Serum Concentrations Of Fatty Acids Research Articles

PSIX-6 Algal oil as an alternative source of docosahexaenoic acid in feline diets

Abstract The global demand for eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplementation by humans and their necessity in companion animal foods has raised questions related to environmental sustainability and nutrient content of fish oil. The combination of reported diminishing EPA and DHA content in fish oil and the forecasting of a significant decline in global fish stocks over the next decade make it critical to consider alternative sources of omega-3 fatty acids to reduce dependence on fish harvests. Cultured algal oil has been identified as a promising and viable alternative to fish-based oils. As such, the purpose of this study was to determine the inclusion level of algal oil in cat foods necessary to deliver the same serum concentrations of DHA provided from fish oil. Cats (n = 26) were first fed a control food formulated to avoid ingredients that contain long chain omega-3 fatty acids [ɑ-linolenic (ALA), EPA, and DHA] for 5 wk, to establish a baseline serum concentrations of these fatty acids. Cats were then randomized into two groups, and fed test foods containing either fish oil or algal oil in sequential increasing levels of DHA (0.2%, 0.4%, and 0.6%) for 5-wk periods each. Blood was analyzed for serum DHA and EPA concentrations after each of these feeding periods. A regression analysis was used to calculate a bioequivalence factor between fish oil and algal oil inclusion levels. There was no difference (P > 0.05) in intake or body weight between cats consuming diets containing algal oil or fish oil. Analysis of serum fatty acid concentrations showed that increasing fish and algal oil had no effect (P > 0.05) on serum linolenic acid, ALA, or arachidonic acid; however, increasing fish and algal oil did have an effect on DHA such that serum DHA was increased at similar rates as fish oil (P = 0.050) and algal oil (P = 0.026) levels were increased in the diet. Although increasing levels of fish and algal oil both increased serum EPA concentrations (P < 0.001), fish oil increased serum EPA to a greater extent than algal oil when fed at all levels. Overall, these data indicate that inclusion of algal oil is a good alternative dietary source of DHA, but less of EPA, and that algal oil will need to be added to the diet in higher concentrations to achieve similar serum EPA concentrations as fish oil.

Influence of administration timing of San-Huang-Xie-Xin-Tang treatment on attenuating Salmonella enterica serovar Typhimurium infection.

Salmonella infections are a serious global health concern, particularly in developing countries, and are further exacerbated by the emergence of antibiotic resistance. San-Huang-Xie-Xin-Tang (SHXXT), a traditional herbal medicine with potent anti-inflammatory properties, has recently gained attention as an alternative treatment. Our study emphasizes on the importance of precise timing in accordance with traditional Chinese medicine principles. A mouse infection model was established while different administration times of SHXXT were recorded for the body weight, clinical scores, bacterial counts in blood, and organs. Additionally, cytokine levels, fatty acids, and amino acids in the serum were also monitored. We found that administering SHXXT 1 day after Salmonella enterica subsp. enterica serovar Typhimurium (S. Typhimurium) infection (T1 group) leads to positive outcomes. This includes restoration of body weight, improved clinical scores, and reduced bacterial counts in blood and vital organs. Interferon-gamma levels remained consistently high across all treatment groups 6 days post-infection. However, the T1 group showed exclusive suppression of serum levels of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β). The timing of administration significantly influenced serum fatty acid concentrations, countering Salmonella-induced disruptions, aligning with TNF-α and IL-1β levels. SHXXT had also restored amino acid profiles disrupted by the infection, with notable effects when administered at the correct timing. Our research highlights SHXXT's potential in treating S. Typhimurium infection, emphasizing the importance of precise timing in line with traditional Chinese medicine principles for effective treatment at different disease stages.

Mechanisms linking hypertriglyceridemia to acute pancreatitis.

