Tissue Fatty Acid Research Articles

Fatty Acid Transport and Signaling: Mechanisms and Physiological Implications.

Long-chain fatty acids (FAs) are components of plasma membranes and an efficient fuel source and also serve as metabolic regulators through FA signaling mediated by membrane FA receptors. Impaired tissue FA uptake has been linked to major complications of obesity, including insulin resistance, cardiovascular disease, and type 2 diabetes. Fatty acid interactions with a membrane receptor and the initiation of signaling can modify pathways related to nutrient uptake and processing, cell proliferation or differentiation, and secretion of bioactive factors. Here, we review the major membrane receptors involved in FA uptake and FA signaling. We focus on two types of membrane receptors for long-chain FAs: CD36 and the G protein-coupled FA receptors FFAR1 and FFAR4. We describe key signaling pathways and metabolic outcomes for CD36, FFAR1, and FFAR4 and highlight the parallels that provide insight into FA regulation of cell function.

Dietary linseed oil affects the polyunsaturated fatty acid and transcriptome profiles in the livers and breast muscles of ducks.

Linseed oil, an important source of dietary α-linolenic acid, is used to provide meat enriched in n-3 PUFA. We investigated the effects of dietary linseed oil (0, 0.5, 1, and 2%) on growth performance, meat quality, tissue fatty acid (FA), and transcriptome profiles in ducks. The result showed that dietary linseed oil had no effect on growth performance. Increasing dietary linseed oil enrichment raised n-3 PUFA and linoleic acid (LA) levels in both the liver and breast muscle, but decreased dihomo-gamma-linolenic acid (DGLA) and arachidonic acid (ARA) levels in the liver. The liver n-3 PUFA content was negatively correlated with duck body weight. Transcriptome analysis showed that dietary linseed oil caused hepatic changes in genes (SCD, FADS1, FADS2, and ACOT6) related to the biosynthesis of unsaturated fatty acids. Besides, dietary linseed oil also affected the expression of genes related to PUFAs and downstream metabolites (such as linoleic acid, steroid hormone, progesterone, etc.) metabolic pathways in both liver and breast muscle. Key genes involved in PUFA synthesis and transport pathways were examined by RT-qPCR, and the results verified that hepatic expression levels of FADS1 and FADS2 decreased, and those of FABP4 and FABP5 increased when 2% linseed oil was added. CD36 expression level increased in breast muscle when 2% linseed oil was added. Thus, 2% dietary linseed oil supplementation produces n-3 PUFA-enriched duck products by regulating the PUFA metabolic pathways, which could be advantageous for health-conscious consumers.

Effect of n-6/n-3 PUFA ratio on body fat deposition, tissues fatty acid composition and key genes expression of liver lipid metabolism in silver foxes (Vulpes vulpes fulva) during the winter fur-growth period.

The proportion of n-6/n-3 polyunsaturated fatty acid (PUFA) plays an important role in regulating lipid metabolism. This study aimed to investigate the effects of dietary n-6/n-3 PUFA ratios on body fat deposition, tissues fatty acid composition, and gene expression of liver lipid metabolism of silver foxes during the winter fur growth period. Forty-eight age-matched male silver foxes with similar body weights were randomly divided into four dietary groups for 47 days, which were fed n-6/n-3 PUFA ratio with 3, 18, 41, and 136 experimental diets, respectively. Dietary n-6/n-3 PUFA ratio did not significantly influence fat deposition parameters except for hepatic fat content. The variation trend of the fatty acid composition of liver, intramuscular fat, and subcutaneous fat in silver fox was directly related to dietary fatty acid content (p < 0.05). With the dietary n-6/n-3 PUFA ratio increasing, the expression of liver fatty acid synthase (FAS) mRNA and peroxisome proliferator-activated receptor (PPAR) mRNA exhibited the trend of first decreasing and then increasing (p < 0.05), whereas L-fatty acid binding protein (L-FABP) mRNA expression showed a gradual increasing trend (p < 0.05). In summary, silver foxes fed an n-6/n-3 PUFA ratio 18:1 diet (supplementing with 9.38% corn oil and 4.62% soybean oil) was more conducive to lipid decomposition, PUFA transport, and utilization of tissues, thereby meeting it for supplying energy and withstanding the cold.

