Potential implication of serum lipid levels as predictive indicators for monitoring oral lichen planus.

Compelling evidence indicates that dyslipidemia is positively associated with oral lichen planus (OLP). The types and magnitude of lipid metabolism disturbance in peripheral blood of OLP patients have been investigated in different studies. Yet, consensus on how these different lipid components varied in levels for the development of OLP lesions has not been reached so far. Herein, a total of 8 eligible studies were recognized, which enrolled 533 cases of OLP and 499 healthy controls. The analysis showed that the average total triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) levels were considerably higher, and high-density lipoprotein cholesterol (HDL-C) levels were significantly lower in OLP patients compared to healthy controls. Collectively, the lipid profile panel maybe serve as the potential predictive indicator for screening OLP.

Consumption of ultra-processed foods could influence the metabolic syndrome odds: A cross-sectional study.

Metabolic syndrome (MetS) prevalence has augmented globally during recent decades. Over the past years, the consumption of ultra-processed foods (UPFs) has grown significantly worldwide. So, the present research investigated the association between UPFs and MetS in an Iranian sample. This cross-sectional research was conducted on people (n = 8841) in the Fasa cohort study, Fars province, Iran. The participants' dietary consumption over a year, UPF consumption, and MetS diagnosis were evaluated through a 125-item modified food frequency questionnaire, the NOVA food group classification, and the Adult Treatment Panel III of the National Cholesterol Education Program, respectively. The association between the quartiles (Q) of UPF intake and the odds of MetS was estimated using the backward LR method of multivariate analysis. In the multivariate model, after adjusting potential confounders, the association between UPF intake and the odds of MetS was significant (Q4: odds ratio (OR = 3.27; 95% confidence interval (CI): 2.76-3.89). Also, the odds of increasing triglycerides (TG), blood pressure, and fasting blood sugar (FBS) and decreasing high-density lipoprotein cholesterol (HDL-C) were significantly higher in the last quartile compared to the first quartile of UPFs (TG: OR = 1.71; 95% CI: 1.49-1.97, blood pressure: OR = 1.53; 95% CI: 1.30-1.79, FBS: OR = 1.30; 95% CI: 1.10-1.54, and HDL-C: OR = 1.22; 95% CI: 1.08-1.39). The current research found a relationship between UPF intake and MetS and its components, indicating a diet-containing UPFs can be related to the occurrence of noncommunicable diseases.

Lipoprotein alterations in endocrine disorders - a review of the recent developments in the field.

Dyslipidemia is one of the most common disorders worldwide, which, if left untreated, results in a multitude of complications. Thus proper diagnostics, which includes identifying of secondary causes of dyslipidemia is crucial. Endocrine disorders are an important cause of secondary dyslipidemia. This paper aims to review the publications on lipoprotein alterations in endocrine disorders from the past two years and provide an overview of the recent discoveries in this dynamically developing and large field. Significant changes in lipoprotein serum concentrations are present in most endocrinological diseases and can be modified with proper treatment. Some lipoproteins have also been proposed as markers in some endocrine diseases, e.g., thyroid carcinoma. From the scope of endocrine disorders, the largest number of studies explored the lipoprotein changes in polycystic ovary syndrome and in women during the menopausal and peri-menopausal period. Even though the association of thyroid disorders with dyslipidemia is already well studied, new research has delivered some exciting findings about lipoprotein alterations in euthyroid patients with either positive antithyroid peroxidase antibodies or reduced sensitivity to thyroid hormones. The problem of the adverse metabolic profile, including dyslipidemia in hypoprolactinemia has been recognized. Moreover, this review describes other significant discoveries encompassing lipoprotein alterations in disorders of the adrenals, thyroid, parathyroid glands, pituitary, and gonads. The up-to-date knowledge of the influence of endocrine disorders and hormonal changes on serum lipoproteins is prudent as it can significantly impact therapeutic decisions.

Efficacy and Safety of Pemafibrate Extended-Release Tablet: a Phase 3, Multicenter, Randomized, Double-Blind, Active-Controlled, Parallel-Group Comparison Trial.

