Serum Fatty Acid Research Articles

Impact of Maternal Omega-3 Fatty Acid Intake on Ovine Placental and Fetal Tissue Metabolism

ObjectivesDietary supplementation of omega-3 fatty acids such as docosahexaenoic acid (DHA) during pregnancy is often recommended to support optimal fetal brain development and cognitive function of the offspring. DHA supplementation also influences cardiometabolic risk parameters in adults, but its effect on fetal metabolism and subsequent risk is poorly understood. The aim of this study was to determine the effects of maternal DHA supplementation (MDS) on placental and fetal nutrient handling during pregnancy.MethodsWhite-faced ewes were fed either a control diet (Show-rite NewCo Lamb Feed) or a DHA-supplemented diet (control diet + 3% w/w algae-derived DHA) from 2–3 weeks before pregnancy until mid-gestation (75 days), after which a C-section was performed to collect the placenta and fetal tissues for metabolic analyses.ResultsMDS significantly increased serum DHA levels and decreased serum triglycerides in the uterine (maternal) circulation, but not umbilical (fetal) circulation. Nevertheless, MDS resulted in significant DHA enrichment of the placenta and all fetal tissues examined, and differentially affected the protein expression of the four major fatty acid transport proteins FATP1, FATP4, CD36 and FABP in placenta, muscle, liver and heart, but had no effect on kidney or brain. Consistent with these findings, MDS tended to increase the capacity for fat over pyruvate oxidation in fetal muscle and heart, but favored a greater capacity for glucose uptake and oxidation in fetal liver.ConclusionsThis study is the first to validate use of an ovine model for investigating the impact of maternal DHA supplementation on fetal metabolism and development. Results demonstrate a complex tissue-specific effect of MDS on fetal tissue carbohydrate and fatty acid metabolism that favors a greater capacity for serum glucose disposal and fatty acid oxidation. Whether these changes ultimately impact nutrient metabolism and cardiometabolic risk in the offspring later in life merits further investigation.Funding SourcesColorado Agricultural Experiment Station.

Omega 3 Fatty Acids vs Omega 6 Fatty Acids

ObjectivesDietary lipids have a very important role in nutrition and must be ingested in an appropriate proportion. Objective: To study the effect of w3 fatty acid supplementation of a diet containing sunflower oil (rich in fatty acids omega 6) as fat source, on serum fatty acid profiles of growing rats.MethodsWeanling Wistar rats received during 10 days normocaloric diet and fat was provided by sunflower oil (S group). The others groups received the same diet supplemented with 24mg/day of fish oil (SF group) or chía oil (SCh group). Control group (C) received AIN´93 diet. Serum fatty acids profiles were determined by gas chromatography. Statistical analysis used ANOVA test.ResultsResults: (expressed as %Area) SERUM: OLEIC C:10.11 ± 1.84, S:12.13 ± 3.84, SCh:12.74 ± 1.56, SF: 13.12 ± 2.82; ARACHIDONIC C:13.40 ± 4.39, S:17.61 ± 4.09, SCh: 15.75 ± 0.89, SF:15.41 ± 1.76; LINOLEIC C:20.52 ± 3.37, S: 19.80 ± 3.36, SCh: 21.14 ± 2.12, SF: 18.92 ± 3.87; LINOLENIC (ALA) C:0.93 ± 0.27a, S:0.19 ± 0.06 b, SCh: 0.28 ± 0.08b, SF:0.22 ± 0.05b; EPA C:0.80 ± 0.22, S:0.68 ± 0.15, SCh: 0.74 ± 0.18, SF: 0.67 ± 0.14; DHA C:1.60 ± 0.55a, S:1.14 ± 0.35a, SCh:1.70 ± 0.45a, SF:4.22 ± 0.93b. Media that didn't present a letter (a, b) in common, were different (p < 0.01). In sera, S, SF and SCh groups showed lower ALA levels compared to C. SF group presented high levels of DHA. Diet S was mainly a contributor to linoleic acid with a ratio w6/w3 = 250 (recommended value: 5–10).ConclusionsThe diet containing sunflower oil as fat source shows that ω6 family route was exacerbated; by the other hand ω3 family was depressed. Chia supplement showed a tendency towards higher values of w3 family but were significantly lower than C. Fish oil supplement increase significantly DHA values. Diet containing sunflower oil as fat source provoked changes in serum fatty acids profiles and the supplementation with w3 fatty acid provided by chía or fish oil do not increase ALA values significantly. Diet influences the serum fatty acid profile, being not only important the percentage of lipids on it but also the different fatty acids pattern.Funding SourcesUBACyT: 20020190100093BA.

