Baicalin Attenuates High Fat Diet-Induced Obesity and Liver Dysfunction: Dose-Response and Potential Role of CaMKKβ/AMPK/ACC Pathway

Background/Aims: The aim of this study was to gain more insight into the beneficial effects of mango fruit powder on the early metabolic adverse effects of a high-fat diet. Methods: The progressive dose-response effects of mango fruit powder on body composition, circulating parameters, and the expression of genes related to fatty acid oxidation and insulin sensitivity in key tissues were studied in mice fed a moderate (45%) high-fat diet. Results: Findings suggest that mango fruit powder exerts physiological protective effects in the initial steps of insulin resistance and hepatic lipid accumulation induced by a high-fat diet in mice. Moreover, AMPK and SIRT1 appear as key regulators of the observed improvement in fatty acid oxidation capacity, as well as of the improved insulin sensitivity and the increased glucose uptake and metabolism through the glycolytic pathway capacity in liver and skeletal muscle. Conclusion: In summary, this study provides evidence that the functional food ingredient (Careless^TM) from mango fruit prevents early metabolic alterations caused by a high-fat diet in the initial stages of the metabolic syndrome.

Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 82%

Consumption of a Mango Fruit Powder Protects Mice from High-Fat Induced Insulin Resistance and Hepatic Fat Accumulation

Sabater

Ribot

Priego

et al. 2017

“…Additionally, baicalin may attenuate chronic hypoxia-induced pulmonary hypertension and cor pulmonale by downregulating the p38 MAPK/MMP-9 pathway [39]. Besides, evidence showed that baicalin attenuated HFD-induced obesity and liver dysfunction, with dose-dependently inhibited hepatic CaMKKβ/AMPK/ACC pathway [40]. In the present study, we found that baicalin attenuated cardiac hypertrophy in response to hypertrophic stimuli, accompanied by restoration of PPARα and PPARβ/δ.…”

Section: Discussionsupporting

confidence: 55%

Baicalin Attenuates Cardiac Dysfunction and Myocardial Remodeling in a Chronic Pressure-Overload Mice Model

Zhang

Liao

Zhu

et al. 2017

Background/Aims: Baicalin has been shown to be effective for various animal models of cardiovascular diseases, such as pulmonary hypertension, atherosclerosis and myocardial ischaemic injury. However, whether baicalin plays a role in cardiac hypertrophy remains unknown. Here we investigated the protective effects of baicalin on cardiac hypertrophy induced by pressure overload and explored the potential mechanisms involved. Methods: C57BL/6J-mice were treated with baicalin or vehicle following transverse aortic constriction or Sham surgery for up to 8 weeks, and at different time points, cardiac function and heart size measurement and histological and biochemical examination were performed. Results: Mice under pressure overload exhibited cardiac dysfunction, high mortality, myocardial hypertrophy, increased apoptosis and fibrosis markers, and suppressed cardiac expression of PPARα and PPARβ/δ. However, oral administration of baicalin improved cardiac dysfunction, decreased mortality, and attenuated histological and biochemical changes described above. These protective effects of baicalin were associated with reduced heart and cardiomyocyte size, lower fetal genes expression, attenuated cardiac fibrosis, lower expression of profibrotic markers, and decreased apoptosis signals in heart tissue. Moreover, we found that baicalin induced PPARα and PPARβ/δ expression in vivo and in vitro. Subsequent experiments demonstrated that long-term baicalin treatment presented no obvious cardiac lipotoxicity. Conclusions: The present results demonstrated that baicalin attenuates pressure overload induced cardiac dysfunction and ventricular remodeling, which would be due to suppressed cardiac hypertrophy, fibrosis, apoptosis and metabolic abnormality.

“…Pina-Zentella et al [54] reported that taurine enhances the rate of lipolysis in isolated adipocytes by stimulating protein kinase A (PKA) activity. The aforementioned events explain the logic sequelae of dyslipidemia in the current study, evidenced by marked elevation in the total cholesterol, triglycerides, LDL-C and reduction of serum HDL-C. NAFLD is reported to closely associate with risk factors such as dyslipidemia and increased hepatic contents [55, 56]. In this study, CAF-D caused significant elevation of serum ALT, AST, ALP and GGT indicating hepatic dysfunction, cellular leakage and loss of functional integrity of membrane hepatocytes with more specificity of ALT enzyme in liver injury assessment [57].…”

Section: Discussionmentioning

confidence: 93%

A Novel Role of SIRT1/ FGF-21 in Taurine Protection Against Cafeteria Diet-Induced Steatohepatitis in Rats

Elwahab

Ramadan

Schaalan

et al. 2017

Background: Non-alcoholic fatty liver disease (NAFLD) is one of the alarmingly rising clinical problems in the 21^st century with no effective drug treatment until now. Taurine is an essential amino acid in humans that proved efficacy as a non-pharmacological therapy in a plethora of diseases; however, its impact on NAFLD remains elusive. The aim of the current study is to evaluate the protective mechanism of taurine in experimental steatohepatitis induced by junk food given as cafeteria-diet (CAF-D) in male albino rats. Methods: Forty adult male albino rats of local strain between 8-10 weeks old, weighing 150 ± 20 g, were divided into four equal groups: Group I (control group), Group II (Taurine group), Group III (CAF-D for 12 weeks) and Group IV (CAF-D +Taurine). CAF-D was given in addition to the standard chow for 12 weeks, where each rat was given one piece of beef burger fried in 15 g of sunflower oil, one teaspoonful of mayonnaise, and one piece of petit pan bread, weighing 60g/ piece. In the serum, liver function tests; ALT, AST, ALP, GGT and the lipid profile; TG, TC, HDL-C added to reduced glutathione (GSH) were assessed colorimetrically, while fibroblast growth factor (FGF)-21, adiponectin & interleukin (IL)-6 via ELISA. The same technique was used for the assays of the hepatic levels of FGF-21, silent information regulator (SIRT1), malondialdehyde (MDA),IL-10, tumor necrosis factor-α (TNF-α) as well as the apoptotic markers; caspase-3 and B-cell lymphoma (Bcl-2). Results: The cafeteria-diet induced steatohepatitis was reflected by significantly increased body and liver weight gain, elevation of liver enzymes; ALT, AST, ALP and GGT added to the dyslipidemic panel, presented as increased TC, TG, LDL-C and decreased HDL-C levels. The steatosis-induced inflammatory milieu, marked by elevated serum levels of FGF-21, IL-6, hepatic TNF-α, as well as reduced IL-10 and adiponectin, was associated with steatosis- induced hepatic oxidative stress, reflected by increased hepatic MDA and decreased GSH levels, along with stimulated caspase-3 and decline in BcL-2 hepatic levels. These pathological disturbances were significantly ameliorated by taurine supplementation and evidenced histopathologically. The cross talk between hepatic FGF-21 and SIRT1 and their association to the induced perturbations are novel findings in this study. Taurine's efficacy in restoration of hepatic structure and function is partially via the increase in SIRT1 and associated reduction of FGF-21. Conclusion: The findings of the current study prove the protective role of taurine in NAFLD via a novel role in the amelioration of FGF-21/ SIRT1 axis, which could be considered a new therapeutic target.