Plasma Free Fatty Acid Concentrations Research Articles

The Effect of Green Tea Extract on Fat Oxidation during 1hour Arm Cycle Exercise

PURPOSE: Decaffeinated Green Tea Extract (GTE) supplementation can increase fat oxidation during leg exercise, but many people cannot perform leg exercise. The purpose of this study was to investigate the effect of GTE supplementation on fat utilization during 1h arm cycle exercise. We hypothesized that GTE supplementation will increase lipolysis and fat oxidation. METHODS: This was a randomized, controlled, triple blind study with a crossover design. 8 healthy adults (4 females, 23-37yrs) performed an incremental arm cycle test to exhaustion followed by 4 time trials at fixed workloads. After an 8h fast subjects did 1h of arm cycling at 50% Wpeak. Subjects were randomly assigned to either decaffeinated GTE (650mg, 611mg EGCG) or placebo (PLA) for 4wks. Subjects then repeated the 1hr arm cycle trial. A 4wk washout period was followed by the corresponding crossover trial. 5ml of blood were drawn pre and post exercise while respiratory gases were collected continuously. Plasma glycerol and free fatty acid (FFA) concentrations were assessed with commercially available analysis kits. The study was powered at 1-β > 95%, with α = 0.05 given a reported effect size of F = 3.39 for the time by treatment interaction. RESULTS: Mean VO2 during all 1hr trials showed no significant differences (.83-.89 ± .19-.25 L/min, p = .460). Similarly, mean total energy expenditure (EE) showed no differences across all trials (264.58 - 266.15 kcal, p = .420). The percentage of total EE from fat oxidation was higher after GTE supplementation compared to PLA, but this difference was not significant (22.83 ± 11.57 to 25.38 ± 11.3 % vs. 23.39 ± 9.97 to 20.69 ± 8.9%, p = .532). There were no significant changes in g/min of fat oxidized between treatments before and after supplementation (GTE = .11 ± .08 to .12 ± .06 vs. PLA = .10 ± .05 to .09 ± .04, p = .220. Blood Glycerol concentration increased post exercise in all trails, with no significant differences between treatments (8.55 ± 3.44 mg/dl to 8.47 ± 2.6 vs. 10.05 ± 2.86 to 8.99 ± 3.51 mg/dl, p = .527). FFA concentration was also increased post exercise for both groups with no significant difference between treatments (8.30 ± 3.8 mg/dl to 8.69 ± 2.59 vs. 9.06 ± 4.49 to 7.16 ± 3.79, p = .234). CONCLUSION: These results suggest that there is no effect of 1m GTE supplementation on fat utilization during 1hr arm cycle exercise at 50% Wpeak.

The effect of dry period length and postpartum level of concentrate on milk production, energy balance, and plasma metabolites of dairy cows across the dry period and in early lactation