Effect of cow's milk with different PUFA n-6: n-3 ratios on performance, serum lipid profile, and blood parameters of grower gilts.

The concern with human health has increased the interest in producing foods enriched with polyunsaturated fatty acids (PUFA), directly or naturally, by inclusion in the animals’ diet. The positive effects such as antithrombotic, anti-inflammatory, and hypolipidemic have been observed in pigs and rats, used as human models for study. The present study evaluated the effect of cow’s milk with different lipid profiles on performance, serum fatty acid profile, biochemical analysis, and a complete blood count of gilts used as a human model. At 34 days, thirty gilts were equally distributed in three treatments. Experimental treatments were milk from cows without the oil supplementation (C), milk from cows fed an enriched diet with linseed oil (n-3), and milk from cows fed an enriched diet with soybean oil (n-6). Milk supplementation was performed until 190 days old, provided once in the morning. The n-3 and n-6 milk reduced the concentration of myristic acid in the blood and increased the leukocytes. Milk enriched with n-3 compared to n-6 reduced the stearic acid. In conclusion, milk with a better PUFA profile can reduce saturated fatty acids in the blood and alter the concentration of cells in the defense system.

MO668: An Increase of Free Fatty Acids on Patients Starting Peritoneal Dialysis Suggests an Increased Cardiovascular Risk Beyond Classical Dyslipidemia Biomarkers

Abstract BACKGROUND AND AIMS Chronic kidney disease (CKD) produces profound changes in lipid metabolism, and these associated lipid disorders, in turn, contribute to the progression of CKD and its cardiovascular complications. Patients on peritoneal dialysis have a more atherogenic lipid profile than non-dialysis-dependent CKD patients or on HD. In the general population, the reduction of total cholesterol and LDL levels is associated with improved clinical outcomes in terms of morbidity and mortality; however, several studies have failed to obtain these same results in patients on dialysis. The use of lipidomics to detect a broader panel of lipid species can improve the prediction of the different alterations that influence cardiovascular mortality. METHOD This is a single-center prospective observational study of a cohort of CKD patients who start renal replacement therapy with continuous ambulatory peritoneal dialysis (CAPD). Data from 39 patients were examined. All samples for routine laboratories and lipidomics studies were obtained the day before starting CAPD (T0) and 6 months after (T1). Samples were analysed on an Ultra-Performance Liquid Chromatography system. The differences in the lipid profile analytical variables between baseline and 6 months after the start of CAPD were analysed. For the lipidomic analysis, each compound was grouped with its possible adducts and compound class based on the International Lipid Classification. RESULTS Thirty-nine patients were enrolled the study. Their mean age was 57.9 ± 16.3 years. The underlying renal diseases were glomerular disease (15 patients), diabetic kidney disease (10), congenital kidney disease (4), hypertensive kidney disease (2), interstitial nephropathy (2) and others (6). Hypertension was present in 96.3% of the patients, diabetes mellitus in 30.8% and 30 of the 39 patients had dyslipidemia (76.9%). Of the group of patients with dyslipidemia, only one of them was not on statin treatment. Table 1 shows the results of the analytical variables of lipid profile, serum glucose and renal function before and 6 months after initiating CAPD. The levels of CT and LDL were lower 6 months after CAPD initiation, but these were not statistically significant. Using the plasma lipid profile, with a mass spectrometry approach, a significant increase (P &amp;lt; 0.05) in total free fatty acids (FFA) was observed from T0 to T1. FFA (16:1) and FFA (18:0) were the FFAs with the highest peak response (Fig. 1). CONCLUSION Our LC-QTOF/MS-based lipidomics approach to study the effect of starting renal replacement therapy with CAPD in patients with CKD shows that total FFAs increased after 6 months on this technique. Within this group of lipids, FA 16:1 (palmitoleic acid) and FA 18:0 (stearic acid) were the ones that increased the most. An earlier study demonstrated that FFA levels are increased in the plasma of CKD patients; moreover, they have reported that higher levels of saturated fatty acids in serum correlate with sudden cardiac death in patients starting HD. Likewise, monounsaturated fatty acids are the products of stearoyl-CoA desaturase (SCD) catalyzed reactions and act as substrates to synthesize phospholipids and triglycerides. The activity of SCD is very high in patients with cardiovascular disease, hypertension and diabetes.

