Plasma NEFA Research Articles

Increased body fat content in horses alters metabolic and physiological exercise response, decreases performance, and increases locomotion asymmetry.

ABSTRACTThis study examined the effect of altered body weight (BW) and body fat content on exercise performance and recovery. Nine horses were divided into two groups, and changes in BW and fat content were induced by feeding a high (HA) or restricted (RA) energy allowance for 36 days in a cross‐over design. In the last week of each treatment, BW and body condition score (BCS) were recorded, body fat percentage was estimated using ultrasound, and a standardized incremental treadmill exercise test (SET) and competition‐like field test were performed (scored by judges blinded to treatments). Blood samples were collected, and heart rate (HR), rectal temperature (RT), and respiratory rate (RR) were also recorded. Objective locomotion analyses were performed before and after the field test. Body weight, body fat percentage, and BCS were higher (5–8%) in HA than in RA horses (p < 0.05). In SET, HA horses showed higher HR, plasma lactate concentration, RR, and RT than RA horses (p < 0.05), and lower VLa4, hematocrit (Hct), plasma glucose, and plasma NEFA concentrations (p < 0.05). Hct was also lower in HA horses in the field test, while RA horses showed higher scores (p < 0.05). After both tests, resting plasma lactate concentrations were reached faster in RA than in HA horses (p < 0.05). Objective locomotion asymmetry was higher in HA than in RA (p < 0.05). These results clearly show that increased BW and body fat content in horses lower physiological fitness in terms of VLa4, plasma lactate removal, Hct levels, plasma glucose availability and reduce true performance evaluated by blinded judges.

Plasma cholesterol levels and short-term adaptations of metabolism and milk production during feed restriction in early lactating dairy cows on pasture.

Low plasma total cholesterol (TC) concentrations are characteristic during the negative energy balance in early lactating dairy cows. The objective was to investigate short-term effects of different TC concentrations during an aggravated energy deficiency through a 1-week concentrate withdrawal on adaptations of metabolism and milk production. Multiparous Holstein cows (n=15) were investigated during 3week beginning at 24±7 DIM (mean±SD). Cows were kept on pasture and received additional concentrate in experimental week 1 and 3, while in week 2, concentrate was withdrawn. Blood was sampled once and milk twice daily. Based on their average TC concentration during week 1 (prior to concentrate withdrawal), cows were retrospectively assigned into a high (H-Chol; n=8, TC≥3.36mmol/L) and a low TC groups (L-Chol; n=7, TC<3.36mmol/L). Concentrations of phospholipids and lipoproteins were higher in H-Chol compared to L-Chol throughout the study (p<0.05). During concentrate withdrawal, milk yield, glucose and insulin concentrations decreased similarly in both groups, while milk fat, milk acetone and plasma BHB were higher in H-Chol compared to L-Chol (p<0.05). Compared to initial values, plasma NEFA, TAG and VLDL increased in both groups within 2days after concentrate withdrawal (p<0.05). Concentrations of NEFA during week 2 were greater in L-Chol compared to H-Chol (p<0.05). Despite reintroduction of concentrate, milk yield in H-Chol remained lower for two more days compared to week 1 (p<.05), whereas milk yield recovered immediately in L-Chol. Activity of aspartate aminotransferase was higher in H-Chol compared to L-Chol in week 2 (p<0.05). Greater plasma TC concentrations were associated with a reduced increase of NEFA. Further research is warranted if TC concentrations are related to adipose tissue mobilization and fatty acid turnover.

Plasma 3-hydroxyisobutyrate (3-HIB) and methylmalonic acid (MMA) are markers of hepatic mitochondrial fatty acid oxidation in male Wistar rats

ObjectiveDiscovery of specific markers that reflect altered hepatic fatty acid oxidation could help to detect an individual's risk of fatty liver, type 2 diabetes and cardiovascular disease at an early stage. Lipid and protein metabolism are intimately linked, but our understanding of this crosstalk remains limited. MethodsIn male Wistar rats, we used synthetic fatty acid analogues (3-thia fatty acids) as a tool to induce hepatic fatty acid oxidation and mitochondrial biogenesis, to gain new insight into the link between fatty acid oxidation, amino acid metabolism and TCA cycle-related intermediate metabolites in liver and plasma. ResultsRats treated with 3-thia fatty acids had 3-fold higher hepatic, but not adipose and skeletal muscle, expression of the thioesterase 3-hydroxyisobutyryl-CoA hydrolase (Hibch), which controls the formation of 3-hydroxyisobutyrate (3-HIB) in the valine degradation pathway. Consequently, 3-thia fatty acid-stimulated hepatic fatty acid oxidation and ketogenesis was accompanied by decreased plasma 3-HIB and increased methylmalonic acid (MMA) concentrations further downstream in BCAA catabolism. The higher plasma MMA corresponded to higher MMA-CoA hydrolase activity and hepatic expression of GTP-specific succinyl-CoA synthase (Suclg2) and succinate dehydrogenase (Sdhb), and lower MMA-CoA mutase activity. Plasma 3-HIB correlated positively to plasma and hepatic concentrations of TAG, plasma total fatty acids, plasma NEFA and insulin/glucose ratio, while the reverse correlations were seen for MMA. ConclusionOur study provides new insight into TCA cycle-related metabolic changes associated with altered hepatic fatty acid flux, and identifies 3-HIB and MMA as novel circulating markers reflective of mitochondrial β-oxidation in male Wistar rats.

