Journal of Nutritional Biochemistry

Fatty acid metabolism contributes to energy supply and plays an important role in regulating immunity. Free fatty acids (FFAs) bind to free fatty acid receptors (FFARs) on the cell surface and mediate effects through the intra-cellular FFAR signaling pathways. FFAR4, also known as G-protein coupled receptor 120 (GPR120), has been identified as the primary receptor of omega-3 polyunsaturated fatty acids (ω-3 PUFAs). FFAR4 is a promising target for treating metabolic and inflammatory disorders due to its immune regulatory functions and the discovery of highly selective and efficient agonists...

A prolonged high-fat and high-sucrose (HFHS) diet induces hepatic inflammation and mediates hepatic stellate cell (HSC) activation, which result in hepatic fibrosis. Aberrant activation of the innate immune system components, such as the NOD-like receptor protein 3 (NLRP3) inflammasome, has been implicated in HSC activation and hepatic fibrosis. We have previously shown that p-coumaric acid (PCA)-enriched peanut sprout extracts exert anti-inflammatory effects. However, it is unknown whether PCA reduces hepatic fibrosis by modulating innate immunity and HSC activation...

Phytoestrogens play pivotal roles in controlling not only the endocrine system but also inflammatory metabolic disorders. However, the effects of dietary phytoestrogens on allergic diseases and underlying mechanisms remain unclear. In this study, we revealed the unique metabolic conversion of phytoestrogen to exert anti-allergic properties, using an ovalbumin-induced allergic rhinitis mouse model. We found that dietary secoisolariciresinol diglucoside (SDG), a phytoestrogen abundantly present in flaxseeds, alleviated allergic rhinitis by the microbial conversion to enterodiol (ED)...

Branched fatty acid esters of hydroxy fatty acids (FAHFAs) are endogenous lipids reported to have antidiabetic and anti-inflammatory effects. Recently, we showed that 9-PAHPA and 9-OAHPA increased insulin sensitivity in mice when incorporated to a chow diet or to a high fat and high sucrose diet (HFHS). However, preventive supplementation with 9-PAHPA and 9-OAHPA in HFHS mice did not impair significant weight gain or the development of hyperglycemia. The aim of this work was therefore to study whether in two animal models of obesity, namely the classical diet-induced obesity (DIO) and the db/db mice, 9-PAHPA may have beneficial effects against obesity and liver and skeletal muscle metabolic dysfunction...

Diabetic retinopathy (DR) is one of the most prevalent microvascular complications caused by diabetes mellitus. Previous studies demonstrate that microvascular endothelial inflammation caused by chronic hyperglycemia and hyperlipidemia plays a key role in the pathogenesis of DR. However, the detailed mechanisms on how endothelial inflammation contributes to DR are not fully understood. The STING pathway is an important innate immune signaling pathway. Although STING has been implicated in multiple autoimmune and metabolic diseases, it is not clear whether STING is involved in the pathogenesis of DR...

Mitochondrial ROS generation plays an essential role in the process of adipocyte differentiation and is involved in the development of obesity and associated metabolic diseases. Various dietary flavonoids possess the substantial anti-adipogenic activity. However, it is unclear whether these flavonoids inhibit adipocyte differentiation by reducing ROS generation. In this study, the effects of six common dietary flavonoids on adipocyte differentiation were assessed in 3T3-L1 cells. The flavonoids with the same backbone of 5,7-dihydroxylflavone, including flavones apigenin, chrysin, luteolin and flavonols kaempferol, myricetin, quercetin, dose-dependently inhibited 3T3-L1 adipocyte differentiation, suggesting an associated hierarchy of inhibitory capability: luteolin > quercetin > myricetin > apigenin/kaempferol > chrysin...

Observational study indicated that folic acid (FA) supplementation may protect against tuberculosis-drug-induced liver injury (TBLI). The aim is to investigate the effect and mechanism of FA on TBLI in rats. Liver injury was induced by a daily gavage of isoniazid (INH) and rifampicin (RIF) in the model and FA groups. Rats in the FA group were also treated with 2.5 mg/kg body weight FA. Rats in the control group were not treated. Eight rats were used in each group. The severity of liver injury was measured by the serum levels of hepatic enzymes and histological score...

Folic acid, a water-soluble B-vitamin, has been demonstrated to decrease the risk of first stroke and improve its poor prognosis. However, the molecular mechanisms responsible for the beneficial effect of folic acid on recovery from ischemic insult remain largely unknown. Excessive activation of the N-methyl-d-aspartate receptors (NMDARs) has been shown to trigger synaptic dysfunction and excitotoxic neuronal death in ischemic brains. Here, we hypothesized that the effects of folic acid on cognitive impairment may involve the changes in synapse loss and NMDAR expression and function following cerebral ischemia/reperfusion injury...

Dietary restriction through low-calorie intake or intermittent fasting benefits many organs, including the brain. This study investigated the neuroprotective effects of fasting in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease. We found that fasting every other day rather than weekly increased the levels of brain-derived neurotrophic factor and glial-derived neurotrophic factor in the nigrostriatal pathway. Therefore, we maintained the animals on alternate-day fasting for 2 weeks and injected MPTP (30 mg/kg/day, intraperitoneally [i...

Citrus peel is rich in bioactive components, especially polyphenols, which are considered to have great potential in the prevention of intestinal diseases. The intestinal mucus barrier is the first defense against the invasion of foreign substances. In this study, we aimed to explore the possibility and mechanism of citrus peel in alleviating the mucus barrier damage in high-fat-diet (HFD) mice. We found that citrus peel powder (CPP) supplementation effectively reduced body weight, fat weight, intestinal permeability, hyperlipidemia, and systemic inflammation in HFD-fed mice...