The effect of fibre intervention on serum and faecal short-chain fatty acids in human with overweight or obesity: a systematic review of human intervention studies

Overweight/ obesity is associated with cardiovascular diseases, which both contribute to the severity of coronavirus disease 2019 (COVID-19). Nutritional interventions focusing on dietary fibre and prebiotics interventions have been implemented. Fibre has been suggested to modulate gut-derived metabolites short-chain fatty acid (SCFA). We conducted a systematic review on fibre (including prebiotics) interventions to depict its effect on SCFA from faecal and blood using standard methodologies. PubMed, Cochrane, Embase, CINAHL, and Scopus databases were systematically searched to yield peer-reviewed articles published until 31 December 2021. We included 17 articles describing fibre (including prebiotics) intervention in adult individuals with overweight/obesity. These interventions were broadly described into 3 groups: (i) fibre type food items (n = 8); (ii) fibre supplementations (i.e. prebiotics) (n = 8); (iii) prebiotic supplementation combined with CRD (n = 1). Fibre type food items intervention mostly affected the changes of acetate in faecal, whilst propionate mostly changed in the blood. Interestingly, intervention with fibre supplementation affects more the increase of faecal and blood acetate. Furthermore, fibre intervention might have an impact on the gut microbiota. Nevertheless, more well-controlled human studies are needed, with a more personalized approach.

Independent factors affecting hemorrhagic and ischemic stroke in patients aged 40\u201369\xa0years: a cross-sectional study

BackgroundIntracerebral hemorrhage (ICH) and acute ischemic stroke (AIS) have common vascular risk factors; however, ICH often occurs in adults aged < 70 years. Intracerebral hemorrhage and AIS in adults aged < 70 years should be preventable; however, it is unclear why different subtypes of ICH or AIS occur among adults aged < 70 years with vascular risk factors. This study aimed to identify independent variables for ICH or AIS onset in patients aged < 70 years.MethodsWe included patients aged 40–69 years who experienced ICH or AIS between August 2016 and July 2019. Patients aged < 40 years were excluded because other diseases, rather than vascular risk factors, are often associated with stroke etiology in this age group. Data on age, systolic blood pressure (SBP), serum lipids, and serum fatty acid levels were compared between patients with ICH and those with AIS. In addition, we conducted multivariable logistic regression analyses to identify independent factors among the variables, such as blood pressure or biomarkers, with significant differences between the two groups.ResultsOf the 1252 acute stroke patients screened, 74 patients with ICH and 149 patients with AIS met the inclusion criteria. After excluding variables with multicollinearity, SBP, glycated hemoglobin (HbA1c), and eicosapentaenoic acid (EPA) proportion (%) of total fatty acids were identified as independent factors affecting ICH and AIS. The SBP and EPA% threshold values for ICH compared to AIS were ≥ 158 mmHg and ≤ 2.3%, respectively. The HbA1c threshold value for AIS compared to ICH was ≥ 6.1%.ConclusionsSystolic blood pressure, HbA1c, and EPA%, were independent factors between ICH and AIS. Patients aged 40–69 years with high SBP and low EPA% were at a higher risk of ICH than AIS, and those with a high HbA1c were at a higher risk of AIS than ICH.

