In Vivo Monitoring of Glycerolipid Metabolism in Animal Nutrition Biomodel-Fed Smart-Farm Eggs.

Although many studies have examined the biochemical metabolic pathways by which an egg (egg yolk) lowers blood lipid levels, data on the molecular biological mechanisms that regulate and induce the partitioning of hepatic glycerolipids are missing. The aim of this study was to investigate in vivo monitoring in four study groups using an animal nutrition biomodel fitted with a jugular-vein cannula after egg yolk intake: CON (control group, oral administration of 1.0 g of saline), T1 (oral administration of 1.0 g of pork belly fat), T2 (oral administration of 1.0 g of smart-farm egg yolk), and T3 (oral administration of T1 and T2 alternately every week). The eggs induced significant and reciprocal changes in incorporating 14C lipids into the total glycerolipids and releasing 14CO2, thereby regulating esterification and accelerating oxidation in vivo. The eggs increased phospholipid secretion from the liver into the blood and decreased triacylglycerol secretion by regulating the multiple cleavage of fatty acyl-CoA moieties' fluxes. In conclusion, the results of the current study reveal the novel fact that eggs can lower blood lipids by lowering triacylglycerol secretion in the biochemical metabolic pathway of hepatic glycerolipid partitioning while simultaneously increasing phospholipid secretion and 14CO2 emission.

Metformin Inefficiency to Lower Lipids in Vitamin B12 Deficient HepG2 Cells Is Alleviated via Adiponectin-AMPK Axis.

Background: Prolonged metformin treatment decreases vitamin B12 (B12) levels, whereas low B12 is associated with dyslipidaemia. Some studies have reported that metformin has no effect on intrahepatic triglyceride (TG) levels. Although AMP-activated protein kinase (AMPK) activation via adiponectin lowers hepatic TG content, its role in B12 deficiency and metformin has not been explored. We investigated whether low B12 impairs the beneficial effect of metformin on hepatic lipid metabolism via the AMPK-adiponectin axis. Methods: HepG2 was cultured using custom-made B12-deficient Eagle's Minimal Essential Medium (EMEM) in different B12-medium concentrations, followed by a 24-h metformin/adiponectin treatment. Gene and protein expressions and total intracellular TG were measured, and radiochemical analysis of TG synthesis and seahorse mitochondria stress assay were undertaken. Results: With low B12, total intracellular TG and synthesized radiolabelled TG were increased. Regulators of lipogenesis, cholesterol and genes regulating fatty acids (FAs; TG; and cholesterol biosynthesis were increased. FA oxidation (FAO) and mitochondrial function were decreased, with decreased pAMPKα and pACC levels. Following metformin treatment in hepatocytes with low B12, the gene and protein expression of the above targets were not alleviated. However, in the presence of adiponectin, intrahepatic lipid levels with low B12 decreased via upregulated pAMPKα and pACC levels. Again, combined adiponectin and metformin treatment ameliorated the low B12 effect and resulted in increased pAMPKα and pACC, with a subsequent reduction in lipogenesis, increased FAO and mitochondrion function. Conclusions: Adiponectin co-administration with metformin induced a higher intrahepatic lipid-lowering effect. Overall, we emphasize the potential therapeutic implications for hepatic AMPK activation via adiponectin for a clinical condition associated with B12 deficiency and metformin treatment.

The roles of DGAT1 and DGAT2 in human myotubes are dependent on donor patho-physiological background.