AIMS: Pemafibrate, a selective peroxisome proliferator-activated receptor α modulator that lowers serum triglyceride levels and increases high-density lipoprotein cholesterol levels, is approved for treating dyslipidemia as twice-daily immediate-release (IR) tablets. A once-daily extended-release (XR) tablet has also been developed. We aimed to confirm the non-inferiority of XR (0.2 or 0.4 mg/day; once daily) to IR (0.2 mg/day; twice daily) in lowering triglyceride levels in patients with hypertriglyceridemia. METHODS: This phase 3, multicenter, randomized, double-blind study included patients with fasting triglycerides ≥ 200 mg/dL who received IR (0.2 mg/day) or XR (0.2 or 0.4 mg/day). The primary efficacy endpoint was the percentage change in fasting triglyceride levels from baseline to 4, 8, and 12 weeks. Common treatment effects at weeks 4 through 12 were compared between groups using repeated analysis of covariance. RESULTS: In 356 randomized patients, fasting triglyceride levels decreased by 48.0%, 43.8%, and 48.0% with IR 0.2, XR 0.2, and XR 0.4 mg/day, respectively, confirming the non-inferiority of both XR regimens to IR. The proportion of patients who achieved fasting triglycerides ＜150 mg/dL was 45.7%, 37.4%, and 51.7%, while the percentage change of triglycerides in the subgroup with baseline triglycerides ≥ 500 mg/dL was -59.3%, -52.2%, and -66.3% with IR 0.2, XR 0.2, and XR 0.4 mg/day, respectively. CONCLUSIONS: XR (0.2 and 0.4 mg/day) was non-inferior to IR (0.2 mg/day). XR 0.4 mg/day demonstrated a more potent triglyceride-lowering effect than XR 0.2 mg/day and should be considered for patients with high triglyceride levels.

Nutrition and Aging in Dogs and Cats.

Aging is often associated with chronic inflammation and declining health. Both veterinarians and owners of aging dogs and cats are interested in nutritional solutions and strategies to prevent signs of age-related disease, increase longevity, and improve quality of life. Physiological decreases in muscle mass, decreased immunity, and a decrease in sense acuity are some of the changes often seen in otherwise healthy senior pets; however, there may also be an increase in risk for pathologies such as renal, cardiovascular, musculoskeletal, and neoplastic diseases. Aging may also lead to cognitive decline and even cognitive dysfunction. Some nutritional strategies that may be helpful with the prevention and treatment of age-related diseases include supplementation with ω3 polyunsaturated fatty acids and antioxidant nutrients that can help modulate inflammation and benefit osteoarthritis, renal disease, cancer, and more. Supplementation with medium-chain triglycerides shows promise in the treatment of canine cognitive dysfunction as these may be metabolized to ketone bodies that are utilized as an alternative energy source for the central nervous system. Additionally, a high intake of dietary phosphorus in soluble and bioavailable forms can lead to renal disease, which is of greater concern in senior pets. There are no published guidelines for nutritional requirements specific to senior pets and as a result, products marketed for senior dogs and cats are highly variable.

Comparative analysis of four nutritional scores in predicting adverse outcomes in biopsy-confirmed diabetic kidney Disease.

Malnutrition is associated with adverse outcomes in patients with diabetic kidney disease (DKD). However, it is uncertain which nutritional assessment tools are most effective in predicting the adverse outcomes of DKD. This retrospective study was conducted at a single center and included 367 patients diagnosed with DKD based on biopsy results between August 2009 and December 2018. Four nutritional assessment indices, namely the Prognostic Nutritional Index (PNI), Geriatric Nutritional Risk Index (GNRI), Triglycerides (TG) × Total Cholesterol (TC) × Body Weight (BW) Index (TCBI), and Controlling Nutritional Status (CONUT) score, were selected and calculated. We aimed to assess the association between these nutritional scores and adverse outcomes, including progression to end-stage kidney disease (ESKD), cardiovascular diseases events (CVD), and all-cause mortality. Univariate and multivariate Cox regression analyses, Kaplan-Meier analysis, along with Restricted cubic spline analysis were used to examine the relationship between nutritional scores and adverse outcomes. Furthermore, the area under the curve (AUC) was calculated using time-dependent receiver operating characteristics to determine the predictive value of the four nutritional scores alone and some combinations. Lastly, ordered logistic regression analysis was conducted to explore the correlation between the four nutritional scores and different renal histologic changes. The incidence of ESKD, CVD, and all-cause mortality was significantly higher in patients with DKD who had a lower PNI, lower GNRI, and higher CONUT score. Additionally, The TCBI performed the worst in terms of grading and risk assessment. The PNI offer the highest predictive value for adverse outcomes and a stronger correlation with renal histologic changes compared to other nutritional scores. Patients diagnosed with DKD who have a worse nutritional status are more likely to experience higher rates of adverse outcomes. The PNI might offer more valuable predictive values and a stronger correlation with different renal histologic changes compared to other nutritional scores.