Hypertriglyceridemia (HTG) is a metabolic disorder, defined when serum or plasma triglyceride concentration (seTG) is >1.7 mM. HTG can be categorized as mild to very severe groups based on the seTG value. The risk of acute pancreatitis (AP), a serious disease with high mortality and without specific therapy, increases with the degree of HTG. Furthermore, even mild or moderate HTG aggravates AP initiated by other important etiological factors, including alcohol or bile stone. This review briefly summarizes the pathophysiology of HTG, the epidemiology of HTG-induced AP and the clinically observed effects of HTG on the outcomes of AP. Our main focus is to discuss the pathophysiological mechanisms linking HTG to AP. HTG is accompanied by an increased serum fatty acid (FA) concentration, and experimental results have demonstrated that these FAs have the most prominent role in causing the consequences of HTG during AP. FAs inhibit mitochondrial complexes in pancreatic acinar cells, induce pathological elevation of intracellular Ca2+ concentration, cytokine release and tissue injury, and reduce the function of pancreatic ducts. Furthermore, high FA concentrations can induce respiratory, kidney, and cardiovascular failure in AP. All these effects may contribute to the observed increased AP severity and frequent organ failure in patients. Importantly, experimental results suggest that the reduction of FA production by lipase inhibitors can open up new therapeutic options of AP. Overall, investigating the pathophysiology of HTG-induced AP or AP in the presence of HTG and determining possible treatments are needed.

Metabolic profiles and follicular dynamics of prepubertal and pubertal Santa Inês ewe lambs with dietary restriction and supplementation with roasted whole soybeans

The objectives of this study were to evaluate moderate feed restriction and lipid supplementation on follicular dynamics, serum concentrations of fatty acids, and metabolic profile of prepubertal and pubertal ewe lambs. Thirty-five Santa Inês ewe lambs were randomly assigned according to body weight in an unbalanced block design with a 2 × 2 factorial arrangement, which consisted of level of intake (ad libitum - AL or restricted - FR), lipid supplementation (with or without whole roasted soybean). Ewe lambs in the FR group had 85% of the diet offered to those in the AL group. Ovulation was retrospectively defined by serum progesterone sample ≥ 1 ng/mL. The physiological status, ovulating (OV) and not ovulating (NOV), was considered as a two-level covariate. Dry matter and ether extract intake were greater in unsupplemented than supplemented AL ewe lambs that had ovulated (intake level x lipid supplementation x physiological status, P < 0.05). Plasma glucose and serum triglyceride concentrations were higher (P < 0.05) in supplemented animals, but no changes were observed in serum insulin concentrations (P > 0.05). In the unsupplemented animals, serum high-density lipoprotein (HDL) and cholesterol concentrations were higher in FR animals than in AL animals; serum HDL and cholesterol concentrations did not differ between lipid-supplemented groups (intake level x lipid supplementation, P < 0.05). Serum HDL was higher (P < 0.05) in animals that had ovulated than in animals that had not ovulated. In supplemented ewe lambs, serum stearic concentrations were greater in the AL group than in the FR group; conversely, in unsupplemented animals, stearic concentrations were lower in the AL group than in the FR group (intake level x lipid supplementation, P < 0.05). The linoleic serum concentrations were not affected (P > 0.05) by intake level, lipid supplementation, or physiological status. The number of follicular waves was greater (P < 0.05) in AL ewe lambs than in FR ewe lambs. There was no main effect of treatment or interaction effects (P > 0.05) on the number of follicles, follicular diameter, or growth rate of the largest follicle. In conclusion, lipid supplementation with roasted whole soybeans improved the metabolic profile of ewe lambs, with no concomitant effect on follicular dynamics or linoleic serum concentration. Except for a reduction in the number of follicular waves, the follicular dynamics were not altered by moderate FR. Despite the higher serum HDL concentrations in ewe lambs that had ovulated, the follicular development was not enhanced.

Dietary Ground Flaxseed Increases Serum Alpha-Linolenic Acid Concentrations in Adult Cats.

