👤 Puya Yazdi

Apolipoprotein B is an essential causal marker of cardiovascular disease. Studies have attempted to understand the impact of fatty acids on cardiovascular disease risk by measuring changes in apolipoprotein B. Linoleic acid is an omega-6 polyunsaturated fatty acid that has demonstrated effects on cardiovascular disease outcomes. This study attempts to investigate the causal association of plasma concentrations of linoleic acid with apolipoprotein B via Mendelian Randomization, in addition to confounders of this relationship. The UK Biobank was used to obtain participant data for omega-6 polygenic risk scores, linoleic acid, and apolipoprotein B concentrations, in addition to confounding variable data. This study excluded individuals with a cardiovascular disease diagnosis or taking cholesterol-lowering medications. Multivariable regression was utilized to identify statistically significant impacts on apolipoprotein B, followed by Mendelian Randomization via two-stage least-squares analysis. Multivariable regression identified a statistically significant association of apolipoprotein B with linoleic acid, monounsaturated fatty acids, saturated fatty acids, age, sex, fasting, BMI, alcohol intake frequency, vigorous exercise, and smoking status. Two-stage least-squares analysis found a statistically significant causal association of genetically predicted linoleic acid on apolipoprotein B concentration (b = 0.23; 95 % CI: 0.207-0.243; p < 0.001), with the first stage of the analysis yielding an eigenvalue of 755.79 and F-statistic of 2796.93 and the second stage of the analysis yielding a statistically significant Wald χ This study demonstrates a causal association of linoleic acid with apolipoprotein B concentrations. Future studies should evaluate this association and the confounders of this relationship. Show less

Although primary cilia are well established as important sensory and signaling structures, their function in most tissues remains unknown. Obesity is a feature associated with some syndromes of cilia dysfunction, such as Bardet-Biedl syndrome (BBS) and Alström syndrome, as well as in several cilia mutant mouse models. Recent data indicate that obesity in BBS mutant mice is due to defects in leptin receptor trafficking and leptin resistance. Furthermore, induction of cilia loss in leptin-responsive proopiomelanocortin neurons results in obesity, implicating cilia on hypothalamic neurons in regulating feeding behavior. Here, we directly test the importance of the cilium as a mediator of the leptin response. In contrast to the current dogma, a longitudinal study of conditional Ift88 cilia mutant mice under different states of adiposity indicates that leptin resistance is present only when mutants are obese. Our studies show that caloric restriction leads to an altered anticipatory feeding behavior that temporarily abrogates the anorectic actions of leptin despite normalized circulating leptin levels. Interestingly, preobese Bbs4 mutant mice responded to the anorectic effects of leptin and did not display other phenotypes associated with defective leptin signaling. Furthermore, thermoregulation and activity measurements in cilia mutant mice are inconsistent with phenotypes previously observed in leptin deficient ob/ob mice. Collectively, these data indicate that cilia are not directly involved in leptin responses and that a defect in the leptin signaling axis is not the initiating event leading to hyperphagia and obesity associated with cilia dysfunction. Show less