Triacylglycerol Levels Research Articles

Dietary oleic acid intake increases the proportion of type 1 and 2X muscle fibers in mice

Skeletal muscle is one of the largest metabolic tissues in mammals and is composed of four different types of muscle fibers (types 1, 2A, 2X, and 2B); however, type 2B is absent in humans. Given that slow-twitch fibers are superior to fast-twitch fibers in terms of oxidative metabolism and are rich in mitochondria, shift of muscle fiber types in direction towards slower fiber types improves metabolic disorders and endurance capacity. We previously had reported that oleic acid supplementation increases type 1 fiber formation in C2C12 myotubes; however, its function still remains unclear. This study aimed to determine the effect of oleic acid on the muscle fiber types and endurance capacity. An in vivo mouse model was used, and mice were fed a 10% oleic acid diet for 4 weeks. Two different skeletal muscles, slow soleus muscle with the predominance of slow-twitch fibers and fast extensor digitorum longus (EDL) muscle with the predominance of fast-twitch fibers, were used. We found that dietary oleic acid intake improved running endurance and altered fiber type composition of muscles, the proportion of type 1 and 2X fibers increased in the soleus muscle and type 2X increased in the EDL muscle. The fiber type shift in the EDL muscle was accompanied by an increased muscle TAG content. In addition, blood triacylglycerol (TAG) and non-esterified fatty acid levels decreased during exercise. These changes suggested that lipid utilization as an energy substrate was enhanced by oleic acid. Increased proliferator-activated receptor γ coactivator-1β protein levels were observed in the EDL muscle, which potentially enhanced the fiber type transitions towards type 2X and muscle TAG content. In conclusion, dietary oleic acid intake improved running endurance with the changes of muscle fiber type shares in mice. This study elucidated a novel functionality of oleic acid in skeletal muscle fiber types. Further studies are required to elucidate the underlying mechanisms. Our findings have the potential to contribute to the field of health and sports science through nutritional approaches, such as the development of supplements aimed at improving muscle function.

Effects of Daily Consumption of Scallop Oil Prepared from Internal Organs of Japanese Giant Scallop (Patinopecten yessoensis) on Serum Lipid Composition and Its Safety: A Randomized, Double-blind, Placebo-controlled, Parallel Group Comparison Study.

Scallop oil (SCO) prepared from the internal organs of the Japanese giant scallop (Patinopecten yessoensis) contains eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and phospholipids (PL). It was previously shown that SCO consumption improves cholesterol and triacylglycerols (TG) contents in mice. The present study demonstrated the effects of daily SCO consumption (1.2 g/day, containing 376 mg of EPA, 63 mg of DHA, and 150 mg of PL) for 12 weeks in human subjects. In this randomized, doubleblind, placebo-controlled, parallel group comparison study, 70 Japanese subjects with serum TG levels ≥120 but < 200 mg/dL were recruited and randomly assigned to the SCO or placebo group. All subjects ingested six capsules per day for 12 weeks. We conducted medical interviews, body composition measurements, vital sign examinations, and blood sampling at weeks 0 (baseline), 4, 8, and 12, and measured peripheral blood flow at weeks 0 and 12. In the case of subjects with higher serum TG levels, SCO consumption decreased the changes in serum TG and malondialdehyde-low density lipoprotein (MDA-LDL) levels compared with the placebo group. Safety assessment revealed no medically significant changes due to continuous SCO consumption. The findings indicate that 1.2 g/day of SCO consumption may be beneficial for reducing serum TG and MDA-LDL levels in persons with higher TG levels.

Differential expression of brummer and levels of TAG in different developmental stages Aedes aegypti (Diptera: Culicidae), including fasted adults.

