An obesogenic diet enriched with blue mussels protects against weight gain and lowers cholesterol levels in C57BL/6 mice.

Obesity is linked to several health complications, such as cardiovascular disease, insulin resistance, and hypertension. Dyslipidemia in obesity is one of the prime causes for health complications. We have previously shown that blue mussels (BM) are a rich source of omega (n)-3 polyunsaturated fatty acids (PUFA) and increase the mRNA expression of peroxisome-proliferator activated receptor and adiponectin, thereby inducing anti-obesity and insulin sensitizing effects in vitro. However, the in vivo effects of BM on obesity and metabolic regulation are not known. We hypothesized that dietary intake of BM will prevent weight gain and improve lipid profile of C57BL/6 mice fed a high-fat diet (HFD). Mice were fed a HFD supplemented with 5% w/w BM (BM-HFD) for 4 weeks, and then switched to a HFD for 4 weeks. Mice fed a BM-HFD showed significantly lower body weight gain and abdominal fat, compared to the HFD. Furthermore, a BM-HFD significantly reduced plasma and hepatic total and low-density lipoprotein (LDL)-cholesterol, compared to HFD. The decrease in cholesterol levels coincided with inhibition of hepatic sterol regulatory element-binding protein-2 and HMG-CoA reductase mRNA expression, and an increase in LDL-receptor gene expression in the BM-HFD group, compared to the HFD group. In conclusion, our findings have established that BM reduces body weight gain in mice. BM may have potential to lower cholesterol levels by inhibiting cholesterol synthesis, thereby protecting against obesity and perhaps heart disease.

A high fat-high sucrose diet enriched in blue mussels protects against systemic inflammation, metabolic dysregulation and weight gain in C57BL/6 mice.

High fat-high sucrose (HF-HS) diet, known as the western diet, has been shown to induce the onset of obesity via increasing metabolic inflammation, insulin resistance and adipose tissue dysfunction. Hyperleptinemia, hyperglycemia and dyslipidemia are also the primary observations of obesogenic diet induced obesity. We have previously reported anti-adipogenic and insulin sensitizing effects of blue mussels (BM) using 3T3-L1 cells. BM is a rich source of omega-3 polyunsaturated fatty acids, phytosterols and other micronutrients that has been shown to elicit benefits under obese conditions using in-vitro cell culture models. However, no studies to date have established the anti-obesity effects, safety and efficacy of BM in an in-vivo animal model. In the present study, we fed a HF-HS diet supplemented with different concentrations of BM freeze-dried powder (1.25, 2.5 and 5% w/w) to C57BL/6 mice for 12weeks. A HF-HS diet caused rapid weight gain, hyperglycemia, dyslipidemia, hyperleptinemia, and increased plasma levels of inflammatory cytokines; interleukin (IL)-6 and tumor necrosis factor (TNF)-α. Incorporating 2.5% BM in the HF-HS diet prevented weight gain, dyslipidemia, hyperglycemia and reduced the levels of inflammatory cytokines and leptin mRNA expression. Furthermore, plasma from 2.5% BM increased cholesterol efflux capacity of J774 macrophage cells, compared to plasma from HF-HS diet. There was no effect of 1.25% BM on any tested parameters, while 5% BM was not palatable after four weeks. In conclusion, our findings have established the efficacy and safety of BM using C57BL/6 mice, demonstrating that BM has the potential to target obesity and related complications.

A high fat diet enriched with sea cucumber gut powder provides cardio-protective and anti-obesity effects in C57BL/6 mice.

We have previously reported that sea cucumber (SC) inhibits fat accumulation and insulin resistance in 3T3-L1 cells. The present study investigated the anti-obesity and cardio-protective effects of SC freeze-dried gut powder using C57BL/6 as an animal model. Male mice were fed a normal chow diet, a high fat diet (HFD) or a HFD enriched with 2.5, 5 or 7.5% SC gut powder for 4, 8 and 12weeks. Diets enriched with SC caused a significant reduction in body weight gain and fat weight, compared to the HFD, without affecting food intake. Both 2.5% and 5% SC treatment showed a significant reduction in plasma glucose, triacylglycerol (TG), total cholesterol (TC) and non-esterified fatty acids, compared to the HFD. However, animals fed the 7.5% SC diet showed an increase in liver weight, liver TG and TC, compared to the HFD diet. Diets enriched with 2.5% SC caused an increase in adiponectin mRNA expression in adipose tissue and reduced plasma interleukin-6, compared to the HFD diet. Fecal cholesterol excretion increased after 2.5% SC treatment, coinciding with an increase in ATP-binding cassette-5 and -8 mRNA expression in the small intestine. Although both 2.5 and 5% SC treatment caused weight and fat reduction to a similar extent, 2.5% SC was more effective at improving the metabolic profile. None of the tested SC doses caused any toxic effects. Our findings demonstrate for the first time that SC freeze-dried gut powder has the potential as a nutraceutical to target obesity and related disorders.

