The impact of short-term changes in sleeping and eating patterns on glucometabolic health and gut microbiota in healthy young adults: a proof-of-concept controlled feeding study

Epidemiological studies showed that night workers are at higher risk of developing chronic metabolic diseases.However,no study has investigated the changes in circadian rhythms caused by a combined effect of sleep and diet in a real-life setting on cardiometabolic health,gut microbiota,and psychological status in healthy people.A 4-week step-wise misaligned-realigned controlled-feeding trial with a 2×2 factorial design(sleep and diet)was conducted on healthy young adults.At first,subjects experienced a one-week circadian rhythm misalignment with a high-fat fast-food diet,extended eating window,and delayed sleep schedules,then gradually transited to a complete circadian rhythm realignment with a high-fiber balanced diet,8-h timerestricted eating,and normal sleep schedules.Circadian rhythm misalignment led to significantly higher levels of fasting glucose and homeostatic model assessment for insulin resistance(HOMA-IR)of subjects compared to baseline and failed to recover to the baseline level in circadian rhythm realignments.Notably,the incremental area under the curve(iAUC)of postprandial glucose decreased with circadian rhythm adjustments as compared to that in circadian rhythm misalignment,suggesting circadian rhythm realignment by sleep or/and diet could partly restore glucose metabolism impaired by a short-term circadian rhythm misalignment.However,circadian rhythm changes did not result in overall perturbations of gut microbiota diversities.

Oxidative stress mediates glycidol-induced endothelial injury and its protection by 6-C-(E-2-fluorostyryl)naringenin

Glycidol is a common lipid-derived foodborne toxicant mainly presents in refined oils and related foodstuffs.Vascular endothelial cells may be potential targets of the deleterious effects associated with glycidol exposure.In human umbilical vein endothelial cells(HUVECs),we found that glycidol treatment promoted endothelialto-mesenchymal transition(EndMT)at a lower concentration(0.5 mmol/L),while induced apoptosis and inflammation at a higher concentration(1 mmol/L).These harmful effects were achieved by the activation of NF-κB/MAPK signaling pathway and were mediated by reactive oxygen species(ROS).In addition,the protective potential of 6-C-(E-2-fluorostyryl)naringenin(6-CEFN)against glycidol was evaluated and compared with naringenin.HUVECs pre-treated with 6-CEFN,but not naringenin,displayed resistance to endothelial dysfunction caused by glycidol.

An overview of potential cardioprotective benefits of xanthophylls in atherosclerosis:an evidence-based review

Atherosclerosis,as the most prevalent form of cardiovascular disease,is characterized by oxidized lowdensity lipoprotein(ox-LDL)accumulation in the vascular wall,increased inflammation of the large arteries,dysfunction of the endothelial cells(ECs)and vascular smooth muscle cells(VSMCs),which may eventually lead to the formation of plaques.Xanthophylls,one of the main groups of carotenoids,have been proposed as preventive agents or adjunct therapies to prevent and slow the progression of atherosclerosis due to their cardioprotective properties.However,the underlying preventive mechanism of action of xanthophylls on the pathogenesis of atherosclerosis remains unclear,and clinical evidence of the effect of xanthophylls on atherosclerosis have not yet been summarized and critically reviewed.In this regard,we conducted a comprehensive literature search in four scientific databases(Pub Med,Google Scholar,Science Direct and Web of Science)and carefully analyzed the existing evidence to provide meaningful insights on the association between xanthophylls and atherosclerosis from various aspects.Based on the evidence from in vitro and in vivo studies,we explored several potential mechanisms,including antioxidant effect,anti-inflammatory effect,regulation of lipid metabolism,and modulation of ECs and VSMCs dysfunction,and we found that a clear picture of regulatory pathways of xanthophylls on atherosclerosis prevention and treatment is still lacking.In addition,epidemiological studies suggested the possible relationship among high dietary intake of xanthophylls,high plasma/serum xanthophylls and a reduced risk of atherosclerosis.Direct evidence from interventional studies investigating the effect of xanthophylls on atherosclerosis is very sparse,whilst indirect clinical evidence was only limited to astaxanthin and lutein.Therefore,well-designed long-term randomized controlled trials(RCTs)are highly recommended for future studies to investigate the effective dose of different xanthophylls on atherosclerosis prevention and their possible ancillary effect in conjunction with drug therapies on different stages of atherosclerosis.