Lipid storage in the form of triacylglycerol (TAG)is essential for insect life, as it enables flight, development, and reproduction. The activity of the lipase brummer (bmm) has been shown to be essential to insects' homeostasis. The objective of this study was to evaluate how bmm expression occurs in Aedes aegypti larvae and adults, and to observe TAG levels during fasting in adult females. The bmm sequence was identified in A. aegypti and exhibited a patatin-like phospholipase domain reinforced by the presence of a catalytic dyad with serine and aspartate residues, revealing a high degree of similarity with other organisms. Bmm expression was differentiated in the larvae and adult fat body (FB)following TAG reserve dynamics. Bmm was expressed three times in larval stages L3, L4, and pupae compared with L1 and L2, which could indicate its role in the maturation of these insects. In the postemergence (PE)and post-blood meal (PBM)FB of adult insects, bmm expression varied over several days. PE adults showed a pronounced bmm increase from the third day onward compared with those not subjected to fasting. This was accompanied by a decrease in TAG from the third day onward, suggesting the participation of bmm. Six hours after blood feeding, TAG levels increased in mosquitos reared in the absence of sucrose, suggesting lipid accumulation to guarantee reproduction. Bmm responded positively to fasting, followed by TAG mobilization in adult FB. During the previtellogenic period, bmm levels responded to low TAG levels, unlike the PBM period.

Effects of co-supplementation of chromium and magnesium on metabolic profiles, inflammation, and oxidative stress in impaired glucose tolerance.

To evaluate the effects of chromium (Cr) and magnesium (Mg) ions on metabolic profiles, inflammation, and oxidative stress with impaired glucose tolerance (IGT) and insulin resistance (IR). 120 individuals with IGT and IR were randomly divided into four groups treated with (1) chromium, (2) magnesium, (3) chromium and magnesium or (4) placebo. Metabolic and inflammatory indicators were measured at baseline and after 3months intervention. Comparison among groups showed that fasting plasma glucose (FPG), 2 h post glucose (2hPPG), fasting insulin (FINS) and homeostatic model assessment for insulin resistance (HOMA-IR) in Cr + Mg group were significantly decreased compared with the other three groups (p < .05), and high density lipoprotein (HDL-c) levels were higher. 8-iso prostaglandin F2 alpha (8-iso-PGF2a) decreased in Cr, Mg, and Cr + Mg groups compared with placebo (p < .05), and 8-iso-PGF2a decreased in Cr + Mg groups compared with Cr group and Mg groups (p > .05). Intra-group comparison showed that the levels of FPG, 2hPPG and FINS in Cr + Mg group were significantly decreased after intervention (p < .05), and FINS in Mg group was significantly decreased (p < .01). The levels of HDL-c and triacylglycerol (TG) in Cr + Mg group were significantly improved (p < .05). The level of HDL-c in Mg group was significantly improved compared with baseline (p < .05). Compared with baseline, high-sensitivity C-reactive protein (hsCRP) levels in Cr + Mg group and Mg group were significantly decreased (p < .05). The co-supplementation of Cr and Mg improves glycemic and lipid levels and reduces the inflammatory response and oxidative stress profiles of individuals with impaired glucose tolerance and insulin resistance.

Breviscapine alleviates myocardial ischemia-reperfusion injury in diabetes rats.

To investigate the protective effect of breviscapine on myocardial ischemia-reperfusion injury (MIRI) in diabetes rats. Forty rats were divided into control, diabetes, MIRI of diabetes, and treatment groups. The MIRI of diabetes model was established in the latter two groups. Then, the treatment group was treated with 100 mg/kg breviscapine by intraperitoneal injection for 14 consecutive days. After treatment, compared with MIRI of diabetes group, in treatment group the serum fasting blood glucose, fasting insulin, homeostasis model assessment of insulin resistance, and glycosylated hemoglobin levels decreased, the serum total cholesterol, triacylglycerol, and low-density lipoprotein cholesterol levels decreased, the serum high-density lipoprotein cholesterol level increased, the heart rate decreased, the mean arterial pressure, left ventricular ejection fraction, and fractional shortening increased, the serum cardiac troponin I, and creatine kinase-MB levels decreased, the myocardial tumor necrosis factor α and interleukin-6 levels decreased, the myocardial superoxide dismutase level increased, and the myocardial malondialdehyde level decreased (all P < 0.05). For treating MIRI of diabetes in rats, the breviscapine can reduce the blood glucose and lipid levels, improve the cardiac function, reduce the myocardial injury, and decrease the inflammatory response and oxidative stress, thus exerting the alleviating effect.

