Background: Lipoprotein lipase (LPL) and serum 25-hydroxyvitamin D [25(OH)D] play important roles in the regulation of lipid metabolism. Although dyslipidemia is associated with insulin resistance (IR) and type 2 diabetes (T2D), there are limited data available regarding the relationship of LPL and 25(OH)D to IR and T2D at a population level. The objective of the present study is to investigate the associations of LPL and 25(OH)D with IR and T2D in a Chinese population. Methods: The study cohort consisted of 2708 subjects (1326 males, 1382 females; mean age 48.5 ± 12.6 years) in main communities of Harbin, China. Serum 25(OH)D, LPL, free fatty acids (FFAs), fasting glucose (FG), fasting insulin, lipid profile, apoA and apoB concentrations were measured. Results: Serum 25(OH)D concentration was positively associated with LPL (β = 0.168, P < 0.001). LPL was inversely associated with IR and T2D. Subjects in the lowest quartile of LPL had the highest risk of IR [odds ratio (OR) = 1.85, 95% CI = 1.22-2.68] and T2D (OR = 1.65, 95% CI = 1.14-2.38). Serum 25(OH)D was also inversely associated with IR and T2D. Vitamin D deficiency [25(OH)D < 20 ng/ml] was associated with an increasing risk of IR (OR = 1.91, 95% CI = 1.23-2.76) and T2D (OR = 2.06, 95% CI = 1.37-3.24). The associations of 25(OH)D with IR and T2D were attenuated by further adjustment for LPL. Conclusions: LPL is associated with serum 25(OH)D, IR and T2D in the Chinese population. These results suggest a potential mediating role of LPL in the associations of 25(OH)D with IR and T2D.

Background: Calcium deficiency is a global public-health problem. Although the initial stage of calcium deficiency can lead to metabolic alterations or potential pathological changes, calcium deficiency is difficult to diagnose accurately. Moreover, the details of the molecular mechanism of calcium deficiency remain somewhat elusive. To accurately assess and provide appropriate nutritional intervention, we carried out a global analysis of metabolic alterations in response to calcium deficiency. Methods: The metabolic alterations associated with calcium deficiency were first investigated in a rat model, using urinary metabonomics based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry and multivariate statistical analysis. Correlations between dietary calcium intake and the biomarkers identified from the rat model were further analyzed to confirm the potential application of these biomarkers in humans. Results: Urinary metabolic-profiling analysis could preliminarily distinguish between calcium-deficient and non-deficient rats after a 2-week low-calcium diet. We established an integrated metabonomics strategy for identifying reliable biomarkers of calcium deficiency using a time-course analysis of discriminating metabolites in a low-calcium diet experiment, repeating the low-calcium diet experiment and performing a calcium-supplement experiment. In total, 27 biomarkers were identified, including glycine, oxoglutaric acid, pyrophosphoric acid, sebacic acid, pseudouridine, indoxyl sulfate, taurine, and phenylacetylglycine. The integrated urinary metabonomics analysis, which combined biomarkers with regular trends of change (types A, B, and C), could accurately assess calcium-deficient rats at different stages and clarify the dynamic pathophysiological changes and molecular mechanism of calcium deficiency in detail. Significant correlations between calcium intake and two biomarkers, pseudouridine (Pearson correlation, r = 0.53, P = 0.0001) and citrate (Pearson correlation, r = -0.43, P = 0.001), were further confirmed in 70 women. Conclusions: To our knowledge, this is the first report of reliable biomarkers of calcium deficiency, which were identified using an integrated strategy. The identified biomarkers give new insights into the pathophysiological changes and molecular mechanisms of calcium deficiency. The correlations between calcium intake and two of the biomarkers provide a rationale or potential for further assessment and elucidation of the metabolic responses of calcium deficiency in humans.

Lipid overload contributes to cardiac complications of diabetes and obesity. However, the underlying mechanisms remain obscure. This study investigates the role of gamma-aminobutyrate transaminase (ABAT), the key enzyme involved in the catabolism of γ-aminobutyric acid (GABA), in lipid overload-induced cardiac injury. Microarray revealed a down-regulation of ABAT mRNA expression in high fat diet (HFD)-fed mouse hearts, which correlated with a reduction in ABAT protein level and its GABA catabolic activity. Transgenic mice with cardiomyocyte-specific ABAT over-expression (Tg-ABAT/tTA) were generated to determine the role of ABAT in lipid overload-induced cardiac injury. Feeding with a HFD to control mice for 4 months reduced ATP production and the mitochondrial DNA copy number, and induced myocardial oxidative stress, hypertrophy, fibrosis and dysfunction. Such pathological effects of HFD were mitigated by ABAT over-expression in Tg-ABAT/tTA mice. In cultured cardiomyocytes, palmitate increased mitochondrial ROS production, depleted ATP production and promoted apoptosis, all of which were attenuated by ABAT over-expression. With the inhibition of ABAT’s GABA catabolic activity, the protective effects of ABAT remained unchanged in palmitate-induced cardiomyocytes. Thus, ABAT protects the mitochondrial function in defending the heart against lipid overload-induced injury through mechanisms independent of its GABA catabolic activity, and may represent a new therapeutic target for lipid overload-induced cardiac injury.