The roles of DGAT1 and DGAT2 in lipid metabolism and insulin responsiveness of human skeletal muscle were studied using cryosections and myotubes prepared from muscle biopsies from control, athlete, and impaired glucose regulation (IGR) cohorts of men. The previously observed increases in intramuscular triacylglycerol (IMTG) in athletes and IGR were shown to be related to an increase in lipid droplet (LD) area in type I fibers in athletes but, conversely, in type II fibers in IGR subjects. Specific inhibition of both diacylglycerol acyltransferase (DGAT) 1 and 2 decreased fatty acid (FA) uptake by myotubes, whereas only DGAT2 inhibition also decreased fatty acid oxidation. Fatty acid uptake in myotubes was negatively correlated with the lactate thresholds of the respective donors. DGAT2 inhibition lowered acetate uptake and oxidation in myotubes from all cohorts whereas DGAT1 inhibition had no effect. A positive correlation between acetate oxidation in myotubes and resting metabolic rate (RMR) from fatty acid oxidation in vivo was observed. Myotubes from athletes and IGR had higher rates of de novo lipogenesis from acetate that were normalized by DGAT2 inhibition. Moreover, DGAT2 inhibition in myotubes also resulted in increased insulin-induced Akt phosphorylation. The differential effects of DGAT1 and DGAT2 inhibition suggest that the specialized role of DGAT2 in esterifying nascent diacylglycerols and de novo synthesized FA is associated with synthesis of a pool of triacylglycerol, which upon hydrolysis results in effectors that promote mitochondrial fatty acid oxidation but decrease insulin signaling in skeletal muscle cells.

Impact of the Combination of Probiotics and Digital Poultry System on Behavior, Welfare Parameters, and Growth Performance in Broiler Chicken.

Recently, applied technology in the form of the combination of a probiotics and a digital poultry system, with the convergence of Information and Communications Technology and farm animals, has enabled a new strategy to overcome the livestock production crisis caused by climate change, while maintaining sustainable poultry farming in terms of care, feeding, and environmental management systems for poultry. The aim of this study was to investigate the biological mechanisms of animal behavioral welfare and production improvement using the combination of a probiotics and a digital poultry system in broiler chickens. A total of 400 one-day-old male broilers (ROSS 308) were randomly divided into four treatment groups, with five replicates each (20 birds/replicate pen) in a completely randomized design: control group with a conventional poultry system without probiotics (CON), conventional poultry system with 500 ppm of probiotics (CON500), digital poultry control system without probiotics (DPCS), and digital poultry system with 500 ppm of probiotics (DPS500). All experimental animals were reared for 35 days under the same standard environmental conditions. The experimental results indicated that the animal behavioral welfare, which includes drinking, eating, locomotion, grooming, and resting, in addition to foot pads, knee burns, plumage, and gait scores, as well as the growth performance of the broiler chickens, were improved by maintaining immune function and cecal microbiota balance via interaction between the combination of a probiotics and a digital poultry system. In conclusion, it was found that the combined system showed improved broiler growth performance and animal behavioral welfare. Thus, further studies of molecular biological mechanisms by the use of such a combined system to improve the nutritional composition and quality of chicken meats are recommended.

Molecular Mechanism for Hepatic Glycerolipid Partitioning of n-6/n-3 Fatty Acid Ratio in an Obese Animal Biomodels.

The n-6/n-3 metabolic pathway associated with hepatic glycerolipid portioning plays a key role in preventing obesity. In this nutrition metabolism study, we used in vivo monitoring techniques with 40 obese male Sprague-Dawley strain rats attached with jugular-vein cannula after obesity was induced by a high-fat diet to determine the molecular mechanism associated with hepatic glycerolipid partitioning involving the n-6/n-3 metabolic pathway. Rats were randomly assigned to four groups (10 animals per group), including one control group (CON, n-6/n-3 of 71:1) and three treatment groups (n-6/n-3 of 4:1, 15:1 and 30:1). They were fed with experimental diets for 60 days. Incorporation rates of [14C]-labeling lipid into glycerolipid in the liver were 28.87−37.03% in treatment groups fed with diets containing an n-6/n-3 ratio of 4:1, 15:1 and 30:1, which were significantly (p < 0.05) lower than that in the CON (40.01%). However, 14CO2 emission % of absorbed dose showed the opposite trend. It was significantly (p < 0.05) higher in a treatment groups (n-6/n-3 of 4:1, 15:1 and 30:1, 30.35−45.08%) than in CON (27.71%). Regarding the metabolic distribution of glycerolipid to blood from livers, phospholipid/total glycerolipid (%) was significantly (p < 0.05) lower in CON at 11.04% than in treatment groups at 18.15% to 25.15%. Moreover, 14CO2/[14C]-total glycerolipid (%) was significantly (p < 0.05) higher in treatment groups at 44.16−78.50% than in CON at 39.50%. Metabolic distribution of fatty acyl moieties flux for oxidation and glycerolipid synthesis in the liver were significantly (p < 0.05) better in order of 4:1 > 15:1 > 30:1 than in the CON. Our data demonstrate that n-6/n-3 of 4:1 could help prevent obesity by controlling the mechanism of hepatic partitioning through oxidation and esterification of glycerolipid in an obese animal biomodel.