Association of serum PUFA and linear growth over 12 months among 6-10 years old Ugandan children with or without HIV.

To quantify PUFA-associated improvement in linear growth among children aged 6-10 years. Serum fatty acids (FA), including essential FA (EFA) (linoleic acid (LA) and α-linolenic acid (ALA)) were quantified at baseline using GC-MS technology. FA totals by class (n-3, n-6, n-9, PUFA and SFA) and FA ratios were calculated. Height-for-age Z-score (HAZ) relative to WHO population reference values were calculated longitudinally at baseline, 6 and 12 months. Linear regression models estimated PUFA, HIV status and their interaction-associated standardised mean difference (SMD) and 95 % CI in HAZ over 12 months. Community controls and children connected to community health centre in Kampala, Uganda, were enrolled. Children perinatally HIV-infected (CPHIV, n 82), or HIV-exposed but uninfected (CHEU, n 76) and community controls (n 78). Relative to highest FA levels, low SFA (SMD = 0·31, 95 % CI: 0·03, 0·60), low Mead acid (SMD = 0·38, 95 % CI: 0·02, 0·74), low total n-9 (SMD = 0·44, 95 % CI: 0·08, 0·80) and low triene-to-tetraene ratio (SMD = 0·42, 95 % CI: 0·07, 0·77) predicted superior growth over 12 months. Conversely, low LA (SMD = -0·47, 95 % CI: -0·82, -0·12) and low total PUFA (sum of total n-3, total n-6 and Mead acid) (SMD = -0·33 to -0·39, 95 % CI: -0·71, -0·01) predicted growth deficit over 12 months follow-up, regardless of HIV status. Low n-3 FA (ALA, EPA and n-3 index) predicted growth deficits among community controls. EFA sufficiency may improve stature in school-aged children regardless of HIV status. Evaluating efficacy of diets low in total SFA, sufficient in EFA and enriched in n-3 FA for improving child growth is warranted.

Association of Gut Microbiota With Metabolism in Rainbow Trout Under Acute Heat Stress.

Global warming is one of the most common environmental challenges faced by cold-water fish farming. Heat stress seriously affects the feeding, growth, immunity, and disease resistance of fish. These changes are closely related to the destruction of intestinal barrier function, the change of intestinal microbiota, and metabolic dysfunction. However, the causal relationship between the phenotypic effects of heat stress as well as intestinal and metabolic functions of fish is unknown. In the current study, the optimal growth temperature (16°C) of rainbow trout was used as the control group, while the fish treated at 22.5°C, 23.5°C, and 24.5°C for 24 h, respectively, were the treatment groups. The 16S rRNA gene sequencing analysis showed that with the increase in temperature, the relative abundance and diversity of intestinal microbiota decreased significantly, while the number of Mycoplasma, Firmicutes, and Tenericutes increased significantly. Non-targeted metabolomics analysis by liquid chromatography-mass spectrometry analysis and correlation analysis showed that the changes of metabolites related to amino acids, vitamins, and short-chain fatty acids in serum of rainbow trout under acute heat stress were strongly correlated with the decrease of relative abundance of various intestinal microbiota, especially Morganella, Enterobacter, Lactobacillus, Lawsonia, and Cloacibacterium. In addition, we also found that acute heat stress seriously affected the intestinal structure and barrier function, and also caused the pathological damage of epithelial cells. These results indicate that the gut microbiome of acute heat-stressed rainbow trout could mediate metabolite transfer through the gut barrier by affecting its integrity. Significant changes in gut morphology, permeability, antioxidant capacity, and pro-inflammatory cytokine levels were observed. Therefore, it is necessary to explore the changes of intestinal microbiota under heat stress to help understand the regulatory mechanism of heat stress and protect the intestinal health of rainbow trout from the negative effects of rising water temperature.