Comparative Analyses of EPA-Phosphatidylcholine, EPA-Lysophosphatidylcholine, and DHA-Lysophosphatidylcholine on DHA and EPA Repletion in n-3 PUFA-Deficient Mice.

Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) play an important role in maintaining the physiological functions of tissues, and the beneficial effects of DHA/EPA in phospholipid forms have been widely reported. Although lysophosphatidylcholine (LPC) is considered to be the preferred form of DHA supplementation for the brain, the kinetics of DHA and EPA recovery and corresponding changes of n-6 docosapentaenoic acid (DPA) and arachidonic acid (AA) levels in different phospholipid molecules and different tissues after administration of EPA in phosphatidylcholine (PC) and LPC forms and DHA in the LPC form are not clear. Here, we measured the total fatty acids in tissues and fatty acid composition of different phospholipid molecules after gavage administration of equal molar amounts of EPA/DHA in mice with n-3 polyunsaturated fatty acid (PUFA) deficiency induced by maternal dietary deprivation of n-3 PUFA during pregnancy and lactation. The results showed that dietary supplementation with EPA-PC, EPA-LPC, and DHA-LPC exhibited different priorities for EPA or DHA accretion and supplementation efficiency curves in different tissues during the developing period. EPA-PC exhibited a more optimal efficacy in DHA and EPA repletion in serum and hepatic total fatty acids. In terms of DHA recovery in the brain, EPA-LPC and DHA-LPC showed great effects. Meanwhile, the DHA level in total fatty acids and major fractions of phospholipids (PC, PE, and PI + PS) in the heart and bone marrow with the supplementation of DHA-LPC displayed a relatively considerable increase compared with that of EPA supplementation groups. The study provides a reference for the time course of DHA or EPA recovery in phospholipid molecular species in different tissues after the supplementation of EPA-PC, EPA-LPC, and DHA-LPC.

Erythrocyte, Whole Blood, Plasma, and Blubber Fatty Acid Profiles in Oceanaria-Based versus Wild Alaskan Belugas (Delphinapterus leucas)

This investigation compared the fatty acid (FA) levels found in erythrocyte (RBC) membranes, plasma, whole blood (WB), and blubber from wild Alaskan (Bristol Bay) belugas (Delphinapterus leucas) (BBB, n = 9) with oceanaria-based belugas (OBB, n = 14) fed a controlled diet consisting of primarily herring (Clupea harengus) and capelin (Mallotus villosus). FA patterns in RBCs, WB, and plasma varied considerably between BBB and OBB animals. Focusing on RBC FA levels of known dietary origin, the OBBs had markedly higher levels of 20:1n9,11 and 22:1n9,11. RBC levels of these fatty acids were 1% and 0.2% in the BBBs, but 8.2% and 4.5%, respectively, in the OBBs (p &lt; 0.05 both). These long-chain mono-unsaturated FAs (LC-MUFAs) are rich in herring and capelin but not in the prey species (i.e., salmonids, smelt, cod, and shrimp) generally available to BBBs. As for the marine omega-3 poly-unsaturated fatty acids [PUFAs; 20:5n3 (eicosapentaenoic acid) and 22:6n3 (docosahexaenoic acid)], the former was higher in the OBBs vs. BBBs (16% vs. 11%, p &lt; 0.05), but the latter was low and similar in both (3.8% vs. 4%). Similar patterns were seen in the other sample types, except that DHA% was higher in BBB than OBB animals in both plasma (12.6% vs. 8.7%) and in blubber (12% vs. 4.9%) (p &lt; 0.05). A physiologically important omega-6 PUFA, 20:4n6 (arachidonic acid) was approximately 2× higher in BBB than OBB within RBC (22% vs. 12%), WB (16% vs. 7%), plasma (11.5% vs. 4.6%) and blubber (4.6% vs. 2.4%), respectively. While blubber FAs have been evaluated historically and relatively easy to procure with biopsy darts in the field, this study proposes that blood-based FAs collected during health assessments or subsistence hunts, especially RBC or WB FAs, may be more convenient to handle using dried blood spot cards (DBS) with limited cold storage and simplifies shipping requirements, and may more accurately reflect tissue FA status.

OPA1 Regulates Lipid Metabolism and Cold-Induced Browning of White Adipose Tissue in Mice.