Lanifibranor Reduces Inflammation and Improves Dyslipidemia in Lysosomal Acid Lipase-Deficient Mice

Background and AimsRecent studies showed that patients suffering from lysosomal acid lipase deficiency (LAL-D) benefit from enzyme replacement therapy (ERT), however, liver histolopathology improved in some but not all patients. We hypothesized that the pan-PPAR agonist lanifibranor may have beneficial effects on liver inflammation in LAL knockout (Lal-/-) mice based on its promising results in alleviating liver inflammation in patients with metabolic dysfunction-associated steatohepatitis. MethodsFemale Lal-/- mice were daily gavaged with lanifibranor or vehicle for 21 days. The effects of the treatment were assessed by measuring body and organ weights, plasma lipids and lipoproteins, as well as hematological parameters, followed by liver proteomics and metabolomics. ResultsLanifibranor treatment slightly altered organ weights without affecting the total body weight of Lal-/- mice. We observed major changes in the proteome, with multiple proteins related to lipid metabolism, peroxisomal, and mitochondrial activities being upregulated and inflammation-related proteins being downregulated in the livers of treated mice. Hepatic lipid levels and histology remained unaltered, whereas plasma triacylglycerol and total cholesterol levels were decreased and the lipoprotein profile of lanifibranor-treated Lal-/- mice improved. ConclusionsLanifibranor treatment positively affected liver inflammation and dyslipidemia in Lal-/- mice. These findings suggest the necessity of a further combined study of lanifibranor with ERT in Lal-/- mice to improve the phenotype. Moreover, there is a compelling rationale for conducting clinical trials to assess the efficacy of lanifibranor as a potential treatment option for LAL-D in humans.

Body fat, lipid profile and selected hormones in active male Polish students characterized by lower and higher normal thyroid-stimulating hormone levels

Abstract Study aim: To evaluate the relationship between body fat, lipid profile and selected hormones in the context of lower and higher normal thyroid-stimulating hormone (TSH) levels in active male students. Material and methods: A total of 112 male students of the Faculty of Physical Education volunteered to participate in the study. Body weight, height and waist circumference were measured using standard medical equipment. The percentage of body fat was determined from the sum of the thickness of four skinfolds. Circulating lipids, TSH, glucose and insulin level were measured. Results: Biochemical characteristics revealed that the circulating total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triacylglycerol (TG) levels were significantly lower in students with lower normal TSH levels vs. students with higher normal TSH levels. The analysis of distorted metabolic variables indicated that for students with higher normal TSH levels the frequency of disturbances was significantly higher than in students with lower normal TSH levels. Additionally, this group was characterized by a significantly higher percentage of fat in the body. Conclusion: In young, physically active men, certain metabolic disorders related to plasma lipid profiles may be observed despite normal TSH levels.

Microemulsion co-delivering curcumin and DHA-rich algal oil alleviates nonalcoholic fatty liver disease

The combined effect of curcumin and docosahexaenoic acid (DHA) on liver injury has not yet been reported. We determined the synergistic effect of curcumin and DHA on the protection of WRL-68 cells from palmitic acid-induced injury, and on the inhibition of LX2 cells. A microemulsion to co-deliver both compounds was prepared by ultrasonic emulsification. Mice were fed a high-fat diet for 10 weeks to induce mild non-alcoholic fatty liver disease (NAFLD). At a dose of 5 mg/kg curcumin and 30 mg/kg DHA, the microemulsion successfully lowered serum triacylglycerol (TG) and low-density lipoprotein cholesterol levels, and significantly attenuated NAFLD. A pharmacokinetic study in rats showed that the microemulsion had a higher Cmax value for curcumin, a greater AUC0–24 value and a longer t1/2 value for both curcumin and DHA. This investigation provides a novel application of a combination of functional food ingredients to treat chronic liver disease.

Effects of Dietary Oxidized Phytosterol on Lipid Metabolism in Rats.

