Journal of Lipids最新文献

Paternal exposure to high-fat diets or individual fatty acids (FAs) including arachidonic acid (AA) modifies progeny traits by poorly understood mechanisms. Specific male reproductive system FAs may be involved in paternal inheritance, as they can modify a range of cellular components, including the epigenome. Our objective was to determine FAs in compartments of the male reproductive system that potentially affect ejaculate composition-right and left testicular interstitial fluid (TIF), vesicular gland fluid (VGF), and epididymal adipose tissue (EAT)-in mice exposed to AA or vehicle daily for 10 days (n = 9-10/group). Whole blood (WB) and interscapular brown adipose tissue (IBAT) FA profiles were used as reference. AA significantly affected only VGF FAs relative to vehicle, that is, increased and decreased levels of arachidic and docosahexaenoic acid, respectively, versus vehicle (0.28% ± 0.01% and 0.23% ± 0.03%, respectively, p = 0.049, and 2.42% ± 0.47% and 3.00% ± 0.58%, respectively, p = 0.041). AA affected distinct FAs in WB. Additionally, we uncovered AA-dependent and AA-independent FA laterality. Myristic acid was higher in AA-exposed left versus right TIF (0.68% ± 0.35% and 0.60% ± 0.11%, respectively, p = 0.004). Right TIF contained higher oleic and linoleic acid and lower stearic acid than left TIF (29.01% ± 3.07% and 24.00% ± 2.18%, respectively, p = 0.005; 9.14% ± 1.88% and 7.05% ± 1.36%, respectively, p = 0.005; and 21.90% ± 2.92% and 26.01% ± 2.46%, respectively, p = 0.036), irrespective of exposure to AA. The TIF oleic/stearic acid ratio suggested higher Stearoyl-CoA Desaturase 1 activity in the right versus the left testis (1.35 ± 0.32 and 1.00 ± 0.17, respectively, p = 1.0 × 10^-4). Multitissue comparisons revealed that TIF and VGF FA profiles were distinct from WB, EAT, or IBAT counterparts, suggesting tissue-specific FA fingerprints. In conclusion, AA modulated selected VGF long-chain FAs that may impact on uterine inflammation and subsequent embryonic development. AA altered local FA synthesis or selective uptake, rather than eliciting passive uptake from WB. Additionally, we uncover a significant laterality of testis FAs that may result in asymmetric sperm cell phenotypes.

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.

The study examined Strychnos pungens Soler. (family LOGANIACEAE) fruit as a potential source of vegetable oil. Ripe fruits collected from a forested site in Zimbabwe were processed to determine the partitioning of fresh and dry fruit biomass. The oil was extracted from the seed coat using a hand-operated screw press, and its physiological properties were analyzed. Seeds contributed the most to the fresh weight of the fruit, followed by the shell and pulp. The seed coat was a significant component of the seeds. The seed coat, but not the pulp of the fruit, was found to contain screw press-extractable oil, the yield of which was substantial, amounting to around 39% of the dry weight of the seed coat. The oil was found to have a high free fatty acid content and a moderate iodine value (83 gI₂/100 g), indicating a degree of unsaturation. Furthermore, the oil contained carotenoids and tocols, which serve as antioxidants that help to protect the oil from oxidation. The oil had a high content of monounsaturated oleic acid (78.3%), which is known for its stability and health benefits. The low levels of saturated and polyunsaturated fatty acids make it a high oleic oil. The volatile profile of the oil included compounds with pleasant fruity aromas that enhance its flavour and fragrance. The results highlighted the need for waste management strategies if S. pungens is industrialized as an oil crop. Significant waste, including shells, pulp, cake residue, and seed kernels, would need proper handling and valorisation. In summary, the research showed that S. pungens has the potential to be a valuable source of high-quality vegetable oil with good oxidative stability and health benefits, primarily due to its high content of oleic acid and antioxidant compounds.

Triterpenoids have been identified as potential novel lipid-lowering drugs for the treatment of hypertriglyceridemia. This study investigated the potential antilipogenic and/or antilipolytic effects of two triterpenoids (ARM-2 and RA-5) isolated from the stem bark of Protorhus longifolia (Benrh.) Engl. Employing a combination of in silico predictions and in vitro assays, the interactions between these triterpenoids and key proteins involved in lipogenesis and lipolysis were investigated. In silico molecular docking analysis predicted a favourable binding affinity of both triterpenoids to PPARγ, SREBP-1, and AMPK, with lower binding affinity to C/EBPα, pancreatic lipase, and hormone-sensitive lipase (HSL). Both triterpenoids exhibited in vitro inhibition of pancreatic lipase with K_i and IC₅₀ values ranging from 28.7 to 52.9 μM and 27.6 to 35.8 μM, respectively. Total and neutral lipid accumulation in differentiated 3T3-L1 adipocytes and the oleic acid-induced HepG2 cell model was inhibited, with ARM-2 showing better inhibition than RA-5. In the HepG2 model, the inhibitory activity of the two triterpenoids (at 25 and 100 μM) was comparable to 50 μM lovastatin, although the latter was cytotoxic, whereas both ARM-2 and RA-2 lacked cytotoxicity. Associated gene expression was similar to the effect of simvastatin where the expression of SREBP-1, PPARγ, C/EBPα, and HSL was reduced and that of AMPK was unchanged. In vitro studies confirmed that ARM-2 and RA-5 also inhibited adipocyte lipolysis, where the reduction in glycerol release by 25 and 100 μM was similar to 50 μM lovastatin and simvastatin. This study identifies that the triterpenoids, ARM-2 and RA-5, have the potential to modulate lipogenesis and lipolysis.