Supplementation of guanidinoacetic acid and betaine improve growth performance and meat quality of ducks by accelerating energy metabolism

This study was conducted to investigate the effects of guanidinoacetic acid (GAA) and betaine on growth performance, meat quality and metabolism of ducks. A total of 384-one-day-old Cherry Valley meat ducks (55.75 ± 0.55 g) were randomly assigned to four treatments with 6 replicates of 16 ducks. Ducks were fed a basal diet (control) or a test diet supplemented with 0.6 g GAA/kg, 2.0 g betaine/kg, or 0.6 g GAA/kg + 2.0 g betaine/kg. The results showed that compared with the control group, GAA and betaine improved feed conversation ratio from day 1 to 14 and 1 to 35 and body weight at 35 days of age (p < .05). GAA and betaine increased breast muscle percentage while reduced abdominal fat percentage, and drip loss and shear force of breast muscle (p < .05). GAA and betaine lowered free serine, methionine, tryptophan and total amino acid contents in muscles, increased free serine, aspartic acid, phenylalanine and tryptophan contents in plasma (p < .05). There was a synergistic effect on non-esterified fatty acid, lactic acid and uric acid between GAA and betaine. GAA and betaine increased the creatine kinase activity in plasma and creatine and ATP content in breast muscle, decreased the lactate dehydrogenase and L-arginine: glycine amidino transferase activities (p < .05). In conclusion, supplementation of GAA and betaine improved the growth performance and meat quality of ducks by accelerating energy metabolism. There was a synergistic effect on NEFA, LA and UA concentrations in plasma of ducks between GAA and betaine. Highlights Supplementing GAA and betaine improved the growth performance and meat quality of ducks. Adding GAA and betaine accelerated the energy metabolism of ducks. There was a synergistic effect on non-esterified fatty acid, lactic acid and uric acid concentrations in the plasma of ducks between GAA and betaine.

PSVI-21 Effect of preconditioning pre-shipment and injectable antioxidant trace elements and vitamins on growth, antioxidant status, and plasma metabolites and insulin concentration in weaned beef cattle

Abstract The aim of this study was to evaluate the effect of weaning preconditioning and parenteral supplementation of minerals and vitamin on growth and plasma total antioxidant status (TAS), glucose, NEFA, and insulin concentrations, in calves at feedlot arrival. Sixty male Angus-cross calves were randomly assigned to 4 treatments (n=15/treatment). Treatments were arranged in a 2x2 factorial design; the main factors were mineral and vitamins supplementation (supplementation (S) vs no supplementation (NS)), and preconditioning (preconditioning (P) vs. not (NP)). Supplementation was applied subcutaneously on d -45, -26 and 0 and provided Cu, Mn, Se, Zn, and vitamins A and E (Adaptador Min-Vit ®, Biogénesis Bagó). Preconditioning consisted in a 26-day period between weaning and transportation at feedlot (d0) with the animals remaining in the same location. Blood samples were collected on d -26, 0 and 15. Animals were weighted on d-45, -26, 0, 8, 15 and 29. On d0 calves were load into a truck and drove for 5-hours to the feedlot. Data were analyzed using a mixed model as a 2x2 factorial, using repeated measurements. Body weight was greater on d 0, 8 15 and 29 group on groups NP, followed by S-P, and the lowest for NS-P (Triple interaction P &amp;lt; 0.01). Treatment did not affect (P ˃ 0.1) plasma insulin and glucose concentrations. There was a triple interaction (P &amp;lt; 0.08) for plasma TAS and NEFA concentration. Plasma TAS concentration was grater due to a decrease in its concentration for the S-P and NS-NP from d0 to d8, but not in the other treatments. Plasma NEFA concentration had the greater increase in the NP groups followed by S-NP on d0. In conclusion, 26-days precondition weaning decrease body weight compare with a traditional weaning. Mineral and vitamin supplementation in precondition weaning partially reduced that effect