Shortening or omitting the dry period (DP) improves energy balance (EB) in early lactation because of a reduction in milk yield. Lower milk yield results in lower energy demands and requires less energy intake. The aim of this study was to evaluate the effects of DP length and concentrate level postpartum on milk yield, feed intake, EB, and plasma metabolites between wk -4 and 7 relative to calving of cows of second parity or higher. Holstein-Friesian dairy cows (n = 123) were assigned randomly to 1 of 2 DP lengths: 0-d DP (n = 81) or 30-d DP (n = 42). Prepartum, cows with a 0-d DP received a lactation ration based on grass silage and corn silage (6.4 MJ of net energy for lactation/kg of dry matter). Cows with a 30-d DP received a dry cow ration based on grass silage, corn silage, and straw (5.4 MJ of net energy for lactation/kg of dry matter). Postpartum, all cows received the same basal lactation ration as provided to lactating cows prepartum. Cows with a 0-d DP were fed a low level of concentrate up to 6.7 kg/d based on the requirement for their expected milk yield (0-d DP-L; n = 40) or the standard level of concentrate up to 8.5 kg/d (0-d DP-S; n = 41), which was equal to the concentrate level for cows with a 30-d DP (30-d DP-S; n = 42) based on requirements for their expected milk yield. Prepartum dry matter intake, concentrate intake, basal ration intake, energy intake, plasma β-hydroxybutyrate (BHB), and insulin concentrations were greater and plasma free fatty acids (FFA) and glucose concentrations were lower, but EB was not different in cows with a 0-d DP compared with cows with a 30-d DP. During wk 1 to 3 postpartum, milk fat yield and plasma BHB concentration were lower and dry matter intake and concentrate intake were greater in cows with a 0-d DP compared with cows with a 30-d DP. During wk 4 to 7 postpartum, fat- and protein-corrected milk (FPCM), lactose content, and lactose and fat yield were lower in 0-d DP-L or 0-d DP-S cows compared with 30-d DP-S cows. Basal ration intake, EB, body weight, plasma glucose, and insulin and insulin-like growth factor-1 concentrations were greater and plasma FFA and BHB concentrations were lower in 0-d DP-L and 0-d DP-S cows compared with 30-d DP-S cows. Concentrate and energy intake were lower in 0-d DP-L cows than in 0-d DP-S or 30-d DP-S cows. Milk yield and concentrations of plasma metabolites did not differ in wk 4 to 7, although EB was lower in wk 6 and 7 postpartum in 0-d DP-L cows than in 0-d DP-S cows. In conclusion, a 0-d DP reduced milk yield and improved EB and metabolic status of cows in early lactation compared with a 30-d DP. Reducing the postpartum level of concentrate of cows with a 0-d DP did not affect fat- and protein-corrected milk yield or plasma FFA and BHB concentrations in early lactation but did reduce EB in wk 6 and 7 postpartum.

Determinants of the increase in ketone concentration during SGLT2 inhibition in NGT, IFG and T2DM patients.

To examine metabolic factors that influence ketone production after sodium-glucose cotransport inhibitor (SGLT2) administration. Fasting plasma glucose (FPG), insulin, glucagon, free fatty acid and ketone concentrations were measured in 15 type 2 diabetes mellitus (T2DM) and 16 non-diabetic subjects before and at day 1 and day 14 after treatment with empagliflozin. Empagliflozin caused a 38 mg/dL reduction in FPG concentration in T2DM patients. However, it caused only a small but significant (7 mg/dL) reduction in the FPG concentration in impaired fasting glucose (IFG) subjects and did not affect FPG concentration in normal glucose tolerant (NGT) subjects. Empagliflozin caused a significant increase in mean plasma glucagon, free fatty acid (FFA) and ketone concentrations in T2DM subjects. However, empagliflozin did not cause a significant change in mean plasma insulin, glucagon or ketone concentrations in non-diabetic subjects. An index that integrates change in plasma glucose, insulin and FFA concentration at day 1 strongly correlates with plasma ketone concentration at day 1 (r = 0.85, P < .001) and day 14 (r = 0.63, r = 0.01) and predicts, with 86% sensitivity and 83% specificity, subjects at the top tertile for plasma ketone concentration after empagliflozin treatment. Results of the present study demonstrate that SGLT2 inhibition exerts different metabolic effects in non-diabetic individuals as compared to diabetic patients.

Interaction between plasma fetuin-A and free fatty acids predicts changes in insulin sensitivity in response to long-term exercise.

