Journal of Lipids最新文献

Background: G1, a specific agonist targeting the G protein-coupled receptor 30 (GPR30), has demonstrated significant involvement in combating obesity and regulating glucose homeostasis. Nevertheless, the beneficial effects of G1 treatment have solely been investigated in animal models under normal feeding conditions, leaving its therapeutic potential in high-fat feeding scenarios unexplored. Material and Methods: To address this gap, our study employed an ovariectomized high-fat diet mouse model to assess the therapeutic effects of G1 in combating obesity and metabolic dysfunction. Results: The findings revealed that G1 treatment resulted in weight loss, but concurrently led to increased blood glucose levels and insulin resistance. Treatment with G1 resulted in an amplification of fat mobilization and an enhancement of pyruvate carboxylase activity in mice fed a high-fat diet. Moreover, the combined impact of G1 treatment and a high-fat diet on pyruvate metabolism, as well as the regulation of crucial gluconeogenesis enzymes such as pyruvate dehydrogenase kinase 4 (PDK4), phosphoenolpyruvate carboxykinase (PEPCK), and glucose transporter 2 (GLUT2), expedites the elevation of blood glucose and the progression of insulin resistance. Conclusions: These findings indicate that G1 treatment is influenced by a high-fat diet, potentially disrupting glucolipid metabolism and promoting insulin resistance alongside its antiobesity effects. Consequently, further investigation is imperative to thoroughly explore this potential toxic side effect of G1 therapy.

Recent evidence suggests that the majority of cholesterol-laden cells found in atherosclerotic lesions are vascular smooth muscle cells (VSMC) that have transdifferentiated into macrophage-like cells (MLC). Furthermore, cholesterol-laden MLC of VSMC origin have demonstrated impaired ABCA1-dependent cholesterol efflux, but it is poorly understood why this occurs. A possible mechanism which may at least partially be attributed to cholesterol-laden MLC demonstrating attenuated ABCA1-dependent cholesterol efflux is a miR-33a expression, as a primary function of this microRNA is to silence ABCA1 expression, but this has yet to be rigorously investigated. Therefore, the VSMC line MOVAS cells were used to generate miR-33a knockout (KO) MOVAS cells, and we used KO and wild-type (WT) MOVAS cells to delineate any possible proatherogenic role of miR-33a expression in VSMC. When WT and KO MOVAS cells were cholesterol-loaded to convert into MLC, this resulted in the WT MOVAS cells to exhibit impaired ABCA1-dependent cholesterol efflux. In the cholesterol-loaded WT MOVAS MLC, we also observed a delayed restoration of the VSMC phenotype when these cells were exposed to the ABCA1 cholesterol acceptor, apoAI. These results imply that miR-33a expression in VSMC drives atherosclerosis by triggering MLC transdifferentiation via attenuated ABCA1-dependent cholesterol efflux.

Cardiovascular disease causes significant personal, financial, and societal burden and is a major cause of mortality and morbidity globally. Dyslipidemia has proven to be a major factor that contributes to its increased incidence; thus, since a long time, low-density lipoprotein cholesterol-lowering therapies have been employed to reduce coronary artery disease-associated mortality. The first-line therapy for hyperlipidemia and dyslipidemia is statins. Evidence showed that statins decrease the level of LDL-C resulting in a lower risk of CVD (20-25% for every decrease of 1 mmol/L). However, due to statin intolerance in some patients and despite using maximal doses, they have not been successful in lowering cardiovascular-associated mortality. Moreover, bococizumab was recently suspended due to its higher immunogenicity with time, resulting in less efficacy with long-term use. Alternatives to statins are PCSK9 inhibitors which are administered subcutaneously every two or four weeks. They are injectables with considerable lipid-lowering properties. This narrative review discusses their genetics, safety, tolerability, and cost-effectiveness. It also quantifies their benefit in certain subgroups by analyzing the findings from recent randomized clinical trials. Current data from phase 2 and 3 trials (ORION, ODYSSEY, and FOURIER) suggest a favorable profile for evolocumab, alirocumab, and inclisiran with minimal tolerable side effects and superior efficacy in statin-intolerant patients. Their cost-effectiveness has not yet been established clearly, but future outcomes seem promising.

Phospholipids are asymmetrically distributed across mammalian plasma membrane. The function of P4-ATPases is to maintain the abundance of phosphatidylserine (PS) and phosphatidylethanolamine (PE) in the inner leaflet as lipid flippases. Transmembrane protein 30A (TMEM30A, also named CDC50A), as an essential β subunit of most P4-ATPases, facilitates their transport and functions. With TMEM30A knockout mice or cell lines, it is found that the loss of TMEM30A has huge influences on the survival of mice and cells because of PS exposure-triggered apoptosis signaling. TMEM30A is a promising target for drug discovery due to its significant roles in various systems and diseases. In this review, we summarize the functions of TMEM30A in different systems, present current understanding of the protein structures and mechanisms of TMEM30A-P4-ATPase complexes, and discuss how these fundamental aspects of TMEM30A may be applied to disease treatment.

