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            ‐Synephrine exhibits anti‐adipogenic activity by activating the Akt/GSK3β signaling pathway in 3T3‐L1 adipocytes

Guo, Lixia; Chen, Gang; Yin, Zhongyi; Zhang, Yonghong; Zheng, Xiangkuo

doi:10.1111/jfbc.13033

Cited by 16 publications

(12 citation statements)

References 37 publications

(48 reference statements)

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“…Lastly, p-synephrine suppresses the 3T3-L1 cell adipogenesis by reducing the expression level of CCAAT-enhancer-binding protein α (C/EBPα) and peroxisome proliferator-activated receptor γ (PPARγ), which subsequently leads to a reduction in the fatty acid-binding protein 4 (aP2) expression. Specifically, different treatments with p-synephrine activate the protein kinase B (PKB/Akt) pathway and sequentially inhibits glycogen synthase kinase 3β (GSK3β) activity [24]. The Akt signaling pathway plays a pivotal role in modulating adipogenesis while GSK3β is a crucial protein involved in cell signaling [25].…”

Section: Binding Capacity and Mechanisms Of Actionmentioning

confidence: 99%

Effects of p-Synephrine during Exercise: A Brief Narrative Review

et al. 2021

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The p-synephrine is the principal phytochemical found in bitter orange (Citrus aurantium). This substance is widely included in dietary supplements for weight loss/body fat reduction due to its potential benefits of increasing fat oxidation. For years, p-synephrine-containing dietary supplements have been marketed without proper knowledge of their true effectiveness to enhance fat utilization, especially when combined with exercise. However, the effects of p-synephrine on fat oxidation during exercise have been investigated in the last few years. The aim of the current discussion is to summarize the evidence on the effects of p-synephrine intake on fat oxidation and performance during exercise. Previous investigations have demonstrated that the acute intake of p-synephrine does not modify running sprint performance, jumping capacity, or aerobic capacity. However, the acute intake of p-synephrine, in a dose of 2–3 mg/kg of body mass, has been effective to enhance the rate of fat oxidation during incremental and continuous exercise. This effect has been observed in a range of exercise workloads between 30% and 80% of peak oxygen uptake (VO2peak). The p-synephrine has the ability to increase the maximal rate of fat oxidation during exercise of increasing intensity without affecting the workload at which maximal fat oxidation is obtained (Fatmax). The effect of p-synephrine on fat oxidation is normally accompanied by a concomitant reduction of carbohydrate utilization during exercise, without modifying the energy expended during exercise. The shifting in substrate oxidation is obtained without any effect on heart rate during exercise and the prevalence of adverse effects is negligible. Thus, the acute use of p-synephrine, or p-synephrine-containing products, might offer some benefits for those individuals seeking higher fat utilization during exercise at low to moderate intensities. However, more research is still necessary to determine if the effect of p-synephrine on fat oxidation during exercise is maintained with chronic ingestion, in order to ascertain the utility of this substance in conjunction with exercise programs to produce an effective body fat/weight loss reduction.

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Section: Binding Capacity and Mechanisms Of Actionmentioning

confidence: 99%

Effects of p-Synephrine during Exercise: A Brief Narrative Review

et al. 2021

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“…The Akt pathway and the extracellular signal-regulated kinase (ERK) 1/2 pathway are shown to be responsible for adipogenesis (14,15). The Akt is in a key position to promote insulin-like growth factor-1 expression and adipocyte differentiation, while Akt pathway inhibition is shown to reduce adipogenesis (16).…”

Section: Introductionmentioning

confidence: 99%

Alliin inhibits adipocyte differentiation by downregulating Akt expression: Implications for metabolic disease