Association between fetal abdominal growth trajectories, maternal metabolite signatures early in pregnancy, and childhood growth and adiposity: prospective observational multinational INTERBIO-21st fetal study.

BACKGROUND: Obesity predominantly affects populations in high-income countries and those countries facing epidemiological transition. The risk of childhood obesity is increased among infants who had overweight or obesity at birth, but in low-resource settings one in five infants are born small for gestational age. We aimed to study the relationships between: (1) maternal metabolite signatures; (2) fetal abdominal growth; and (3) postnatal growth, adiposity, and neurodevelopment. METHODS: In the prospective, multinational, observational INTERBIO-21st fetal study, conducted in maternity units in Pelotas (Brazil), Nairobi (Kenya), Karachi (Pakistan), Soweto (South Africa), Mae Sot (Thailand), and Oxford (UK), we enrolled women (≥18 years, with a BMI of less than 35 kg/m2, natural conception, and a singleton pregnancy) who initiated antenatal care before 14 weeks' gestation. Ultrasound scans were performed every 5±1 weeks until delivery to measure fetal growth and feto-placental blood flow, and we used finite mixture models to derive growth trajectories of abdominal circumference. The infants' health, growth, and development were monitored from birth to age 2 years. Early pregnancy maternal blood and umbilical cord venous blood samples were collected for untargeted metabolomic analysis. FINDINGS: From Feb 8, 2012, to Nov 30, 2019, we enrolled 3598 pregnant women and followed up their infants to 2 years of age. We identified four ultrasound-derived trajectories of fetal abdominal circumference growth that accelerated or decelerated within a crucial 20-25 week gestational age window: faltering growth, early accelerating growth, late accelerating growth, and median growth tracking. These distinct phenotypes had matching feto-placental blood flow patterns throughout pregnancy, and different growth, adiposity, vision, and neurodevelopment outcomes in early childhood. There were 709 maternal metabolites with positive effect for the faltering growth phenotype and 54 for the early accelerating growth phenotype; 31 maternal metabolites had a negative effect for the faltering growth phenotype and 76 for the early accelerating growth phenotype. Metabolites associated with the faltering growth phenotype had statistically significant odds ratios close to 1·5 (ie, suggesting upregulation of metabolic pathways of impaired fetal growth). The metabolites had a reciprocal relationship with the early accelerating growth phenotype, with statistically significant odds ratios close to 0.6 (ie, suggesting downregulation of fetal growth acceleration). The maternal metabolite signatures included 5-hydroxy-eicosatetraenoic acid, and 11 phosphatidylcholines linked to oxylipin or saturated fatty acid sidechains. The fungicide, chlorothalonil, was highly abundant in the early accelerating growth phenotype group. INTERPRETATION: Early pregnancy lipid biology associated with fetal abdominal growth trajectories is an indicator of patterns of growth, adiposity, vision, and neurodevelopment up to the age of 2 years. Our findings could contribute to the earlier identification of infants at risk of obesity. FUNDING: Bill & Melinda Gates Foundation.

How to Improve the Biocompatibility of Peritoneal Dialysis Solutions (without Jeopardizing the Patient's Health).

Peritoneal dialysis (PD) is an important, if underprescribed, modality for the treatment of patients with end-stage kidney disease. Among the barriers to its wider use are the deleterious effects of currently commercially available glucose-based PD solutions on the morphological integrity and function of the peritoneal membrane due to fibrosis. This is primarily driven by hyperglycaemia due to its effects, through multiple cytokine and transcription factor signalling-and their metabolic sequelae-on the synthesis of collagen and other extracellular membrane components. In this review, we outline these interactions and explore how novel PD solution formulations are aimed at utilizing this knowledge to minimise the complications associated with fibrosis, while maintaining adequate rates of ultrafiltration across the peritoneal membrane and preservation of patient urinary volumes. We discuss the development of a new generation of reduced-glucose PD solutions that employ a variety of osmotically active constituents and highlight the biochemical rationale underlying optimization of oxidative metabolism within the peritoneal membrane. They are aimed at achieving optimal clinical outcomes and improving the whole-body metabolic profile of patients, particularly those who are glucose-intolerant, insulin-resistant, or diabetic, and for whom daily exposure to high doses of glucose is contraindicated.