Simple SummaryThe use of flaxseed in complete pet foods as a source of omega-3 fatty acids, and in particular alpha-linolenic acid, has been studied extensively in dogs. However, to date, no scientific published literature exists on the impacts of feeding whole ground flaxseed as an ingredient in cat food on nutrient digestibility, fatty acid bioavailability, and overall health in cats. In addition, dietary flaxseed inclusion has been challenged as providing little nutritional value for cats by not changing serum fatty acid levels and lowering nutrient digestibility. Therefore, the objective of this study was to directly evaluate the effects of adding ground flaxseed to dry cat food on fatty acid bioavailability, stool consistency, nutrient digestibility, and overall health in adult cats. These results clearly exhibit that a flaxseed-supplemented diet resulted in no changes in stool quality or nutrient digestibility, and elicited an increase in serum alpha-linolenic acid concentrations in healthy cats. Overall, these results clearly demonstrate that ground flaxseed can be used to modulate serum fatty acid concentrations and serve as a bioavailable source of alpha-linolenic acid in commercial cat food.We evaluated effects of dietary ground flaxseed on fecal and serum alpha-linolenic acid (ALA) concentrations, nutrient digestibility, and stool quality in female and male adult cats (n = 20 (8 males, 12 females); 3.95 ± 1.49 years of age (mean ± SD); 3.88 ± 0.82 kg BW). We hypothesized that adding ground flaxseed would increase serum ALA compared with feeding no flax, without changing nutrient digestibility. Cats were fed as-is 2.6% added-flaxseed (flax, n = 10) or no-flax (control, n = 10) diets (2.66 vs. 0.78% ALA of total fatty acids; crude protein 35%, fat 20%, fiber 3% as-fed) twice daily to maintain body weight for 28 days. Fecal collections were conducted on days 23–27 for total-tract nutrient digestibility, stool quality (scale 1–5; 1 = watery diarrhea, 5 = hard, dry, crumbly) and long-chain fatty acid (LCFA) analyses. Blood was collected on days 0, 14, and 28 for serum LCFA and chemistry analysis. Digestibility and fecal data were analyzed by ANOVA (SAS v9.4, Cary, NC, USA) and a repeated measures ANOVA for serum ALA. Flax-fed cats, compared with control-fed, had greater (p < 0.05) serum ALA after 14 days (4.00 vs. 0.71 µg/mL) and 28 days (7.83 and 3.67 µg/mL). No differences were observed in stool quality, and dry matter, protein, fat, and ALA digestibility. However, metabolizable energy was greater in the flax vs. control diet (4.18 vs. 3.91 kcal/g; p < 0.05). Overall, these data demonstrate that ground flaxseed added to cat diets increases serum ALA within 14 days, with no detriments to nutrient digestibility. We conclude that flaxseed can be used as a bioavailable source of ALA in cat diets.

β-hydroxybutyrate impairs monocyte function via the ROS-NLR family pyrin domain-containing three inflammasome (NLRP3) pathway in ketotic cows.

Cows with ketosis display severe metabolic stress and immune dysfunction which renders them more susceptible to infections. Monocytes, one of the major subtypes of white blood cells, play an important role in innate immune defense against infections. Thus, the aim of this study was to investigate alterations in immune function, reactive oxygen species (ROS) production and activity of the NLR family pyrin domain containing 3 (NLRP3) inflammasome pathway in monocytes (CD14+) of cows with clinical ketosis (CK). Twelve healthy multiparous Holstein cows [blood β-hydroxybutyrate (BHB) concentration < 1.2 mM] and 12 cows with CK (BHB > 3.0 mM) at 3 to 14 days in milk were used for blood sample collection. To determine effects of BHB on phagocytosis, ROS and protein abundance of the NLRP3 inflammasome pathway in vitro, monocytes isolated from healthy cows were treated with 3.0 mM BHB for 0, 6, 12 or 24 h. Dry matter intake (22.7 vs. 19.0 kg) was lower in cows with CK. Serum concentrations of fatty acids (0.30 vs. 0.88 mM) and BHB (0.52 vs. 3.78 mM) were greater in cows with CK, whereas concentration of glucose was lower (4.09 vs. 2.23 mM). The adhesion, migration and phagocytosis of monocytes were lower in cows with CK, but apoptosis and ROS content were greater. Protein abundance of NLRP3, cysteinyl aspartate specific proteinase 1 (caspase 1) and interleukin-1B p17 (IL1B p17) were greater in monocytes of cows with CK, while abundance of NADPH oxidase isoform 2 (NOX2) was lower. Compared with 0 h BHB, ROS content and apoptosis were greater in the monocytes challenged for 6, 12 or 24 h BHB. Compared with 0 h BHB, protein abundance of NLRP3, caspase 1, IL1B p17 and concentration of IL1B in medium were greater in the monocytes challenged for 6, 12 or 24 h BHB. However, compared with 0 h BHB, protein abundance of NOX2 and phagocytosis of monocytes were lower in the monocytes challenged for 6, 12 or 24 h BHB. Overall, the data suggested that exogenous BHB activated the ROS-NLRP3 pathway, which might be partly responsible for immune dysfunction of dairy cows with CK.

Metabolomic Abnormalities in Serum from Untreated and Treated Dogs with Hyper- and Hypoadrenocorticism.

