Modulation of Adipocyte Differentiation and Proadipogenic Gene Expression by Sulforaphane, Genistein, and Docosahexaenoic Acid as a First Step to Counteract Obesity

Valli, Veronica; Heilmann, Katharina; Danesi, Francesca; Bordoni, Alessandra; Gerhäuser, Clarissa

doi:10.1155/2018/1617202

Cited by 30 publications

(15 citation statements)

References 42 publications

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“…This is evidenced by an increasing number of studies that utilize this model to screen for anti-obesity properties of plant extracts and their natural products [14,27]. During the differentiation of 3T3-L1 pre-adipocytes, the changes in cell size and number are known to be regulated by adipogenic transcription factors, including CCAAT/enhancer binding protein (C/EBPs) and PPARγ [28]. These transcription factors are known to promote adipogenesis in various cell models of obesity, as reviewed elsewhere [29].…”

Section: Discussionmentioning

confidence: 99%

Impact of Isoorientin on Metabolic Activity and Lipid Accumulation in Differentiated Adipocytes

et al. 2020

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The current study explored the effect of isoorientin on the metabolic activity and lipid accumulation in fully differentiated 3T3-L1 adipocytes. To achieve this, the 3T3-L1 pre-adipocytes were differentiated for eight days and treated with various concentrations of isoorientin (0.1–100 μM) for four hours. Subsequently, the metabolic activity, lipid accumulation, and mitochondrial respiration were assessed. Furthermore, to unravel the molecular mechanisms that might elucidate the bioactivity of isoorientin, protein expression of the genes involved in insulin signaling and energy expenditure, such as AKT and AMPK, were investigated. The results showed that isoorientin, at different doses, could block lipid storage and enhance glycerol release, with a concomitant improvement of the metabolic activity and mitochondrial function. Although the observed beneficial effects of isoorientin on these cultured 3T3-L1 adipocytes were not consistent at all concentrations, it was clear that doses between 1 and 10 μM were most effective compared to the untreated control. Moreover, the activity of isoorientin was comparable to tested positive controls of CL-316,2431, isoproterenol, insulin, and metformin. Mechanistically, protein expression of AKT and AMPK, was enhanced with isoorientin exposure, suggesting their partial role in modulating lipid metabolism and mitochondrial biogenesis. Indeed, our results showed that isoorientin has the ability to enhance mitochondrial respiration, as we observed an increase in the ATP and oxygen consumption rate. Therefore, we concluded that isoorientin has a potential to impact mitochondrial activity, lipid metabolism and energy expenditure using an in vitro experimental model of obesity.

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Section: Discussionmentioning

confidence: 99%

Impact of Isoorientin on Metabolic Activity and Lipid Accumulation in Differentiated Adipocytes

et al. 2020

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“…21,114,115 Several studies revealed that flavonoids (Table 2), either alone or in combination, suppressed adipocyte differentiation and adipogenesis through mechanisms involving the reduction of PPARγ, C/EBPα, C/EBPβ, and SREBP-1c transcription, as well as related pathways. Genistein alone, 93,129,132,[136][137][138] or in combination with guggulsterone, 133 as well as naringenin, 138,157,158 luteolin, 93 hesperidin, 93 rutin, 170 kaempferol, 93,141,142,152 and myricetin 145,146 suppressed adipocyte differentiation and adipogenesis, as well as lipid accumulation through the downregulation of either early-and/or late-stage transcription factors in 3T3-L1 adipocytes (see Table 2). Furthermore, in HFD-obese mice, myricetin, 149 cyanidin, 94 rutin, 171 and eriodyctiol 123 decreased adipocyte hypertrophy and lipid accumulation through the downregulation of PPARγ and/or C/EBPα and SREBP-1c.…”