PSI-12 Effects of supplementing propionate in a finishing diet on dry matter intake, glucose clearance, and blood metabolites

Abstract The objective of this experiment was to determine if supplementing propionate alters DMI, glucose clearance rate, and blood metabolite concentrations in steers fed a finishing diet. Holstein (n = 15) steers were individually fed a finishing diet ad-libitum. Steers were allocated by BW to receive: no Ca propionate (CON), 100 g/d (LOW), or 300 g/d (HIGH) in the diet. Orts were collected and weighed daily to determine DMI. Blood samples were collected on d 0, 7, and 21, and BW recorded on d 0, 14, and 28. A glucose tolerance test was conducted on d 14 and 28 of the trial. Samples were analyzed for whole blood glucose and lactate, and plasma NEFA. Data were analyzed using a mixed model with treatment, day and their interaction included, with day as a repeated measure. The CON treatment had greater (P &amp;lt; 0.01) DMI than LOW and HIGH. BW was greater for CON throughout the experiment and all treatments had an increased BW on day 28 (P = 0.03 for the interaction). Whole blood glucose concentrations tended (P = 0.09) to be higher on d 21 than d 0 and 7, but was not affected by treatment (P = 0.58). Plasma NEFA concentrations were lower (P = 0.05) for CON than other treatments, and greater (P = 0.002) on d 0 than d 7 and 21. Whole blood lactate concentrations were greater (P = 0.05) on d 7, than d 0 and 21, but was not effected by treatment (P = 0.13). There was no treatment (P ≥ 0.16) or day effect (P ≥ 0.36) on glucose peak, plateau, or clearance rate. These data indicate that supplemental propionate may decrease dry matter intake but might not alter glucose clearance rate.

Adipocyte-specific deletion of Tcf7l2 induces dysregulated lipid metabolism and impairs glucose tolerance in mice

Aims/hypothesisTranscription factor 7-like 2 (TCF7L2) is a downstream effector of the Wnt/β-catenin signalling pathway implicated in type 2 diabetes risk through genome-wide association studies. Although its expression is critical for adipocyte development, the potential roles of changes in adipose tissue TCF7L2 levels in diabetes risk are poorly defined. Here, we investigated whether forced changes in Tcf7l2 expression in adipocytes affect whole body glucose or lipid metabolism and crosstalk between disease-relevant tissues.MethodsTcf7l2 was selectively ablated in mature adipocytes in C57BL/6J mice using Cre recombinase under Adipoq promoter control to recombine Tcf7l2 alleles floxed at exon 1 (referred to as aTCF7L2 mice). aTCF7L2 mice were fed normal chow or a high-fat diet for 12 weeks. Glucose and insulin sensitivity, as well as beta cell function, were assessed in vivo and in vitro. Levels of circulating NEFA, selected hormones and adipokines were measured using standard assays.ResultsReduced TCF7L2 expression in adipocytes altered glucose tolerance and insulin secretion in male but not in female mice. Thus, on a normal chow diet, male heterozygote knockout mice (aTCF7L2het) exhibited impaired glucose tolerance at 16 weeks (p = 0.03) and increased fat mass (1.4 ± 0.1-fold, p = 0.007) but no changes in insulin secretion. In contrast, male homozygote knockout (aTCF7L2hom) mice displayed normal body weight but impaired oral glucose tolerance at 16 weeks (p = 0.0001). These changes were mechanistically associated with impaired in vitro glucose-stimulated insulin secretion (decreased 0.5 ± 0.1-fold vs control mice, p = 0.02) and decreased levels of the incretins glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide (0.6 ± 0.1-fold and 0.4 ± 0.1-fold vs control mice, p = 0.04 and p < 0.0001, respectively). Circulating levels of plasma NEFA and fatty acid binding protein 4 were increased by 1.3 ± 0.1-fold and 1.8 ± 0.3-fold vs control mice (p = 0.03 and p = 0.05, respectively). Following exposure to a high-fat diet for 12 weeks, male aTCF7L2hom mice exhibited reduced in vivo glucose-stimulated insulin secretion (0.5 ± 0.1-fold vs control mice, p = 0.02).Conclusions/interpretationLoss of Tcf7l2 gene expression selectively in adipocytes leads to a sexually dimorphic phenotype, with impairments not only in adipocytes, but also in pancreatic islet and enteroendocrine cells in male mice only. Our findings suggest novel roles for adipokines and incretins in the effects of diabetes-associated variants in TCF7L2, and further illuminate the roles of TCF7L2 in glucose homeostasis and diabetes risk.Graphical abstract

Nonesterified Fatty Acids and Depression in Cancer Patients and Caregivers.