Lipoproteins are among the contributors of energy for the survival of cancer cells. Studies indicate there are complex functions and metabolism of lipoproteins in cancer. The current review is aimed at providing updates from studies related to the monitoring of lipoproteins in different types of cancer. This had led to numerous clinical and experimental studies. The review covers the major lipoproteins such as LDL cholesterol (LDL-C), oxidized low-density lipoprotein cholesterol (oxLDL-C), very low-density lipoprotein cholesterol (VLDL-C), and high-density lipoprotein cholesterol (HDL-C). This is mainly due to increasing evidence from clinical and experimental studies that relate association of lipoproteins with cancer. Generally, a significant association exists between LDL-C with carcinogenesis and high oxLDL with metastasis. This warrants further investigations to include Mendelian randomization design and to be conducted in a larger population to confirm the significance of LDL-C and its oxidized form as prognostic markers of cancer.

Background: Familial hypercholesterolemia (FH) is a common autosomal dominant disease. Its diagnosis in Iran was uncommon. Iran registry of FH (IRFH) has been started from 2017 from Isfahan. In this study, we report the four-year FH registry.

Methods: The Iran FH registry is an ongoing study which is followed by a dynamic cohort. It has been started from 2017. The patients are selected from laboratories due to high cholesterol level and who have history of premature cardiovascular disease. The Dutch Lipid Clinic Network (DLCN) criteria are used for the detection of FH. Cascade screening is performed for detection of first-degree relative of patients.

Results: Among the 997 individuals included in this registry, they were 522 (mean age 51.41 ± 12.91 year), 141 (mean age 51.66 ± 8.3 year), and 129 (mean age 41 ± 16.5 year) patients from laboratories, premature cardiovascular disease, and relatives, respectively. In total, 263 patients were diagnosed with probable or definite FH, and others were in the possible group. Low-density lipoprotein cholesterol (LDL) level was 141.42 ± 45.27 mg/dl in the laboratory group and 54.9% of patients were on LLT treatment. In patients with premature cardiovascular disease and FH, the LDL level was 91.93 ± 32.58 and was on LLT treatment. The LDL concentration in the first relative of FH patients was 152.88 ± 70.77 and 45.7% of them are on LLT therapy.

Conclusions: Most of FH patients were underdiagnosed and undertreated before their inclusion in the IRFH. Cascade screening helps in the improvement of diagnosis.

The present study consists of analyzing the phytochemical composition of Ipomoea batatas leaf powders and evaluating their antihyperlipidemic effect on rats receiving a high-fat diet. Ipomoea batatas leaves were collected from four agroecological areas of Cameroon, and powders were obtained after washing, drying, grinding, and sieving. Standard analytical methods were used to determine the phytochemical composition of two varieties (IRAD-tib1yellow-V1 and IRAD-1112white-V2) from North Z1, Adamawa Z2, West Z3, Center Z4. The effect of I. batatas leaf powder on lipid metabolism was assessed in vivo by feeding different groups of rats with a high-fat diet supplemented with 5 and 10% of I. batatas leaf powder during 30 days. At the end of the experimentation, total cholesterols, triglycerides, LDL- (low-density lipoprotein-) cholesterol, HDL- (High-density lipoprotein-) cholesterol, ASAT (aspartate aminotransferase), ALAT (alanine aminotransferase), and creatinine were measured using commercial enzymatic kits (Spinreact, Spain). The results of phytochemical analysis of I. batatas leaf powders revealed that the total phenol content ranged from 660.173 mg GAE/100 gDW (Z1V2) to 657.76 mg GAE/100 gDW (Z3V2), the flavonoids content ranged from 282.25 mgEC/100 gDW (Z3V1) to 325.05 mgEC/100 gDW (Z4V2), and the anthraquinone content ranged from 324.05 mg/100 gDW (Z3V2) to 326.72 mg/100 gDW (Z4V2). The total antioxidant capacity ranged from 19.00 (Z1V1) to 23.48 mg AAE/gDW (Z3V2), while the IC₅₀ ranged from 1.58 mg/mL (Z1V1) to 3.08 mg/mL (Z3V2). Rats fed a high-fat diet and supplemented with 5 and 10% of I. batatas leaf powder showed a significant (p < 0.05) reduction in body weight compared to the control with a reduction rate ranging from 6 to 10%. The consumption of I. batatas leaf powder for 30 days significantly (p < 0.05) reduced serum total cholesterol, LDL-cholesterol, triglycerides, ALAT, and creatinine level. These results suggest the use of I. batatas leaves as a phytomedicine in the treatment of cardiovascular diseases.