Prevalence of Metabolic Syndrome and Its Risk Factors Influence on Microvascular Complications in Patients With Type 1 and Type 2 Diabetes Mellitus.

BACKGROUND: Diabetes mellitus (DM) long-term macrovascular and microvascular complications pose significant health risks and increase mortality. In DM patients, metabolic syndrome (MetSy) either precedes or coexists with the condition. Central obesity, poor glycemic control, hypertension, elevated triglycerides (TG), and low high-density lipoproteins (HDL-C) are the components of MetSy. The purpose of this study is to investigate related diabetic microvascular complications in type 1 DM (T1DM) by comparing them with type 2 DM (T2DM), determine potential risk factors, and estimate prevalence based on the diagnosis of MetSy. METHODOLOGY: This study included 160 T1DM and 160 T2DM patients, totaling 320 DM patients. It was carried out from April 20, 2022, to September 31, 2023, at the Sheikh Zayed Hospital, Rahim Yar Khan, in the Outdoor Diabetic Clinic and Medicine Department. A unique questionnaire was utilized to gather socio-demographic, general, clinical, and laboratory data for the MetSy criteria set forth by the International Diabetes Federation (IDF). The blood pressure, BMI, and waist circumference (WC) were measured, while venous fasting blood was used to assess biochemical markers such as HDL-C, TG, and fasting blood sugar. The microvascular diabetes complications were identified using abdominal ultrasound, fundus ophthalmoscopy, and routine laboratory tests. We quantified and analyzed these variables individually for T1DM and T2DM patients with or without MetSy and compared them in the presence or absence of diabetes microvascular complications. RESULTS: MetSy prevalence was 25.62% (41, n=160) for T1DM and 60.62% (97, n=160) for T2DM, totaling 43.12%. Among T1DM patients with MetSy, the majority were married males, aged 36-49 years, with a BMI of 26.69±2.20 kg/m2 and a WC of 85.12±4.23, and 67.5% (108) patients had diabetes microvascular complications. Comparatively, in T2DM with MetSy, the majority were married females aged 50-59 years with a BMI of 29.79 ± 4.65 kg/m² and a large WC of 93.43±4.49, and 75% (123) patients had diabetes microvascular complications. Overall, this study noted significant p-values for hypertension, elevated TG, low HDL-c, high WC, obesity, female gender in T2DM, and above 36 years of age in both groups with MetSy. Diabetic retinopathy (DR) at 32.4% (p<0.001) was the most prevalent T1DM microvascular complication, followed by nephropathy (30.6%), neuropathy (DN) at 28.1%, and gastroparesis (DG) at 22.3%. Whereas in T2DM, the prevalence of DN was 36.3% (p<0.001), followed by DKD (29.3%), DG (28.9%), and DR (24.9%). CONCLUSION: Nearly a quarter of T1DM patients had MetSy, with increasing percentages of overweight and obese patients who are more likely to have DR, DKD, or DN. MetSy affects two-thirds of T2DM patients, with married obese females aged 50-59 being more susceptible than males, who are more likely to suffer DN, DKD, or DG. Risk factors that contribute to the MetSy burden in T1DM and T2DM include hypertension, poor glycemic management, low HDL-C, high TG, and a higher BMI or WC. Increasing age, female gender in T2DM, longer diabetes duration, and co-morbid hypertension were independent predictors of microvascular complications. DR, DN, DKD, and gastroparesis are the most prevalent diabetic microvascular sequelae. The clinical management of diabetic patients with healthy lifestyle adaptations, good glycemic control, antihypertensives, and statins will contribute greatly to MetSy prevention.

The effect of conjugated linoleic acid supplementation in comparison with omega-6 and omega-9 on lipid profile: a graded, dose-response systematic review and meta-analysis of randomized controlled trials.