Increasing evidence indicate that cancer stem cells (CSCs) are the key driver of tumor initiation and recurrence. The cellular and soluble components of the tumor microenvironment (TME) impact on cancer initiation and progression, such as cytokines and chemokines. Thus, targeting CSCs and TME is a novel anti-cancer approach. Resveratrol (RES), a bioactive phytochemical extracted from various plants, exhibits tumor-suppressing activities in lung cancer, yet the mechanism remains poorly understood. Our data showed that the expression level of IL-6 was positively correlated with the presence of lung cancer stem-like cells (LCSCs) in human lung cancer tissues...

The objective of this study was to assess whether acute green tea (GT) supplementation attenuates inflammatory and oxidative stress biomarkers induced by high-fat, high-saturated (HFHS) meals in obese women, and to assess its ability to modulate circulating microRNA (miRNA) expression. This was a randomized, double-blind, crossover study. The study included obese women over 18 years old who had no comorbidities. In the first moment, patients were instructed to take 2 capsules of placebo or GT (738 mg) at 10:00 p...

The health benefits of n-3 polyunsaturated fatty acids (PUFAs) in multiple age-related diseases are associated with telomere length. Telomerase is intimately related to inflammation and oxidative stress, but whether the underlying function of n-3 PUFAs on telomere maintenance is based on telomerase activation or related mechanisms remains unclear. Herein, we utilized late-generation (G4) telomerase-deficient (Terc-/- ) mice to perform a lifelong docosahexaenoic acid (DHA) intervention to determine the potential of DHA in telomere maintenance and health promotion...

Previous studies demonstrated that oral administration of Saskatoon berry powder (SBp) reduced fasting plasma glucose (FPG), insulin resistance, lipids and inflammatory markers in diet-induced insulin resistant rodents. Mechanism for the beneficial effects of SB remains unclear. The present study examined the effects of high fat-high sucrose (HFHS) diet supplemented with or without 5% SBp, cyanidin-3-glucoside (C3G, an anthocyanin rich in SBp) at a dosage of C3G in 5% SBp, or equimolar concentration of protocatechuic acid (PCA, a relatively stable metabolite of C3G) for 11 weeks on FPG, cholesterol, triglycerides, insulin, homeostatic model assessment of insulin resistance (HOMA-IR), circulatory inflammatory markers, fecal microbiota and short chain fatty acids in mice...

Obesity causes inflammation which may lead to development of co-morbidities like cardiovascular diseases. Cocoa is a popular food ingredient that has been shown to mitigate obesity and inflammation in preclinical models. Cocoa typically undergoes fermentation and roasting prior to consumption, which can affect the polyphenol content in cocoa. The aim of this study was to compare the effect of fermentation and roasting protocols on the ability of cocoa to mitigate obesity, gut barrier dysfunction, and chronic inflammation in high fat (HF)-fed, obese C57BL/6J mice...

Inflammatory bowel disease (IBD) is a chronic disorder associated with the inflammation in the digestive tract. The exact cause of IBD is unknown; nevertheless, in IBD, the homeostasis of key regulatory factors involved in intestinal immunity has been documented to be disrupted. Despite the lack of a viable treatment for IBD, synthetic drugs and monoclonal antibodies are currently used to treat it. However, these treatments have side effects, and the high relapse rate limits their usage. Dietary polyphenols constitute a great variety of compounds and have shown an array of biological properties...

PD-L1 interacts with its receptor PD-1 on T cells to negatively regulate T cell function, leading to cancer cell immune escape from the immune surveillance. Therefore, targeting PD-L1 is considered to be an attractive approach for cancer immunotherapy. In this study, we demonstrated for the first time that ω-3 polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA) reduced the expression of PD-L1 in cancer cells both in vitro and in vivo. Promotion of PD-L1 ubiquitin-proteasome degradation by DHA resulted in a decrease of PD-L1 expression, leading to reduction of PD-L1 and PD-1 interaction, and reversing PD-L1-mediated immune suppression, which in turn contributed to the inhibitory effect on tumor growth...

Adoption of an obesogenic diet such as a high fat diet (HFD) results in obesity, bacterial dysbiosis, chronic inflammation and cancer. Gut bacteria and their metabolites are recognized by interleukin-1 (IL-1R)/toll-like receptors (TLRs) which are essential to maintain intestinal homeostasis. Moreover, host extracellular microRNAs (miRNAs) can alter bacterial growth in the colon. Characterization of the underlying mechanisms may lead to identifying fecal oncogenic signatures reflecting colonic health. We hypothesize that a HFD accelerates the inflammatory process and modulates IL-1R/TLR pathways, gut microbiome, and disease-related miRNA in the colon...

Auricularia polytricha and Flammulina velutipes are two dietary mushrooms mostly consumed in China and known for their traditional use on gastric ulceration and to boost bowel movement. Considering the gut-liver axis, which has been recognized for its role in the autoimmune modulation, and the implications of the intestinal barrier in the pathogenesis of liver diseases that remain unclear, the therapeutic effects of A. polytricha (APE) and F. velutipes (FVE) on inflammatory bowel disease (IBD)-induced liver injury in mice was investigated as well as their potential mechanism via the signaling pathways they could involve...

Fat and fructose are the two major components over-represented in the Western diet. The aim of this study was to determine the combined effects of different types of dietary fat and fructose on the development of nonalcoholic fatty liver disease (NAFLD) in a murine model. Eight-week-old male C57BL/6J mice were fed with high-fat diet enriched with saturated fat (HSF), or omega-6 polyunsaturated fat (n6HUSF), or omega-3 polyunsaturated fat (n3HUSF) with 42% of calories derived from the fat. Fructose supplementation was given via 10% fructose (w/v) in the drinking water ad libitum for 20 weeks...