ABSTRACTBackgroundNonesterified fatty acids (NEFAs) are known to have inflammatory effects. The inflammatory hypothesis of depression suggests that omega-3 (ω-3) and omega-6 (ω-6) fatty acids might be negatively and positively correlated with depression, respectively.ObjectiveAn exploratory study was conducted to determine the association between dietary free fatty acids and depressive symptoms in cancer patients and caregivers.MethodsAssociations between depression and the NEFA pool were investigated in 56 cancer patients and 23 caregivers using a combination of nonparametric tests and regularized regression. Plasma NEFAs were measured using thin layer and gas chromatography with flame ionization detection. Depression was characterized both as a continuous severity score using the GRID-Hamilton Depression Rating Scale (GRID Ham-D), and as a categorical diagnosis of major depression by structured clinical interview.ResultsInitial hypotheses regarding the relation between depression and omega-3 or omega-6 fatty acids were not well supported. However, elaidic acid, a trans-unsaturated fatty acid found in hydrogenated vegetable oils, was found to be negatively correlated with continuous depression scores in cancer patients. No significant associations were found in caregivers.ConclusionsAn unexpected negative association between elaidic acid and depression was identified, supporting recent literature on the role of G protein–coupled receptors in depression. Further research is needed to confirm this result and to evaluate the potential role of G protein agonists as therapeutic agents for depression in cancer patients.

Impact of substituting compound feed with increasing levels of fresh grass-clover on nitrogen metabolism and plasma metabolites of sows

The purpose of this study was to identify biomarkers for fresh grass-clover intake and determine the digestibility and energy value of fresh grass to estimate voluntary fresh grass-clover intake in sows kept on pasture according to organic production practice. A total of sixteen multiparous dry sows (Danish Landrace x Danish Yorkshire) were housed in metabolism cages for 2 periods of 5 d. To study dietary effects, sows were fed one of four mixed treatments where increasing proportions of a basal commercial organic sow compound feed was partly replaced with 0, 2, 4, or 6 kg fresh grass-clover collected 3 wk after the previous cut. Sows were fed similar amounts of metabolizable energy (ME). Total collection of urine and feces was performed on a daily basis for 5d, and blood samples were collected from the jugular vein on the last day of feeding. Plasma metabolites were analyzed using a non-targeted liquid chromatography-mass spectrometry (LCMS) approach. Analyzed plasma metabolites (area under the curve in arbitrary units from the LCMS) were screened for correlation with grass intake. Data on nutrient digestibility and plasma metabolites were analyzed using a MIXED procedure while accounting for repeated measurements. Apparent total tract digestibilities of dry matter, organic matter, nitrogen, and energy of fresh grass-clover were 72, 64, 71, and 68%, respectively, using the regression method. The N intake increased linearly with increasing fresh grass-clover intake (P < 0.001). There was no evidence of altered N deposition and N utilization in response to increasing grass intake (P > 0.05). There was a linear increase in plasma urea content (2.64 to 4.39 mM) when grass intake increased from 0 to 6 kg/d (P = 0.02). Plasma glucose, lactate, creatinine and NEFA, and triglycerides were not affected by increased grass-clover intake. The daily ME contribution from fresh grass-clover (MJ/d) was found to be highly positively correlated with plasma pipecolic acid (Y = 0.0289 X; r2 = 0.91; P < 0.001) and a metabolite tentatively identified as plasma bisnorbiotin (Y = 0.482 X; r2 = 0.92; P < 0.001). In conclusion, fresh grass-clover intake of sows was highly correlated with plasma pipecolic acid and plasma bisnorbiotin concentration and apparent total tract digestibility of DM, OM, N, and energy estimated for 100% fresh grass-clover intake in dry sows was 64 to 72% using the regression method.

Grass clover intake and effects of reduced dietary protein for organic sows during summer