Combination effects of wild rice and phytosterols on prevention of atherosclerosis in LDL receptor knockout mice.

Dietary modifications including healthy eating constitute one of the first line strategies for prevention and treatment of atherosclerotic cardiovascular diseases (CVD), including atherosclerosis. In this study, we assessed anti-atherogenic effects of a combination of wild rice and phytosterols in low-density lipoprotein receptor knockout (LDL-r-KO) mice. Male LDL-r-KO mice were divided into four groups and fed with: (1) control diet; (2) the control diet containing 60% (w/w) wild rice; (3) the control diet containing 2% (w/w) phytosterols; or (4) the control diet containing both wild rice and phytosterols for 20weeks. All diets were supplemented with 0.06% (w/w) dietary cholesterol. Blood samples, hearts, and feces were collected and used for biochemical and histological examination. Consumption of 60% (w/w) wild rice in combination with 2% (w/w) phytosterols significantly reduced the size and severity of atherosclerotic lesions in the aortic roots as compared to those in the control group. This effect was associated with significant reductions in plasma total, LDL and VLDL cholesterol concentrations as well as an increase in fecal cholesterol excretion. In conclusion, the dietary combination of wild rice and phytosterols prevents atherogenesis in this animal model. Further investigations are needed to understand mechanisms of action and potential clinical outcome of such dietary intervention.

Cardiovascular benefits of probiotics: a review of experimental and clinical studies.

The microbiota inhabiting the human gastro-intestinal tract is reported to have a significant impact on the health of an individual. Recent findings suggest that the microbial imbalance of the gut may play a role in pathogenesis of cardiovascular diseases (CVD). Therefore, several studies have delved into the aspect of altering gut microbiota with probiotics as an approach to prevent and/or treat CVD. The World Health Organization defines probiotics as live microorganisms that, when consumed in adequate amounts, have a positive influence on the individual's health. The present review focuses on strategies of human dietary intervention with probiotic strains and their impact on cardiovascular risk factors like hypercholesterolemia, hypertension, obesity and type-2 diabetes. Accumulating evidence shows probiotics to lower low density lipoproteins (LDL)-cholesterol and improve the LDL/high density lipoproteins (HDL) ratio, as well as lower blood pressure, inflammatory mediators, blood glucose levels and body mass index. Thus, probiotics have the scope to be developed as dietary supplements with potential cardiovascular health benefits. However, there is not only ambiguity regarding the exact strains and dosages of the probiotics that will bring about positive health effects, but also factors like immunity and genetics of the individual that might influence the efficacy of probiotics. Therefore, further studies are required not only to understand the mechanisms by which probiotics may beneficially affect the cardiovascular system, but also to rule out any of their probable negative effects on health. The present review aims to critically appraise the complexity of the available data with regard to the cardiovascular benefits of probiotics.

Transcriptional Regulation of Brain-Derived Neurotrophic Factor (BDNF) by Methyl CpG Binding Protein 2 (MeCP2): a Novel Mechanism for Re-Myelination and/or Myelin Repair Involved in the Treatment of Multiple Sclerosis (MS).

Multiple sclerosis (MS) is a chronic progressive, neurological disease characterized by the targeted immune system-mediated destruction of central nervous system (CNS) myelin. Autoreactive CD4+ T helper cells have a key role in orchestrating MS-induced myelin damage. Once activated, circulating Th1-cells secrete a variety of inflammatory cytokines that foster the breakdown of blood-brain barrier (BBB) eventually infiltrating into the CNS. Inside the CNS, they become reactivated upon exposure to the myelin structural proteins and continue to produce inflammatory cytokines such as tumor necrosis factor α (TNFα) that leads to direct activation of antibodies and macrophages that are involved in the phagocytosis of myelin. Proliferating oligodendrocyte precursors (OPs) migrating to the lesion sites are capable of acute remyelination but unable to completely repair or restore the immune system-mediated myelin damage. This results in various permanent clinical neurological disabilities such as cognitive dysfunction, fatigue, bowel/bladder abnormalities, and neuropathic pain. At present, there is no cure for MS. Recent remyelination and/or myelin repair strategies have focused on the role of the neurotrophin brain-derived neurotrophic factor (BDNF) and its upstream transcriptional repressor methyl CpG binding protein (MeCP2). Research in the field of epigenetic therapeutics involving histone deacetylase (HDAC) inhibitors and lysine acetyl transferase (KAT) inhibitors is being explored to repress the detrimental effects of MeCP2. This review will address the role of MeCP2 and BDNF in remyelination and/or myelin repair and the potential of HDAC and KAT inhibitors as novel therapeutic interventions for MS.