Many in vitro studies have revealed the toxic effects of oxidized phytosterols (OPSs); however, their effects on lipid metabolism are not well understood in vivo. Therefore, we examined the bioavailability of OPS and compared the effects of dietary phytosterols (PSs) or OPS on lipid metabolism in rats. OPS was detected in the plasma and liver of rats administered 50 mg of OPS for 3 days. Rats were fed the AIN76 diet (C group), basal diet plus 0.25% PS (P group), or 0.25% OPS (O group) for 4 weeks. Dietary OPS but not PS reduced hepatic fatty acid synthase activity. Liver triacylglycerol (TG) levels tended to be lower in the P group than in the C group and were significantly lower in the O group. The mRNA expression level of HMG-CoA reductase in the liver was the lowest in the O group, whereas that of CYP27A1 was the highest in the O group. The mRNA expression levels of NPC1L1 in the intestinal mucosa were significantly lower in the P and O groups than in the C group. Consistent with these modulations, plasma total cholesterol (TC) and HDL-C levels were similar between the C and P groups but tended to be higher or significantly higher in the O group. Liver TC levels were significantly lower in the P and O groups than in the C group. Moreover, fecal neutral and acidic steroid levels were the highest in the O group. The mRNA expression level of Δ6 desaturase in the liver was significantly higher in both the P and the O groups than in the C group. The Δ6 desaturation indices of fatty acids in the total liver lipids were the highest in the O group. Thus, dietary OPS may modulate lipid metabolism in the liver.

Nucleotide polymorphism-based study utilizes human plasma liposomes to discover potential therapeutic targets for intervertebral disc disease.

While intervertebral disc degeneration (IVDD) is crucial in numerous spinally related illnesses and is common among the elderly, the complete understanding of its pathogenic mechanisms is still an area of ongoing study. In recent years, it has revealed that liposomes are crucial in the initiation and progression of IVDD. However, their intrinsic mediators and related mechanisms remain unclear. With the development of genomics, an increasing amount of data points to the contribution of genetics in the etiology of disease. Accordingly, this study explored the causality between liposomes and IVDD by Mendelian randomization (MR) analysis and deeply investigated the intermediary roles of undetected metabolites. According to MR analysis, 179 liposomes and 1400 metabolites were evaluated for their causal association with IVDD. Single nucleotide polymorphisms (SNPs) are strongly associated with the concentrations of liposomes and metabolites. Consequently, they were employed as instrumental variables (IVs) to deduce if they constituted risk elements or protective elements for IVDD. Furthermore, mediation analysis was conducted to pinpoint possible metabolic mediators that link liposomes to IVDD. The inverse variance weighting (IVW) was the main analytical technique. Various confidence tests in the causality estimates were performed, including consistency, heterogeneity, pleiotropy, and sensitivity analyses. Inverse MR analysis was also utilized to estimate potential reverse causality. MR analysis identified 13 liposomes and 79 metabolites markedly relevant to IVDD. Moreover, the mediation analysis was carried out by choosing the liposome, specifically the triacylglycerol (48:2) levels, which were found to be most notably associated with an increased risk of IVDD. In all, three metabolite-associated mediators were identified (3-methylcytidine levels, inosine 5'-monophosphate (IMP) to phosphate ratio, and adenosine 5'-diphosphate (ADP) to glycine ratio). The analysis's findings suggested possible causal connections between liposomes, metabolites, and IVDD, which could act as both forecast and prognosis clinical indicators, thereby aiding in the exploration of the pathogenesis behind IVDD.

Hypoglycemic And Hypolipidemic Biochemical Effects of Bee Venom on Experimentally Induced Diabetes in Rats