Mitochondria play a vital role in white adipose tissue (WAT) homeostasis including adipogenesis, fatty acid synthesis, and lipolysis. We recently reported that the mitochondrial fusion protein optic atrophy 1 (OPA1) is required for induction of fatty acid oxidation and thermogenic activation in brown adipocytes. In the current study we investigated the role of OPA1 in WAT function in vivo. We generated mice with constitutive or inducible knockout of OPA1 selectively in adipocytes. Studies were conducted under baseline conditions, at thermoneutrality, following high-fat feeding or during cold exposure. OPA1 deficiency reduced mitochondrial respiratory capacity in white adipocytes, impaired lipolytic signaling, repressed expression of de novo lipogenesis and triglyceride synthesis pathways, and promoted adipose tissue senescence and inflammation. Reduced WAT mass was associated with hepatic triglycerides accumulation and glucose intolerance. Moreover, mice deficient for OPA1 in adipocytes had impaired adaptive thermogenesis and reduced cold-induced browning of subcutaneous WAT and were completely resistant to diet-induced obesity. In conclusion, OPA1 expression and function in adipocytes are essential for adipose tissue expansion, lipid biosynthesis, and fatty acid mobilization of WAT and brown adipocytes and for thermogenic activation of brown and beige adipocytes.

Integrated microbiome and metabolome analysis reveals the potential therapeutic mechanism of Qing-Fei-Pai-Du decoction in mice with coronavirus-induced pneumonia.

Current studies have shown that gut microbiota may be closely related to the severity of coronavirus disease 2019 (COVID-19) by regulating the host immune response. Qing-Fei-Pai-Du decoction (QFPDD) is the recommended drug for clinical treatment of patients with COVID-19 in China, but whether it exerts a therapeutic effect by modulating the immune response through gut microbiota remains unclear. In this study, we evaluated the therapeutic effects of QFPDD in pneumonia model mice and performed 16S rRNA sequencing and serum and lung tissue metabolomic analysis to explore the underlying mechanisms during the treatment. Then, Spearman correlation analysis was performed on gut microbiome, serum metabolome, and immune-inflammation-related indicators. Our results suggest that QFPDD can restore the richness and diversity of gut microbiota, and multiple gut microbiota (including Alistipes, Odoribacter, Staphylococcus, Lachnospiraceae_NK4A136_group Enterorhabdus, and unclassified_f_Lachnospiraceae) are significantly associated with immune-inflammation-related indicators. In addition, various types of lipid metabolism changes were observed in serum and lung tissue metabolome, especially glycerophospholipids and fatty acids. A total of 27 differential metabolites (DMs) were significantly correlated with immune-inflammation-related indicators, including 9 glycerophospholipids, 7 fatty acids, 3 linoleic acid, 2 eicosanoids, 2 amino acids, 2 bile acids, and 2 others. Interestingly, these DMs showed a good correlation with the gut microbiota affected by QFPDD. The above results suggest that QFPDD can improve the immune function and reduce inflammation in pneumonia model mice by remodeling gut microbiota and host metabolism.

Construction of a testis Elovl4 gene knockout mouse model based on Cre/loxP system

Very long chain polyunsaturated fatty acids (VLC-PUFAs) are unique fatty acids in tissues of mammals such as retina and testis, and the key enzyme of its biosynthesis is very long chain fatty acid elongase 4 (Elovl4). Development of an animal model of tissue-specific knockout of Elovl4 gene is conducive to the in-depth study of the biological function of VLC-PUFAs. Therefore, we constructed Stra8-Cre mice and Elovl4 floxed mice based on Cre/loxP system, and obtained the (Elovl4[flox/+], Stra8-Cre) heterozygous knockout mice by hybridization. Subsequently, female mice were selected to cross with male mice with homozygous Elovl4[flox/flox] to gain homozygous mice (Elovl4[flox/flox], Stra8-Cre) through genotype identification and screening. RT-PCR, qRT-PCR, Western blotting, immunohistochemistry and immunofluorescence techniques were used to detect the knock-out efficiency of Elovl4 in testis. The expression of Elovl4 in testis of both heterozygous and homozygous knockout mice were significantly down-regulated at mRNA and protein levels, but were not affected in other tissues. In summary, we constructed a mouse model with specific knockout of Elovl4 gene in testis, which provides a reliable animal model for studying the effect of VLC-PUFAs on the reproductive function of male mice and the underpinning molecular mechanisms.

