Acute oral treatment with resveratrol and Lactococcus Lactis Subsp. Lactis decrease body weight and improve liver proinflammatory markers in C57BL/6 mice.

The present study aimed to evaluate the effects of resveratrol, a nutraceutical polyphenol, and Lactococcus lactis (bacteria probiotic), on metabolic parameters and hepatic proinflammatory markers expression. C57BL/6 mice were divided into 4 groups: Standard (ST), Lactococcus lactis (LL), Resveratrol (RSV), and Lactococcus lactis plus resveratrol (LL + RSV). Lactococcus lactis and resveratrol were administered by orogastric gavage. Blood parameters were assessed (total cholesterol, triglycerides, ALT and AST). IL-6 mRNA expression was evaluated by Real-time PCR and TNF-α protein expression was assessed by immunohistochemistry. The main findings showed that resveratrol and Lactococcus lactis association decreased body weight, aspartate aminotransferase and total cholesterol levels. LL and LL + RSV decreased triglycerides levels and IL-6 and TNF-α expression. These results open a perspective of using resveratrol and Lactococcus lactis to improve metabolic parameters and Lactococcus lactis in preventing inflammation and the hepatic diseases development.

Lactococcus lactis and Resveratrol Decrease Body Weight and Increase Benefic Gastrointestinal Microbiota in Mice.

BACKGROUND: The microbiome is now known for its important role in whole-body homeostasis. A dysbiosis of the normal microbiota is correlated with metabolic disorders. In this sense, the search for compounds able to modulate the microbiome is needed. Resveratrol, a natural compound found in grapes seems to be a promising candidate. OBJECTIVE: In this study, our motivation was to evaluate the effects of the association between Resveratrol and Lactococcus lactis, a probiotic, on the composition of the gastrointestinal microbiota and body weight of mice. METHODS: Twenty female mice were divided into 4 groups: (1) standard diet, (2) standard diet plus Lactococcus lactis, (3) standard diet plus resveratrol, and (4) standard diet plus Lactococcus lactis and resveratrol. At the end of the treatment period, samples of blood, mucus, stomach, and small and large intestines were collected for analysis. Total levels of Immunoglobulin A and Immunoglobulin E, Lac+ and Lac- bacteria and Lactobacillus were measured. RESULTS: The main results indicate that the association between resveratrol and probiotics was able to decrease mice body weight, as compared to the other groups, in addition to decrease the number of Lac- bacteria and increasing the number of Lac+ bacteria. The levels of secretory IgA were also decreased, compared to the animals treated with only probiotics or resveratrol. CONCLUSION: We observed potential synergism between Resveratrol and Lactococcus lactis mainly in modulating the stomach and intestinal microbiota.

Nuclear sirtuins and inflammatory signaling pathways.

The regulation of chronic inflammation has received considerable research attention in recent years because of its contribution to the pathogenesis of chronic diseases such as arthritis, diabetes, metabolic syndrome and obesity. Thus, strategies that inhibit the inflammatory state may be beneficial in improving the pathophysiology of several inflammation-related disorders. Sirtuins are a family of histone deacetylases that contain seven enzymatic activities in mammals (SIRT1-SIRT7) and function to suppress gene transcription by epigenetic mechanisms. Nuclear sirtuins (SIRT 1, 2, 6 and 7) in particular may play an important role in the regulation of inflammatory responses. In the present review, we assessed the roles of nuclear sirtuins in inflammatory reactions: SIRT1 has been shown to suppress NF-κb activity, the master regulator of cellular inflammatory response, decrease COX-2 and iNOS production, and increase antioxidant gene expression that suppressed inflammation. SIRT2 activity included the deacetylation of p65 subunit of NF-κß and RIP-1, while SIRT6 has been shown to interact with p65/RelA bound to the NF-κß promoter region and repress transcriptional activity. Furthermore, recent studies have shown that the absence of SIRT7 produced an increase in inflammation, illustrating that SIRT7 also functioned to decrease inflammation. Given their significant roles in the regulation of chronic inflammation, nuclear sirtuins represent potential therapeutic targets in the control of chronic inflammatory diseases.

Effects of Dietary Macronutrient Composition on FNDC5 and Irisin in Mice Skeletal Muscle.

BACKGROUND: Fibronectin type III domain containing 5 (FNDC5) and its protein product Irisin are therapeutic targets for obesity-associated disorders. Irisin plays an important role in energy regulation, inducing browning of white adipocytes, and improving obesity. We aimed to investigate the association between muscle Irisin expression and dietary quality. METHODS: Twenty-eight female mice were divided into four groups and fed the following experimental diets for 60 days: standard diet (SD), high-carbohydrate diet (HCD), high-fat diet (HFD), and high-protein diet (HPD). We evaluated body weight, food intake, serum total cholesterol, triacylglycerol, and glucose. We also performed glucose tolerance and insulin sensitivity tests. Expression of FNDC5 was evaluated by quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR) of soleus muscle. Western blot was used to assess Irisin protein expression. RESULTS: The major finding of the present study was that HFD and HCD were associated with a downregulation of FNDC5. In addition to these results, we noted a significant reduction in skeletal muscle Irisin level. HPD prevented reductions of both FNDC5 and Irisin levels, as well as increased brown adipose tissue, compared to the control group. CONCLUSIONS: In conclusion, we observed that the HPD type of diet can change both FNDC5 expression and Irisin levels. Thus, the HPD might be the most appropriate diet to achieve high amounts of Irisin, a target molecule for the treatment of obesity and its co-morbidities.

