Bergamot leaf extract treats cardiorenal metabolic syndrome and associated pathophysiological factors in rats fed with a high sugar fat diet

Siqueira, Juliana Silva; Vieira, Taynara Aparecida; Nakandakare-Maia, Erika Tiemi; Palacio, Thiago Luiz Novaga; Sarzi, Felipe; Garcia, Jéssica Leite; Paula, Bruno Henrique de; Bazan, Silméia Garcia Zanati; Baron, Giovanna; Tucci, Luigi; Janda, Elżbieta; Altomare, Alessandra; Gado, Francesca; Ferron, Artur Júnio Togneri; Aldini, Giancarlo; Francisqueti-Ferron, Fabiane Valentini; Corrêa, Camila Renata

doi:10.1016/j.mce.2022.111721

Cited by 9 publications

(7 citation statements)

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“…Citrus Bergamia flavonoids efficiently prevent NAFLD, systemic redox imbalance and other features of metabolic syndrome in rats fed with CAF diet [10,14]. These original findings have been subsequently confirmed in other models and extended to NASH [15,[54][55][56] and NAFLD patients with metabolic syndrome patients in subsequent studies [17,18,56]. Accordingly, the rats used in the present study responded to BPF supplementation with a strong reduction of lipid accumulation in CAF-fed livers characterized by a 60% and 80% decrease in fat content and numbers of big lipid droplets, respectively, confirmed by histopathological analysis of liver sections.…”

Section: Discussionmentioning

confidence: 72%

Dramatic Suppression of Lipogenesis and No Increase in Beta- Oxidation Are the Main Effects of Bergamot Flavonoids on Gene Expression in Fatty Liver Disease

Parafati,

La Russa,

Lascala

et al. 2024

Preprint

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Bergamot flavonoids have been shown to prevent metabolic syndrome, non-alcoholic fatty liver disease (NAFLD) and stimulate autophagy in animal models and patients. To investigate further the mechanism of polyphenol-dependent effects, we performed RT2-PCR array analysis on 168 metabolism, transport and autophagy-related genes expressed in rat livers exposed for 14 weeks to different diets: standard, cafeteria (CAF) and CAF diet supplemented with 50 mg/kg of Bergamot Polyphenol Fraction (BPF). CAF diet caused a strong upregulation of the gluconeogenesis pathway (Gck, Pck2) and a moderate (>1.7 fold) induction of genes regulating lipogenesis (Srebf1, Pparg, Xbp1), lipid and cholesterol transport or lipolysis (Fabp3, Apoa1, Lpl) and inflammation (Il6). However, only one -oxidation gene (Cpt1a) and a few autophagy genes were modulated in the CAF group compared to controls. While most of these transcripts were significantly modulated by BPF, we observed a particularly potent effect on lipogenesis genes, like Acly, Acaca, Fasn and Scd1, which were suppressed far below the mRNA levels of control livers as confirmed by alternative primers-based RT2-PCR analysis and western blotting. These effects were accompanied by downregulation of pro-inflammatory cytokines (Il6, Tnfa, and Il10) and diabetes-related genes. Few autophagy (Map1Lc3a, Dapk) and no -oxidation gene expression changes were observed, suggesting minor transcriptional effects on autophagy. In conclusion, chronic BPF supplementation efficiently prevents NAFLD by modulating hepatic energy metabolism and inflammation gene expression programs, with no effect on -oxidation, but profound suppression of de-novo lipogenesis.

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Section: Discussionmentioning

confidence: 72%

Dramatic Suppression of Lipogenesis and No Increase in Beta- Oxidation Are the Main Effects of Bergamot Flavonoids on Gene Expression in Fatty Liver Disease

Parafati,

La Russa,

Lascala

et al. 2024

Preprint

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“…Additionally, although not statistically significant, a slight reduction in waist circumference of approximately 2.2 cm was observed in the high-dose treatment group. These findings suggest that the insulin sensitivity improving properties of bergamot extract may have contributed to this effect [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Metabolic and vascular effect of a new standardized bergamot phytocomplex: a three-arm, placebo controlled, double-blind clinical trial