The adrenal glands play a major role in metabolic processes, and both excess and insufficient serum cortisol concentrations can lead to serious metabolic consequences. Hyper- and hypoadrenocorticism represent a diagnostic and therapeutic challenge. Serum samples from dogs with untreated hyperadrenocorticism (n = 27), hyperadrenocorticism undergoing treatment (n = 28), as well as with untreated (n = 35) and treated hypoadrenocorticism (n = 23) were analyzed and compared to apparently healthy dogs (n = 40). A validated targeted proton nuclear magnetic resonance (1H NMR) platform was used to quantify 123 parameters. Principal component analysis separated the untreated endocrinopathies. The serum samples of dogs with untreated endocrinopathies showed various metabolic abnormalities with often contrasting results particularly in serum concentrations of fatty acids, and high- and low-density lipoproteins and their constituents, which were predominantly increased in hyperadrenocorticism and decreased in hypoadrenocorticism, while amino acid concentrations changed in various directions. Many observed serum metabolic abnormalities tended to normalize with medical treatment, but normalization was incomplete when compared to levels in apparently healthy dogs. Application of machine learning models based on the metabolomics data showed good classification, with misclassifications primarily observed in treated groups. Characterization of metabolic changes enhances our understanding of these endocrinopathies. Further assessment of the recognized incomplete reversal of metabolic alterations during medical treatment may improve disease management.

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.

Long-Chain Polyunsaturated Fatty Acid Concentrations and Association with Weight Gain in Pregnancy.

Lower concentrations of omega-3 (ω-3) and higher concentrations of omega-6 (ω-6) have been associated with excess weight in adults; however, the information on this relationship in pregnancy remains in its infancy. This study aimed to investigate the association between plasma levels of ω-3 and ω-6 long-chain polyunsaturated fatty acids (PUFAs) and weight gain during the gestational period. This is a prospective cohort study involving 185 pregnant women registered with the prenatal services of a municipality in the northeast of Brazil. The dosage of the serum concentration of fatty acids and the anthropometric measurements were carried out at the baseline, and the women’s weight information in the first, second, and third trimesters was collected from their pregnancy cards. Serum fatty acids were determined with the help of gas chromatography. The response variable of this study is the latent variable weight gain in pregnancy, derived from three variables: gestational weight in the first, second, and third trimesters. The main exposure was the plasma concentrations of PUFAs. Structural equation modeling was used for the data analysis. The mean age of the pregnant women was 26.74 years old (SD: 5.96 years). Most of the women had not completed high school (84%) and had a low income (70.86%). It was observed that the ω-3 PUFAs, represented by ALA plasm (alpha-linolenic acid), DHA (docosahexaenoic acid), and the EPA/ALA ratio (eicosapentaenoic acid to alpha-linolenic acid ratio), were negatively associated with the weight gain during pregnancy construct (−0.20, −0.12, and −0.14, respectively). Meanwhile, the PUFAs represented by the ratio between the ω-6 category acids ARA and LA (arachidonic acid and linoleic acid) had a direct and positive association (0.22) with that construct. Excess maternal weight gain was associated with ω-3 and ω-6 plasma levels. The women with the greatest gestational weight gain were the ones that presented the highest ARA/LA ratio (ω-6) and the lowest plasma concentrations of ALA, DHA, and EPA/ALA ratio (ω-3).

Abstract 10915: Unappreciated Mechanisms of Fatty Acid Uptake in the Kidney: Fatty Acids Are Taken Up from Both Basolateral and Apical Side

