induced body weight gain. Based on our previous studies on C57Bl/6J mice ( Kshatriya et al, 2019 , 2020 ; Hao et al, 2020 ; Zhao D. et al, 2020 ), the oral dose of RK that achieves effective prevention of body weight gain without any evidence of toxicity is 200 mg/kg ( Hao et al, 2020 ). To further identify the mechanism for weight gain prevention, the 200 mg/kg dose was used to determine the acute converging effects of weight gain prevention and the metabolic signature of long-term (>10 weeks) administration.…”

“…Several in vitro studies have shown that RK has effects on fat metabolism by suppressing pre-adipocyte differentiation and fat accumulation, increasing lipolysis, and increasing fat oxidation ( Park, 2010 , 2015 ; Leu et al, 2017 , 2018 ; Tsai et al, 2017 ). Previous studies have demonstrated that oral RK administered coincidently with access to a high-fat diet (HFD) for 2–10 weeks prevents diet-induced weight gain and adiposity in mice ( Morimoto et al, 2005 ; Kshatriya et al, 2019 , 2020 ). 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 ).…”

Sex-Specific Effects on Total Body Fat Gain with 4-Week Daily Dosing of Raspberry Ketone [4-(4-Hydroxyphenyl)-2-butanone] and Ketogenic Diet in Mice

“…In recent years, RK has been marketed as a dietary supplement for weight loss [ 4 ]. However, rodent studies have shown that RK prevents body weight gain, suppresses fat accumulation, and increases fat oxidation and lipolysis, suggesting a potential to maintain weight loss [ 5 , 6 , 7 , 8 , 9 , 10 ]. Furthermore, in vitro and in silico enzyme kinetics studies suggest that RK may act as an α-glucosidase inhibitor to inhibit carbohydrate hydrolysis and potentially reduce postprandial blood glucose levels [ 11 ].…”