Changes in the Serum Fatty Acid Profile After Anhepatic Phase of Orthotopic Liver Transplantation Procedure.

During orthotopic liver transplantation (OLT), the patients’ body remains deprived of this organ for some time, which could cause critical changes in the levels of various metabolites in the circulation, including fatty acids. Thus, the aim of this study was to determine whether the liver transplantation procedure leads to significant changes in the FA profile in serum lipids after the anhepatic phase. Our gas chromatography–mass spectrometry analysis revealed that after transplantation, serum levels of myristic and palmitic acids significantly decreased, whereas serum levels of very long-chain FAs containing 20 or more carbons in their chains were increased. These results indicate that the anhepatic phase during liver transplantation produces significant changes in serum fatty acid levels, and emphasizes the role of the liver in the metabolism of very long-chain fatty acids.

An exploratory study on the role of serum fatty acids in the short-term dietary therapy of gingivitis

A previous randomised controlled trial showed that an anti-inflammatory diet (AID) significantly reduced gingival inflammation despite constant plaque values. This exploratory study investigated the role of serum fatty acids in relation to the observed clinical effects. Therefore, data of thirty participants with gingivitis, following either a pro-inflammatory dietary pattern (PID) rich in saturated fat, omega 6 fatty acids, and refined carbohydrates or an AID for 4 weeks, were correlated with corresponding serum samples for a variety of fatty acids. Changes in the fatty acid profile and effects on clinical periodontal parameters were analysed. Results showed that the polyunsatured:saturated fatty acids ratio (PUFA:SFA ratio) and nervonic acid level were significantly higher in the AID group than in the PID group at the end of the study. Significant intragroup differences were seen only in the AID group. Diverse fatty acids showed heterogeneous relations to clinical parameters. This study demonstrated that the serum fatty acid profile was not fundamentally associated with the clinical gingivitis-lowering effects of an AID in short-term, although some fatty acids showed individual relations to clinical parameters with respect to inflammation. Hence, short-term effects of dietary therapy on gingivitis may be rather based on carbohydrate-related effects and/or micronutrients.

A rapid method for the screening of fatty acids in lipids in plasma or serum without prior extraction

Serum or plasma are the commonly used blood fractions to determine the relationship between dietary and circulating fatty acids in health and disease. Most methods available for the measurement of fatty acids in serum or plasma (referred to as serum henceforth) require prior extraction with organic solvents. We have determined that it is possible to directly convert the lipids in aqueous biological samples to fatty acid methyl esters (FAME) without prior extraction, providing that the ratio of serum to transmethylation solvent does not exceed 10%. Our in-vial transmethylation system uses 50uL serum pipetted into 2 mL screw top GC vials containing 1 mL of 1% H2SO4 in methanol at 50 °C and subsequent FAME extracted in the same vial into 300uL heptane. The system yields both compositional and quantitative analysis of the fatty acids of serum identical to conventional standard methods. Evaluation of our new serum assay confirms significant correlations between the fatty acid measures and those obtained from conventional standard assay for all fatty acids (r > 0.99, P<0.0001), including the n-6 (r = 0.998, P<0.0001) and n-3 long chain polyunsaturated fatty acids (r = 0.993, P<0.0001). There were high levels of agreement between methods on Bland -Altman analysis, indicating the interchangeability of the methods. These results establish our new method as reliable for the assessment of fatty acid composition of small volumes of serum useful for high throughput situations that limits the volume of organic solvents and technical input.

Black Truffle Extract Exerts Antidiabetic Effects through Inhibition of Inflammation and Lipid Metabolism Regulation.