Introduction: The kidney combusts a large amount of fatty acid (FA) for body fluid homeostasis. Despite the high demand for FA, however, little is known about the mechanisms of FA uptake. We aimed to determine how FAs are taken up by tubular epithelial cells. Methods and Results: Immunohistochemistry showed that CD36, known as an important FA transporter in the heart, was also expressed in the basolateral side of proximal tubule epithelial cells (PTECs). The uptake of 125 I-BMIPP, radio-labeled FA tracer, was significantly reduced in the kidney in CD36 knockout mice 1 min after its injection compared with wild-type mice, while the significant difference disappeared 30 min after the injection. In vivo imaging with two-photon microscopy revealed that BODIPY-C 12 , fluorescence-labeled FA tracer, was accumulated in the basolateral side (blood side) of PTECs shortly after its injection, which was followed by accumulation in the apical side (primary urine side), suggesting bidirectional FA uptake by PTECs. A large amount of neutral lipid was accumulated in the kidney when serum FA concentration was increased by accelerated lipolysis by administration of a β3 adrenergic receptor agonist. Immunofluorescence with cell-specific antibodies revealed that the cells with the most abundant lipid accumulation were PTECs, followed by tubular epithelial cells of the distal nephron. In addition, neutral lipid accumulation was enhanced even in the distal nephron when PTECs were injured with administrations of diphtheria toxin (DT) in mice overexpressing DT-receptor in a PTEC-specific manner. Importantly, the PTEC-injured mice exhibited marked albuminuria, suggesting disturbance of protein reabsorption. Despite marked albuminuria, however, urinary FA was not detected at all, suggesting complete FA reabsorption independently of albumin reabsorption in the kidney. Conclusions: Our results revealed the unique and prominent capability of proximal and distal tubular epithelial cells to take up FA from both blood (CD36-dependent) and primary urine (CD36-independent) and to store them as neutral lipids. We further suggest that the kidney acts not only as FA consuming tissue but also as FA keeping tissue to completely reabsorb FA from primary urine for unwasted energy use.

Serum concentration of fatty acids in children with obesity and nonalcoholic fatty liver disease

ObjectivesIt has been suggested that circulating fatty acids (FAs) take part in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) in children with obesity. The aims of this study were to evaluate the serum FA concentration in this pediatric population. MethodsThe prospective study included 80 children with obesity and suspected liver disease. Patients with viral hepatitis, autoimmune, toxic, and selected metabolic liver diseases were excluded. Criteria for NAFLD diagnosis included liver steatosis in ultrasound as well as elevated alanine transaminase (ALT) serum activity. The total intrahepatic lipid content (TILC) was assessed by magnetic resonance proton spectroscopy (1H-MRS). Fasting serum FA concentrations were measured in all children using gas-liquid chromatography. ResultsNAFLD was diagnosed in 31 children. Total FA concentration was significantly higher (P < 0.01) in all obese children as well as in obese children with NAFLD compared with controls. In children with NAFLD, a significant, positive correlation was found between total FA concentration and cholesterol (R = 0.47, P < 0.01), triacylglycerols (R = 0.78, P < 0.001), and insulin (R = 0.45, P < 0.011). In a group of children with obesity, TILC correlated positively with saturated FA concentration (R = 0.23, P < 0.05). ConclusionData from the present study do support the hypothesis that FAs are potentially involved in the pathogenesis of NAFLD in children with obesity.

Investigation of Body Development in Growing Holstein Heifers With Special Emphasis on Body Fat Development Using Bioelectrical Impedance Analysis.

This study analyzed skeletal development, body condition, and total body fat development of growing heifers. A total of 144 female primiparous Holstein cattle from four commercial dairy farms with different degrees of stillbirth rates were examined during the rearing period. This included measurements in body condition, fat tissue, metabolic, and endocrine factors. Pelvic measurements and the sacrum height were analyzed to assess skeletal development. The body condition was classified via body condition scoring, bioelectrical impedance analysis (BIA), back fat thickness measurements, and the body mass. For the first time, BIA was used as an appropriate method to evaluate the fat tissue content of cattle throughout the rearing period. This analysis technique can be performed on heifers aged 8–15 months. Throughout that period, the fat content decreased while the skeletal development increased. In addition, high free fatty acid concentrations in serum of the animals with high frame development were found, supporting our hypothesis that stored energy of body fat deposits is used for skeletal growth. Furthermore, we were able to demonstrate complex endocrine relationships between fat metabolism and skeletal growth by using specific markers, such as leptin, insulin growth factor-1 (IGF-1), and estradiol (E2). Food analysis showed high crude protein (CP) levels in the total mixed ration above recommendation for daily protein intake of all farms. However, there was a positive correlation between CP and the body frame measurements in our study. In summary, we established a novel regression formula for BIA analysis (“BIA-Heine”) in heifers to evaluate the body composition throughout different ages and physiological stages in the development of heifers. This special formula allows the evaluation of fat tissue without a whole-body analysis and therefore provides an innovative technique for animal welfare support.