Tissue composition and meat quality of lambs fed diets containing whole-plant sesame silage as a replacement for whole-plant corn silage

The purpose of this study was to evaluate the effects of the replacement of whole-plant corn silage (WPCS) by whole-plant sesame silage (WPSS) in diets of lambs on leg tissue composition, physicochemical properties, and fatty acids profile of the meat. Forty castrated Santa Inês crossbred lambs presenting an average initial body weight (iBW) of 21.8 ± 1.97 kg were distributed in a randomized block design with four treatments [four replacement levels: (control (no sesame), 333, 670, and 1000 g/kg of DM)] in ten replications. No effect (P > 0.05) of replacing WPCS with WPSS was observed on DM intake, final weight at slaughter, weight gain, leg weight, the proportion of muscle (M), bone (B), fat (F), and other tissues, muscularity, M:B ratio, M:F ratio, protein content, ash, pH, water holding capacity, cooking losses, shear force, color parameters (L*, a*, b*, C* and H*), ƩPUFA, ƩMUFA:ƩSFA ratio, Ʃn-6:Ʃn-3 ratio, h:H, atherogenicity index (AI) and on the activity of enzymes Δ9-desaturase C18 and elongase. WPSS promoted quadratic increase (P < 0.05) in the moisture content and quadratic increase trend in C4:0 (P = 0.08). The inclusion of WPSS caused linear increases (P < 0.05) in the concentrations of C18:1 n-11trans, C18:2 c9trans-11 (CLA), ƩMUFAtrans, and ƩPUFA:ƩSFA ratio, and linear increase trend in C18:2 trans10c12 (P = 0.06) and C18:3 n-3 (P = 0.08). It was observed a linear decrease (P < 0.05) in the contents of C16:0, total FA, ƩSFA, ƩMUFA, ƩMUFAcis, and desirable FA, and a linearly decreasing trend in the thrombogenicity index (TI; P = 0.07). Ʃn-6 presented quadratic reduction (P = 0.03), while Ʃn-3 (P = 0.07) and Δ9-desaturase C16 enzyme activity (P = 0.06) tended toward quadratic reduction. WPSS can fully replace WPCS as it does not compromise performance, tissue composition, and meat physicochemical parameters, and improves the quality of meat fat as it reduces ƩSFA and TI and increases CLA content and PUFA:SFA ratio.

A dose-response study with omega-3 rich canola oil as a novel source of docosahexaenoic acid (DHA) in feed for Atlantic salmon (Salmo salar) in seawater; effects on performance, tissue fatty acid composition, and fillet quality

Long-chain omega-3 rich oils from crops genetically modified with algal genes are a promising new source of the omega-3 fatty acid DHA (docosahexaenoic acid; 22:6n-3) in Atlantic salmon diets. In this study, the fish oil and fish meal content were held constant across diets, and conventional canola oil was replaced with DHA canola (DHA-CA) oil in a step-wise manner at 0%, 25%, 50%, and 100% replacement, respectively. Growth of salmon, reared in seawater, from approximately 465 g to 1.5 kg was equal across all dietary treatments. Survival was >98% in all cases, with no difference between the dietary groups. Digestibility of lipids was high, approximately 93% in all dietary groups. Fatty acid retention in whole body was also high, with greater retention of α-linolenic acid (ALA, 18:3n-3) and eicosapentaenoic acid (EPA; 20:5n-3) in groups containing higher proportions of DHA-CA oil. Fillet, liver, and intestinal fatty acid compositions were influenced by the different fatty acid contents of the diets, with progressively higher inclusion of ALA, EPA, and DHA and a higher n-3:n-6 ratio in fish fed the 25%, 50%, and 100% DHA-CA diets. Increased dietary inclusion levels of DHA reduced the conversion to 1-14C labelled ALA to 1-14C EPA in liver cells, but some conversion of ALA to 1-14C EPA was maintained even at high dietary DHA levels. There was also a significant increase in anti-inflammatory pro-resolving lipid mediators, resolvins, with increased dietary DHA-CA. The visual colour impression of both muscle and skin was improved at higher DHA-CA inclusion levels in diets.Overall, our findings demonstrates that DHA-CA oil is an effective ingredient in Atlantic salmon diets in seawater, and that fatty acids (FA) from this oil are incorporated into the fish tissues in a manner equivalent to FA from conventional sources, with positive effects on fillet quality.