Energy spent on thermoregulation and locomotive activity may increase the energy requirements of outdoor relative to indoor housed sows, whilst their protein requirement most likely is comparable on a daily basis but lower per kg of feed. The purpose of this study was to quantify the energy and protein intake from compound feed and grazing and the energy and protein needed for maintenance, maternal retention, milk production, thermoregulation and locomotive activity in organic sows during summer, to understand how nutrition of organic sows could be improved. A total of 41 2nd parity sows (Landrace x Yorkshire; 239 kg at insemination) were reared outdoor under organic conditions for six months. Sows were fed one of two iso-energetic diets, either commercial available gestation and lactation diets (control strategy), or a 12% lower protein supply obtained by diluting the control diets with a low protein supplement. Sows had ad libitum access to a plentiful grass clover sward and were supplied similar amounts of metabolizable energy (ME) from compound feed equivalent to 10% above the energy recommended for indoor sows. Collections of plasma and urine were performed on d 60 and d 100 of gestation and plasma, urine and milk was collected on d 5, 20 and 40 of lactation. On all sample collection days, sows (and piglets; n=671) were weighed individually, sows were back fat scanned and heart rate and locomotive activity was registered with a global positioning system (GPS) tracker. Sow body composition was estimated using a deuterium dilution technique, which allowed retention or mobilisation of protein and fat to be calculated. Grass intake was estimated via plasma pipecolic acid. Daily grass clover intake was on average 420 g DM/d during gestation, 574 g DM/d at peak lactation and 472 g DM/d on d 40 of lactation, corresponding to 2.4, 3.2 and 2.6 kg of fresh grass. There was an increased grass clover intake in the low protein group, as they consumed 14% more grass (37 g DM/d extra) than the sows fed the normal protein compound feed (P=0.007). Estimated milk yield peaked at 16.3 kg/d on d20. This experiment showed no effects of dietary protein level on urinary pH, urea or creatinine and no effects on plasma glucose, urea, lactate, triglycerides, creatinine or NEFA concentrations. It was possible to reduce the protein content of organic compound feed in the summer time as grazing pregnant sows obtained 16-17% of their daily SID lysine requirement from the sward in mid and late gestation. In conclusion, the daily protein- and amino acid requirements were met by feed and grass consumption during pregnancy but not in early and at peak lactation due to insufficient feed intake. The total energy requirement of high yielding second parity outdoor sows during a normal Danish summer was found to be around 32 MJ ME/d during gestation and approximately 130 MJ ME/d at peak lactation.

Physio-biochemical responses and growth performance of buffalo heifers to betaine supplementation during hot humid season under field conditions

In order to find out the effect of betaine supplementation on physiological (rectal temperature, skin temperature, respiration rate and pulse rate) responses, morphological (body length, heart girth and height at withers) parameters, stress markers (cortisol and NEFA levels), growth hormone, dry matter intake (DMI) and body weight of buffalo heifers during hot humid season under field conditions, 14 buffalo heifers were selected and equally divided into 2 groups, i.e. control and treatment (supplemented betaine @ 25 g/animal/day over the farmers practice). Blood samples were collected at fortnightly interval from both the groups and analyzed for stress markers. THI was calculated for measuring the stress levels on buffalo heifers, which remained 􀀡76 indicating severe stress. Physiological responses were significantly lower in treatment group than control. Morphological parameters, body weight and DMI were higher in treatment than control. Plasma cortisol and NEFA levels were significantly lower, whereas plasma growth hormone was significantly higher in treatment group compared to control. ADG was significantly higher in treatment group compared to control. Positive correlation was observed between THI and stress markers, physiological responses and negatively correlated with ADG, DMI and growth hormone. It can be concluded that betaine acted as a potent growth promoter by lowering the levels of stress markers and enhancing the ADG and DMI of buffalo heifers.

1845-P: Maternal Overnutrition Causes DNA Alkylation in Fetal Liver, Suppresses FasL, and Upregulates HIF-1 Signaling Pathway in Neonatal Liver in Nonalcoholic Steatohepatitis (NASH)-Based Hepatocellular Carcinoma in Offspring

Nonalcoholic steatohepatitis (NASH), a progressive form of nonalcoholic fatty liver disease (NAFLD), is associated with hepatocellular carcinoma (HCC). The worldwide prevalence of NAFLD in children suggests an early-life origin. To examine the impact of intrauterine nutrition on the development of NASH/HCC, female C57BL/6J mice were fed with either high-fat diet (HFD) or control diet (CD) during gestation. After weaning, the male offspring were fed with CD, generating two groups of male offspring, HFD and CD. HFD remarkably elevated plasma NEFA and ALT. Consistently, HFD had severe form of NASH, presenting the fibrosis, accompanied with HCC. Synchrotron micro-CT showed the architectural remodeling of the parenchyma in HFD at 14.5 days postcoitum (dpc), one week and 15 weeks of age, not in CD. In the liver of HFD at 14.5dpc, gene ontology term enrichment analysis suggested that up-regulated differentially expressed genes (DEGs) significantly enriched in DNA alkylation, bile secretion, and the down-regulated DEGs mainly enriched in neuronal system, cell maturation. KEGG pathway analysis found down-regulated DEGs significantly enriched in five pathways including Graft-versus-host disease (LogP -24.785) such as FasL, and up-regulated HIF-1 signaling pathway in the liver of HFD at one week of age. On the contrary, 15-week-old HFD had increased cytoplasmic pimonidazole staining, but no nuclear staining of HIF-1α in HCC cells, which suggests breakdown of hypoxic response mechanism, concomitantly with up-regulated miR199a-5p, miR-1949, miR214-3p and miR-3090-5p, which target HIF-1α. This study demonstrates that the early exposure to an overnutrition in utero, subsequent neonatal and adult nutritional alternation cause NASH/HCC in offspring, accompanied by multiple changes in gene expressions. This means a “multi-hit theory.” Disclosure T. Takiyama: None. R. Bessho: None. K. Sawamoto: None. Y. Takiyama: Other Relationship; Self; Abbott, Boehringer Ingelheim Pharmaceuticals, Inc., Merck &amp; Co., Inc., Ono Pharmaceutical Co., Ltd., Roche Diagnostics K.K., Taisho Pharmaceutical Co., Ltd.

