Potential Mediators of Causal Associations of Circulating Triglycerides With Blood Pressure: Evidence From Genetic and Observational Data.

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.

Effect of Hedan Tablets on Body Weight and Insulin Resistance in Patients with Metabolic Syndrome.

INTRODUCTION: Apart from their recognized lipid-lowering effect, Hedan tablets, a mixture of Chinese herbal medicines, have demonstrated a certain weight-loss effect in clinical practice. The aim of this randomized, double-blind, placebo-controlled study was to verify the effect of Hedan tablets on body weight (BW) and insulin resistance (IR) in patients with metabolic syndrome (MetS). METHODS: A total of 62 eligible patients with MetS were divided into two groups: the treatment group (Hedan tablets at 4.38 g/day tid) and the control group (placebo treatment). Both groups attended follow-ups at 8, 16, and 24 weeks during the process. The parameters of the assessment include lipid level, BW, triglyceride (TG) to high-density lipoprotein cholesterol (HDLc) ratio (TG/HDLc), homeostasis model assessment for IR (HOMA-IR) index, and adiponectin. RESULTS: Patients in the treatment group showed a significant decrease in BW compared to those in the control group (-4.47 vs. 0.06 kg) after 8 weeks of treatment. A significant decrease in body mass index (BMI) was also observed in the treatment group after 16 weeks of treatment (-1.79 vs. -0.03 kg/m2). In the treatment group, 20 out of 31 (64.5%) patients lost 5-10% BW and 4 out of 31 (12.9%) patients lost over 10% BW after 24 weeks of treatment. Although there were no significant changes in the patients' HOMA-IR, the treatment group showed a significant reduction in TG/HDLc (-0.98 vs. -0.19) after 8 weeks of treatment and a significant increase in adiponectin (6.87 vs. -0.43) after 16 weeks of treatment. DISCUSSION/CONCLUSION: The Hedan tablets significantly improve BW, BMI, TG/HDLc, and adiponectin in patients with MetS. Thus, Hedan tablets may be used as an adjunct to existing MetS management methods.

Hyperinsulinemia negatively affects the association between insulin resistance and blood pressure.

BACKGROUND AND AIMS: Although hyperinsulinemia and insulin resistance (IR) together cause metabolic diseases, the available evidence fails to link hyperinsulinemia with blood pressure (BP) elevation. To further understand the role of hyperinsulinemia in the pathophysiology of hypertension, we conducted this study to investigate the moderating effect of fasting insulin (FINS) on the association between IR and BP. METHODS AND RESULTS: The health screening data of 72,076 individuals were analyzed for this moderation analysis. IR was indicated by the homeostatic model assessment of insulin resistance (HOMA-IR), triglyceride-glucose index (TyG), and triglyceride to high-density lipoprotein cholesterol ratio (TG/HDLc). In the adjusted model, three IR indicators were considered independent variables; FINS was used as a moderator, and systolic BP (SBP) and diastolic BP (DBP) were used as dependent variables. The regression coefficient of the interaction term between the three IR indicators and FINS was significantly negative in all moderation models. Simple slope tests and the Johnson-Neymann technique also indicated that FINS negatively moderated the association between IR and BP. CONCLUSIONS: This moderation analysis showed that FINS negatively mediated the association between IR and BP, suggesting that hyperinsulinemia may buffer, not reinforce, the effect of IR on hypertension.

Secretion of Gut Hormones and Expression of Sweet Taste Receptors and Glucose Transporters in a Rat Model of Obesity.

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.