Conjugated linoleic acid (CLA) is a geometrical isomer of linoleic acid, which has anti-inflammatory, anti-diabetic, anti-cancer, and anti-obesity properties. However, the studies reported inconstant results about the CLA-related effects on lipid profiles. As a result, meta-analysis and systematic review were performed to survey the CLA supplementation-related effect on lipid profile including high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol (TC), and triglycerides (TG). To identify the relevant research, a systematic comprehensive search was initiated on the medical databases such as Scopus and PubMed/Medline until December 2022. The overall effect size was estimated by weighted mean difference (WMD) and 95% confidence interval (CI) in a random effect meta-analysis. In the final quantitative analysis, the meta-analysis considered 35 randomized controlled trials (RCTs) with 1,476 participants (707 controls and 769 cases). The pooled results demonstrated that CLA supplementation, compared with olive oil, significantly increased serum TG levels (WMD: 0.05 mmol/L; 95% CI: 0.01 to 0.1; p = 0.04; I2 = 0.0%, p = 0.91). With regard to TC level, CLA supplementation compared with placebo significantly reduced TC concentrations (WMD: -0.08 mmol/L; 95% CI: -0.14 to -0.02; p < 0.001; I2 = 82.4%). Moreover, the non-linear dose-response analysis indicated a decreasing trend of TC serum level from the 15th week of CLA supplementation compared with olive oil (Pnon-linearity = 0.01). The present meta-analysis and systematic review of 35 RCTs showed that the CLA intervention was able to raise the level of TG in comparison to olive oil; however, it can decrease TC level compared with placebo and olive oil.

Plasma lipids paediatric reference intervals: Indirect estimation using a large 14-year database.

OBJECTIVES: Establishing direct reference intervals (RIs) for paediatric patients is a very challenging endeavour. Indirect RIs can address this problem, using existing clinical laboratory databases from real-world data research. Compared to the traditional direct method, the indirect approach is highly practical, widely applicable, and low-cost. Considering the relevance of dyslipidemia in the paediatric age, to provide better laboratory services to the local paediatric population, we established population-specific lipid RIs via data mining. METHODS: Our laboratory information system was searched for cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) of patients aged less than 18 years, performed from January 2009 until December 2022. RIs were estimated using RefineR algorithm. RESULTS: Values from 215,594 patients were initially collected. After refining data on the basis of specific exclusion criteria that left 17,933 patients, we determined the RIs for each analyte, including corresponding 95% confidence interval (95% CI). Age and sex partitions were required for proper stratification of the heterogenous subpopulations. Age-related variations in TC and TG values were observed mainly in children until 5 years. RIs were defined for children less than 3 years and for those of 3-18 years. In our population, the obtained RIs were comparable with those of the literature, but the upper TG limit in subjects under the age of 3 (2.03 mmol/L with 95% CI: 1.45-2.86) was lower than that previously reported. CONCLUSIONS: Our RIs, necessary for paediatric lipid monitoring, are tailored to the serviced patient population as should be done whenever possible.

StarD5 levels of expression correlate with onset and progression of steatosis and liver fibrosis.

BACKGROUND AND AIMS: Insufficient expression of steroidogenic acute regulatory lipid transfer protein 5 (StarD5) on liver cholesterol/lipid homeostasis is not clearly defined. METHODS: The ablation of StarD5 was analyzed in mice on a normal or western diet (WD) to determine its importance in hepatic lipid accumulation and fibrosis compared to wild type (WT) mice. Rescue experiments in StarD5-/- mice and hepatocytes were performed. RESULTS: In addition to increased hepatic triglyceride/cholesterol levels, global StarD5-/- mice fed a normal diet displayed reduced plasma triglycerides and liver VLDL secretion as compared with WT counterparts. Insulin levels and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) scoring were elevated, demonstrating developing insulin resistance (IR). WD fed StarD5-/- mice up-regulated TAZ expression with accelerated liver fibrosis when compared to WD-fed WT mice. CYP7B1's suppression coupled with chronic accumulation of toxic oxysterol levels correlated with presentation of fibrosis. 'Hepatocyte selective' StarD5 overexpression in StarD5-/- mice restored expression, reduced hepatic triglycerides, and improved HOMA-IR. Observations in 2 additional mouse and one human NASH model were supportive. CONCLUSIONS: StarD5's downregulation with hepatic lipid excess is a previously unappreciated physiologic function appearing to promote lipid storage for future needs. Conversely, StarD5's lingering downregulation with prolonged lipid/cholesterol excess accelerates fatty liver's transition to fibrosis; mediated via dysregulation in the oxysterol signaling pathway.

The Association Between the Triglyceride to High-Density Lipoprotein Cholesterol Ratio and the Incidence of Type 2 Diabetes Mellitus in the Japanese Population.

