Aims Metabolic syndrome (MetS) is diagnosed using fixed thresholds that may not fully reflect the continuous accumulation of cardio-metabolic risk. We investigated whether whole blood viscosity (WBV) increases progressively with increasing MetS burden and explored the relative contribution of individual MetS components to hemorheologic alterations. Methods We analyzed 38,574 adults (21,914 men and 16,660 women) who underwent comprehensive health examinations between January and April 2021. Whole blood viscosity was measured by cone-plate viscometry at shear rates of 300 s-1 (systolic blood viscosity [SBV]) and 5 s-1 (diastolic blood viscosity [DBV]). MetS was defined according to NCEP-ATP III criteria. Associations between WBV and MetS burden were evaluated using logistic regression, ANCOVA, regression tree analyses, ROC analyses, and sex-by-viscosity interaction testing. Results WBV increased progressively with each additional MetS component in both sexes (p for trend <0.001). After full adjustment for hematocrit, age, smoking status, eGFR, white blood cell count, and AST/ALT, higher SBV was associated with MetS in both women (OR 1.45, 95% CI 1.32–1.58, per 1-SD increase) and men (OR 1.27, 95% CI 1.22–1.33, per 1-SD increase). Regression tree analyses identified triglycerides and waist circumference as metabolic factors associated with elevated WBV. Sex-stratified analyses demonstrated a stronger association between WBV and MetS in women than in men. Conclusions WBV increased in parallel with accumulating cardio-metabolic risk burden, including among individuals who did not meet diagnostic criteria for MetS. WBV may serve as a complementary marker associated with metabolic risk burden, particularly among women and individuals with hypertriglyceridemia or central adiposity.
D. Lee, Byoungduck Han, Hongyup Ahn et al.· Frontiers in Endocrinology· 0 citations
BACKGROUND AND PURPOSE
Lobeglitazone is a thiazolidinedione and PPARγ agonist that improves metabolic parameters and hepatic steatosis, but its mechanisms are not fully understood. This study investigated the effects of lobeglitazone on hepatic transcriptomic and metabolic profiles in a rat model of obesity and Type 2 diabetes mellitus.
EXPERIMENTAL APPROACH
Male Otsuka Long-Evans Tokushima fatty rats were fed a high-fat, high-carbohydrate (HF/HC) diet for 15 weeks and treated with lobeglitazone or vehicle. Metabolic parameters, liver function and histology were assessed. RNA sequencing was conducted to identify changes in hepatic gene expression, and metabolomic profiling was performed on liver and plasma samples. Mechanistic validation was conducted in HepG2 cells using siRNA-mediated PPARγ knockdown.
KEY RESULTS
Lobeglitazone treatment improved glucose tolerance and decreased plasma triglyceride and total cholesterol levels. Histological analyses indicated reduced hepatic steatosis, ballooning and lobular inflammation, reflecting protection against hepatic steatosis. RNA sequencing revealed 334 DEGs between the HF/HC-lobeglitazone and HF/HC groups, with pathway enrichment analyses indicating modulation of pathways related to central carbon metabolism. Five pyruvate metabolism-associated genes were down-regulated by lobeglitazone. Quantitative PCR confirmed selected transcriptomic changes, although mitochondrial pyruvate carrier (MPC) 1 and 2 mRNA levels were not significantly altered. In contrast, MPC1 and MPC2 protein levels were markedly reduced. Metabolomics showed increased hepatic and plasma pyruvate, amino acids involved in pyruvate production and hydroxybutyrates, suggesting reduced mitochondrial pyruvate flux. Functional assays demonstrated decreased mitochondrial pyruvate levels following lobeglitazone treatment. PPARγ knockdown abolished lobeglitazone-induced down-regulation of MPC proteins.
CONCLUSIONS AND IMPLICATIONS
Lobeglitazone treatment was associated with improved hepatic steatosis and liver-associated metabolic parameters, accompanied by transcriptional and metabolomic changes related to mitochondrial pyruvate metabolism. These findings are correlative and provide new insights into the hepatic actions of lobeglitazone in metabolic disease.
Hyekyung Yang, S. Son, Youngmi Song et al.· British Journal of Pharmacol...· 0 citations
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