Lipid profile and liver lipids of OLETF rats during ARB treatment and after its removal

The metabolic syndrome (MetS) affects 20% of the US population. MetS comprises several disorders that raise the risk of atherosclerosis, insulin resistance, and diabetes. Angiotensin receptor blockers (ARBs) are used to ameliorate hypertension associated with metabolic disorders. Nonetheless, the potential benefits of ARBs on the metabolic state are not fully appreciated. ARB treatment reduces overproduction and accumulation of hepatic triacylglycerols (TAG), but whether ARB treatment has favorable effects in fatty livers associated with insulin resistance is still unknown. Furthermore, the compliance on the usage of ARBs should also be addressed, as MetS patients may be under variating treatments, exposing them to secondary effects due to the ARB treatment removal. To evaluate the benefits of ARB treatment and implications of its removal on the lipid profile, four groups (n=4–6) of 25‐week‐old rats were used: (1) lean, strain‐control Long‐Evans Tokoshima Otsuka (LETO), (2) obese, insulin resistant Otsuka Long‐Evans Tokoshima Fatty (OLETF), 3) ARB‐treated OLETF, (10 mg olmesartan/kg/d × 8 wks), and 4) OLETF ± ARB (10 mg olmesartan/kg/d × 4 wks then removed until dissection). An oral glucose challenge (GC) was performed prior to dissection and tissues collected from a subset of animals in each group at defined time points (T0, 3 an 6hr). We measured different components of the lipid profile, during the ARB treatment and after its removal. Plasma NEFA, TAG and cholesterol levels remain unchanged with ARB treatment, as well as with ARB removal. ARB treatment did not change the liver levels of cholesterol, but prevented the increase shown by OLETFs during the GC. ARB removal shown increased cholesterol after 6 hr of the GC. ARB treatment decreased liver TAG and throughout the GC. ARB removal increased TAG liver levels during the GC. Suggesting that lipid profiles may not change during static sampling during or after ARB treatment. ARB treatment reduces liver TAG concentration, and even with ARB removal suggesting that plasma levels do not accurately reflect tissue levels. Following the GC, the ARB removal group demonstrated an increase in levels, suggesting that treatment non‐compliance results in rapid return to basal levels and increased potential for hepatic dysfunction. Further investigation on lipid transport and metabolic regulation during ARB treatment and removal may yield insight for a wider perspective for treatment of traits linked to MetS.Support or Funding InformationThis work was supported by NIH MHIRT.

Betatrophin knockdown induces beiging and mitochondria biogenesis of white adipocytes.

Remodeling of energy-storing white fat into energy-consuming beige fat has led to a promising new approach to alleviate adiposity. Several studies have shown adipokines can induce white adipose tissue (WAT) beiging through autocrine or paracrine actions. Betatrophin, a novel adipokine, has been linked to energy expenditure and lipolysis but not clearly clarified. Here, we using high-fat diet-induced obesity to determine how betatrophin modulate beiging and adiposity. We found that betatrophin-knockdown mice displayed less white fat mass and decreased plasma TG and NEFA levels. Consistently, inhibition of betatrophin leads to the phenotype change of adipocytes characterized by increased mitochondria contents, beige adipocytes and mitochondria biogenesis-specific markers both in vivo and in vitro. Of note, blocking AMP-activated protein kinase (AMPK) signaling pathway is able to abolish enhanced beige-like characteristics in betatrophin-knockdown adipocytes. Collectively, downregulation of betatrophin induces beiging in white adipocytes through activation of AMPK signaling pathway. These processes suggest betatrophin as a latent therapeutic target for obesity.