Oversupply of bulk saturated fatty acids (SFA) induces metabolic disorders and myocardial dysfunction. We investigated whether, without causing metabolic disorders, the uptake of individual dietary SFA species alters lipid profiles and induces myocardial dysfunction. C57BL/6 mice were fed various customized long-chain SFA diets (40% caloric intake from SFA), including a beef tallow (HBD), cocoa butter (HCD), milk fat (HMD) and palm oil diet (HPD), for 6 months. An isocaloric fat diet, containing medium-chain triglycerides, served as a control (CHD). Long-term intake of dietary long-chain SFA differentially affected the fatty acid composition in cardiac phospholipids. All long-chain SFA diets increased the levels of arachidonic acid and total SFA in cardiac phospholipids. The preferential incorporation of individual SFA into the cardiac phospholipid fraction was dependent on the dietary SFA species. Cardiac ceramide content was elevated in all mice fed long-chain SFA diets, while cardiac hypertrophy was only presented in mice fed HMD or HPD. We have demonstrated that the intake of long-chain SFA species differentially alters cardiac lipid profiles and induces cardiac dysfunction, without causing remarkable metabolic disorders.

Early identification of individuals at risk for gestational diabetes mellitus (GDM) is essential for mitigating its adverse effects on both maternal and foetal health. This study aimed to evaluate the predictive value of the cardiometabolic index (CMI), systemic inflammation response index (SIRI), and serum adipsin levels for GDM. A total of 1660 pregnant women were enrolled in this study conducted in Suzhou, China. Baseline clinical data, including blood glucose levels, lipid profiles, and blood cell counts, were collected at 12 weeks of gestation. GDM was diagnosed between 24 and 28 weeks of gestation. Logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the associations and predictive performance of CMI, SIRI, and adipsin for GDM. Compared with non-GDM participants, those with GDM exhibited significantly higher CMI and SIRI values and lower serum adipsin levels at baseline. Increased CMI and SIRI, as well as reduced adipsin levels, were independently associated with a higher risk of GDM in both unadjusted and adjusted models (all P < 0.05). The composite model incorporating all three biomarkers achieved a higher area under the curve (AUC) of 0.918 compared with the individual models for CMI (AUC = 0.825), SIRI (AUC = 0.802), and adipsin (AUC = 0.724). CMI, SIRI, and serum adipsin are independently associated with GDM risk, and their combination provides a promising multi-biomarker strategy for early GDM prediction. Further studies are needed to validate these findings in diverse populations.

Vitamin D deficiency and inadequate calcium intake are supposed to be potentially related to cardiovascular outcomes, however, their combined association with hypertension remains unclear. In this cross-sectional study among 2,352 subjects, dietary calcium intake was assessed by using a valid food frequency questionnaire, and serum 25-hydroxyvitamin D (25OHD) was measured by the Ultra Performance Liquid Chromatography system. Hypertension was defined as a level of systolic pressure ≥140 mmHg or diastolic pressure ≥90 mmHg, or both, or administration of antihypertensive medications. Vitamin D status was classified into deficiency (25OHD<20 ng/mL), insufficiency (20 ng/mL≤25OHD<30 ng/mL) and sufficiency (25OHD≥30 ng/mL), while dietary calcium intake was divided into tertiles as low, medium, and high. Two-way analysis of variance (ANOVA) and multivariable logistic regression models were adopted. A significant interaction between vitamin D status and dietary calcium intake in relations to systolic blood pressure (p=0.042) and hypertension (p=0.029) indicates the associations of dietary calcium intake with systolic blood pressure and hypertension depend on the vitamin D status, and vice versa. Only in the vitamin D deficiency group, dietary calcium intake was significantly associated with systolic blood pressure level (β=−0.162, p<0.001) and prevalence of hypertension (odd ratio=2.20, p<0.001). The significance was not substantially compromised after further adjustment for confounding factors. In conclusion, the combination of vitamin D deficiency and low dietary calcium intake, rather than alone, is associated with hypertension.