THE SIMVASTATIN EFFECT ON ACETYL COA CARBOXYLASE1 AND FATTY ACID SYNTHASE GENE EXPRESSION IN RAT FED WITH HIGH FAT DIETS AND ITS ASSOCIATION WITH FATTY ACID PROPORTION AND CONCENTRATION

The aim of study was to determine the effect of different dosages of simvastatin on gene expression of Acetyl CoA Carboxylase 1 (ACC1) and Fatty Acid Synthase (FAS) in Wister rat hepatic tissues fed with high fat diets (HFD) and its association with serum fatty acid proportion and concentration. Four groups of rats (G1 to G4) were included. ACC1 and FAS expressions were analyzed by Real time quantitative polymerase chain reaction. Fatty acid concentration was measured by gas chromatography. There were significant differences when G4 versus G3, G4 and G3 versus G1 and G4 and G3 versus G2 was compared for total fatty acid concentration. The proportion of oleic acid to stearic acid showed significant decrease when G4 versus G3, G4 versus G2 and G4 versus G1 groups were compared, but the proportion of stearic acid to palmitic acid, linoleic acid to oleic acid (G3 versus G4) and oleic acid to palmitic acid in G4 increased when compared to G1, G2 and G3 groups. Treatment with simvastatin significantly increases or decreases some fatty acid ratio, serum fatty acid and total fatty acid concentrations. We also found that HFD led to no significant differences in ACC1 and FAS mRNA expression. Simvastatin increases proportion of linoleic acid to oleic acid, oleic acid to palmitic acid and oleic acid to stearic acid. Thus, statin therapy may be considered in prevention of cardiovascular and myocardial risk.

Intravenous trimethylamine N-oxide infusion does not modify circulating markers of liver health, glucose tolerance, and milk production in early-lactation cows

In rodents and humans, the gut bacteria-derived metabolite trimethylamine N-oxide (TMAO) has been implicated in the progression of cardiovascular disease, chronic kidney disease, fatty liver, and insulin resistance; however, the effects of TMAO on dairy cattle health and milk production have not been defined. We aimed to determine whether intravenous TMAO infusion modifies measures of liver health, glucose tolerance, and milk production in early-lactation cows. Eight early-lactation Holstein cows (30.4 ± 6.41 d in milk; 2.88 ± 0.83 lactations) were enrolled in a study with a replicated 4 × 4 Latin square design. Cows were intravenously infused TMAO at 0 (control), 20, 40, or 60 g/d for 6 d. Washout periods lasted 9 d. Intravenous glucose tolerance tests (GTT) occurred on d 5. Blood was collected daily. Milk was collected on d -1, 0, 5, and 6. Urine was collected on d -1 and 6. Circulating metabolites, milk components, and TMAO concentrations in milk, urine, and plasma were quantified. Data were analyzed using a mixed model that included the fixed effects of treatment. Concentrations of TMAO in plasma, milk, and urine increased linearly with increasing dose. Dry matter intake and milk production were not modified by treatment. Daily plasma triacylglycerol, fatty acid (FA), and glucose concentrations were not modified. Serum albumin, total protein, globulin, total bilirubin, direct bilirubin, aspartate aminotransferase, γ-glutamyl transferase, and glutamate dehydrogenase concentrations were also not modified by treatment. Serum GTT glucose, FA, and insulin concentrations were not modified by treatment. Plasma total, reduced, and oxidized glutathione concentrations were also not modified by treatment. We conclude that a 6-d intravenous infusion of TMAO does not influence measures of liver health, glucose tolerance, or milk production in early-lactation dairy cows.

Abstract P212: Comparison Of Vascular Risk Factors And Serum Fatty Acids At Admission Between Intracerebral Hemorrhage And Acute Ischemic Stroke

