👤 Iqra Sohail

Hypertriglyceridemia (HTG) increases cardiovascular and pancreatitis risk. Antisense oligonucleotide (ASO) therapies like volanesorsen and olezarsen target ApoC-III mRNA to reduce ApoC-III, enhancing lipoprotein lipase activity and lowering triglycerides (TGs). This meta-analysis evaluates the efficacy and safety of these ASOs in severe HTG. A systematic review (PROSPERO: CRD42024577110) was conducted following PRISMA, sourcing studies from PubMed, Scopus, Cochrane CENTRAL, and ClinicalTrials.gov until July 2024. Randomized controlled trials (RCTs) involving severe HTG (≥200 mg/dL) treated with volanesorsen or olezarsen vs. placebo were included. Data were synthesized using a random effects model in RevMan 5.4, and bias was assessed with the Cochrane tool. Of 31 identified articles, 9 RCTs (341 patients treated with ASOs, 209 controls) were included. ASOs significantly reduced TG levels [mean difference (MD): -53.72; 95% confidence interval (CI): -77.04 to -30.40; p<0.00001]. Reductions were also seen in very low-density lipoprotein cholesterol (MD: -55.76; p<0.00001), ApoC-III (MD: -74.78; p<0.00001), and APOB48 (MD: -69.45; p<0.00001). Olezarsen uniquely reduced APOB (MD: -15.60; p<0.00001). Non-high-density lipoprotein cholesterol (HDL-C) decreased (MD: -23.25; p<0.00001), while HDL-C increased (MD: +42.14; p<0.00001). Volanesorsen was linked to higher low-density lipoprotein-cholesterol (MD: +62.74; p=0.004). For safety, local injection reactions, thrombocytopenia, and nausea were more common with volanesorsen. Acute pancreatitis occurred only in the placebo group (relative risk: 0.15; p=0.0004), indicating ASO protection. This meta-analysis confirms that ASOs effectively lower TGs and improve lipid profiles in severe HTG. Show less

The melanocortin-4 receptor is a G protein-coupled receptor and a key regulator of appetite and metabolism. It can interact with the melanocortin-receptor accessory protein 2, a single transmembrane helix protein known to interact with several different G protein-coupled receptors. However, the consequences of this interaction are not completely understood. Here we report that co-expression of melanocortin-receptor accessory protein 2 has multiple effects on the melanocortin-4 receptor: it enhances G protein-mediated signaling and simultaneously impairs β-arrestin2 recruitment and, consequently, internalization. In addition, co-expression of melanocortin-receptor accessory protein 2 leads to an increased number of monomers of melanocortin-4 receptor by disrupting receptor oligomers. A structural homology model of the active state melanocortin-4 receptor - melanocortin-receptor accessory protein 2 - Gα Show less

Children with diabetes mellitus (DM) have an increased risk for cardiovascular disease (CVD), a risk potentially exacerbated by elevated lipoprotein(a) (Lp(a)). While other cholesterol parameters are screened in this population, Lp(a) is often overlooked despite being an independent CVD risk factor. Lp(a) levels are historically believed to not change over an individual's life and are genetically determined, but newer literature suggests variation. This study investigated Lp(a) levels and their relationship with glycated hemoglobin A Children and adolescents aged 5 to 18 years with incident DM had baseline Lp(a) and lipid profiles. Repeat Lp(a) and HbA Seventy-six children were included for evaluation: 76% with type 1% and 23% type 2 DM. Baseline median (Q1-Q3) Lp(a) was 43.3 nmol/L (13-73.7 nmol/L), 17 of which were elevated (≥75 nmol/L). Of the 22 participants with follow-up, 8 were abnormal: A total of 4 whose baseline Lp(a) were abnormal remained so and 4 with normal levels became abnormal. A positive correlation was found between 3-month Lp(a) values and HbA Children with DM have abnormal Lp(a) levels at a prevalence of approximately 20%, so this should be considered in CVD risk stratification. Further, observed Lp(a) fluctuations suggest value in serial Lp(a) assessments due to nongenetic influences. Without Lp(a) quantification, CVD risk characterization in children with DM may be inaccurate and should be considered for a comprehensive assessment. Show less

Type 2 diabetes mellitus (T2DM), a metabolic disorder, has the hallmarks of persistent hyperglycemia, insulin resistance, and dyslipidemia. Protein-tyrosine phosphatase 1B (PTP1B) was found to be overexpressed in many tissues in the case of T2DM and involved in the negative regulation of insulin signaling. So, PTP1B inhibition can act as a therapeutic target for T2DM. Numerous studies claimed the anti-inflammatory, hypoglycemic, hepatoprotective, and hypolipidemic activities of Show less