Chen

Dong

et al. 2021

Exp Ther Med

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Obesity is currently an important health problem and is associated with an increased likelihood of various diseases. The efficacies of various natural treatments have been assessed for their utility in treating obesity. Alliin (S-allyl-L-cysteine sulfoxides) is considered the major component of garlic and has a wide range of natural antioxidant properties. However, the direct effects of alliin on obesity have not been well clarified. The present study investigated the effects and possible mechanisms of alliin on adipocyte differentiation. The 3T3-L1 cells were treated with alliin (0-40 µg/ml) during adipogenic differentiation. The effect of alliin on lipid accumulation was evaluated by Oil red O staining. Reverse transcription-quantitative PCR was performed to investigate the expression levels of adipogenic differentiation-related genes. The accumulation of lipid droplets was markedly inhibited following alliin treatment. The expression levels of multiple adipogenic transcription markers, such as CCAAT/enhancer-binding protein (C/EBP) β, C/EBP α and peroxisome proliferation-activity receptor γ, were markedly decreased following treatment with alliin during adipogenic differentiation. Expression levels of several adipocyte-related genes were subsequently suppressed. Additionally, alliin suppressed PKB/Akt and PI3K expression. These results suggested that alliin exhibits anti-adipogenic activity by downregulating major adipogenic differentiation-related genes and Akt/PI3K expression. Alliin may have a potential therapeutic effect on metabolic disease.

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“…However, anti-adipogenic effects examined in this study only focused on the protein expression of PPARγ, C/EBPα, and adiponectin [ 35 ]. In the same cell lines, p -synephrine at 10 µM exhibited a maximal inhibitory effect (26% reduction) on the formation of red-labeled lipid droplets via the regulation of Akt, glycogen synthase kinase 3β (GSK3β), β-catenin, PPARγ, C/EBPα, fatty acid-binding protein 4 (aP2), and glycogen synthase (GS) [ 34 ]. However, the detailed mechanisms underlying the anti-adipogenic effects of hispidulin and p -synephrine are not yet completely clear.…”

Section: Discussionmentioning

confidence: 99%

“…Subsequently, a mechanistic study was conducted to observe the changes in the levels of adipogenic marker proteins, including PPARγ and C/EBPα, which were highlighted by two previous studies on the effects of hispidulin or p -synephrine [ 34 , 35 ]. The anti-adipogenic effect of the combination of hispidulin and p -synephrine was accompanied by a decreased protein expression of PPARγ and C/EBPα.…”

Section: Discussionmentioning

confidence: 99%

“…Accumulated results demonstrate that hispidulin shows low or negligible toxicity in both in vitro and in vivo experimental models [ 31 , 32 , 33 ]. Recently, an in vitro study indicated that p -synephrine and hispidulin suppressed adipogenesis in 3T3-L1 adipocytes [ 34 , 35 ]. The agonists of the gamma-aminobutyric acid type A receptor (GABA A -R) expressed in adipose tissues have been shown to be valuable in the treatment of obesity [ 36 ].…”

Section: Introductionmentioning

confidence: 99%

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Combined Anti-Adipogenic Effects of Hispidulin and p-Synephrine on 3T3-L1 Adipocytes

et al. 2021

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Hispidulin is abundant in Arrabidaea chica, Crossostephium chinense, and Grindelia argentina, among others. p-Synephrine is the main phytochemical constituent of Citrus aurantium. It has been used in combination with various other phytochemicals to determine synergistic effects in studies involving human participants. However, there have been no reports comparing the anti-adipogenic effects of the combination of hispidulin and p-synephrine. The current study explores the anti-adipogenic effects of hispidulin alone and in combination with p-synephrine in a murine preadipocyte cell line, 3T3-L1. Co-treatment resulted in a greater inhibition of the formation of red-labeled lipid droplets than the hispidulin or p-synephrine-alone treatments. Co-treatment with hispidulin and p-synephrine also significantly inhibited adipogenic marker proteins, including Akt, mitogen-activated protein kinases, peroxisome proliferator-activated receptor gamma, CCAAT/enhancer-binding protein alpha, glucocorticoid receptor, and CCAAT/enhancer-binding protein β. Although further studies are required to assess the effects of each drug on pharmacokinetic parameters, a combination treatment with hispidulin and p-synephrine may be a potential alternative strategy for developing novel anti-obesity drugs.

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p ‐Synephrine exhibits anti‐adipogenic activity by activating the Akt/GSK3β signaling pathway in 3T3‐L1 adipocytes

Cited by 16 publications

References 37 publications

Effects of p-Synephrine during Exercise: A Brief Narrative Review

Effects of p-Synephrine during Exercise: A Brief Narrative Review

Alliin inhibits adipocyte differentiation by downregulating Akt expression: Implications for metabolic disease

Combined Anti-Adipogenic Effects of Hispidulin and p-Synephrine on 3T3-L1 Adipocytes

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