Effects of dietary cholesterol and phospholipid levels on growth performance, antioxidant capacity, and tissue fatty acid in the juvenile mud crab Scylla paramamosain Estampador, 1950 (Decapoda: Brachyura: Portunidae)

Abstract To investigate whether an interaction between the levels of dietary cholesterol (CHOL) and phospholipid (PL) exists in the growth performance, antioxidant, and immune parameters of juvenile Scylla paramamosainEstampador, 1950, a 3 × 3 factorial feeding trial was conducted in polypropylene tanks with nine diets containing three CHOL levels (0.5%, 1.0%, 1.5% of dry weight) and three PL levels (0.5%, 1.0%, 1.5% of dry weight). After the eight-week feeding trial, crabs fed the diets with 0.5% CHOL and 1.0 or 1.5% PL achieved the best growth performance with a relatively higher survival rate. Hemolymph CHOL, low-density lipoprotein cholesterol (LDLC), and high-density lipoprotein cholesterol (HDLC) increased with the increasing dietary CHOL levels, whereas decreased LDLC levels were observed as dietary PL levels increased. With the increasing dietary levels of PL, the activities of superoxide dismutase (SOD), glutathione S-transferase (GST), glutathione peroxidase (GSH-Px), and total antioxidant capacity (T-AOC) were markedly enhanced in crabs fed the basal diets with 0.5 or 1.0% CHOL and PL. Tissue fatty acid composition reflected dietary fatty acids. Increasing dietary PL levels resulted in rising contents of total n-6 polyunsaturated fatty acids (PUFA) in the hepatopancreas and muscle. A synergistic effect between CHOL and PL was not observed on growth performance but such effect was found instead in the biochemical indices of hemolymphs and the antioxidant capacity of the hepatopancreas. These results suggest that proper dietary levels of 0.5% CHOL and 1.0–1.5% PL could maintain solid growth performance and antioxidant capacity of juvenile S. paramamosain.

The influence of feeding media enriched with different oils on the fatty acid composition of the Black soldier fly (Hermetia illucens)

The black soldier fly (Hermetia illucens) has emerged as an interesting alternative protein source in animal feed due to its ability to grow on various substrates. Although it has many rearing benefits and possible applications, it has an unfavourable fatty acid profile if used for human consumption due to its high content of lauric acid and low content of polyunsaturated fatty acids. In order to investigate whether the lipid composition of black soldier fly larvae can be altered, the feeding media were supplemented with varying concentrations of fish, linseed or coconut oil (1, 2.5 and 5%). Two-week-old larvae were collected, measured and their tissue fatty acid composition was determined. The fatty acid profile of the larvae showed significant plasticity, depending on the life stage and the fatty acid composition of the feeding media. The addition of 2.5 and 5% of different oils significantly changed the fatty acid composition of larvae, depending on the type and percentage of oil. The n6/n3 ratio was considerably improved by supplementing fish and linseed oil. The addition of linseed oil increased the content of linolenic acid, but bioconversion to eicosapentaenoic and docosahexaenoic acids was low. In contrast, the addition of fish oil significantly increased the content of eicosapentaenoic and docosahexaenoic acids in the larvae. The content of lauric acid significantly increased after coconut addition. The trial showed that by using different oils, the lipid composition of black soldier fly larvae could be specifically changed to increase the beneficial long chain n3 polyunsaturated fatty acids, and the amount of lauric or linolenic acid.

Ablation of PI3K-p110alpha Impairs Maternal Metabolic Adaptations to Pregnancy.

Pregnancy requires adaptations in maternal metabolism to support fetal growth. The phosphoinositol-3-kinase (PI3K) signalling pathway controls multiple biological processes and defects in this pathway are linked to metabolic disorders including insulin resistance and glucose intolerance in non-pregnant animals. However, relatively little is known about the contribution of PI3K signalling to the maternal metabolic adaptations during pregnancy. Using mice with partial inactivation of the PI3K isoform, p110α (due to a heterozygous dominant negative mutation; Pik3ca-D933A), the effects of impaired PI3K-p110α signalling on glucose and insulin handling were examined in the pregnant and non-pregnant states and related to the morphological, molecular, and mitochondrial changes in key metabolic organs. The results show that non-pregnant mice lacking PI3K-p110α are glucose intolerant but exhibit compensatory increases in pancreatic glucose-stimulated insulin release and adipose tissue mitochondrial respiratory capacity and fatty acid oxidation. However, in pregnancy, mutant mice failed to show the normal increment in glucose intolerance and pancreatic β-cell mass observed in wild-type pregnant dams and exhibited further enhanced adipose tissue mitochondrial respiratory capacity. These maladaptations in pregnant mutant mice were associated with fetal growth restriction. Hence, PI3K-p110α is a key regulator of metabolic adaptations that support fetal growth during normal pregnancy.