Abstract Aims: To explore whether the triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C) was independently associated with the risk of incident type 2 diabetes mellitus (T2DM) in a large Japanese cohort. Methods: A secondary analysis was performed using open-access data from a retrospective cohort study. A total of 12,716 eligible participants who had standard medical examinations at the Murakami Memorial Hospital were included in this study. New-onset T2DM was the main outcome during follow-up. The risk of T2DM based on the TG/HDL-C ratio was evaluated using Cox regression analysis and Kaplan-Meier analysis. Subgroup analysis was performed to understand further the significance of the TG/HDL-C ratio in particular populations. To assess the potential of the TG/HDL-C ratio for predicting T2DM, a receiver operating characteristic (ROC) analysis was performed. Results: One hundred fifty new-onset T2DM cases were observed during a median follow-up of 5.39 years. The incidence of T2DM increased with a rise in the TG/HDL-C ratio based on the Kaplan-Meier curves (P < 0.0001). After controlling for potential confounding variables, the TG/HDL-C ratio was positively related to incidence of T2DM (hazard ratio = 1.08, 95% confidence interval: 1.01-1.15, P = 0.0239). In subgroup analysis, those with a body mass index of ≥18.5 and <24 kg/m2 showed a significantly positive relationship. The area under the ROC curve for the TG/HDL-C ratio as a T2DM predictor was 0.684. The optimal TG/HDL-C ratio cutoff value for T2DM was 1.609, with a sensitivity of 54.7% and a specificity of 73.6%. Conclusion: The authors' results showed a significant relationship between the TG/HDL-C ratio and the incidence of T2DM in the Japanese population.

Tracking of serum lipid levels from childhood to adulthood: Systematic review and meta-analysis.

BACKGROUND AND AIMS: The utility of lipid screening in pediatric settings for preventing adult atherosclerotic cardiovascular diseases partly depends on the lifelong tracking of lipid levels. This systematic review aimed to quantify the tracking of lipid levels from childhood and adolescence to adulthood. METHODS: We systematically searched MEDLINE, Embase, Web of Science, and Google Scholar in March 2022. The protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO; ID: CRD42020208859). We included cohort studies that measured tracking of lipids from childhood or adolescence (<18 years) to adulthood (≥18) with correlation or tracking coefficients. We estimated pooled correlation and tracking coefficients using random-effects meta-analysis. Risk of bias was assessed with a review-specific tool. RESULTS: Thirty-three studies of 19 cohorts (11,020 participants) were included. The degree of tracking from childhood and adolescence to adulthood differed among lipids. Tracking was observed for low-density lipoprotein cholesterol (pooled r = 0.55-0.65), total cholesterol (pooled r = 0.51-0.65), high-density lipoprotein cholesterol (pooled r = 0.46-0.57), and triglycerides (pooled r = 0.32-0.40). Only one study included tracking of non-high-density lipoprotein cholesterol (r = 0.42-0.59). Substantial heterogeneity was observed. Study risk of bias was moderate, mostly due to insufficient reporting and singular measurements at baseline and follow-up. CONCLUSIONS: Early-life lipid measurements are important for predicting adult levels. However, further research is needed to understand the tracking of non-high-density lipoprotein cholesterol and the stability of risk classification over time, which may further inform pediatric lipid screening and assessment strategies.

Influencia de la concentración de triglicéridos en la lipoproteína(a) en función de la dislipidemia / Influence of triglyceride concentration in lipoprotein (a) as a function of dyslipidemia

Introducción Recientemente se ha demostrado una relación inversa entre la concentración en sangre de la lipoproteína(a) (Lp[a]) y los triglicéridos (TG). A mayor tamaño de lipoproteínas de muy baja densidad (VLDL), mayor presencia de VLDL ricas en apoliproteína E (apo E) y en sujetos con genotipo apo E2/E2, Lp(a) más baja. El mecanismo de esta asociación contrapuesta es desconocido. El objetivo de nuestro análisis fue evaluar la correspondencia Lp(a)-TG en los pacientes atendidos en las Unidades de Lípidos incluidos en el registro de la Sociedad Española de Arteriosclerosis (SEA) comparando las diferentes dislipidemias. Pacientes y métodos Se incluyeron 5.275 usuarios de ≥ 18 años registrados antes del 31 de marzo de 2023, con datos de concentración de Lp(a) e información completa del perfil lipídico sin tratamiento. Resultados La media de edad fue de 53,0 ± 14,0 años, con 48% de mujeres. Un total de 9,5% (n = 502) tenían diabetes mellitus (DM) y 1.184 sujetos (22,4%) presentaban obesidad. La mediana de TG fue de 130 mg/dL (rango intercuartílico [IQR] 88,0-210) y de Lp(a) 55,0 nmol/L (IQR 17,9 -156). La concentración de Lp(a) mostró una asociación negativa con la de TG cuando los valores de estos superaban los 300 mg/dL. Los pacientes con TG > 1.000 mg/dL mostraron el menor nivel de Lp(a) 17,9 nmol/L y los usuarios con TG < 300 mg/dL, presentaron una media de Lp(a) de 60,1 nmol/L. En pacientes sin DM ni obesidad, la relación inversa de Lp(a)-TG fue especialmente importante (p < 0,001). La mediana de Lp(a) fue de 58,3 nmol/L en aquellos con TG < 300 mg/dL y 22,0 nmol/L si TG > 1.000 mg/dL. No se encontró asociación entre TG y Lp(a) en sujetos con DM y obesidad, ni en los que contaban con hipercolesterolemia familiar (HF). En los que padecen hiperlipemia combinada multifactorial con TG < 300 mg/dL la Lp(a) fue 64,6 nmol/L, en el rango de 300-399 mg/dL de TG la Lp(a) desciende hasta 38,8 nmol/L y hasta 22,3 nmol/L si TG > 1.000 mg/dL. Conclusiones ... (AU)