Metformin Reduces Lipogenesis Markers in Obese Mice Fed a Low-Carbohydrate and High-Fat Diet.

Lipogenesis is the process by which fatty acids are synthesized. In metabolic syndrome, an insulin resistant state along with high plasma levels of free fatty acids (FFA) and hyperglycemia may contribute to the lipogenic process. The aim of the present study was to investigate the effects of oral administration of metformin on the expression of lipogenic genes and glycemic profile in mice fed with low-carbohydrate high-fat diet by evaluating their metabolic profile. SWISS male mice were divided into 4 groups (N = 7) that were fed with standard (ST), standard plus metformin (ST + MET), low-carbohydrate high-fat diet (LCHFD) and low-carbohydrate high-fat diet plus metformin (LCHFD + MET) (100 mg kg-1 diet) diets respectively. Food intake, body weight and blood parameters, such as glucose tolerance, insulin sensitivity, glucose, HDL-c, total cholesterol, triglycerides, ASL and ALT levels were assessed. Histological analyses were performed on hematoxylin and eosin-stained epididymal adipose tissue histological specimens. The expression levels of peroxisome proliferator-activated receptor (PPARγ), sterol regulatory element-binding protein 1 (SREBP1), fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC), were assessed by RT-PCR. This study showed that metformin decreased adipocyte area, body weight and food consumption in obese animals when compared to the standard group. Furthermore, the expression of lipogenic markers in adipose tissue were diminished in obese animals treated with metformin. This data showed that oral administration of metformin improved glucose and lipid metabolic parameters in white adipose tissue by reducing the expression of lipogenesis markers, suggesting an important clinical application of MET in treating obesity-related diseases in metabolic syndrome.

Distinct metabolic effects of resveratrol on lipogenesis markers in mice adipose tissue treated with high-polyunsaturated fat and high-protein diets.

OBJECTIVE: A healthy diet is essential for the prevention of metabolic syndrome. The present study evaluated the effect of resveratrol associated with high-polyunsaturated fat and high-protein diets on expression of adipogenic and lipogenic genes. RESEARCH METHODS & PROCEDURES: FVB/N mice were divided into 6 groups (n=7 each) and fed with experimental diets for 60days: standard (ST), high-fat diet (HFD), and high-protein diet (HPD), with and without resveratrol (RSV) (4g/kg diet). The body weight, food intake, energy intake (kcal), and blood parameters (HDL-C, total cholesterol, glucose, and triglyceride levels) were assessed. Real-time PCR was performed to analyze the expression of adipogenesis and lipogenesis markers: PPARγ, SREBP-1c, ACC and FAS in samples from perigonadal adipose tissue. RESULTS: In the HPD+RSV group, resveratrol decreased body weight, body adiposity, adipose tissue weight, adipocyte area, total cholesterol, ACC and FAS expression, and increased HDL-cholesterol in comparison to HPD. In the HPD group there was a decrease in adipocyte area, as well as PPARγ, SREBP-1c and ACC expression in comparison to ST. While in HFD+RSV, resveratrol decreased levels of total cholesterol in comparison to HFD. In the HFD group there was decrease in body weight, and PPARγ, SREBP-1c and ACC expression in comparison to ST. CONCLUSIONS: The obtained results show that resveratrol decreases lipogenesis markers and metabolic parameters in the setting of a high-protein diet. Moreover, resveratrol decreased total cholesterol in both diets. These results point to the increased potential of resveratrol use in prevention of metabolic syndrome, acting on different dietary compositions.

Brain activation of SIRT1: role in neuropathology.

Sirtuins (SIRTs) are a family of regulatory proteins of genetic information with a high degree of conservation among species. The SIRTs are heavily involved in several physiological functions including control of gene expression, metabolism, and aging. SIRT1 has been the most studied sirtuin and plays important role in the prevention and progression of neurodegenerative diseases acting in different pathways of proteins involved in brain function. SIRT1 activation regulates important genes that also exert neuroprotective actions such as p53, nuclear factor kappa B, peroxisome proliferator-activated receptor-gamma (PPARγ), PPARγ coactivator-1α, liver X receptor, and forkhead box O. It is well established in literature that growing population aging, oxidative stress, inflammation, and genetic factors are important conditions to development of neurodegenerative disorders. However, the exact pathophysiological mechanisms leading to these diseases remain obscure. The sirtuins show strong potential to become valuable predictive and prognostic markers for diseases and as therapeutic targets for the treatment of a variety of neurodegenerative disorders. In this context, the aim of the current review is to present an actual view of the potential role of SIRT1 in modulating the interaction between target genes and neurodegenerative diseases on the brain.