Background: Identifying β-cells dysregulation in type 2 diabetes mellitus (T2DM) is crucial. Weight fluctuations are frequently observed during diabetes treatment. However, the relationship between body composition changes and islet β-cell function in individuals with T2DM remains insufficiently investigated. Methods: This retrospective longitudinal study encompassed a cohort of 775 T2DM patients, who underwent body composition measuring using dual-energy X-ray absorptiometry (DEXA) and followed up for a median of 2.29 years. Key metrics included body mass index (BMI), fat mass index (FMI), trunk fat mass index (TFMI), muscle mass index (MMI), appendicular skeletal muscle mass index (ASMI), muscle/fat mass ratio (M/F), and the appendicular skeletal muscle mass/trunk fat mass ratio (A/T) were then categorized and grouped. Insulin, C-peptide, and glucose levels were assessed concurrently following a glucose load. β-cell function included insulin resistance (HOMA-IR), insulin sensitivity (Matsuda index (MI)), and insulin secretion evaluated by HOMA-β and C-peptidogenic index (CGI). Results: Although no significant changes in BMI were observed, patients with T2DM at readmission exhibited higher FMI, TFMI, and ASMI, as well as elevated levels of HOMA-IR, MI, and CGI compared to baseline measurements. And lower MI, higher levels of CGI, and HOMA-IR were observed in BMI increased group. Univariate correlation analysis revealed a negative association between changes in BMI (ΔBMI) and ΔMI, while positive associations were observed in both ΔHOMA-IR and ΔCGI. Among body composition indexes, ΔFMI exhibited the strongest correlation with ΔHOMA-IR (r = 0.255, p < 0.001), and ΔASMI was positively associated with ΔMI and ΔCGI (r = 0.131 and 0.194, respectively). Moreover, increased levels of BMI and FMI were associated with a greater risk of progressive insulin resistance compared to the decreased, whereas the trend was converse in ASMI and A/T. Conclusions: Increased FMI may partially contribute to the deterioration of insulin resistance, while increased ASMI is associated with improved insulin sensitivity and secretion. Maintaining an appropriate BMI and muscle/fat ratio is conductive to prevent the progression of insulin resistance in patients with T2DM.

Adipose tissue is mainly composed by adipocytes. Moreover, mesenchymal stromal/stem cells (MSCs), macrophages, endothelial cells, and extracellular matrix components are present. The variety of molecules as cytokines and growth factors of its structure very rich in blood vessel makes it also similar to a true endocrine organ that however needs still to be fully investigated. In our study, we used human lipoaspirate to obtain mechanically microfragmented fat (MiFAT) which was washed and then devitalized by freezing-thawing cycles. In our experiments, thawed MiFAT was used to stimulate cultures of MSCs from two different sources (adipose tissue and gingiva papilla) in comparison with a traditional stimulation in vitro obtained by culturing MSCs with adipogenic medium. MSCs stimulated with MiFAT showed a very early production of lipid droplets, after only 3 days, that correlated with an increased expression of adipokines. Furthermore, a significant upregulation of PPAR gamma 1 alpha coactivator (PPARGC1A) was observed with an overexpression of uncoupling protein 1 (UCP1) that suggest a pattern of differentiation compatible with the beige-brown fat.

Topical drug delivery employing drug nanocarriers has shown prominent results in treating topical ailments, especially those confined to the skin and eyes. Conventional topical formulations persist with drug and disease-related challenges during treatment. Various nanotechnology-driven approaches have been adopted to mitigate the issues associated with conventional formulations. Among these, cubosomes have shown potential applications owing to their liquid crystalline structure, which aids in bioadhesion, retention, sustained release, and loading hydrophilic and hydrophobic moieties. The phase transition behavior of glyceryl monooleate, the concentration of stabilizers, and critical packing parameters are crucial parameters that affect the formation of cubosomes. Microfluidics-based approaches constitute a recent advance in technologies for generating stable cubosomes. This review covers the recent topical applications of cubosomes for treating skin (psoriasis, skin cancer, cutaneous candidiasis, acne, and alopecia) and eye (fungal keratitis, glaucoma, conjunctivitis, and uveitis) diseases. The article summarizes the manufacturing and biological challenges (skin and ocular barriers) that must be considered and encountered for successful clinical outcomes. The patented products are successful examples of technological advancements within cosmeceuticals that support various topical applications with cubosomes in the pharmaceutical field.

