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Background: Existing evidence indicates that elevated triglycerides may affect blood pressure, but the underlying mechanisms are not fully understood. Herein, we aim to identify the intermediaries of associations of triglyceride with systolic blood pressure and diastolic blood pressure using the Mendelian randomization (MR) framework. Methods: Triglyceride-associated single nucleotide polymorphisms were extracted and used to match phenotypes in PhenoScanner. From the broad spectrum of possible triglyceride-associated traits, potential mediators linking triglyceride to blood pressure were screened out by MR and MR-based mediation analysis. Moreover, cross-sectional observational data of 206 341 adults were used to validate the mediators identified at the genetic level. Results: Among the nearly 100 raw phenotypes matched by 313 triglyceride-associated single nucleotide polymorphisms, 39 traits were filtered and integrated into subsequent analysis. By further filtering using MR analysis, only pulse rate and lymphocyte count (LC) were identified as independent mediators. MR-based mediation analysis showed that genetically predicted LC could mediate 9.2% of the association of triglyceride with systolic blood pressure; genetically predicted pulse rate and LC could mediate 18.3% and 17.6% of the association of triglyceride with DBP, respectively. Observational data also support the mediating role of pulse rate and LC. Conclusions: The current findings highlighted the mediating role of pulse rate and LC on the causal pathway from triglyceride to blood pressure and may contribute to a better understanding of the pathogenic mechanism by which high triglyceride affects other cardiometabolic factors.

Objectives: This study was undertaken to compare gut hormone secretion between high-fat-fed and control rats, and to examine the corresponding changes in the expression of sweet taste receptors and glucose transporters in the small intestine and hypothalamus. Methods: Four-week-old male Sprague Dawley rats were fed a standard or high-fat diet for 8 weeks (10 in each group), followed by an oral glucose tolerance test (50% glucose solution, 2 g/kg). Blood was sampled for glucose, insulin, glucagon-like peptide-1 (GLP-1) and polypeptide YY (PYY) assays. One week later, small intestinal and hypothalamic tissue were analyzed for sweet taste receptor and glucose transporter expression by real-time PCR. Results: After oral glucose, plasma GLP-1 concentrations were higher in high-fat-fed than standard-fat-fed rats (group × time interaction, p < 0.01) with significant differences at t = 15 min (p < 0.01) and 30 min (p < 0.05). Plasma PYY concentrations were lower in high-fat-fed than control rats at t = 0, 15 min (p < 0.05, respectively) and 120 min (p < 0.01). There were no differences in the expression of sweet taste receptors or glucose transporters between high-fat-fed and control rats in the duodenum, ileum, or hypothalamus. Conclusions: Changes in GLP-1 and PYY secretion after a high-fat diet appear unrelated to any changes in the expression of sweet taste receptors or glucose transporters. Impaired PYY secretion with high-fat feeding suggests that PYY analogues may provide a potential therapy in the treatment of obesity.

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