Black truffle, a culinary and medical fungus, is highly valued worldwide for its nutritional and therapeutic importance. To enhance the existing knowledge about the beneficial properties, this study investigates the antioxidant, antihyperlipidemic, and anti-inflammatory effects of black truffle extract in in vitro biochemical assays and animal study. Briefly, black truffle extract was administered orally to treat streptozotocin- (STZ-) induced diabetic Wistar rats for 45 days. At the end of the experimental duration, rats were sacrificed to perform biochemical and gene expression analyses related to lipid regulatory and inflammatory pathways. Our results indicated that total cholesterol, triglycerides, free fatty acids, phospholipids, and low-density lipoprotein in different tissues and circulation were significantly increased in diabetic rats. Furthermore, the β-hydroxy β-methylglutaryl-CoA enzyme was also significantly increased; lipoprotein lipase and lecithin–cholesterol acyltransferase enzymes were significantly decreased in diabetic rats. However, the above conditions were reversed upon black truffle extract feeding. Furthermore, black truffle extract was also found to downregulate the expression of proinflammatory cytokines (tumor necrosis factor-α and interleukin-6) and lipid regulatory genes (serum regulatory element-binding protein-1 and fatty acid synthase). The truffle extract-treated effects were comparable to glibenclamide and medication commonly used to treat diabetes mellitus. Overall, our results suggested that black truffle possesses strong antihyperlipidemic and anti-inflammatory effects on diabetic rats. These findings will enhance the current knowledge about the therapeutic importance of black truffles. They might be exploited as a possible food supplement or even as a natural source of pharmaceutical agents for diabetes prevention and treatment.

The Impact of Kidney Transplantation on the Serum Fatty Acid Profile in Patients with End-Stage Kidney Disease.

Epidemiological data indicate that metabolic disturbances and increased cardiovascular risk in renal transplant patients are a significant and common problem. Therefore, it is important to search for new solutions and, at the same time, counteract the negative effects of currently used therapies. In this study, we examined the effect of kidney transplantation on the serum levels of fatty acids (FAs) in order to assess the role of these compounds in the health of transplant patients. The FA profile was analyzed by gas chromatography-mass spectrometry in the serum of 35 kidney transplant recipients, just before transplantation and 3 months later. The content of total n-3 polyunsaturated FAs (PUFAs) decreased after transplantation (3.06 ± 0.13% vs. 2.66 ± 0.14%; p < 0.05). The total amount of ultra-long-chain FAs containing 26 and more carbon atoms was significantly reduced (0.08 ± 0.009% vs. 0.05 ± 0.007%; p < 0.05). The desaturation index (18:1/18:0) increased after transplantation (3.92 ± 0.11% vs. 4.36 ± 0.18%; p < 0.05). The study showed a significant reduction in n-3 PUFAs in renal transplant recipients 3 months after transplantation, which may contribute to increased cardiovascular risk in this patient population.

A Food-Based Intervention in a Military Dining Facility Improves Blood Fatty Acid Profile.

Enhancing dietary omega-3 highly unsaturated fatty acids (n-3 HUFA) intake may confer neuroprotection, brain resiliency, improve wound healing and promote cardiovascular health. This study determined the efficacy of substituting a few common foods (chicken meat, chicken sausage, eggs, salad dressings, pasta sauces, cooking oil, mayonnaise, and peanut butter) lower in omega-6 polyunsaturated fatty acids (n-6 PUFA) and higher in n-3 HUFA in a dining facility on blood fatty acid profile. An eight-week prospective, between-subjects (n = 77), repeated measures, parallel-arm trial was conducted. Participants self-selected foods consumed from conventionally produced foods (control), or those lower n-6 PUFA and higher n-3 HUFA versions (intervention). Changes in blood omega-3 index, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), n-6 PUFA, lipid profile, and food satisfaction were main outcomes. Between-group differences over time were assessed using a linear mixed model to measure the effect of diet on blood serum fatty acids and inflammatory markers. The intervention group achieved a higher omega-3 index score (3.66 ± 0.71 vs. 2.95 ± 0.77; p < 0.05), lower total n-6 (10.1 ± 4.6 vs. 15.3 ± 6.7 µg/mL; p < 0.05), and higher serum concentration of EPA (5.0 ± 1.31 vs. 4.05 ± 1.56 µg/mL; p < 0.05) vs. controls. Satisfaction in intervention foods improved or remained consistent. Substitution of commonly eaten dining facility foods with like-items higher in DHA and EPA and lower in n-6 PUFA can favorably impact fatty acid status and the omega-3 index.