Background Recently, an inverse relationship between the blood concentration of lipoprotein(a) (Lp(a)) and triglycerides (TG) has been demonstrated. The larger the VLDL particle size, the greater the presence of VLDL rich in apoliprotein E and in subjects with the apoE2/E2 genotype, the lower Lp(a) concentration. The mechanism of this inverse association is unknown. The objective of this analysis was to evaluate the Lp(a)–TG association in patients treated at the lipid units included in the registry of the Spanish Society of Atherosclerosis (SEA) by comparing the different dyslipidemias. Patients and methods Five thousand two hundred and seventy-five subjects ≥18 years of age registered in the registry before March 31, 2023, with Lp(a) concentration data and complete lipid profile information without treatment were included. Results The mean age was 53.0 ± 14.0 years, with 48% women. The 9.5% of subjects (n = 502) had diabetes and the 22.4% (n = 1184) were obese. The median TG level was 130 mg/dL (IQR 88.0–210) and Lp(a) 55.0 nmol/L (IQR 17.9–156). Lp(a) concentration showed a negative association with TG concentration when TG values exceeded 300 mg/dL. Subjects with TG > 1000 mg/dL showed the lowest level of Lp(a), 17.9 nmol/L, and subjects with TG < 300 mg/dL had a mean Lp(a) concentration of 60.1 nmol/L. In subjects without diabetes or obesity, the inverse association of Lp(a)–TG was especially important (p < 0.001). The median Lp(a) was 58.3 nmol/L in those with TG < 300 mg/dL and 22.0 nmol/L if TG > 1000 mg/dL. No association was found between TG and Lp(a) in subjects with diabetes and obesity, nor in subjects with familial hypercholesterolemia. In subjects with multifactorial combined hyperlipemia with TG < 300 mg/dL, Lp(a) was 64.6 nmol/L; in the range of 300–399 mg/dL of TG, Lp(a) decreased to 38. 8 nmol/L, and up to 22.3 nmol/L when TG > 1000 mg/dL. Conclusions ... (AU)

Carboxyl-terminal sequences in APOA5 are important for suppressing ANGPTL3/8 activity.

Apolipoprotein AV (APOA5) lowers plasma triglyceride (TG) levels by binding to the angiopoietin-like protein 3/8 complex (ANGPTL3/8) and suppressing its capacity to inhibit lipoprotein lipase (LPL) catalytic activity and its ability to detach LPL from binding sites within capillaries. However, the sequences in APOA5 that are required for suppressing ANGPTL3/8 activity have never been defined. A clue to the identity of those sequences was the presence of severe hypertriglyceridemia in two patients harboring an APOA5 mutation that truncates APOA5 by 35 residues ("APOA5Δ35"). We found that wild-type (WT) human APOA5, but not APOA5Δ35, suppressed ANGPTL3/8's ability to inhibit LPL catalytic activity. To pursue that finding, we prepared a mutant mouse APOA5 protein lacking 40 C-terminal amino acids ("APOA5Δ40"). Mouse WT-APOA5, but not APOA5Δ40, suppressed ANGPTL3/8's capacity to inhibit LPL catalytic activity and sharply reduced plasma TG levels in mice. WT-APOA5, but not APOA5Δ40, increased intracapillary LPL levels and reduced plasma TG levels in Apoa5-/- mice (where TG levels are high and intravascular LPL levels are low). Also, WT-APOA5, but not APOA5Δ40, blocked the ability of ANGPTL3/8 to detach LPL from cultured cells. Finally, an antibody against a synthetic peptide corresponding to the last 26 amino acids of mouse APOA5 reduced intracapillary LPL levels and increased plasma TG levels in WT mice. We conclude that C-terminal sequences in APOA5 are crucial for suppressing ANGPTL3/8 activity in vitro and for regulating intracapillary LPL levels and plasma TG levels in vivo.