Introduction: Dietary triglycerides influence fatty acid (FA) serum concentrations and weight percentages (wt%), which may be associated with the onset of intracerebral hemorrhage (ICH) or acute ischemic stroke (AIS). Hypothesis: There are significant differences between FAs at the admission of ICH and AIS. Methods: We included patients admitted between 2016 and 2019 within 24 h of ICH or AIS onset and calculated correlation coefficients between their ages, serum FA concentrations, and FA wt% values. We evaluated differences in age, average blood pressure (ABP), glucose, A1c, serum lipids, and FAs between two groups. Excluding variables with multicollinearity, we performed multiple logistic regression (MLR) analysis to identify independent variables distinguishing ICH from AIS. We estimated the threshold values of independent variables using the area under the curve values derived from the receiver operating characteristic (ROC) curves. Results: Our inclusion criteria were met by 141 of ICH patients and 525 of AIS patients. In the ICH group, age, A1c, and eicosapentaenoic acid (EPA) levels were smaller than those in the AIS group. ABP, high-density lipoprotein cholesterol (HDL-C), myristic acid (MyA), linoleic acid (LiA) concentrations, and MyA wt% were higher than those in the AIS group. MLR analysis between two groups indicated that age, ABP, A1c, HDL-C were independent variables. Serum FA levels were not independent. ROC curves showed that the threshold values of age, ABP, A1c, and HDL-C for ICH onset were ≤ 69 years, ≥ 126.6 mmHg, ≤ 6.0%, and ≥ 1.62 mmol/L, respectively. In 27 patients with age ≤ 69 , ABP ≥ 126.6, A1c ≤ 6.0%, and HDL-C ≥ 1.62 and 87 patients with age &gt; 69 , ABP&lt; 126.6, A1c &gt; 6.0, and HDL-C &lt; 1.62, there were 19 (70.4%) and 9 (10.3%) patients with ICH, the MyA concentrations were 108 and 73 μmol/L (p &lt; 0.001), the LiA concentration were 2,900 and 2,410μmol/L (p &lt; 0.001), and the EPA wt% were 1.4 and 2.0% (p=0.059), respectively. Conclusions: Younger patients with higher ABP, lower A1c, and higher HDL-C suffered from not AIS but ICH, and their MyA and LiA concentrations were higher than older patients without them.

Long-chain omega-3 fatty acid serum concentrations across life stages in the USA: an analysis of NHANES 2011–2012

ObjectiveTo determine reference ranges of circulating long-chain (LC) omega-3 fatty acids: eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) in a nationally representative population of Americans. To provide...

Time-of-day effects of consumption of fish oil–enriched sausages on serum lipid parameters and fatty acid composition in normolipidemic adults: A randomized, double-blind, placebo-controlled, and parallel-group pilot study

ObjectivesThe body clock controls diurnal rhythms of nutrient digestion, absorption, and metabolism. Fish oil (FO) contains abundant ω-3 polyunsaturated fatty acids (PUFA), including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), that are thought to lower triglyceride (TG) levels. This randomized, placebo-controlled, double-blind, parallel-group trial aimed to confirm the effects of the time of FO intake on TG in healthy Japanese adults. MethodsTwenty healthy Japanese adults (age, 20–60 y) were assigned to either a group that consumed sausages enriched with FO (DHA 1010 mg; EPA 240 mg) in the morning and a placebo (DHA 40 mg; EPA 15 mg) in the evening (BF-FO) or another group that consumed FO-enriched sausages in the evening and the placebo in the morning (DN-FO). Serum lipid parameters, fatty acid (FA) composition, and messenger RNA expression of lipogenic genes in circulating blood cells were evaluated in fasting blood samples before, as well as after 4 and 8 wk of FO intake. ResultsSerum concentrations of TG and total saturated FA were significantly decreased in the BF-FO group, whereas those of ω-3 PUFA were significantly and identically increased in both groups. Serum concentrations of ω-6 PUFA were significantly decreased in the BF-FO but not the DN-FO group. Messenger RNA expression of the lipogenic genes ACLY, SCD, and FASN were similarly reduced in both groups. ConclusionsThese findings suggested that the timing of FO intake affects both serum FA concentrations and TG metabolism in normolipidemic humans. The mechanisms of these effects of FO on lipid metabolism require further investigation.

Inhibition of cell death inducing DNA fragmentation factor-α-like effector c (CIDEC) by tumor necrosis factor-α induces lipolysis and inflammation in calf adipocytes