Ghrelin antagonist regulates metabolic hormone receptorsin the hypothalamus of ewes

Abstract This study evaluates the effects of ghrelin antagonist on mRNA abundance for metabolic hormone receptors in feed-restricted ewes. Ewes were randomly assigned to one of three treatments; Control (CO): feed above maintenance energy intake requirements and daily subcutaneous saline infusion; Feed restriction (FR): feed restricted and daily subcutaneous saline infusion; Ghrelin antagonist (GA): feed restricted and daily subcutaneous of 7.5 μg/kg of d -Lys3-GHRP-6. Blood was sampled on days 1, 4, 9, and 13, relative to the start of the experiment, to quantify plasma glucose, NEFA and ghrelin concentrations. At day 13, the hypothalamus was collected to evaluate relative mRNA expression. The CO ewes had lesser plasma NEFA concentration compared with FR and GA ewes. There was a treatment by time interaction for plasma glucose concentration, all treatment started with similar plasma glucose concentration, but at day 13 CO ewes had a greater plasma concentration than FR and GA. Relative mRNA expression for glucagon receptor in GA ewes tended to be lesser compared with CO and FR treated ewes. There were no differences in insulin receptor mRNA relative expression between the groups. Ghrelin receptor mRNA relative expression tended to be greater in the GA compared with the CO treated ewes. There was no effect of GA on leptin receptors. However, there was a tendency toward greater relative expression of leptin receptor mRNA in the FR compared with the CO ewes. Relative expression of adiponectin receptor mRNA was lesser in the GA compared with CO and FR ewes. Cortisol receptor relative mRNA expression was greater in the FR compared with the CO ewes. Restricting dietary intake of ewes change mRNA relative expression of cortisol and leptin receptors in the hypothalamus of ewes. These variations are countered with ghrelin antagonist. Ghrelin antagonist modifies the mRNA relative expression of ghrelin, glucagon and adiponectin receptors. These results suggest that ghrelin could regulates metabolic hormone activity by modifying the relative expression of their receptors mRNA.

Effects of Supplementation with Anti-Inflammatory Compound Extracted from Herbs in Healthy and Obese Cats.

BackgroundObesity has become a serious public health problem all over the world, and prevalence of obesity has increased in cats. Obesity is characterized by continuous low-grade inflammation based on oxidative stress by excessively produced reactive oxygen species (ROS). Supplementation with anti-oxidant and anti-inflammatory compounds is very effective to relieve the obesity condition. A plant extract mixture containing Rhus verniciflua and some other herbs, Rv-PEM01-99, shows anti-oxidant and anti-inflammatory effects in animals. The aim of this study was to evaluate the effects of supplementation with Rv-PEM01-99 as an anti-inflammatory compound in healthy and obese cats.Materials and MethodsTen healthy mix breed cats and four obesity disease cats were used. The healthy cats were randomly divided into control and test groups. Anti-inflammatory compound, Rv-PEM01-99, in which quercetin derivative is the main component, was supplemented to the healthy test group and the obesity disease cats at the dose of 100–120 mg/kg/day (2.5–3.0 mg/kg/day as quercetin) for 4 weeks. Metabolites, hormones and enzymes were measured before and after the compound supplementation.ResultsThe anti-inflammatory compound supplementation decreased serum amyloid A (SAA) concentrations as inflammatory markers in both healthy and obesity disease cats. In obesity disease cats, plasma total cholesterol concentrations and AST and ALT activities decreased significantly after the compound supplementation.ConclusionQuercetin derivative seems to have strong anti-inflammatory activities. In the healthy cats, anti-inflammatory compound supplementation decreased plasma NEFA and SAA concentrations. In the obesity disease cats, the compound supplementation may have alleviated obesity disease by relieving inflammation and improvement of lipid metabolism in livers.

Physiological responses, energy metabolites and prolactin levels of buffaloes supplemented with dietary astaxanthin, prill fat and their combination during heat stress

Study was conducted to assess the effect of dietary supplementation of astaxanthin, prill fat and their combination on physiological responses, energy metabolites and prolactin levels in buffaloes during summer season. Twenty four lactating buffaloes were equally divided into four groups, viz. Gr I (control), Gr II (astaxanthin supplementation @ 0.25 mg/kg body wt/day), Gr III (prill fat @ 100 g/animal/day) and Gr IV (combination of both). The respiration rate was lower in treatment groups than control. Plasma glucose in combination group was higher than control. Plasma NEFA was lower in treatment groups compared to control. Prolactin level was lower in supplemented groups compared to control. Based on the results it can be concluded that astaxanthin supplementation helped in ameliorating effects of heat stress whereas prill fat worked as source of energy to maintain the energy balance in lactating buffaloes. The combinations of both the products are more effective as far as stress markers and increase in milk production is concerned but due to higher price of astaxanthin the cost benefit ratio is lower than prill fat supplementation alone. Therefore, farmers prefer to feed prill fat to their lactating buffaloes during summer conditions.