Abstract Background:‎ Diabetes mellitus (DM) is the highest prevalent endocrine illness that exhibits hyperglycemia, ‎hyperlipidemia and protein metabolism disorders also elevated risk of several complications, including ‎vascular disorders. A variety of polypeptide agents can be found in bee venom. The two main ingredients ‎of bee venom are phospholipase A2 and mellitin. These constituents enhance the release of insulin from ‎the Beta islands of pancreas. The purpose of the current work was to demonstrate the hypoglycemic and ‎hypolipidemic effects of bee venom on male diabetic rats that induced by alloxan. ‎ Methods:‎ ‎ The experimental investigation was carried out on 40 male rats (weight from180 to 220 g) which were ‎assigned to four groups (10/each): (the first) a negative control group (not receiving therapy), (the ‎second) a positive control group (diabetic group) injected with alloxan only (160 mg/kg), (the third) ‎diabetic group administered with Vildagliptin (6mg/kg) and the forth diabetic group treated with Bee ‎venom (0.5mg/kg). After two months of the investigation, blood samples were assembled. ‎ Results:‎ Bee Venom (0.5mg/kg) lowered significantly (p≤0.05) the level of serum glucose, which was followed ‎by a substantial rise in the level of HDL and insulin when contrasted to the rats with diabetes. Total lipid, ‎cholesterol, triacylglycerol and LDL levels were considerably reduced in the diabetic group that received ‎BV.‎ Conclusion:‎ There is a growing interest in the bee venom's use as a natural product rather than chemical drugs for ‎treatment of diabetes mellitus because of the manner it affects rats biochemically, particularly its ‎prospective anti-diabetic and anti-hyperlipidemia qualities.‎

Characterization of Palm Fatty Acid Distillate, Diacylglycerol Regioisomers, and Esterification Products Using High-Performance Size Exclusion Chromatography.

High-performance size exclusion chromatography (HPSEC) equipped with an evaporative light scattering detector (ELSD) was utilized for characterization of palm fatty acid distillate (PFAD) and its esterified products, with a particular focus on lipid profiles and diacylglycerol (DAG) regioisomers. The separation of triacylglycerol (TAG), DAG, monoacylglycerol (MAG), and free fatty acid (FFA) was achieved through a single 100-Å Phenogel column, coupled with a 2-cm C18 guard, utilizing toluene/acetic acid (100:0.25, v/v) as the mobile phase. This separation was based on size sieving principles and the interactions between the hydroxyl group(s) and the Phenogel matrix. The limit of detection (LOD) and limit of quantification (LOQ) for the esterified PFAD products analyzed by this method fell within the range of 4.8-5.5 μg/mL and 14.7-16.7 μg/mL, respectively. Additionally, the same column, paired with a 2-cm silica guard and a mobile phase comprised of toluene/isooctane/acetic acid (35:65:0.15, v/v/v), was used for the characterization of DAG regioisomers within the esterified PFAD. LODs and LOQs for sn-1,3-DAG and sn- 1,2-DAG were determined to be 39.2 and 118.7 μg/mL, and 32.8 and 99.5 μg/mL, respectively. Investigation of esterified PFAD products prepared using 4% H2SO4 at 120°C. After 2 h, the analysis revealed the highest MAG content at 31.85%, accompanied by 51.54% DAG, 2.35% TAG, and a residual 14.27% FFA. Notably, as the reaction time extended, the MAG content decreased, while both DAG and TAG levels exhibited an increasing trend. Further examination of DAG regioisomers during PFAD esterification, under varying catalyst concentrations (2-10%) and reaction temperatures (80-140°C), demonstrated a significant increase in the percentage of sn-1,3-DAG, inversely correlated with the reduction in FFA from 2% H 2 SO 4 and 80°C onwards. Remarkably, the percentage of sn-1,2-DAG remained relatively stable regardless of changes in catalyst concentrations or temperatures, confirming its susceptibility to isomerization into the thermodynamically more stable sn-1,3-DAG form. This study provides valuable insights into the composition and behavior of esterified PFAD products.

Lipidomic Characterization of Whey Concentrates Rich in Milk Fat Globule Membranes and Extracellular Vesicles.