Activation of hepatic acetyl-CoA carboxylase by S-nitrosylation in response to diet.

Nitric oxide (NO), produced primarily by nitric oxide synthase (NOS) enzymes, is known to influence energy metabolism by stimulating fat uptake and oxidation. The effects of NO on de novo lipogenesis, however, are less clear. Here we demonstrate that hepatic expression of eNOS is reduced following prolonged administration of a hypercaloric high-fat diet. This results in marked reduction in the amount of S-nitrosylation of liver proteins including notably Acetyl-CoA Carboxylase (ACC), the rate-limiting enzyme in de novo lipogenesis. We further show that ACC S-nitrosylation markedly increases enzymatic activity. Diminished eNOS expression and ACC S-nitrosylation may thus represent a physiological adaptation to caloric excess by constraining lipogenesis. Our findings demonstrate that S-nitrosylation of liver proteins is subject to dietary control and suggest that de novo lipogenesis is coupled to dietary and metabolic conditions through ACC S-nitrosylation.

Quantification of lipoprotein lipase in mouse plasma with a sandwich enzyme-linked immunosorbent assay.

To support in vivo and in vitro studies of intravascular triglyceride metabolism in mice, we created rat monoclonal antibodies (mAbs) against mouse LPL. Two mAbs, mAbs 23A1 and 31A5, were used to develop a sandwich ELISA for mouse LPL. The detection of mouse LPL by the ELISA was linear in concentrations ranging from 0.31 ng/ml to 20 ng/ml. The sensitivity of the ELISA made it possible to quantify LPL in serum and in both pre-heparin and post-heparin plasma samples (including in grossly lipemic samples). LPL mass and activity levels in the post-heparin plasma were lower in Gpihbp1-/- mice than in wild-type mice. In both groups of mice, LPL mass and activity levels were positively correlated. Our mAb-based sandwich ELISA for mouse LPL will be useful for any investigator who uses mouse models to study LPL-mediated intravascular lipolysis.

The causal associations of circulating lipids with Barrett's Esophagus and Esophageal Cancer: a bi-directional, two sample mendelian randomization analysis.

OBJECTIVE: The causal associations of circulating lipids with Barrett's Esophagus (BE) and Esophageal Cancer (EC) has been a topic of debate. This study sought to elucidate the causality between circulating lipids and the risk of BE and EC. METHODS: We conducted two-sample Mendelian randomization (MR) analyses using single nucleotide polymorphisms (SNPs) of circulating lipids (n = 94,595 - 431,167 individuals), BE (218,792 individuals), and EC (190,190 individuals) obtained from the publicly available IEU OpenGWAS database. The robustness and reliability of the results were ensured by employing inverse-variance weighted (IVW), weighted median, MR-Egger, and MR-PRESSO methods. The presence of horizontal pleiotropy, heterogeneities, and stability of instrumental variables were assessed through MR-Egger intercept test, Cochran's Q test, and leave-one-out sensitivity analysis. Additionally, bidirectional MR and multivariable MR (MVMR) were performed to explore reverse causality and adjust for known confounders, respectively. RESULTS: None of the testing methods revealed statistically significant horizontal pleiotropy, directional pleiotropy, or heterogeneity. Univariate MR analyses using IVW indicated a robust causal relationship between increased triglycerides and BE (odds ratio [OR] = 1.79, p-value = 0.009), while no significant association with EC was observed. Inverse MR analysis indicated no evidence of reverse causality in the aforementioned outcomes. In MVMR analyses, elevated triglycerides (TRG) were significantly and positively associated with BE risk (OR = 1.79, p-value = 0.041). CONCLUSION: This MR study suggested that genetically increased triglycerides were closely related to an elevated risk of BE, potentially serving as a biomarker for the diagnosis of BE in the future.

New approaches to triglyceride reduction: Is there any hope left?

