Genetic insights of blood lipid metabolites on polycystic ovary syndrome risk: a bidirectional two-sample Mendelian randomization study.

Background: Pathologically, metabolic disorder plays a crucial role in polycystic ovarian syndrome (PCOS). However, there is no conclusive evidence lipid metabolite levels to PCOS risk. Methods: In this study, genome-wide association study (GWAS) genetic data for 122 lipid metabolites were used to assign instrumental variables (IVs). PCOS GWAS were derived from a large-scale meta-analysis of 10,074 PCOS cases and 103,164 controls. An inverse variance weighted (IVW) analysis was the primary methodology used for Mendelian randomization (MR). For sensitivity analyses, Cochran Q test, MR-Egger intercept, MR-PRESSO, leave-one-out analysis,and Steiger test were performed. Furthermore, we conducted replication analysis, meta-analysis, and metabolic pathway analysis. Lastly, reverse MR analysis was used to determine whether the onset of PCOS affected lipid metabolites. Results: This study detected the blood lipid metabolites and potential metabolic pathways that have a genetic association with PCOS onset. After IVW, sensitivity analyses, replication and meta-analysis, two pathogenic lipid metabolites of PCOS were finally identified: Hexadecanedioate (OR=1.85,95%CI=1.27-2.70, P=0.001) and Dihomo-linolenate (OR=2.45,95%CI=1.30-4.59, P=0.005). Besides, It was found that PCOS may be mediated by unsaturated fatty acid biosynthesis and primary bile acid biosynthesis metabolic pathways. Reverse MR analysis showed the causal association between PCOS and 2-tetradecenoyl carnitine at the genetic level (OR=1.025, 95% CI=1.003-1.048, P=0.026). Conclusion: Genetic evidence suggests a causal relationship between hexadecanedioate and dihomo-linolenate and the risk of PCOS. These compounds could potentially serve as metabolic biomarkers for screening PCOS and selecting drug targets. The identification of these metabolic pathways is valuable in guiding the exploration of the pathological mechanisms of PCOS, although further studies are necessary for confirmation.

A comparative study to determine the effects of breed and feed restriction on glucose metabolism of chickens.

The glucose metabolism of poultry draws wide attention as they have nearly twice the fasting blood glucose than that of mammals. To define the relationship between glucose metabolism and breed of chicken, the outcomes from different growth rate chickens showed that Arbor Acres (AA) broilers, a well-known fast-growing breed, had a lower fasting blood glucose concentration and glucose clearance rate when compared to Silky chickens, a Chinese traditional medicinal chicken with black skin and a slow growth rate. Moreover, AA broilers had a relatively slow rise in blood glucose in response to oral glucose solution than the Silky chickens on 21 and 42 d (P < 0.05), which is probably attributed to downregulated expression of pancreatic insulin (INS), and upregulated transcription of phosphoenolpyruvate carboxy kinase 1 (PCK1) and glucose transporter 2 (GLUT2) in the liver of AA broilers (P < 0.05). In response to feeding restriction from 7 to 21 d, both the fasting blood glucose and the response speed of AA broilers to oral glucose were increased on d 21 (P < 0.05), and the serum glucose concentrations after 3 weeks compensatory growth were improved by early feed restriction in AA broilers. Feed restriction could also upregulate the mRNA level of pancreatic INS on d 21 and 42, as well as decrease the expressions of PCK1, glucose-6-phosphatase catalytic (G6PC), and GLUT2 in the liver on d 21 (P < 0.05) when compared to the free feeding group. These results revealed that Silky chickens have a stronger capability to regulate glucose homeostasis than AA broilers, and feed restriction could improve the fasting blood glucose and the response to oral glucose of AA broilers.