Epidemiological and experimental studies have revealed strong associations between dietary lipids and cancer risk. However, the molecular mechanisms underlying the effects of dietary fatty acids on the genesis and progression of cancer have been poorly explored. In this study, we found that a high olive oil diet stimulated cervical cancer (CC) carcinogenesis, and oleic acid (OA), the main lipid in olive oil, was associated with increased malignancy in HeLa cells. OA up-regulated the expression of CD36, which is the best characterized fatty acid transporter. Inhibiting CD36 prevented the tumor-promoting effects of OA, while overexpressing CD36 mimicked the effects of OA. Clinically, CD36 expression was positively correlated with tumor progression and poor prognosis in patients with CC. Furthermore, OA induced Src kinase and downstream ERK1/2 pathway activation in a CD36-dependent manner. Pretreatment of HeLa cells with an Src kinase inhibitor largely blocked the tumor-promoting effect of OA. Our findings suggest that dietary OA exerts a stimulatory effect on CC growth and metastasis, and CD36 might be a promising therapeutic target that acts against CC through an Src/ERK-dependent signaling pathway.
Ectopic fat located in the kidney has emerged as a novel cause of obesity-related chronic kidney disease (CKD). In this study, we aimed to investigate whether inflammatory stress promotes ectopic lipid deposition in the kidney and causes renal injury in obese mice and whether the pathological process is mediated by the fatty acid translocase, CD36. High-fat diet (HFD) feeding alone resulted in obesity, hyperlipidemia, and slight renal lipid accumulation in mice, which nevertheless had normal kidney function. HFD-fed mice with chronic inflammation had severe renal steatosis and obvious glomerular and tubular damage, which was accompanied by increased CD36 expression. Interestingly, CD36 deficiency in HFD-fed mice eliminated renal lipid accumulation and pathological changes induced by chronic inflammation. In both human mesangial cells (HMCs) and human kidney 2 (HK2) cells, inflammatory stress increased the efficiency of CD36 protein incorporation into membrane lipid rafts, promoting FFA uptake and intracellular lipid accumulation. Silencing of CD36 in vitro markedly attenuated FFA uptake, lipid accumulation, and cellular stress induced by inflammatory stress. We conclude that inflammatory stress aggravates renal injury by activation of the CD36 pathway, suggesting that this mechanism may operate in obese individuals with chronic inflammation, making them prone to CKD.
ObjectivesThis study aimed to investigate the dynamic trends in total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) levels with ageing.DesignA Chinese population-based cross-sectional study.SettingA physical examination centre of a general hospital.ParticipantsAdult subjects (178 167: 103 461 men and 74 706 women) without a known medical history or treatments that affect lipid metabolism.Main outcome measuresDynamic trends in the above-mentioned lipid parameters with ageing were explored; turning points of age were established using age stratification and validated by fitted multivariate linear regression modelling.ResultsAge was found to be an independent factor extensively associated with lipid levels in both sexes when adjusted for serum glucose, body mass index, lifestyle, drinking and smoking. Age was positively associated with TC, logarithm-transformed TG (LnTG) and LDL-C levels in men ≤40, ≤40 and ≤60 years old (yo) and in women ≤60, ≤70 and ≤60 yo, respectively. Conversely, age correlated negatively with TC, LnTG and LDL-C levels in men ≥61, ≥41 and ≥61 yo and in women ≥61, ≥71 and ≥61 yo, respectively. TC, TG and LDL-C levels in women were initially lower than those in men but surpassed those in men in 51–55, 61–65 and 51–55 yo age groups. The trends in HDL-C levels with age were relatively irregular, although HDL-C levels in women were higher than in men for all age groups.ConclusionsThe definition of dyslipidaemia, the atherosclerotic cardiovascular disease risk assessment and the initiation/goals of statin therapy should fully consider age-related trends in lipid levels and sex differences.
Online ratings impose significant effects on the behaviors of potential customers. Thus, online merchants try to adopt strategies that affect this rating behavior, and most of these strategies are connected to money, such as the strategies of returning cash coupons if a consumer gives a five-star rating (RI strategy, an acronym for “returning” and “if”) or returning cash coupons directly with no additional requirements (RN strategy, an acronym for “returning” and “no”). The current study explored whether a certain strategy (RN or RI) was more likely to give rise to false rating behaviors, as assessed by event-related potentials. A two-stimulus paradigm was used in this experiment. The first stimulus (S1) was the picture of a product with four Chinese characters that reflected the product quality (slightly defective vs. seriously defective vs. not defective), and the second stimulus (S2) displayed the coupon strategy (RN or RI). The participants were asked to decide whether or not to give a five-star rating. The behavioral results showed that the RI strategy led to a higher rate of five-star ratings than the RN strategy. For the electrophysiological time courses, the N1, N2, and LPP components were evaluated. The slightly defective products elicited a larger amplitude of the N1 component than the seriously defective and not-defective products, reflecting that perceptual difficulty was associated with the processing of the slightly defective products. The RI strategy evoked a less negative N2 and a more positive LPP than the RN strategy, indicating that the subjects perceived less conflict and experienced stronger incentives when processing the RI strategy. These findings will benefit future studies of fake online comments and provide evidence supporting the policy of forbidding the use of the RI strategy in e-commerce.
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