Insulin resistance in cardiovascular disease, uremia, and peritoneal dialysis.

Diabetic nephropathy is highly correlated with the occurrence of other complications of type 1 diabetes (T1D) and type 2 diabetes (T2D) mellitus; for example, hypertension with cardiovascular disease (CVD) being the most frequent cause of death in patients with end-stage renal disease and undergoing renal dialysis. Hyperglycemia and insulin resistance (IR) are responsible for the micro- and macrovascular complications of diabetes through different mechanisms. In particular, IR plays a key role in the etiology of atherosclerosis in both diabetic and non-diabetic patients. IR - exacerbated by organ-level selectivity - is more important than glycemic control per se in determining cardiovascular outcomes. This may be exacerbated by the fact that IR is organ and pathway specific due to the only selective loss of sensitivity to insulin action of specific pathways/processes. Therefore, it is counterintuitive that the use of peritoneal dialysis (PD) in (frequently) diabetic renal disease patients should involve their exposure to high daily doses of glucose peritoneally. In view of the controversy about the causal association between glucose load and CVD in PD patients, we discuss the role that selective IR may play in the progression of CVD in diabetic renal end-stage patients. In discussing these associations, we propose that reducing glucose exposure in PD solutions may be beneficial especially if coupled with strategies that address IR directly, and the avoidance of excessive use of insulin treatment in T2D.

Vitamin B12 Induces Hepatic Fatty Infiltration through Altered Fatty Acid Metabolism.

BACKGROUND/AIMS: Rise in global incidence of obesity impacts metabolic health. Evidence from human and animal models show association of vitamin B12 (B12) deficiency with elevated BMI and lipids. Human adipocytes demonstrated dysregulation of lipogenesis by low B12 via hypomethylation and altered microRNAs. It is known de novo hepatic lipogenesis plays a key role towards dyslipidaemia, however, whether low B12 affects hepatic metabolism of lipids is not explored. METHODS: HepG2 was cultured in B12-deficient EMEM medium and seeded in different B12 media: 500nM(control), 1000pM(1nM), 100pM and 25pM(low) B12. Lipid droplets were examined by Oil Red O (ORO) staining using microscopy and then quantified by elution assay. Gene expression were assessed with real-time quantitative polymerase chain reaction (qRT-PCR) and intracellular triglycerides were quantified using commercial kit (Abcam, UK) and radiochemical assay. Fatty acid composition was measured by gas chromatography and mitochondrial function by seahorse XF24 flux assay. RESULTS: HepG2 cells in low B12 had more lipid droplets that were intensely stained with ORO compared with control. The total intracellular triglyceride and incorporation of radio-labelled-fatty acid in triglyceride synthesis were increased. Expression of genes regulating fatty acid, triglyceride and cholesterol biosynthesis were upregulated. Absolute concentrations of total fatty acids, saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), trans-fatty acids and individual even-chain and odd-chain fatty acids were significantly increased. Also, low B12 impaired fatty acid oxidation and mitochondrial functional integrity in HepG2 compared with control. CONCLUSION: Our data provide novel evidence that low B12 increases fatty acid synthesis and levels of individual fatty acids, and decreases fatty acid oxidation and mitochondrial respiration, thus resulting in dysregulation of lipid metabolism in HepG2. This highlights the potential significance of de novo lipogenesis and warrants possible epigenetic mechanisms of low B12.

The osmo-metabolic approach: a novel and tantalizing glucose-sparing strategy in peritoneal dialysis.