Total Postprandial Hepatic Nonesterified and Dietary Fatty Acid Uptake Is Increased and Insufficiently Curbed by Adipose Tissue Fatty Acid Trapping in Prediabetes With Overweight.

Excessive lean tissue uptake of fatty acids (FAs) is important in the development of insulin resistance and may be caused by impaired dietary FA (DFA) storage and/or increased nonesterified FA (NEFA) flux from adipose tissue intracellular lipolysis. Cardiac and hepatic total postprandial FA uptake of NEFA+DFA has, however, never been reported in prediabetes with overweight. In this study, 20 individuals with impaired glucose tolerance (IGT) and 19 participants with normal glucose tolerance (NGT) and normal fasting glucose underwent postprandial studies with whole-body positron emission tomography/computed tomography (PET/CT) with oral [18F]fluoro-thia-heptadecanoic acid and dynamic PET/CT with intravenous [11C]palmitate. Hepatic (97 [range 36-215] mmol/6 h vs. 68 [23-132] mmol/6 h, P = 0.03) but not cardiac (11 [range 4-24] mmol/6 h vs. 8 [3-20] mmol/6 h, P = 0.09) uptake of most sources of postprandial FA (NEFA + DFA uptake) integrated over 6 h was higher in IGT versus NGT. DFA accounted for lower fractions of total cardiac (21% [5-47] vs. 25% [9-39], P = 0.08) and hepatic (19% [6-52] vs. 28% [14-50], P = 0.04) uptake in IGT versus NGT. Increased adipose tissue DFA trapping predicted lower hepatic DFA uptake and was associated with higher total cardiac FA uptake. Hence, enhanced adipose tissue DFA trapping in the face of increased postprandial NEFA flux is insufficient to fully curb increased postprandial lean organ FA uptake in prediabetes with overweight (ClinicalTrials.gov; NCT02808182).

Accelerated fatty acid composition MRI of epicardial adipose tissue: Development and application to eplerenone treatment in a mouse model of obesity-induced coronary microvascular disease.

PurposeTo develop an accelerated MRI method to quantify the epicardial adipose tissue (EAT) fatty acid composition (FAC) and test the hypothesis that eplerenone (EPL) shifts the EAT FAC toward unsaturation in obese mice.MethodsUndersampled multi‐echo gradient echo imaging employing a dictionary‐based compressed‐sensing reconstruction and iterative decomposition with echo asymmetry and least‐squares–based mapping (IDEAL) was developed, validated, and used to study EAT in obese mice scanned at 7T. Fully sampled and rate 2, 2.5, 3, and 3.5 undersampled image data were acquired, reconstructed, and assessed using RMSE and structural similarity (SSIM). Two groups of mice were studied: untreated (control, n = 10) and EPL‐treated (n = 10) mice fed a high‐fat high‐sucrose diet. MRI included imaging of EAT FAC, EAT volume, and myocardial perfusion reserve.ResultsRate 3 acceleration provided RMSE <5% and structural similarity >0.85 for FAC MRI. After 6 weeks of diet, EPL‐treated compared to untreated mice had a reduced EAT saturated fatty acid fraction (0.27 ± 0.09 vs. 0.39 ± 0.07, P < 0.05) and increased EAT unsaturation degree (4.37 ± 0.32 vs. 3.69 ± 0.58, P < 0.05). Also, EAT volume in EPL‐treated compared to untreated mice was reduced (8.1 ± 0.6 mg vs. 11.4 ± 0.7 mg, P < 0.01), and myocardial perfusion reserve was improved (1.83 ± 0.15 vs. 1.61 ± 0.17, P < 0.05).ConclusionRate 3 accelerated FAC MRI enabled accurate quantification of EAT FAC in mice. EPL treatment shifted the EAT FAC toward increased unsaturation and was associated with improvement of coronary microvascular function.

