Heme oxygenase-1 mediates anti-adipogenesis effect of raspberry ketone in 3T3-L1 cells

Tsai, Yao‐Chou; Yang, Bo-Cheng; Peng, Wen-Huang; Lee, Yen-Mei; Yen, Mao‐Hsiung; Cheng, Pao-Yun

doi:10.1016/j.phymed.2017.05.005

Cited by 30 publications

(19 citation statements)

References 31 publications

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“…Raspberry ketone, 4-(4-hydroxyphenyl) butan-2-one, a phenolic compound found in red raspberry, has emerged as a dietary bioactive compound with beneficial effects on obesity (Cotten et al, 2017; Tsai et al, 2017). Evidence suggests that raspberry ketone reduces body weight and food intake in high-fat diet-fed mice (Cotten et al, 2017) and ovariectomy-induced obese rats (Leu et al, 2017).…”

Section: Autophagy Manipulations In Adipocyte Browningmentioning

confidence: 99%

“…Evidence suggests that raspberry ketone reduces body weight and food intake in high-fat diet-fed mice (Cotten et al, 2017) and ovariectomy-induced obese rats (Leu et al, 2017). In addition, raspberry ketone inhibits 3T3-L1 adipogenesis, revealed by inhibition of expression of adipogenesis markers such as PPAR-γ, C/EBP-α, FAS, and AP2, possibly via inhibition of autophagy, confirmed by decrease of ATG12 and LC3B levels, as well as increase of p62 and mTORC1 levels (Leu et al, 2017; Tsai et al, 2017). It has been recently reported that high concentration of raspberry ketone (100 μM) significantly increases browning of 3T3-L1 adipocytes, revealed by an increase of browning-specific markers, including UCP1 and PGC1α, and lipolysis markers such as hormone-sensitive lipase and triglyceride lipase (Leu et al, 2018).…”

Section: Autophagy Manipulations In Adipocyte Browningmentioning

confidence: 99%

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Autophagy in Adipocyte Browning: Emerging Drug Target for Intervention in Obesity

Jang

Bae

et al. 2019

Front. Physiol.

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Autophagy, lipophagy, and mitophagy are considered to be the major recycling processes for protein aggregates, excess fat, and damaged mitochondria in adipose tissues in response to nutrient status-associated stress, oxidative stress, and genotoxic stress in the human body. Obesity with increased body weight is often associated with white adipose tissue (WAT) hypertrophy and hyperplasia and/or beige/brown adipose tissue atrophy and aplasia, which significantly contribute to the imbalance in lipid metabolism, adipocytokine secretion, free fatty acid release, and mitochondria function. In recent studies, hyperactive autophagy in WAT was observed in obese and diabetic patients, and inhibition of adipose autophagy through targeted deletion of autophagy genes in mice improved anti-obesity phenotypes. In addition, active mitochondria clearance through activation of autophagy was required for beige/brown fat whitening – that is, conversion to white fat. However, inhibition of autophagy seemed detrimental in hypermetabolic conditions such as hepatic steatosis, atherosclerosis, thermal injury, sepsis, and cachexia through an increase in free fatty acid and glycerol release from WAT. The emerging concept of white fat browning–conversion to beige/brown fat–has been controversial in its anti-obesity effect through facilitation of weight loss and improving metabolic health. Thus, proper regulation of autophagy activity fit to an individual metabolic profile is necessary to ensure balance in adipose tissue metabolism and function, and to further prevent metabolic disorders such as obesity and diabetes. In this review, we summarize the effect of autophagy in adipose tissue browning in the context of obesity prevention and its potential as a promising target for the development of anti-obesity drugs.

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Section: Autophagy Manipulations In Adipocyte Browningmentioning

confidence: 99%

Section: Autophagy Manipulations In Adipocyte Browningmentioning

confidence: 99%

Autophagy in Adipocyte Browning: Emerging Drug Target for Intervention in Obesity

Jang

Bae

et al. 2019

Front. Physiol.

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“…A few studies reveal the efficacy of RK in the prevention of fat accumulation. RK has been shown to reduce lipid accumulation and alter expression of lipolytic and adipogenic genes in 3T3-L1 adipocytes [ 10 , 11 , 12 , 13 , 14 ]. Further, it can increase fat oxidation in vitro and the effect may be mediated by heme oxygenase-1 and brown-like adipocyte formation [ 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

“…RK has been shown to reduce lipid accumulation and alter expression of lipolytic and adipogenic genes in 3T3-L1 adipocytes [ 10 , 11 , 12 , 13 , 14 ]. Further, it can increase fat oxidation in vitro and the effect may be mediated by heme oxygenase-1 and brown-like adipocyte formation [ 13 , 14 ]. RK mitigated ovariectomy-induced weight gain [ 12 , 14 ], and reduced high-fat diet induced nonalcoholic steatohepatitis in rats [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

“…In addition, RK and metabolites were detected in the brain and white adipose tissue of normal weight and diet-induced obese mice [ 27 ]. While there is accumulating evidence that RK has direct actions in adipose tissue [ 10 , 11 , 13 ], the ability of RK to activate brain areas involved in feeding and cardiovascular control has not been explored. One central site that overlaps to regulate these two physiological systems, is the nucleus of the solitary tract (NTS) in the caudal hindbrain [ 28 , 29 , 30 ].…”

Section: Introductionmentioning

confidence: 99%

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

2020

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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.

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Indigo Formation and Rapid NADPH Consumption Provide Robust Prediction of Raspberry Ketone Synthesis by Engineered Cytochrome P450 BM3

et al. 2019

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Natural raspberry ketone has a high value in the flavor, fragrance and pharmaceutical industries. Its extraction is costly, justifying the search for biosynthetic routes. We hypothesized that cytochrome P450 BM3 (P450 BM3) could be engineered to catalyze the hydroxylation of 4-phenyl-2-butanone, a naturally sourceable precursor, to raspberry ketone. The synthesis of indigo by variants of P450 BM3 has previously served as a predictor of promiscuous oxidation reactions. To this end, we screened 53 active-site variants of P450 BM3 using orthogonal high-throughput workflows to identify the most streamlined route to all indigo-forming variants. Among the three known and 13 new indigo-forming variants, eight hydroxylated 4-phenyl-2-butanone to raspberry ketone. Previously unreported variant A82Q displayed the highest initial rates and coupling efficiencies in synthesis of indigo and of raspberry ketone. It produced the highest total concentration of raspberry ketone despite producing less total indigo than previously reported variants. Its productivity, although modest, clearly demonstrates the potential for development of a biocatalytic route to raspberry ketone. In addition to validating indigo as a robust predictor of this promiscuous activity, we demonstrate that monitoring rapid NADPH consumption serves as an alternative predictor of a promiscuous reactivity in P450 BM3.

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Heme oxygenase-1 mediates anti-adipogenesis effect of raspberry ketone in 3T3-L1 cells

Cited by 30 publications

References 31 publications

Autophagy in Adipocyte Browning: Emerging Drug Target for Intervention in Obesity

Autophagy in Adipocyte Browning: Emerging Drug Target for Intervention in Obesity

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

Indigo Formation and Rapid NADPH Consumption Provide Robust Prediction of Raspberry Ketone Synthesis by Engineered Cytochrome P450 BM3

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