6 research outputs found
Medicines for Obesity: Appraisal of Clinical Studies with Grading of Recommendations, Assessment, Development, and Evaluation Tool
We evaluated the quality of evidence from phase III/IV clinical trials of drugs against obesity using the principles of Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) tool. Our systematic review evaluates the quality of clinical evidence from existing clinical trials and not the pharmacological efficacy of anti-obesity therapies. A literature search using select keywords in separate was performed in PubMed and ClinicalTrials.gov databases for phase III/IV clinical trials during the last ten years. Our findings indicate that the quality of existing clinical evidence from anti-obesity trials generally ranges from low to moderate. Most trials suffered from publication bias. Less frequently, trials suffered from the risk of bias mainly due to lack of blindness in the treatment. Our work indicates that additional higher-quality clinical trials are needed to gain more confidence in the estimate of the effect of currently used anti-obesity medicines, to allow more informed clinical decisions, thus reducing the risk of implementing potentially ineffective or even harmful therapeutic strategies
Distinct Roles of Apolipoproteins A1 and E in the Modulation of High-Density Lipoprotein Composition and Function
In addition to high-density
lipoprotein cholesterol (HDL-C) levels,
HDL quality also appears to be very important for atheroprotection.
Analysis of various clinical paradigms suggests that the lipid and
apolipoprotein composition of HDL defines its size, shape, and functions
and may determine its beneficial effects on human health. Previously,
we reported that like apolipoprotein A-I (Apoa1), apolipoprotein E
(Apoe) is also capable of promoting the <i>de novo</i> biogenesis
of HDL with the participation of ATP binding cassette A lipid transporter
member 1 (Abca1) and plasma enzyme lecithin:cholesterol acyltransferase
(Lcat), in a manner independent of a functional Apoa1. Here, we performed
a comparative analysis of the functions of these HDL subpopulations.
Specifically, Apoe and Apoa1 double-deficient (<i>Apoe</i><sup><i>–/–</i></sup> × <i>Apoa1</i><sup><i>–/–</i></sup>) mice were infected
with <i>APOA1-</i> or <i>APOE3-</i>expressing
adenoviruses, and APOA1-containing HDL (APOA1-HDL) and APOE3-containing
HDL (APOE3-HDL), respectively, were isolated and analyzed by biochemical
and physicochemical methods. Western blot and lipidomic analyses indicated
significant differences in the apolipoprotein and lipid composition
of the two HDL species. Moreover APOE3-HDL presented a markedly reduced
antioxidant potential and Abcg1-mediated cholesterol efflux capacity.
Surprisingly, APOE3-HDL but not APOA1-HDL attenuated LPS-induced production
of TNFα in RAW264.7 cells, suggesting that the anti-inflammatory
effects of APOA1 are dependent on APOE expression. Taken together,
our data indicate that APOA1 and APOE3 recruit different apolipoproteins
and lipids on the HDL particle, leading to structurally and functionally
distinct HDL subpopulations. The distinct role of these two apolipoproteins
in the modulation of HDL functionality may pave the way toward the
development of novel pharmaceuticals that aim to improve HDL functionality