Night-restricted feeding of dairy cows modifies daily rhythms of feed intake, milk synthesis and plasma metabolites compared with day-restricted feeding.

The timing of feed intake can alter circadian rhythms of peripheral tissues. Milk synthesis displays a daily rhythm across several species, but the effect of feeding time on these rhythms is poorly characterised. The objective of this experiment was to determine if the time of feed intake modifies the daily patterns of milk synthesis, plasma metabolites and body temperature in dairy cows. Sixteen lactating Holstein dairy cows were randomly assigned to one of the two treatment sequences in a cross-over design with 17 d periods. Treatments included day-restricted feeding (DRF; feed available from 07.00 to 23.00 hours) and night-restricted feeding (NRF; feed available from 19.00 to 11.00 hours). Cows were milked every 6 h on the last 7 d of each period, and blood samples were collected to represent every 4 h over the day. Peak milk yield was shifted from morning in DRF to evening in NRF, while milk fat, protein and lactose concentration peaked in the evening in DRF and the morning in NRF. Plasma glucose, insulin, NEFA and urea nitrogen concentration fit daily rhythms in all treatments. Night feeding increased the amplitude of glucose, insulin and NEFA rhythms and shifted the daily rhythms by 8 to 12 h (P < 0·05). Night feeding also phase-delayed the rhythm of core body temperature and DRF increased its amplitude. Altering the time of feed availability shifts the daily rhythms of milk synthesis and plasma hormone and metabolite concentrations and body temperature, suggesting that these rhythms may be entrained by food intake.

Effect of reducing energy intake during the dry period on milk production, udder health, and body condition score of Jersey crossbred cows in the tropical lower Gangetic region.

To find out the effect of reducing energy intake during dry period on milk production, udder health, and body condition, the experiment was conducted on 14 Jersey crossbred cows during whole dry period and continued up to 120days of lactation. Reduction in energy intake was done during far-off period for each dry cow of treatment group as compared to control group. Statistically analyzed data revealed that overall significantly (P < 0.01) lower DMI and WI were recorded in control than treatment group. Overall significantly (P < 0.01) higher total milk production was found in treatment than control group. Overall significantly (P < 0.01) lower milk SCC, MCMT, pH, and EC were found in treatment than control group. Nonsignificant difference in milk fat, SNF, total solid, total protein, and fat:protein ratio was found. Overall significantly (P < 0.01) better quality milk (MBRT) was found in treatment than control groups. BCS during dry period and at calving was significantly (P < 0.01) different between groups. Significantly (P < 0.01) higher plasma NEFA concentration was estimated in control than treatment groups in all stages. No significant difference was found for plasma concentrations of glucose, urea, and total protein. The coefficients of correlation indicated significant (P < 0.01) correlation among BCS, milk production, milk SCC, MCMT, pH, and EC. It can be concluded that reducing energy intake during far-off dry period can lead to achieve optimum BCS at calving. Suitable BCS at calving was beneficial to get higher milk production with improved quality, better maintenance of udder health and body condition of Jersey crossbred cows at tropical lower Gangetic region.

Effects of &amp;lt;i&amp;gt;γ&amp;lt;/i&amp;gt;-Polyglutamic Acid on Blood Glucose and Caecal Short Chain Fatty Acids in Adult Male Mice

γ-Polyglutamic acid (γ-PGA) is a major component of Natto. We hypothesized that γ-PGA could reduce postprandial glucose rise and plasma glucose levels. Mice were fed a 0.1% γ-PGA—containing diet or control diet for 91 days. Maltose and starch tolerance tests were performed, and plasma lipids, glucose levels, and caecal short chain fatty acids (SCFAs) were measured. Mice were co-administered γ-PGA and starch to suppress the initial rise in blood glucose levels. Blood glucose levels at 15 min were significantly lower in the PGA group than in the Con group (P 0.05). The plasma glucose level and NEFA level were also significantly lower in the PGA group (P 0.05), and caecal acetic acid/total caecal SCFAs ratio was significantly increased in the PGA group (P 0.05). Significant negative correlations existed between the caecal acetic acid/propionic acid ratio and the weight of visceral fat/BW (r = -0.57, P = 0.0318). Our results suggest that γ-PGA may effectively prevent metabolic syndrome by lowering blood glucose levels.