Dairy cows with ketosis exhibit signs of pronounced adipose tissue lipolysis and systemic inflammation, both of which exacerbate this metabolic disorder. In nonruminants, CIDEC plays a pivotal role in the formation of large unilocular lipid droplets. The present study aimed to ascertain the role of CIDEC in the lipolytic and inflammatory response of white adipose tissue (WAT) in vivo and in vitro. Subcutaneous adipose tissue and blood samples were collected from 15 healthy cows (blood β-hydroxybutyrate concentration < 1.2 mM) and 15 cows with clinical ketosis (blood β-hydroxybutyrate concentration > 3.0 mM) that had a similar number of lactations (median = 3, range = 2-4) and days in milk (median = 6 d, range = 3-9). Adipocytes isolated from 5 healthy Holstein calves (1 d old, female, 30-40 kg) were used for in vitro studies. Isolated adipocytes were treated with 0, 0.1, 1, or 10 ng/mL TNF-α for 3 h, transfected with CIDEC small interfering RNA for 48 h, or transfected with CIDEC overexpression adenovirus for 48 h followed by treatment with TNF-α (0.1 ng/mL) for 3 h. Serum concentrations of fatty acids were greater, and dry matter intake, milk yield, and serum glucose concentrations lower in cows with clinical ketosis. Protein and mRNA abundance of CIDEC were lesser in subcutaneous WAT of clinically ketotic versus healthy cows. Furthermore, the ratio of phosphorylated hormone sensitive lipase (p-LIPE) to LIPE, phosphorylated RELA (p-RELA) to RELA, and protein abundance of PNPLA2 and phosphorylated inhibitor of κBα (p-NFKBIA) were greater in dairy cows with clinical ketosis. The mRNA abundance of proinflammatory cytokines TNFA and IL1B were greater, and the anti-inflammatory cytokine IL10 was lower in WAT of dairy cows with clinical ketosis. In calf adipocytes, exogenous TNF-α (0.1, 1, or 10 ng/mL) decreased protein and mRNA abundance of CIDEC. In addition, exogenous TNF-α or knockdown of CIDEC reduced the secretion of the anti-inflammatory cytokine IL-10, but increased the ratio of p-LIPE to LIPE, p-RELA to RELA, protein abundance of PNPLA2 and p-NFKBIA, glycerol content, and the secretion of IL-1β in calf adipocytes. Overexpression of CIDEC in TNFα-treated adipocytes attenuated lipolysis and activation of the NF-κB signaling pathway. Overall, these data suggest that inhibition of lipid droplet-associated protein CIDEC by TNF-α contributes to the pronounced lipolysis and inflammation of calf adipocytes, and CIDEC is a relevant target in clinically ketotic cows.

Complex patterns of circulating fatty acid levels in gestational diabetes mellitus subclasses across pregnancy

To investigate the relationship between maternal serum fatty acid levels and gestational diabetes mellitus (GDM) subtypes across pregnancy. A total of 680 singleton mothers enrolled in the Complex Lipids in Mothers and Babies (CLIMB) study in Chongqing, China were included. Clinical information and serum samples were collected at gestational weeks (GWs) 11-14, 22-28, and 32-34. 75g Oral Glucose Tolerance Test (OGTT) was conducted at GW 24-28 and GDM subtypes divided into three groups using International Association of Diabetes and Pregnancy Study Group (IADPSG) guidelines criteria: elevated fasting plasma glucose (FPG group; n=59); 1-h and/or 2-h post-load glucose (1h/2h-PG group; n=94); combined group (FPG&1h/2h-PG group; n=42). Non-GDM pregnancies were included (n=485) as controls. Twenty fatty acids were quantified in serum using gas chromatography-mass spectrometry (GC-MS) analysis. Overall, most serum fatty acid concentrations increased rapidly from the first to second trimester, followed by a plateauing or reduction in the third trimester (p<0.001). In cross sectional analysis, fatty acid concentrations were significantly higher in the FPG group at GW 11-14 and decreased in the 1h/2h-PG group at GW 32-34, relative to controls. Moreover, higher α-linolenic acid (ALA; the second tertile: adjusted odds ratio [aOR]=2.53, 95% CI: 1.17 to 5.47; the third tertile: aOR=2.60, 95% CI: 1.20 to 5.65) and docosahexaenoic acid (DHA; the second tertile: aOR=2.34, 95% CI: 1.10 to 4.97; the third tertile: aOR=2.16, 95% CI: 1.00 to 4.63) were significantly associated with a higher risk of GDM in women with elevated fasting plasma glucose at GW 11-14 (first tertile as reference). Our findings highlight the importance of considering GDM subtypes for the individualised management of GDM in pregnancy. ALA and DHA in early pregnancy are associated with a higher risk of FPG-GDM subtype. This has widespread implications when recommending n-3 PUFAs supplementation for women with GDM.

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, limit of detection (LOQ), limit of quantification (LOD), precision, accuracy, and recovery. 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.