Taurine Activates SIRT1/AMPK/FOXO1 Signaling Pathways to Favorably Regulate Lipid Metabolism in C57BL6 Obese Mice.

SCOPE: The identification of novel therapeutic agents capable of modulating lipid metabolism holds a promising potential in combating obesity and its associated complications. This study is conducted to evaluate the lipid lowering effect of dietary taurine administration on high-fat fed C57BL6 mice and to study the mechanism by which taurine impacts lipid metabolism. METHODS AND RESULTS: C57BL6 mice are grouped into four (n = 6): i) normal diet (ND), ii) a high-fat diet (HFD), iii) HFD + orlistat (STD), iv) HFD + taurine (TAU) group for 12 weeks. The results show that taurine administration for 12 weeks reduces high fat-induced weight gain, and liver weight when compared with HFD fed mice. It also improves serum biochemical parameters like total cholesterol and triglycerides. Sirtuin 1 (SIRT1) activity, Nicotinamide adenine dinucleotide (NAD+) levels, SIRT1 mRNA, and protein expression are increased in HFD + TAU diet group as compared to HFD group. Taurine treatment suppresses the expression of lipogenic genes (sterol regulatory element binding protein 1c [SREBP1c], fatty acid synthase [FAS], Peroxisome proliferator-activated receptor gamma [PPARγ]) and increases the expression of ß-oxidation (peroxisome proliferator-activated receptor alpha [PPARα], liver x receptor beta [LXRß], peroxisome proliferator-activated receptor gamma coactivator 1-alpha [PGC1α], AMP-activated protein kinase [AMPK]) and lipolytic (forkhead box protein O1 [FOXO1]) genes. Further, taurine mitigates hepatic inflammation by suppressing nuclear factor kappa B (NF-κB) gene expression and pro-inflammatory cytokine markers (IL-6, IL-1ß, and TNFα). CONCLUSION: Taurine exerts lipid lowering effects through activating SIRT1/AMPK/FOXO1 signaling pathways and regulating their downstream targets.

Efficacy of a functional food ingredient from Ensete superbum Roxb. Cheesman peel in reducing the severity of ulcerative colitis in a murine model.

Ulcerative colitis is a recurrent inflammatory illness of the colon with an elevated risk of developing colon cancer. The drugs presently used to treat UC cause adverse effects and are limited to symptomatic treatments. To overcome these constraints, naturally derived novel alternative therapies are being tested. Ensete superbum Roxb. Cheesman (wild banana) is used as a folk medicinal plant to treat stomach aches, diarrhea, and dysentery. Previous research has shown that a peel dioxane (PD) fraction obtained from a ripe peel aqueous extract of E. superbum Roxb. Cheesman possesses in vitro antioxidant, anti-inflammatory and anti-colon cancer effects. Furthermore, it has been shown to alleviate 2,4,6-trinitrobenzene sulfonic acid (TNBS) induced ulcerative colitis (UC) in rats. The current study intended to evaluate its efficacy as a functional dietary component added to cold pressed orange juice in colitic rats, and deduce the molecular processes involved in UC amelioration. The PD fraction in orange juice ameliorated colitis by modulating the oxidative stress and inflammatory parameters in the damaged tissue with improved healing activity as indicated by a lower disease activity index (DAI) score. The ameliorative effect was related to the inhibition of the nuclear factor-κB (NF-κB) signaling pathway by downregulating the expression levels of NFκBp65, TNF-α, IL-6 and IL-1ß, followed by the recovery of epithelial barrier integrity. The ameliorating effects were statistically similar (p > 0.05) to those of the standard sulfasalazine treated population. The results suggest that PD fractions can be used as a new functional food and as an adjuvant to prevent IBDs due to their anti-colitic effect; however, it needs to be confirmed in clinical trials.

Lactobacillus fermentum MCC2759 and MCC2760 Alleviate Inflammation and Intestinal Function in High-Fat Diet-Fed and Streptozotocin-Induced Diabetic Rats.

The growing incidence of type 2 diabetes and obesity has become a worldwide crisis with increased socio-economic burden. Changes in lifestyle and food habits resulting in dysbiosis of the gut microbiota and low-grade inflammation are linked to the rising incidence. The aim of this study was to investigate the effects of potential probiotic Lactobacillus fermentum MCC2759 and MCC2760 on intestinal markers of inflammation using a high-fat diet (HFD)-fed model and a streptozotocin (STZ)-induced diabetic model. Lact. fermentum administration showed improved oral glucose tolerance compared with the model controls of HFD (AUC 1518) and STZ (628.8). Plasma insulin levels improved in the Lact. fermentum treated groups of HFD + MCC2759 (129 ± 4.24 pmol/L) and HFD + MCC2760 (151.5 ± 9.19 pmol/L) in HFD study, while in STZ diabetic study, the insulin levels were normalized with Lact. fermentum administration, for D + MCC2759 (120.5 ± 7.77) and D + MCC2760 (138 ± 5.65 pmol/L) groups. The results showed reduction in inflammatory tone in liver, muscle, and adipose tissues of rats in both models with stimulation of anti-inflammatory IL-10 by real-time quantitative polymerase chain reaction. Additionally, the potential probiotic cultures also displayed normalization of markers related to intestinal barrier integrity (ZO-1), TLR-4 receptor, and insulin sensitivity (GLUT-4, GLP-1, adiponectin). Thus, the results suggest that Lact. fermentum could act as potential probiotic for lifestyle-related disorders such as obesity, diabetes, and metabolic syndrome as both prophylactic and adjunct therapies.

Cocoa beans improve mitochondrial biogenesis via PPARγ/PGC1α dependent signalling pathway in MPP+ intoxicated human neuroblastoma cells (SH-SY5Y).

Polyphenols are shown to protect from or delay the progression of chronic neurodegenerative diseases. Mitochondrial dysfunction plays a key role in the pathogenesis of Parkinson's disease (PD). This study was aims to gain insight into the role of ahydroalcoholic extract of cocoa (standardised for epicatechin content) on mitochondrial biogenesis in MPP+ intoxicated human neuroblastoma cells (SHSY5Y). The effects of cocoa on PPARγ, PGC1α, Nrf2 and TFAM protein expression and mitochondrial membrane potential were evaluated. A pre-exposure to cocoa extract decreased reactive oxygen species formation and restored mitochondrial membrane potential. The cocoa extract was found to up-regulate the expression of PPARγ and the downstream signalling proteins PGC1α, Nrf2 and TFAM. It increased the expression of the anti-apoptotic protein BCl2 and increased superoxide dismutase activity. Further, the cocoa extract down-regulated the expression of mitochondria fission 1 (Fis1) and up-regulated the expression of mitochondria fusion 2 (Mfn2) proteins, suggesting an improvement in mitochondrial functions in MPP+ intoxicated cells upon treatment with cocoa. Interestingly, cocoa up-regulates the expression of tyrosine hydroxylase, the rate limiting enzyme in dopamine synthesis. No change in the expression of PPARγ on treatment with cocoa extract was observed when the cells were pre-treated with PPARγ antagonist GW9662. This data suggests that cocoa mediates mitochondrial biogenesis via a PPARγ/PGC1α dependent signalling pathway and also has the ability to improve dopaminergic functions by increasing tyrosine hydroxylase expression. Based on our data, we propose that a cocoa bean extract and products thereof could be used as potential nutritional supplements for neuroprotection in PD.