Peritoneal dialysis (PD) is a viable but under-prescribed treatment for uremic patients. Concerns about its use include the bio-incompatibility of PD fluids, due to their potential for altering the functional and anatomical integrity of the peritoneal membrane. Many of these effects are thought to be due to the high glucose content of these solutions, with attendant issues of products generated during heat treatment of glucose-containing solutions. Moreover, excessive intraperitoneal absorption of glucose from the dialysate has many potential systemic metabolic effects. This article reviews the efforts to develop alternative PD solutions that obviate some of these side effects, through the replacement of part of their glucose content with other osmolytes which are at least as efficient in removing fluids as glucose, but less impactful on patient metabolism. In particular, we will summarize clinical studies on the use of alternative osmotic ingredients that are commercially available (icodextrin and amino acids) and preclinical studies on alternative solutions under development (taurine, polyglycerol, carnitine and xylitol). In addition to the expected benefit of a glucose-sparing approach, we describe an 'osmo-metabolic' approach in formulating novel PD solutions, in which there is the possibility of exploiting the pharmaco-metabolic properties of some of the osmolytes to attenuate the systemic side effects due to glucose. This approach has the potential to ameliorate pre-existing co-morbidities, including insulin resistance and type-2 diabetes, which have a high prevalence in the dialysis population, including in PD patients.

Treatment of human skeletal muscle cells with inhibitors of diacylglycerol acyltransferases 1 and 2 to explore isozyme-specific roles on lipid metabolism.

Diacylglycerol acyltransferases (DGAT) 1 and 2 catalyse the final step in triacylglycerol (TAG) synthesis, the esterification of fatty acyl-CoA to diacylglycerol. Despite catalysing the same reaction and being present in the same cell types, they exhibit different functions on lipid metabolism in various tissues. Yet, their roles in skeletal muscle remain poorly defined. In this study, we investigated how selective inhibitors of DGAT1 and DGAT2 affected lipid metabolism in human primary skeletal muscle cells. The results showed that DGAT1 was dominant in human skeletal muscle cells utilizing fatty acids (FAs) derived from various sources, both exogenously supplied FA, de novo synthesised FA, or FA derived from lipolysis, to generate TAG, as well as being involved in de novo synthesis of TAG. On the other hand, DGAT2 seemed to be specialised for de novo synthesis of TAG from glycerol-3-posphate only. Interestingly, DGAT activities were also important for regulating FA oxidation, indicating a key role in balancing FAs between storage in TAG and efficient utilization through oxidation. Finally, we observed that inhibition of DGAT enzymes could potentially alter glucose-FA interactions in skeletal muscle. In summary, treatment with DGAT1 or DGAT2 specific inhibitors resulted in different responses on lipid metabolism in human myotubes, indicating that the two enzymes play distinct roles in TAG metabolism in skeletal muscle.

In vivo monitoring of hepatic glycolipid distribution of n-6 ∕ n-3 in jugular-vein-cannulated rats as a nutritional research model for monogastric animal.

The metabolic distribution via blood from liver of glycerolipids by omega-6 to omega-3 fatty acid ( n -6  /   n -3) ratio in monogastric animal nutrition is very important. In vivo monitoring technique using jugular-vein-cannulated rats as a nutritional model for monogastric animal can yield important insights into animal nutrition. This study was conducted to determine the effect of different n -6  /   n -3 ratios ( 71 : 1 , 4 : 1 , 15 : 1 , 30 : 1 ) on metabolic distribution of glycerolipids newly synthesized and secreted in the liver of the rats and explore the mechanism involved. Regarding 14 CO 2 released from oxidation of glycerolipid metabolism, it was the highest (22.5 %) in groups with a n -6  /   n -3 ratio of 4 : 1 ( P < 0.05 ). The control group showed the highest total glycerolipid level, followed by the 30 : 1 , 15 : 1 , and 4 : 1 groups in order ( P < 0.05 ). When secreted triacylglycerol level of each group was compared with that of the control group, the 4 : 1 , 15 : 1 , and 30 : 1 groups were decreased by 36.3 %, 20.9 %, and 13.3 %, respectively ( P < 0.05 ). Regarding the distribution of phospholipid against total glycerolipid compared to the control group, the 4 : 1 , 15 : 1 , and 30 : 1 groups were 1.38, 1.29, and 1.17 times higher, respectively ( P < 0.05 ). In the comparison of 14 CO 2 emission against total glycerolipid compared with the control group, the 4 : 1 , 15 : 1 , and 30 : 1 groups were 1.61, 1.52, and 1.29 times higher, respectively ( P < 0.05 ). These results demonstrate that a dietary n -6  /   n -3 fatty acid ratio of 4 : 1 could significantly decrease harmful lipid levels in the blood by controlling the mechanism of metabolic distribution via blood from triglyceride and phospholipid newly synthesized in the liver of cannulated rat.

