OBJECTIVEThe proinflammatory cytokines/adipokines produced from adipose tissue act in an autocrine and/or endocrine manner to perpetuate local inflammation and to induce peripheral insulin resistance. The present study investigates whether lipocalin-2 deficiency or replenishment with this adipokine has any impact on systemic insulin sensitivity and the underlying mechanisms.METHODS AND RESULTSUnder conditions of aging or dietary-/genetic-induced obesity, lipocalin-2 knockout (Lcn2-KO) mice show significantly decreased fasting glucose and insulin levels and improved insulin sensitivity compared with their wild-type littermates. Despite enlarged fat mass, inflammation and the accumulation of lipid peroxidation products are significantly attenuated in the adipose tissues of Lcn2-KO mice. Adipose fatty acid composition of these mice varies significantly from that in wild-type animals. The amounts of arachidonic acid (C20:4 n6) are elevated by aging and obesity and are paradoxically further increased in adipose tissue, but not skeletal muscle and liver of Lcn2-KO mice. On the other hand, the expression and activity of 12-lipoxygenase, an enzyme responsible for metabolizing arachidonic acid, and the production of tumor necrosis factor-α (TNF-α), a critical insulin resistance–inducing factor, are largely inhibited by lipocalin-2 deficiency. Lipocalin-2 stimulates the expression and activity of 12-lipoxygenase and TNF-α production in fat tissues. Cinnamyl-3,4-dihydroxy-α-cyanocinnamate (CDC), an arachidonate lipoxygenase inhibitor, prevents TNF-α expression induced by lipocalin-2. Moreover, treatment with TNF-α neutralization antibody or CDC significantly attenuated the differences of insulin sensitivity between wild-type and Lcn2-KO mice.CONCLUSIONSLipocalin-2 deficiency protects mice from developing aging- and obesity-induced insulin resistance largely by modulating 12-lipoxygenase and TNF-α levels in adipose tissue.

BackgroundVegetarian diets exclude all animal flesh and are being widely adopted by an increasing number of people; however, effects on blood lipid concentrations remain unclear. This meta‐analysis aimed to quantitatively assess the overall effects of vegetarian diets on blood lipids.Methods and ResultsWe searched PubMed, Scopus, Embase, ISI Web of Knowledge, and the Cochrane Library through March 2015. Studies were included if they described the effectiveness of vegetarian diets on blood lipids (total cholesterol, low‐density lipoprotein cholesterol, high‐density lipoprotein cholesterol, and triglyceride). Weighted mean effect sizes were calculated for net changes by using a random‐effects model. We performed subgroup and univariate meta‐regression analyses to explore sources of heterogeneity. Eleven trials were included in the meta‐analysis. Vegetarian diets significantly lowered blood concentrations of total cholesterol, low‐density lipoprotein cholesterol, high‐density lipoprotein cholesterol, and non–high‐density lipoprotein cholesterol, and the pooled estimated changes were −0.36 mmol/L (95% CI −0.55 to −0.17; P<0.001), −0.34 mmol/L (95% CI −0.57 to −0.11; P<0.001), −0.10 mmol/L (95% CI −0.14 to −0.06; P<0.001), and −0.30 mmol/L (95% CI −0.50 to −0.10; P=0.04), respectively. Vegetarian diets did not significantly affect blood triglyceride concentrations, with a pooled estimated mean difference of 0.04 mmol/L (95% CI −0.05 to 0.13; P=0.40).ConclusionsThis systematic review and meta‐analysis provides evidence that vegetarian diets effectively lower blood concentrations of total cholesterol, low‐density lipoprotein cholesterol, high‐density lipoprotein cholesterol, and non–high‐density lipoprotein cholesterol. Such diets could be a useful nonpharmaceutical means of managing dyslipidemia, especially hypercholesterolemia.

Spinal cord injury (SCI) is one of the most debilitating injuries and transplantation of stem cells in a scaffold is a promising strategy for the treatment. However, the stem cell treatment of SCI has been severely impaired by the increased generation of reactive oxygen Video S8. Recording of rat hindlimb motor functions in MnO2 group at Day 14 (MP4) Video S9. Recording of rat hindlimb motor functions in MnO2 group at Day 21 (MP4) Video S10. Recording of rat hindlimb motor functions in MnO2 group at Day 28 (MP4)

Scope: Recent evidences demonstrate that abnormal gut microbiota (GM) might be involved in the pathogenesis of Alzheimer's disease (AD). However, the role of probiotics in preventing AD by regulating GM-gut-brain axis remains unclear. Here, the anti-neuroinflammatory effect and its mechanism of probiotic Clostridium butyricum (CB) against AD is investigated by regulating GM-gut-brain axis. Methods and results: APPswe/PS1dE9 (APP/PS1) transgenic are treated intragastrically with CB for 4 weeks then cognitively tested. Amyloid-(A ) burden, microglial activation, proinflammatory cytokines production, GM, and metabolites butyrate are analyzed. Moreover, A -induced BV2 microglia are pretreated with butyrate, and the levels of cluster of differentiation 11b (CD11b), cyclooxygenase-2 (COX-2), and NF-B p65 phosphorylation are determined. The results show that CB treatment prevents cognitive impairment, A deposits, microglia activation, and production of tumor necrosis factor (TNF)-and interleukin (IL)-1 in the brain of APP/PS1 mice. Meanwhile, abnormal GM and butyrate are reversed after CB treatment. Notably, butyrate treatment reduces the levels of CD11b and COX-2, and suppresses phosphorylation of NF-B p65 in the A -induced BV2 microglia. Conclusions: These findings indicate that CB treatment could attenuate microglia-mediated neuroinflammation via regulating the GM-gut-brain axis, which is mediated by the metabolite butyrate.