Anti-diabetic potential of apigenin,luteolin,and baicalein via partially activating PI3K/Akt/GLUT-4 signaling pathways in insulin-resistant HepG2 cells

Dietary flavonoids are abundant in natural plants and possess multiple pharmacological and nutritional activities.In this study,apigenin,luteolin,and baicalein were chosen to evaluate their anti-diabetic effect in high-glucose and dexamethasone induced insulin-resistant(IR)HepG2 cells.All flavonoids improves the glucose consumption and glycogen synthesis abilities in IR-HepG2 cells via activating glucose transporter protein 4(GLUT4)and phosphor-glycogen synthase kinase(GSK-3β).These fl avonoids signifi cantly inhibited the production of reactive oxygen species(ROS)and advanced glycation end-products(AGEs),which were closely related to the suppression of the phosphorylation form of NF-κB and P65.The expression levels of insulin receptor substrate-1(IRS-1),insulin receptor substrate-2(IRS-2)and phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)pathway in IR-HepG2 cells were all partially activated by the fl avonoids,with variable effects.Furthermore,the intracellular metabolic conditions of the fl avonoids were also evaluated.

Activation of NLRP3 Inflammasome via Drp1 Overexpression in Kupffer Cells Aggravates Ischemia-reperfusion Injury in Hepatic Steatosis

Background and Aims:Donors with fatty livers are considered to address the shortage of livers for transplantation,but those livers are particularly sensitive to ischemia-reperfusion injury(IRI),and an increased incidence of graft failure is observed.Kupffer cells account for 20–35%of liver nonparenchymal cells,and have been shown to participate in the process of IRI and inflammatory reactions of hepatic steatosis.NOD-like receptor thermal protein domain-associated protein 3(NLRP3)is an intracellular sensor activated by Kupffer cells to promote generation and participates in IRI.Dynamics-associated protein 1(Drp1)is one of the main proteins regulating mitochondrial division and exacerbates IRI by affecting mitochondrial dynamics.The mechanism of interaction of Kupffer cells with Drp1 and NLRP3 to aggravate IRI has not been clarified.Methods:A mouse model of hepatic steatosis was established by feeding the mice with a high-fat diet.In vitro experiments were performed using AML12 normal mouse liver cells and RAW264.7 mononuclear macrophage cells cultured in medium with palmitate and oleic acid.Western blotting and immunohistochemical(IHC)staining were used to detect the expression of NLRPP3 and Drp1 in IRI in the control and high-fat diet groups.The expression of F4/80+cells during IRI in hepatic steatosis was verified by IHC staining,and the role of NLRPP3 and Drp1 in Kupffer-cell mediated IRI was investigated by targeting Drp-1 inhibition.Results:Drp1 and NLRP3 expression was increased during IRI in hepatic steatosis,and the expression of Drp1 and NLRP3 were decreased after the elimination of Kupffer cells.That indicated Kupffer cells were involved in the process of IRI in hepatic steatosis through the action of Drp1 and NLRP3.After Drp1 inhibition,liver function was restored and NLRP3 expression level was reduced.Conclusions:Kupffer cells aggravated IRI in hepatic steatosis via NLRP3 and Drp1.Drp1 inhibitors might be useful as specific therapeutics to alleviate IRI in hepatic steatosis and may have promise in case of liver donor shortage.

Impact and inhibitory mechanism of phenolic compounds on the formation of toxic Maillard reaction products in food

As one of the dominant reactions occurring during thermal treatment of food, the Maillard reaction not only leads to the formation of aroma, browning color and taste compounds, but also contributes to the formation of some unpleasant toxic substances including acrylamide,heterocyclic amines and advanced glycation end products.Polyphenols, one of the most abundant antioxidants in the human diet, are contained in different kinds of foods. In this review, some recent studies on the impact of dietary polyphenols on the formation of acrylamide, heterocyclic amines and advanced glycation end products formed during the Maillard reaction are summarized, including the research work conducted with both chemical model systems and real food model systems; the possible inhibitory mechanisms of different polyphenols are also summarized and discussed in this review. Basically we found that some dietary polyphenols not only scavenge free radicals, but also react with reactive carbonyl species,thus lowering the formation of toxic Maillard reaction products. This review provides a useful theoretical foundation for the application of polyphenols in food safety, and suggests some directions for further study of natural products as inhibitors against the formation of toxic substances in thermally processed food.

Antiglycative and anti-inflammatory effects of lipophilized tyrosol derivatives

To expand the application of tyrosol,a series of lipophilized tyrosol derivatives were synthesized via esterification of tyrosol with fatty acids of different chain lengths.The antiglycative activity of tyrosol esters so prepared was subsequently examined in the bovine serumalbumin/glucose system.A quasi-parabolic shape was observed when the activity was plotted against alkyl chain length.Additionally,the anti-inflammatory effects of these derivatives were evaluated against methylglyoxalinduced inflammation in RAW264.7 cells.The same trend on anti-inflammatory activity was found as in the antiglycation study.The results showed that tyrosol esters with C12:0 and C14:0 were two most efficient ones among all the tested derivatives.Thus,some lipophilized tyrosol derivatives were stronger antiglycative and anti-inflammatory agents compared to the parent compound,tyrosol.