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.

Effects of dietary vitamin E and fat supplementation in growing-finishing swine fed to a heavy slaughter weight of 150 kg: II. Tissue fatty acid profile, vitamin E concentrations, and antioxidant capacity of plasma and tissue.

The study aimed to assess the effects of vitamin E (VE) supplementation and fat source on fatty acid (FA) composition, VE concentrations, and antioxidant capacity in plasma and tissues of pigs fed to a heavy slaughter weight (150 kg). A total of 64 pigs (32 barrows, 32 gilts; 28.41 ± 0.83 kg) were blocked by sex and weight, and randomly assigned to one of eight dietary treatments (n = 8 per treatment) in a 4 × 2 factorial arrangement. Fat sources included corn starch (CS), 5% tallow (TW), 5% distiller’s corn oil (DCO), and 5% coconut oil (CN); VE supplementation levels were 11 and 200 ppm. Five-phase diets were formulated to meet requirement estimates of NRC (2012) and fed to pigs for each period of 25 kg from 25 to 150 kg. Increasing VE supplementation level increased C16:1 (P < 0.05) content but decreased C20:0 (P < 0.05) content in backfat and belly fat, while in liver, it increased C17:0 (P < 0.05) but decreased C18:0 (P < 0.05). Compared to the pigs fed the CS diet, the pigs fed the CN diet had greater (P < 0.05) content of total saturated FA, the pigs fed the DCO diet had greater (P < 0.05) content of total polyunsaturated FA content and iodine value, and the pigs fed the TW diet had greater (P < 0.05) content of total monounsaturated FA in backfat, belly fat, and liver. Plasma VE concentrations increased linearly (P < 0.05) with increasing length of feeding but faster (P < 0.05) in the pigs fed the CN and TW diets compared with the CS and DCO diets within the 200 ppm VE level; the pigs fed the DCO diet had the highest plasma VE concentrations (P < 0.05) from Phase 2 to Phase 5 within the 11 ppm VE level. The VE concentrations in liver and loin muscle (P < 0.05) increased with increasing dietary VE level from 11 to 200 ppm, but it was not affected by dietary fat source. There was no effect of VE supplementation and fat source on antioxidant capacity in plasma and liver except that pigs fed the DCO diet had greater liver SOD activity (P < 0.05) than the pigs fed the CN diet. In conclusion, dietary VE supplementation did not affect FA profile in backfat, belly fat, and liver consistently, while dietary FA composition with different fat sources affected much of the FA profile in backfat, belly fat, and liver. The higher level of VE supplementation increased liver and muscle VE concentrations and dietary fat sources affected plasma VE concentrations differently (P < 0.05), wherein the TW and CN diets increased the VE absorption greater than the DCO diet.

Transcriptome and fatty-acid signatures of adipocyte hypertrophy and its non-invasive MR-based characterization in human adipose tissue.

SummaryBackgroundThe adipocyte-hypertrophy associated remodeling of fat cell function is considered causal for the development of metabolic disorders. A better understanding of transcriptome and fatty acid (FA) related alterations with adipocyte hypertrophy combined with less-invasive strategies for the detection of the latter can help to increase the prognostic and diagnostic value of adipocyte size and FA composition as markers for metabolic disease.MethodsTo clarify adipocyte-hypertrophy associated transcriptomic alterations, fat cell size was related to RNA-Seq data from white adipose tissue and size-separated adipocytes. The relationship between adipocyte size and adipose tissue FA composition as measured by GC-MS was investigated. MR spectroscopy (MRS) methods for clinical scanning were developed to characterize adipocyte size and FA composition in a fast and non-invasive manner.FindingsWith enlarged adipocyte size, substantial transcriptomic alterations of genes involved in mitochondrial function and FA metabolism were observed. Investigations of these two mechanisms revealed a reciprocal relationship between adipocyte size and estimated thermogenic adipocyte content as well as depot-specific correlations of adipocyte size and FA composition. MRS on a clinical scanner was suitable for the in-parallel assessment of adipose morphology and FA composition.InterpretationThe current study provides a comprehensive overview of the adipocyte-hypertrophy associated transcriptomic and FA landscape in both subcutaneous and visceral adipose tissue. MRS represents a promising technique to translate the observed mechanistic, structural and functional changes in WAT with adipocyte hypertrophy into a clinical context for an improved phenotyping of WAT in the context of metabolic diseases.FundingCompetence network for obesity (FKZ 42201GI1128), ERC (No 677661, ProFatMRI; No 875488, FatVirtualBiopsy), Else Kröner-Fresenius-Foundation.