Lipids from milk fat globule membranes (MFGMs) and extracellular vesicles (EVs) are considered beneficial for cognitive development and human health. Milk-derived whey concentrates rich in these lipids are therefore used as ingredients in infant formulas to mimic human milk and in medical nutrition products to improve the metabolic fitness of adults and elderly people. In spite of this, there is no consensus resource detailing the multitude of lipid molecules in whey concentrates. To bridge this knowledge gap, we report a comprehensive and quantitative lipidomic resource of different whey concentrates. In-depth lipidomic analysis of acid, sweet, and buttermilk whey concentrates identified 5714 lipid molecules belonging to 23 lipid classes. The data show that the buttermilk whey concentrate has the highest level of fat globule-derived triacylglycerols and that the acid and sweet whey concentrates have the highest proportions of MFGM- and EV-derived membrane lipids. Interestingly, the acid whey concentrate has a higher level of cholesterol whereas sweet whey concentrate has higher levels of lactosylceramides. Altogether, we report a detailed lipid molecular compendium of whey concentrates and lay the groundwork for using in-depth lipidomic technology to profile the nutritional value of milk products and functional foods containing dairy-based concentrates.

Shotgun-Based Mass Spectrometry Analysis of Phospholipid and Triacylglycerol Molecular Species and Eicosanoids in Salmon Muscle Tissue on Feeding Microbial Oil.

The continuous growth of aquaculture places a growing demand on alternative sources of fish oil (FO). Certain microorganisms provide a sustainable replacement for FO due to their content of EPA and DHA, which are essential for fish health. Appreciable evidence shows that changes in feeding sources may alter the nutritional components of salmon; however, the influence of diets on lipid species remains unclear. In this study, the identification and semi-quantification of lipid molecular species in salmon muscle during feeding with a microbial oil (MO) were carried out by focusing on triacylglycerol (TAG) and diacyl-phospholipid using shotgun-based mass spectrometry analysis. DHA in the MO diet was efficiently incorporated into phospholipid structures on feeding, followed by accumulation in salmon muscle. The MO diet elevated the level of certain EPA-containing TAGs, such as TAG C52:5 (16:0_16:0_20:5) and TAG C54:6 (16:0_18:1_20:5), indicating that the MO diet may be an excellent source for enhancement of the abundance of ω3 lipids. Further, prostaglandins (PGs) PGE2 and PGF3α were identified and quantified for the first time in salmonid tissue.

Significance of monitoring the levels of thyroid hormone antibodies and glucose and lipid metabolism antibodies in patients suffer from type 2 diabetes.

The association of thyroid hormone antibodies and glycolipid metabolism indicators with Type 2 diabetes mellitus (T2DM) was explored. As the disease worsens, the levels of thyroglobulin antibody (TGAb), thyroid peroxidase antibody (TPOAb), and thyroid-stimulating hormone (TSH) was increased, and the levels of total tri-iodothyronine (TT3) and total thyroxine (TT4) was decreased (P < 0.001). The severe, medium, and light group had higher level of high-density lipoprotein (HDL), lower level of total cholesterol (TC), low-density lipoprotein (LDL), glycosylated hemoglobin (HbA1c), triacylglycerol (TAG), and fasting blood sugar (FBG) than the control group (P ＜ 0.05). The level of HDL was lower in the severe group than the light group and the medium group, but the levels of TC, LDL, HbA1c, TAG, and FBG were increased with the progress of T2DM (P ＜ 0.001). The levels of TGAb, TPOAb, and TSH in patients with T2DM were positively correlated with the levels of TC, LDL, HbA1c, TAG, and FBG (P < 0.05), and were negatively correlated with HDL levels (P < 0.05). The life quality score was lower in the severe group than the light and the medium group (P < 0.001). Among the above indicators, the predictive value of TT3, TT4, and HbA1c in T2DM was better. Clinically, detecting the levels of thyroid hormone antibodies and glycolipid metabolism indicators had a certain predictive value for the severity of T2DM. Main findings: The results of this study found that the thyroid hormone antibody and glycolipid metabolism levels in T2DM patients were abnormal, and had different degrees of impact on the quality of life of patients. Thus, monitoring these indicators had certain predictive value for the severity of the disease, and also had a certain degree of suggestive effect on the evaluation of diabetic vascular complications. Clinically, attention should be paid to the screening of thyroid disease in diabetic patients, and the assessment and prognosis of thyroid function on diabetes, the control of diabetes, and the prevention and treatment of complications have important clinical significance.