Explore the Anti-Acne Mechanism of Licorice Flavonoids Based on Metabonomics and Microbiome.

Acne vulgaris is one of the most common inflammatory dermatoses in dermatological practice and can affect any gender or ethnic group. Although in previous studies, we had found that licorice flavonoids (LCF) play an anti-acne role by inhibiting PI3K-Akt signaling pathways and mitochondrial activity, the mechanism of LCF regulating skin metabolism, serum metabolism and skin microbes is still unclear. Here, we performed a full spectrum analysis of metabolites in the skin and serum using UHPLC-Triple TOF-MS. The results showed that LCF could treat acne by regulating the metabolic balance of amino acids, lipids and fatty acids in serum and skin. Similarly, we performed Illumina Hiseq sequencing of DNA from the skin microbes using 16S ribosomal DNA identification techniques. The results showed that LCF could treat acne by regulating the skin microbes to interfere with acne and make the microecology close to the normal skin state of rats. In summary, this study confirmed the anti-acne mechanism of LCF, namely by regulating metabolic balance and microbial balance. Therefore, this discovery will provide theoretical guidance for the preparation development and clinical application of the drug.

Fatty acids mediate hepatocyte calcium release and ER stress induction after traumatic injury

Burn injury is one of the most severe injuries affecting almost every organ system. It produces a hypermetabolic stress response characterized by increased free fatty acids in serum. Burn injury is known to adversely alter liver function resulting in metabolic dysfunction. Hepatic changes at the cellular level after burn injury include chronic induction of the ER stress response and insulin resistance, which contributes to liver dysfunction. However, the mechanisms by which burn injury induces acute and lasting changes in hepatic function are poorly understood.

The glucose lowering effects of CL 316,243 dissipate with repeated use and are rescued bycilostamide.

Repeated activation of the beta 3 adrenergic receptor (β3AR) with the agonist CL 316,243 (CL) results in remodeling of white adipose tissue (WAT) characterized by increased mitochondrial enzymes and expression of uncoupling protein 1 (UCP1). β3AR activation also has profound acute metabolic effects including rapidly decreasing blood glucose, secondary to fatty acid‐induced increases in insulin, and increasing energy expenditure. The acute (single dose) effects of β3AR activation have largely been examined in treatment naive animals and under room temperature housing conditions. The current study examined if repeated CL treatment would lead to an attenuation of acute metabolic effects of CL treatment under thermoneutral housing conditions and if this could be rescued with cilostamide, a phosphodiesterase inhibitor. We provide evidence demonstrating that the acute effects of CL to increase serum fatty acids and insulin and reduce blood glucose, but not increases in energy expenditure, are attenuated in mice following repeated treatment with CL. This occurs in parallel with reductions in indices of protein kinase A signaling in WAT including the phosphorylation of hormone sensitive lipase. The findings of attenuated serum fatty acid, insulin, and blood glucose responses were confirmed in both high‐fat fed and UCP1−/− mice repeatedly treated with CL. Desensitization to CL in mice was rescued by cilostamide. Herein, we provide evidence that the glucose lowering, but not thermogenesis inducing, effects of CL are attenuated with repeated treatment and can be rescued by cilostamide. The findings of this study point toward novel adjunct treatment approaches that could be used to maximize therapeutic, glucose lowering effects of β3AR agonists.

Short report - Lethal and aggressive pancreatic cancer: molecular pathogenesis, cellular heterogeneity, and biomarkers of pancreatic ductal adenocarcinoma.