Strength training alters the tissue fatty acids profile and slightly improves the thermogenic pathway in the adipose tissue of obese mice

Obesity is a disease characterized by the exacerbated increase of adipose tissue. A possible way to decrease the harmful effects of excessive adipose tissue is to increase the thermogenesis process, to the greater energy expenditure generated by the increase in heat in the body. In adipose tissue, the thermogenesis process is the result of an increase in mitochondrial work, having as substrate H+ ions, and which is related to the increased activity of UCP1. Evidence shows that stress is responsible for increasing the greater induction of UCP1 expression via β-adrenergic receptors. It is known that physical exercise is an important implement for sympathetic stimulation promoting communication between norepinephrine/epinephrine with membrane receptors. Thus, the present study investigates the influence of short-term strength training (STST) on fatty acid composition, lipolysis, lipogenesis, and browning processes in the subcutaneous adipose tissue (sWAT) of obese mice. For this, Swiss mice were divided into three groups: lean control, obesity sedentary, and obese strength training (OBexT). Obese animals were fed a high-fat diet for 14 weeks. Trained obese animals were submitted to 7 days of strength exercise. It was demonstrated that STST sessions were able to reduce fasting glycemia. In the sWAT, the STST was able to decrease the levels of the long-chain fatty acids profile, saturated fatty acid, and palmitic fatty acid (C16:0). Moreover, it was showed that STST did not increase protein levels responsible for lipolysis, the ATGL, ABHD5, pPLIN1, and pHSL. On the other hand, the exercise protocol decreased the expression of the lipogenic enzyme SCD1. Finally, our study demonstrated that the STST increased browning process-related genes such as PGC-1α, PRDM16, and UCP1 in the sWAT. Interestingly, all these biomolecular mechanisms have been observed independently of changes in body weight. Therefore, it is concluded that short-term strength exercise can be an effective strategy to initiate morphological changes in sWAT.

120 Reproductive Performance, Early Embryo Survival, Fetal Characteristics, and Tissue Fatty Acid Profiles of Sows Fed Linoleic or α-Linolenic Acid

Abstract The objective of this study was to determine the potential reproductive benefits of supplementing sows with linoleic (LA) or α-linolenic acid (α-LA) throughout the preceding lactation and subsequent gestation until 30 d post-rebreeding. Thirty-three second parity sows were allotted to either a control (0.88% LA, 0.10% α-LA), high LA (3.3% LA, 0.10% α-LA,) or high α-LA (0.88% LA, 0.60% α-LA) diet fed throughout lactation and early gestation. At 30 d post-breeding, a subset of sows (n = 18) was harvested to determine embryo survival and fatty acid composition of reproductive and fetal tissues. Number of pigs weaned per litter (P = 0.77) and litter average daily gain (P = 0.34) did not differ among treatments; however, litters from sows supplemented with LA tended to be heavier at weaning (P = 0.09; 55.3, 61.3, and 57.1 kg for control, LA, and α-LA, respectively). Sows supplemented with LA had higher embryo survival (P &amp;lt; 0.01; 57.2, 79.5, and 58.7% for control, LA, and α-LA, respectively), heavier feto-placental units (P &amp;lt; 0.01; 210.3, 279.4 and 235.0 g for control, LA, and α-LA, respectively), and elevated volume of allantoic fluid (P &amp;lt; 0.01; 185.9, 247.9, and 200.8 mL for control, LA, and α-LA, respectively). Concentrations of EFA increased in maternal serum by the dietary EFA supplemented (P &amp;lt; 0.05). Supplementation of LA did not impact linoleic acid or arachidonic acid concentrations in endometrium, chorioallantoic membrane, or fetus; however, α-LA increased (P &amp;lt; 0.05) concentrations of α-linoleic acid in chorioallantoic membrane and eicosapentaenoic acid in serum and endometrium. Supplementation of LA, but not α-LA, throughout lactation and early subsequent gestation was beneficial for embryo survival. The lesser influence of dietary LA and α-LA in fetal tissues may be associated with the intake, transfer, and metabolism of EFA in the chorioallantoic membrane and endometrium.