Catalytic core function of yeast Pah1 phosphatidate phosphatase reveals structural insight into its membrane localization and activity control

The PAH1-encoded phosphatidate (PA) phosphatase is a major source of diacylglycerol for the production of the storage lipid triacylglycerol and a key regulator for the de novo phospholipid synthesis in Saccharomyces cerevisiae. The catalytic function of Pah1 depends on its membrane localization which is mediated through its phosphorylation by multiple protein kinases and dephosphorylation by the Nem1-Spo7 protein phosphatase complex. The full-length Pah1 is composed of a catalytic core (N-LIP and HAD-like domains, amphipathic helix, and the WRDPLVDID domain) and non-catalytic regulatory sequences (intrinsically disordered regions, RP domain, and acidic tail) for phosphorylation and interaction with Nem1-Spo7. How the catalytic core regulates Pah1 localization and cellular function is not clear. In this work, we analyzed a variant of Pah1 (i.e., Pah1-CC (catalytic core)) that is composed only of the catalytic core. Pah1-CC expressed on a low-copy plasmid complemented the pah1Δ mutant phenotypes (e.g., nuclear/ER membrane expansion, reduced levels of triacylglycerol, and lipid droplet formation) without requiring Nem1-Spo7. The cellular function of Pah1-CC was supported by its PA phosphatase activity mostly associated with the membrane fraction. Although functional, Pah1-CC was distinct from Pah1 in the protein and enzymological properties, which include overexpression toxicity, association with heat shock proteins, and significant reduction of the Vmax value. These findings on the Pah1 catalytic core enhance the understanding of its structural requirements for membrane localization and activity control.

Exercise training modifies skeletal muscle clock gene expression but not 24-hour rhythmicity in substrate metabolism of men with insulin resistance.

Twenty-four hour rhythmicity in whole-body substrate metabolism, skeletal muscle clock gene expression and mitochondrial respiration is compromised upon insulin resistance. With exercise training known to ameliorate insulin resistance, our objective was to test if exercise training can reinforce diurnal variation in whole-body and skeletal muscle metabolism in men with insulin resistance. In a single-arm longitudinal design, 10 overweight and obese men with insulin resistance performed 12weeks of high-intensity interval training recurrently in the afternoon (between 14.00 and 18.00h) and were tested pre- and post-exercise training, while staying in a metabolic research unit for 2days under free-living conditions with regular meals. On the seconddays, indirect calorimetry was performed at 08.00, 13.00, 18.00, 23.00 and 04.00h, muscle biopsies were taken from the vastus lateralis at 08.30, 13.30 and 23.30h, and blood was drawn at least bi-hourly over 24h. Participants did not lose body weight over 12weeks, but improved body composition and exercise capacity. Exercise training resulted in reduced 24-h plasma glucose levels, but did not modify free fatty acid and triacylglycerol levels. Diurnal variation of muscle clock gene expression was modified by exercise training with period genes showing an interaction (time × exercise) effect and reduced mRNA levels at 13.00h. Exercise training increased mitochondrial respiration without inducing diurnal variation. Twenty-four-hour substrate metabolism and energy expenditure remained unchanged. Future studies should investigate alternative exercise strategies or types of interventions (e.g. diet or drugs aiming at improving insulin sensitivity) for their capacity to reinforce diurnal variation in substrate metabolism and mitochondrial respiration. KEY POINTS: Insulin resistance is associated with blunted 24-h flexibility in whole-body substrate metabolism and skeletal muscle mitochondrial respiration, and disruptions in the skeletal muscle molecular circadian clock. We hypothesized that exercise training modifies 24-h rhythmicity in whole-body substrate metabolism and diurnal variation in skeletal muscle molecular clock and mitochondrial respiration in men with insulin resistance. We found that metabolic inflexibility over 24h persisted after exercise training, whereas mitochondrial respiration increased independent of time of day. Gene expression of Per1-3 and Rorα in skeletal muscle changed particularly close to the time of day at which exercise training was performed. These results provide the rationale to further investigate the differential metabolic impact of differently timed exercise to treat metabolic defects of insulin resistance that manifest at a particular time of day.