Current Opinion on Usage of L-Carnitine in End-Stage Renal Disease Patients on Peritoneal Dialysis.

The advantages of peritoneal dialysis (PD) over hemodialysis (HD) are well-documented. Notwithstanding, only a small proportion of patients with end-stage renal disease (ESRD) are managed with PD. This may be related to the high glucose load that PD solutions in current use have on the patient. The effects of such excess glucose include the relatively early limitation of the ultrafiltration capacity of the peritoneal membrane, and the metabolic effects associated with hyperglycemia, e.g., decreased insulin sensitivity. This article describes the advantages that may be realized by the glucose-sparing effects of substituting part of the glucose load with other osmotically active metabolites, particularly L-carnitine. The latter is anticipated to have metabolic advantages of its own, especially as in PD patients, high plasma concentrations can be achieved in the absence of renal clearance. Besides its better biocompatibility, L-carnitine demonstrates anti-anemia action due to its effects on erythropoiesis, and positive effects on the longevity and deformability of erythrocytes. Observations from our trials on the use of carnitine-enriched PD solutions have demonstrated the effectiveness of L-carnitine as an efficient osmolyte in PD, and its favorable effect on the insulin sensitivity of the patients. The significance of these findings for future developments in the use of PD in the management of patients with ESRD is discussed.

Hepatic VLDL secretion: DGAT1 determines particle size but not particle number, which can be supported entirely by DGAT2.

We investigated whether, in view of its activity being expressed on both aspects of the endoplasmic reticulum (ER; dual membrane topology), diacylglycerol acyltransferase 1 (DGAT1) plays a distinctive role in determining the triglyceride (TAG) content of VLDL particles secreted by the liver. Mice in which the DGAT1 gene was specifically ablated in hepatocytes (DGAT1-LKO mice) had the same number of VLDL particles (apoB concentration) in the plasma 1 h after Triton 1339 treatment, but these particles were approximately half the size of VLDL particles secreted by control mice and had a proportionately decreased content of TAG, with normal cholesterol and cholesteryl ester contents. Analyses of purified microsomal fractions prepared from 16 h fasted control and DAGT1-LKO mice showed that the TAG/protein ratio in the ER was significantly lower in the latter. Electron micrographs of these livers showed that those from DGAT1-LKO mice did not show the increased lipid content of the smooth ER shown by control livers. The effects of DGAT1- and DGAT2-specific inhibitors on apoB secretion by HepG2 cells showed that DGAT1 is not indispensable for apoB secretion and demonstrated redundancy in the ability of the two enzymes to support apoB secretion. Therefore, our findings show that DGAT1 is essential for the complete lipidation and maturation of VLDL particles within the lumen of the ER, consistent with its dual topology within the ER membrane. In the mouse, DGAT2 can support apoB secretion (particle number) even when TAG availability for full VLDL lipidation is restricted in the absence of DGAT1.

Effect of stocking density on behavioral traits, blood biochemical parameters and immune responses in meat ducks exposed to heat stress.