Triglycerides play a crucial role in the efficient storage of energy in the body. Mild and moderate hypertriglyceridemia (HTG) is a heterogeneous disorder with significant association with atherosclerotic cardiovascular disease (ASCVD), including myocardial infarction, ischemic stroke, and peripheral artery disease and represents an important component of the residual ASCVD risk in statin treated patients despite optimal low-density lipoprotein cholesterol reduction. Individuals with severe HTG (>1,000 mg/dL) rarely develop atherosclerosis but have an incremental incidence of acute pancreatitis with significant morbidity and mortality. HTG can occur from a combination of genetic (both mono and polygenic) and environmental factors including poor diet, low physical activity, obesity, medications, and diseases like insulin resistance and other endocrine pathologies. HTG represents a potential target for ASCVD risk and pancreatitis risk reduction, however data on ASCVD reduction by treating HTG is still lacking and HTG-associated acute pancreatitis occurs too rarely to effectively demonstrate treatment benefit. In this review, we address the key aspects of HTG pathophysiology and examine the mechanisms and background of current and emerging therapies in the management of HTG.

Diagnostic Accuracy of the Triglyceride-Glucose Index (TyG), TyG Body Mass Index, and TyG Waist Circumference Index for Liver Steatosis Detection.

BACKGROUND: The triglyceride-glucose index (TyG) and a combination of body mass index (BMI) and waist circumference (WC) have been proposed as predictive scores for liver steatosis (LS). The aim of this study was to determine the diagnostic accuracy of these indices compared with controlled attenuation parameters (CAPs) and other predictive scores of LS. METHODS: A retrospective analysis of patients who attended a check-up unit in 2021 was performed. LS was determined by CAP. Anthropometric and biochemical parameters for calculating TyG, TyG-BMI, TyG-WC, fatty liver index, and hepatic steatosis index were obtained. ROC curve was used to establish the best cut-off point of each TyG index for LS detection. The accuracy was determined for all patients, as well as for overweight and diabetic patients. RESULTS: Medical records of 855 patients with a median age of 48 [IQR, 44-54] years and a BMI of 25.7 [IQR 23.4-28.1] kg/m2 were included. According to CAP, LS prevalence was 31.8% (n = 272). TyG-BMI and TyG-WC show better AUCs compared with CAP (0.82, 0.81), FLI (0.96, both), and HSI (0.93, 0.85). For diabetic patients, TyG-WC shows an AUC of 0.70. Meanwhile, TyG-BMI shows better accuracy (0.75) compared with CAP. CONCLUSIONS: TyG-BMI and TyG-WC showed a superior predictive accuracy for detecting LS compared with the TyG index.

Relationships of apolipoprotein E genotypes with a cluster of seven in persons with type 2 diabetes.

OBJECTIVE.: The objective of the study was to determine if there would be statistically significant differences or trends among apolipoprotein E genotypes (2/2, 2/3, 2/4, 3/3, 3/4, and 4/4) for each member of the cluster of seven associated with type 2 diabetes (T2D). The cluster of seven includes abdominal obesity, hypertension, platelet hyperaggregability, hyperglycemia, dyslipidemia (decreased plasma levels of high-density lipoprotein cholesterol (HDL-C) and increased plasma levels of triglycerides)), increased low-density lipoprotein (LDL) oxidation, and increased inflammation. METHODS.: Forty-six patients with well-controlled T2D participated in the study. Abdominal obesity (assessed by waist circumference), hypertension (measured by manual sphygmomanometry), platelet hyperaggregability (measured by bleeding time), hyperglycemia (by enzymatic kit and spectrophotometry), decreased plasma levels of HDL-C and increased plasma levels of triglycerides (by enzymatic kit and spectrophotometry), increased LDL oxidation (measured by LDL conjugated dienes using spectrophotometry) and increased inflammation measured by C-reactive protein (CRP) (by EIA kit) were determined. RESULTS.: All genotypes, except 2/2 were found in the population studied. Abdominal obesity did not vary significantly across the five genotypes. However, glucose levels trended progressively higher going from 2/3 to 2/4 to 3/4 to 4/4. Systolic blood pressure was higher in 3/4 compared to 2/4 and trended higher in 3/4 compared to 3/3. Diastolic blood pressure trended higher in 3/3 vs 2/4 and significantly higher in 3/4 compared to 2/4. Triglycerides trended higher in 3/4 vs 3/3 while HDL-C came close to trending downward in 4/4 compared to 2/4. Bleeding time was unaffected by genotype. Plasma LDL conjugated dienes trended higher in 3/4 vs 2/4 and were significantly higher in 3/4 vs 3/3. CRP trended higher in 4/4 vs 2/3. CONCLUSION.: We can conclude that those with at least one 4 allele in the presence of another allele being 2, 3 or 4 is potentially (in the case of trends) deleterious or is deleterious in terms of hyperglycemia, hypertension (systolic and diastolic blood pressure), dyslipidemia, LDL conjugated dienes and CRP levels.