et al. 2023

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IntroductionIn addition to healthy lifestyle and balanced diet, nutraceuticals supplementation may be useful to maintain overall metabolic wellness. The aim of the current study was to assess the metabolic and vascular effects of a new highly standardized bergamot phytocomplex supplementation in healthy volunteers with the features of the metabolic syndrome.Material and methodsWe carried out a double-blind, randomized, placebo-controlled, three-arm, parallel-group clinical trial in 90 adult subjects treated for 12 weeks with two different dosages of a highly standardized bergamot phytocomplex (Endoberg by AKHYNEX and as Kalita®) or placebo. Lipid plasma levels of lipids, glycaemia, plasma hs-CRP, HOMA-IR, body fat, endothelial reactivity and fatty liver index were assessed at baseline, after 6 weeks and at the end of treatment in all subjects.ResultsAt the end of treatment, both tested bergamot extract doses were able to significantly improve atherogenic dyslipidaemia and insulin-sensitivity (p<0.05) compared to placebo. In the high-dose treated group, TC, LDL-C, non-HDL-C, and TG improved versus placebo (p<0.05) just after 6 weeks of treatment. After 12 weeks of treatment, TC decreased by 13.2±2.1%, LDL-C by 17.7±3.2%, Non-HDL-C by 17.5±3.1%, TG by 16.6±3.3%, TG/HDL-C by 22.5±4.4%, HOMA-IR by 12.2±2.1%, gGT by 22.2±4.6%, and hsCRP by 17.9±3.4% versus baseline (p<0.05) and vs. placebo (p<0.05). Percentage body fat and endothelial reactivity improved versus baseline, but not versus placebo, in the high-dose treatment only (p<0.05).ConclusionsThe tested bergamot phytocomplex was able to significantly improve glucose and lipid metabolism, as well as inflammation and might represent a novel multi-target approach to control metabolic syndrome.

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“…In the 20th week, when hypertriglyceridemia (C: 93.0 ± 38.2 vs. HSF: 139.5 ± 69.7, p < 0.001) and insulin resistance (C: 3.8 ± 0.9 vs. HSF: 5.5 ± 1.3, p < 0.001) were detected in the HSF group, a separation point (SP) was adopted once animals exposed to different diet models did not always present the expected response [19,21]. After that, the control and HSF groups of animals, above and below the SP, respectively, were excluded from the experiment.…”

Section: Experimental Protocol and Group Characterizationmentioning

confidence: 99%

“…It has already been described by our group the anti-inflammatory and antioxidant effect of Bergamot leaves in an in vitro model and also the Bergamot leaves' extract potential to attenuate insulin resistance [19]. However, there are still no studies that correlate this effect with the adipose tissue-liver axis in an experimental model of obesity.…”

Section: Introductionmentioning

confidence: 98%

Effect of Bergamot Leaves (Citrus bergamia) in the Crosstalk between Adipose Tissue and Liver of Diet-Induced Obese Rats

Siqueira

Nakandakare-Maia

Vieira

et al. 2023

Livers

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The excessive consumption of diets rich in sugar and fat is associated with metabolic manifestations involving adipose tissue and the liver. Bergamot, due to its antioxidant and anti-inflammatory properties, has been used to treat metabolic disorders. This work aimed to verify the effect of Bergamot leaves extract (BLE) on the crosstalk in the adipose tissue–liver axis of obese rats. For 20 weeks, Wistar rats were distributed into two groups: control (Control) and high sugar–fat (HSF) diet groups. Afterwards, the animals were redistributed into three groups for 10 weeks: control diet + vehicle (Control, n = 08), HSF + vehicle (HSF, n = 08), and HSF + BLE (HSF + BLE, n = 08). The BLE was carried out daily by gavage (50 mg/kg). The HSF group presented obesity, hyperglycemia, hypertriglyceridemia, insulin resistance, hepatic microvesicular steatosis, higher inflammation and oxidative stress in the liver and adipose tissue. In comparison to the HSF group, HSF + BLE animals showed protection by reducing the triglyceride levels, insulin resistance, inflammation and oxidative stress in hepatic and adipose tissues. BLE acted on the inflammation and oxidative stress in the adipose tissue–liver axis in obese rats when compared to the HSF group, which may have reflected on the improvement of insulin resistance and dyslipidemia.

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Bergamot leaf extract treats cardiorenal metabolic syndrome and associated pathophysiological factors in rats fed with a high sugar fat diet

Cited by 9 publications

References 42 publications

Dramatic Suppression of Lipogenesis and No Increase in Beta- Oxidation Are the Main Effects of Bergamot Flavonoids on Gene Expression in Fatty Liver Disease

Dramatic Suppression of Lipogenesis and No Increase in Beta- Oxidation Are the Main Effects of Bergamot Flavonoids on Gene Expression in Fatty Liver Disease

Metabolic and vascular effect of a new standardized bergamot phytocomplex: a three-arm, placebo controlled, double-blind clinical trial

Effect of Bergamot Leaves (Citrus bergamia) in the Crosstalk between Adipose Tissue and Liver of Diet-Induced Obese Rats

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