High stocking density (HSD) and heat stress (HS) caused by climate change can lower blood homeostasis and negatively impact the behavioral traits of animals. The objective of this study was to explore the influence of stocking densities on behavioral traits, blood parameters, immune responses, and stress hormones in meat ducks (Cherry valley, Anas platyrhynchos) exposed to HS. A total of 320 meat ducks were assigned to four groups with different stocking densities using a randomized complete block design. The ducks were then reared for 42 days. The assigned density groups were as follows: (1) control group (CON, three birds m - 2 , normal environmental heat conditions); (2) low stocking density (LSD, three birds m - 2 , heat stress conditions); (3) medium stocking density (MSD, four birds m - 2 , heat stress conditions); and (4) high stocking density (HSD, six birds m - 2 , heat stress conditions). To induce HS, the environment of the poultry house was set to a temperature of 34 ± 2 ∘ C with a relative humidity of 70 % from 11:00 to 16:00 for the finisher period (from day 22 to day 42 of the rearing period). Concentrations of blood triacylglycerol, total cholesterol, low-density lipoprotein cholesterol (LDL-C), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were higher in the HS groups compared with the CON group, with HSD showing the highest levels ( P < 0.05 ). The concentrations of high-density lipoprotein cholesterol (HDL-C) and glucose were lower in the HSD groups than in the CON group ( P < 0.05 ). Red blood cell (RBC) and platelet (PLT) counts were lower in HS groups compared with the CON group, with the HSD group displaying the lowest counts ( P < 0.05 ). Blood pH values were also higher in the HS groups than in the CON group, with the highest values observed in the HSD group ( P < 0.05 ). Concentrations of blood p CO 2 , HCO 3 , and T CO 2 were higher in the HS groups than in the CON group, with HSD showing the lowest levels ( P < 0.05 ). The concentration of PO 2 was higher in CON than in any of the HS groups, with the lowest levels found in the HSD group ( P < 0.05 ). The concentrations of blood IgG and corticosterone were increased in the HS groups compared with the CON group ( P < 0.05 ). Animal behavioral trait scores were also higher in HS groups than in the CON group ( P < 0.05 ); these scores were the highest in the HSD group. Overall, animal behavioral traits, blood biochemical parameters, and immune responses in meat ducks exposed to heat stress were highest in the HSD group, but not significantly different between the LSD or MSD groups.

Differential activation of Fyn kinase distinguishes saturated and unsaturated fats in mouse macrophages.

Diet-induced obesity is associated with increased adipose tissue activated macrophages. Yet, how macrophages integrate fatty acid (FA) signals remains unclear. We previously demonstrated that Fyn deficiency (fynKO) protects against high fat diet-induced adipose tissue macrophage accumulation. Herein, we show that inflammatory markers and reactive oxygen species are not induced in fynKO bone marrow-derived macrophages exposed to the saturated FA palmitate, suggesting that Fyn regulates macrophage function in response to FA signals. Palmitate activates Fyn and re-localizes Fyn into the nucleus of RAW264.7, J774 and wild-type bone marrow-derived macrophages. Similarly, Fyn activity is increased in cells of adipose tissue stromal vascular fraction of high fat-fed control mice, with Fyn protein being located in the nucleus of these cells. We demonstrate that Fyn modulates palmitate-dependent oxidative stress in macrophages. Moreover, Fyn catalytic activity is necessary for its nuclear re-localization and downstream effects, as Fyn pharmacological inhibition abolishes palmitate-induced Fyn nuclear redistribution and palmitate-dependent increase of oxidative stress markers. Importantly, mono-or polyunsaturated FAs do not activate Fyn, and fail to re-localize Fyn to the nucleus. Together these data demonstrate that macrophages integrate nutritional FA signals via a differential activation of Fyn that distinguishes, at least partly, the effects of saturated versus unsaturated fats.

Diacylglycerol acyltransferase 2 links glucose utilization to fatty acid oxidation in the brown adipocytes.

Brown adipose tissue uptake of glucose and fatty acids is very high during nonshivering thermogenesis. Adrenergic stimulation markedly increases glucose uptake, de novo lipogenesis, and FA oxidation simultaneously. The mechanism that enables this concerted response has hitherto been unknown. Here, we find that in primary brown adipocytes and brown adipocyte-derived cell line (IMBAT-1), acute inhibition and longer-term knockdown of DGAT2 links the increased de novo synthesis of fatty acids from glucose to a pool of TAG that is simultaneously hydrolyzed, providing FA for mitochondrial oxidation. DGAT1 does not contribute to this pathway, but uses exogenous FA and glycerol to synthesize a functionally distinct pool of TAG to which DGAT2 also contributes. The DGAT2-dependent channelling of 14C from glucose into TAG and CO2 was reproduced in ß3-agonist-stimulated primary brown adipocytes. Knockdown of DGAT2 in IMBAT-1 affected the mRNA levels of UCP1 and genes important in FA activation and esterification. Therefore, in ß3-agonist activated brown adipocytes, DGAT2 specifically enables channelling of de novo synthesized FA into a rapidly mobilized pool of TAG, which is simultaneously hydrolyzed to provide substrates for mitochondrial fatty acid oxidation.