Section: The Role Of Flavonoids In Adipogenesis Modulationmentioning

confidence: 99%

Flavonoids as antiobesity agents: A review

Rufino

Costa

Carvalho

et al. 2020

Medicinal Research Reviews

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Obesity is a global health problem that affects all age groups in both developing and developed countries. In recent years, the prevalence of overweight and obesity has reached pandemic levels, resulting in a dramatic increase in the incidence of various comorbidities, such as cardiovascular diseases, type 2 diabetes, and cancer, consequently leading to massive health and socioeconomic burdens. Together with lifestyle changes, antiobesity pharmacotherapy is gaining momentum as an adjunctive treatment. However, the available pharmacological approaches have limited use owing to either significant adverse effects or low efficacy. Over the years, natural products have been an important source of lead compounds for drug discovery. Among these, flavonoids are associated with important biological effects and health‐promoting activities. In this review, we discuss the modulatory effects of flavonoids on obesity and their potential mechanisms of action. The literature strongly suggests that most common flavonoids demonstrate a pronounced effect on obesity as shown by their ability to lower body weight, fat mass, and plasma triglycerides/cholesterol, both in in vitro and in vivo models. The impact of flavonoids on obesity can be observed through different mechanisms: reducing food intake and fat absorption, increasing energy expenditure, modulating lipid metabolism, or regulating gut microbiota profile. A better understanding of the known antiobesity mechanisms of flavonoids will enable their potential use to treat this medical condition. Therefore, this review focuses on the putative biological mechanisms through which flavonoids may prevent or treat obesity and highlights new perspectives on future pharmacological use.

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“…Several studies have reported the biochemical pathways activated by genistein and the mode of action of genistein in cell lines and animal models and its potential regarding HRT [12]. Genistein elicits its actions by targeting various enzymes, such as topoisomerase I and II [13], ERs [14], ATP-binding cassette (ABC) transporters [15], protein tyrosine kinases (PTK) [16], peroxisome proliferator-activated receptor-gamma (PPAR-γ) [17,18], mitogen-activated protein kinase (MAPK) A [19], 5α-reductase [20], and protein histidine kinase [21], among others.…”

Section: Genistein and Its Therapeutic Effectsmentioning

confidence: 99%

Genistein as Potential Therapeutic Candidate for Menopausal Symptoms and Other Related Diseases

et al. 2019

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Plant-derived compounds have recently attracted greater interest in the field of new therapeutic agent development. These compounds have been widely screened for their pharmacological effects. Polyphenols, such as soy-derived isoflavones, also called phytoestrogens, have been extensively studied due to their ability to inhibit carcinogenesis. These compounds are chemically similar to 17β-estradiol, and mimic the binding of estrogens to its receptors, exerting estrogenic effects in target organs. Genistein is an isoflavone derived from soy-rich products and accounts for about 60% of total isoflavones found in soybeans. Genistein has been reported to exhibit several biological effects, such as anti-tumor activity (inhibition of cell proliferation, regulation of the cell cycle, induction of apoptosis), improvement of glucose metabolism, impairment of angiogenesis in both hormone-related and hormone-unrelated cancer cells, reduction of peri-menopausal and postmenopausal hot flashes, and modulation of antioxidant effects. Additionally, epidemiological and clinical studies have reported health benefits of genistein in many chronic diseases, such as cardiovascular disease, diabetes, and osteoporosis, and aid in the amelioration of typical menopausal symptoms, such as anxiety and depression. Although the biological effects are promising, certain limitations, such as low bioavailability, biological estrogenic activity, and effects on target organs, have limited the clinical applications of genistein to some extent. Moreover, studies report that modification of its molecular structure may eliminate the biological estrogenic activity and its effects on target organs. In this review, we summarize the potential benefits of genistein on menopause symptoms and menopause-related diseases like cardiovascular, osteoporosis, obesity, diabetes, anxiety, depression, and breast cancer.

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Modulation of Adipocyte Differentiation and Proadipogenic Gene Expression by Sulforaphane, Genistein, and Docosahexaenoic Acid as a First Step to Counteract Obesity

Cited by 30 publications

References 42 publications

Impact of Isoorientin on Metabolic Activity and Lipid Accumulation in Differentiated Adipocytes

Impact of Isoorientin on Metabolic Activity and Lipid Accumulation in Differentiated Adipocytes

Flavonoids as antiobesity agents: A review

Genistein as Potential Therapeutic Candidate for Menopausal Symptoms and Other Related Diseases

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