Thyroid hormone (TH) is essential for maintaining normal physiological processes during pregnancy, including the metabolism of energy materials in both the mother and fetus and the growth and development of fetal bone and nervous system. TH can act on the liver, fat, and other tissues and organs to participate in lipid synthesis and breakdown through multiple pathways. Consequently, abnormal thyroid function is often accompanied by lipid metabolism disorders. Both clinical and subclinical hypothyroidism, as well as dyslipidemia during pregnancy, have been shown to be associated with an increased risk of multiple adverse pregnancy outcomes. Recently, there has been an increased interest in studying the alteration of lipidomic and hypothyroidism (both clinical and subclinical hypothyroidism) during pregnancy. Studies have suggested that altered lipid molecules might be used as potential biomarker and associated with adverse maternal and neonatal outcome. Thus, we summarized the associations between lipid metabolism and clinical or subclinical hypothyroidism during pregnancy in this review. Then, we discussed the underlying mechanisms of thyroid dysfunction and lipid metabolism. In addition, we reviewed the possible effect of dyslipidemia on pregnancy and neonatal outcome. However, the relationship between hypothyroidism during pregnancy and changes in the lipid profile and how to intervene in the occurrence and development of adverse pregnancy outcomes require further study.

Background: Diabetic retinopathy (DR) is a diabetic microvascular complication and a leading cause of vision loss. However, there is a lack of effective strategies to reduce the risk of DR currently. The present study is aimed at assessing the causal effect of lipid-regulating targets on DR risk using a two-sample Mendelian randomization (MR) study.

Method: Genetic variants within or near drug target genes, including eight lipid-regulating targets for LDL-C (HMGCR, PCSK9, and NPC1L1), HDL-C (CETP, SCARB1, and PPARG), and TG (PPARA and LPL), were selected as exposures. The exposure data were obtained from the IEU OpenGWAS project. The outcome dataset related to DR was obtained from the FinnGen research project. Inverse-variance-weighted MR (IVW-MR) was used to calculate the effect estimates by each target. Sensitivity analyses were performed to verify the robustness of the results.

Results: There was suggestive evidence that PCSK9-mediated LDL-C levels were positively associated with DR, with OR (95% CI) of 1.34 (1.02-1.77). No significant association was found between the expression of HMGCR- and NPC1L1-mediated LDL-C levels; CETP-, SCARB1-, and PPARG-mediated HDL-C levels; PPARA- and LPL-mediated TG levels; and DR risk.

Conclusions: This is the first study to reveal a genetically causal relationship between lipid-regulating drug targets and DR risk. PCSK9-mediated LDL-C levels maybe positively associated with DR risk at the genetic level. This study provides suggestive evidence that PCSK9 inhibition may reduce the risk of DR.

Background: Dyslipidemia, an abnormally high level of lipids in the blood, has a negative impact on the health status of the individual and has lately emerged as a major public health concern, especially for low- and middle-income countries (LMIC) globally, including Ghana. However, it is still unclear what the burden and drivers of these lipid abnormalities are, especially among lactating women in the Upper West of Ghana. Thus, this study is aimed at determining the prevalence of dyslipidemia and its associated factors among lactating mothers in the Wa Municipality of Ghana. Methodology. A cross-sectional study was conducted from May to June 2020 in 8 health facilities within the Wa Municipality. Multistage and simple random sampling methods were used to select the facilities and the 200 study subjects. Sociodemographic data were collected using questionnaires, while blood samples were taken to determine the lipid profile of participants. Dietary patterns were also assessed using the Food Frequency Questionnaire (FFQ). Data were processed and analyzed using SPSS 17 software (SPSS, Inc., Chicago, IL). The chi-square test and multiple regression analysis were performed to determine the predictors associated with the various types of dyslipidemia, with statistical significance set at a p value < 0.05.

Results: The prevalence of hypercholesterolemia (LDL-C), hypo-HDL-cholesterolemia, and hypertriglyceridemia (TG) was 57%, 59%, and 22%, respectively. Chi-square and multinomial regression analysis revealed that duration of lactation (X² = 3.95, p = 0.047), religion (AOR = 0.375, 95% CI 0.144-0.978, p = 0.045), low income (AOR = 0.116, 95% CI 0.026-0.514, p = 0.005), middle income (AOR = 0.163, 95% CI 0.044-0.600, p = 0.006), and alcohol intake (AOR = 6.312, 95% CI 1.108-35.949, p = 0.038) were associated with LDL-C, while age (AOR = 0.963, 95% CI 0.910-1.019, p < 0.001) and educational status (AOR = 0.365, 95% CI 0.140-0.954, p = 0.040) predicted HDL status.

Conclusion: Dyslipidemia is common among lactating mothers of Wa Municipality, and it is predicted by lifestyle factors. Furthermore, future research to look at a larger sample size on dyslipidemia during lactation is recommended.