Comparative analysis of triglyceride profiles in human milk from Egyptian and Chinese women across lactation stages

Understanding human milk triacylglycerols (TAGs) provides valuable insights for infant formula development. This study utilized ultra-performance supercritical fluid chromatography to investigate how lactation stages and maternal diet affect TAG profiles. 18:1/16:0/18:1 (O/P/O), 16:0/18:1/16:0 (P/O/P), and 18:1/16:0/18:2 (O/P/L) were most abundant in human milk, accounting for 20% of the total TAGs. Furthermore, significant differences in TAG compositions were observed across the three stages of lactation. Also, there are apparent differences in the TAG of Egyptian and Chinese human milk. Egyptian human milk exhibited higher levels of TAGs esterified with three saturated fatty acids (SSS), TAGs esterified with two saturated fatty acids, and one unsaturated fatty acid (S2U), and total palmitic acid compared to Chinese human milk. On the other hand, TAGs with three long-chain fatty acids (LLL) and TAGs with three unsaturated fatty acids (UUU) were at higher levels in Chinese human milk. Understanding the prevalence of these specific TAGs, particularly related to O/P/O, can help in formulating infant formulas that aim to mimic the composition of human milk more accurately.

Targeted changes in blood lipids improves fibrosis in renal allografts

BackgroundChronic interstitial fibrosis is the primary barrier against the long-term survival of transplanted kidneys. Extending the lifespan of allografts is vital for ensuring the long-term health of patients undergoing kidney transplants. However, few targets and their clinical applications have been identified. Moreover, whether dyslipidemia facilitates fibrosis in renal allograft remains unclear.MethodsBlood samples were collected from patients who underwent kidney transplantation. Correlation analyses were conducted between the Banff score and body mass index, and serum levels of triacylglycerol, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. A rat model of renal transplantation was treated with the lipid-lowering drug, fenofibrate, and kidney fibrosis levels were determined by histochemical staining. Targeted metabolomic detection was conducted in blood samples from patients who underwent kidney transplantation and were divided into fibrotic and non-fibrotic groups. Rats undergoing renal transplantation were fed either an n-3 or n-6 polyunsaturated fatty acid (PUFA)-enriched diet. Immunohistochemical and Masson’s trichrome staining were used to determine the degree of fibrosis.ResultsHyperlipidemia was associated with fibrosis development. Treatment with fenofibrate contributed to improve fibrosis in a rat model of renal transplantation. Moreover, n-3 PUFAs from fibrotic group showed significant downregulation compared to patients without fibrotic renal allografts, and n-3 PUFAs-enriched diet contributed to delayed fibrosis in a rat model of renal transplantation.ConclusionsThis study suggests that hyperlipidemia facilitates fibrosis of renal allografts. Importantly, a new therapeutic approach was provided that may delay chronic interstitial fibrosis in transplanted kidneys by augmenting the n-3 PUFA content in the diet.

Metabolomic and lipidomic landscape of porcine kidney associated with kidney perfusion in heart beating donors and donors after cardiac death

Transplant centers are currently facing a lack of tools to ensure adequate evaluation of the quality of the available organs, as well as a significant shortage of kidney donors. Therefore, efforts are being made to facilitate the effective use of available organs and expand the donor pool, particularly with expanded criteria donors. Fulfilling a need, we aim to present an innovative analytical method based on solid-phase microextraction (SPME) - chemical biopsy. In order to track changes affecting the organ throughout the entire transplant procedure, porcine kidneys were subjected to multiple samplings at various time points. The application of small-diameter SPME probes assured the minimal invasiveness of the procedure. Porcine model kidney autotransplantation was executed for the purpose of simulating two types of donor scenarios: donors with a beating heart (HBD) and donors after cardiac death (DCD). All renal grafts were exposed to continuous normothermic ex vivo perfusion. Following metabolomic and lipidomic profiling using high-performance liquid chromatography coupled to a mass spectrometer, we observed differences in the profiles of HBD and DCD kidneys. The alterations were predominantly related to energy and glucose metabolism, and differences in the levels of essential amino acids, purine nucleosides, lysophosphocholines, phosphoethanolamines, and triacylglycerols were noticed. Our results indicate the potential of implementing chemical biopsy in the evaluation of graft quality and monitoring of renal function during perfusion.