This short report describes the carcinogenesis of the pancreas leading to pancreatic ductal adenocarcinoma (PDAC) determined by molecular, cellular, and functional heterogeneity. Among the diverse types of pancreatic cancers, PDAC is the most lethal, aggressive, and one of the leading cancers associated with the highest mortality. Pancreatic cellular components like pancreatic stellate cells (PSC), mesenchymal stem cells (MSC), and pancreatic fibroblast cells (PFC) exhibit these properties in PDAC. After the appearance of point mutations in KRAS, the mutations in tumor suppressor genes appear sequentially in the order of CDKN2A, TP53, and SMAD4 that eventually resulting in PDAC development. As of today, there are no effective therapeutic options or treatments available for PDAC. The main difficulty in managing PDAC cases is its defiance to chemotherapy and radiotherapy. There were several attempts to identify a suitable biomarker for the early diagnosis and prognosis of PDAC. Anyway, these recently discovered biomarkers vary in their sensitivity and specificities. Some of the other important and reliable biomarkers for PDAC are carbohydrate antigen 19-9 (CA 19-9), carcinoembryonic antigen (CEA), cell migration-inducing hyaluronan binding protein (CEMIP), serum fatty acid metabolite PC-594, and micro-RNAs (miRNAs).

Targeted metabolomics profiles serum fatty acids by HFD induced non-alcoholic fatty liver in mice based on GC-MS

Nonalcoholic fatty liver (NAFLD) is associated with metabolic abnormalities and changes in lipid processing. Fatty acids (FAs) are important signaling molecules in the body and are the main raw materials for lipid synthesis. To explore the lipidomic profile of serum fatty acids in mice, we put the mice on a high-fat diet (HFD) to induce NAFLD. We applied a targeted metabolic analysis approach using gas chromatography-mass spectrometry (GC-MS) and established a method for simultaneous determination of 36 medium and long-chain fatty acids in the serum of mice. This method was validated for linearity, range, sensitivity, precision, accuracy, recovery, stability, and dilution integrity. The levels of most FA species and total FAs were increased in the HFD group (n = 9) compared with the lean group (n = 9). The principal component analysis (PCA) and the orthogonal partial least squares discriminant analysis (OPLS-DA) of all FA species were analyzed in both groups. We found that palmitic acid (16:0), stearic acid (18:0), oleic acid (18:1), and arachidonic acid (20:4) were significantly different (VIP＞1, p＜0.05 and FC＞1.5) in the two groups. We also calculated serum indices measure the activities of different enzymes involved in fatty acid metabolism. The de novo lipogenesis index, elongase index, n-6 FAs, saturated FAs, unsaturated FAs, and SCD1 index 2 were increased in the HFD group compared with the lean group while the n-3 FAs, n-3/n-6 of the index, and SCD1 index 1 were decreased in the HFD group compared with the lean group. Relationships between major FA species and biochemical indicators (LDL-C, TC, TG, ALT, and AST) were evaluated by Pearson analysis. The serum FA concentrations (C16:0, C18:0, C18:1, and C20:4) and serum indices (De novo lipogenesis index, elongase index, saturated FAs, unsaturated FAs and n-6 FAs) positively correlated with LDL-C, TC, TG, ALT, and AST. Collectively, our study provides insights into NAFLD and its effect on lipid metabolism.

Maternal diet-induced obesity during pregnancy alters lipid supply to mouse E18.5 fetuses and changes the cardiac tissue lipidome in a sex-dependent manner.

Maternal obesity during pregnancy has immediate and long-term detrimental effects on the offspring heart. In this study, we characterized the cardiac and circulatory lipid profiles in late gestation E18.5 fetuses of diet-induced obese pregnant mice and established the changes in lipid abundance and fetal cardiac transcriptomics. We used untargeted and targeted lipidomics and transcriptomics to define changes in the serum and cardiac lipid composition and fatty acid metabolism in male and female fetuses. From these analyses we observed: (1) maternal obesity affects the maternal and fetal serum lipidome distinctly; (2) female fetal heart lipidomes are more sensitive to maternal obesity than males; (3) changes in lipid supply might contribute to early expression of lipolytic genes in mouse hearts exposed to maternal obesity. These results highlight the existence of sexually dimorphic responses of the fetal heart to the same in utero obesogenic environment and identify lipids species that might mediate programming of cardiovascular health.