Membrane CD36 functions in the uptake of fatty acids (FAs), oxidized lipoproteins and in signal transduction after binding these ligands. In rodents, CD36 is implicated in abnormal lipid metabolism, inflammation and atherosclerosis. In humans, CD36 variants have been identified to influence free FA and high-density lipoprotein (HDL) levels and to associate with the risk of the metabolic syndrome, coronary artery disease and stroke. In this study, 15 common lipid-associated CD36 single nucleotide polymorphisms (SNPs) were evaluated for the impact on monocyte CD36 expression (protein and transcript) in 104 African Americans. In a subset of subjects, the SNPs were tested for association with monocyte surface CD36 (n=65) and platelet total CD36 (n=57). The relationship between CD36 expression and serum HDL and very low-density lipoproteins (VLDLs) levels was also examined. After a permutation-based correction for multiple tests, four SNPs (rs1761667, rs3211909, rs3211913, rs3211938) influenced monocyte CD36 protein and two (rs3211909, rs3211938) platelet CD36. The effect of the HDL-associated SNPs on CD36 expression inversely related to the impact on serum HDL and potential causality was supported by Mendelian randomization analysis. Consistent with this, monocyte CD36 protein negatively correlated with total HDL and HDL subfractions. In contrast, positive correlations were documented between monocyte CD36 and VLDL lipid, particle number and apolipoprotein B. In conclusion, CD36 variants that reduce protein expression appear to promote a protective metabolic profile. The SNPs in this study may have predictive potential on CD36 expression and disease susceptibility in African Americans. Further studies are warranted to validate and determine whether these findings are population specific.
Fenofibrate and Niaspan decrease plasma VLDL-TG concentration without altering IHTG content. However, the mechanism responsible for the change in VLDL-TG concentration is different for each drug; fenofibrate increases plasma VLDL-TG clearance, whereas nicotinic acid decreases VLDL-TG secretion.
Objectives:The AspireAssist System (AspireAssist) is an endoscopic weight loss device that is comprised of an endoscopically placed percutaneous gastrostomy tube and an external device to facilitate drainage of about 30% of the calories consumed in a meal, in conjunction with lifestyle (diet and exercise) counseling.Methods:In this 52-week clinical trial, 207 participants with a body-mass index (BMI) of 35.0–55.0 kg/m2 were randomly assigned in a 2:1 ratio to treatment with AspireAssist plus Lifestyle Counseling (n=137; mean BMI was 42.2±5.1 kg/m2) or Lifestyle Counseling alone (n=70; mean BMI was 40.9±3.9 kg/m2). The co-primary end points were mean percent excess weight loss and the proportion of participants who achieved at least a 25% excess weight loss.Results:At 52 weeks, participants in the AspireAssist group, on a modified intent-to-treat basis, had lost a mean (±s.d.) of 31.5±26.7% of their excess body weight (12.1±9.6% total body weight), whereas those in the Lifestyle Counseling group had lost a mean of 9.8±15.5% of their excess body weight (3.5±6.0% total body weight) (P<0.001). A total of 58.6% of participants in the AspireAssist group and 15.3% of participants in the Lifestyle Counseling group lost at least 25% of their excess body weight (P<0.001). The most frequently reported adverse events were abdominal pain and discomfort in the perioperative period and peristomal granulation tissue and peristomal irritation in the postoperative period. Serious adverse events were reported in 3.6% of participants in the AspireAssist group.Conclusions:The AspireAssist System was associated with greater weight loss than Lifestyle Counseling alone.
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