The hepatokine fetuin‐A can together with free fatty acids (FFAs) enhance adipose tissue (AT) inflammation and insulin resistance via toll‐like receptor 4 (TLR4). Although some of the health benefits of exercise can be explained by altered release of myokines from the skeletal muscle, it is not well documented if some of the beneficial effects of exercise can be explained by altered secretion of hepatokines. The aim of this study was to examine the effect of interaction between fetuin‐A and FFAs on insulin sensitivity after physical exercise. In this study, 26 sedentary men who underwent 12 weeks of combined endurance and strength exercise were included. Insulin sensitivity was measured using euglycemic‐hyperinsulinemic clamp, and AT insulin resistance was indicated by the product of fasting plasma concentration of FFAs and insulin. Blood samples and biopsies from skeletal muscle and subcutaneous AT were collected. Several phenotypic markers were measured, and mRNA sequencing was performed on the biopsies. AT macrophages were analyzed based on mRNA markers. The intervention improved hepatic parameters, reduced plasma fetuin‐A concentration (~11%, P < 0.01), slightly changed FFAs concentration, and improved glucose infusion rate (GIR) (~33%, P < 0.01) across all participants. The change in circulating fetuin‐A and FFAs interacted to predict some of the change in GIR (β = −42.16, P = 0.030), AT insulin resistance (β = 0.579, P = 0.003), gene expression related to TLR‐signaling in AT and AT macrophage mRNA (β = 94.10, P = 0.034) after exercise. We observed no interaction effects between FFAs concentrations and leptin and adiponectin on insulin sensitivity, or any interaction effects between Fetuin‐A and FFAs concentrations on skeletal muscle TLR‐signaling. The relationship between FFAs levels and insulin sensitivity seemed to be specific for fetuin‐A and the AT. Some of the beneficial effects of exercise on insulin sensitivity may be explained by changes in circulating fetuin‐A and FFAs, promoting less TLR4 signaling in AT perhaps by modulating AT macrophages.

Modeling of free fatty acid dynamics: insulin and nicotinic acid resistance under acute and chronic treatments

Nicotinic acid (NiAc) is a potent inhibitor of adipose tissue lipolysis. Acute administration results in a rapid reduction of plasma free fatty acid (FFA) concentrations. Sustained NiAc exposure is associated with tolerance development (drug resistance) and complete adaptation (FFA returning to pretreatment levels). We conducted a meta-analysis on a rich pre-clinical data set of the NiAc–FFA interaction to establish the acute and chronic exposure-response relations from a macro perspective. The data were analyzed using a nonlinear mixed-effects framework. We also developed a new turnover model that describes the adaptation seen in plasma FFA concentrations in lean Sprague–Dawley and obese Zucker rats following acute and chronic NiAc exposure. The adaptive mechanisms within the system were described using integral control systems and dynamic efficacies in the traditional I_{text{max}} model. Insulin was incorporated in parallel with NiAc as the main endogenous co-variate of FFA dynamics. The model captured profound insulin resistance and complete drug resistance in obese rats. The efficacy of NiAc as an inhibitor of FFA release went from 1 to approximately 0 during sustained exposure in obese rats. The potency of NiAc as an inhibitor of insulin and of FFA release was estimated to be 0.338 and 0.436 {upmu {text{M}}}, respectively, in obese rats. A range of dosing regimens was analyzed and predictions made for optimizing NiAc delivery to minimize FFA exposure. Given the exposure levels of the experiments, the importance of washout periods in-between NiAc infusions was illustrated. The washout periods should be sim2 h longer than the infusions in order to optimize 24 h lowering of FFA in rats. However, the predicted concentration-response relationships suggests that higher AUC reductions might be attained at lower NiAc exposures.

A maternal Western diet during gestation and lactation modifies offspring's microbiota activity, blood lipid levels, cognitive responses, and hippocampal neurogenesis in Yucatan pigs.

A suboptimal early nutritional environment (i.e., excess of energy, sugar, and fat intake) can increase susceptibility to diseases and neurocognitive disorders. The purpose of this study was to investigate in nonobese Yucatan minipigs (Sus scrofa) the impact of maternal diet [standard diet (SD) vs. Western diet (WD)] during gestation and 25 d of lactation on milk composition, blood metabolism, and microbiota activity of sows (n = 17) and their piglets (n = 65), and on spatial cognition (n = 51), hippocampal plasticity (n = 17), and food preferences/motivation (n = 51) in the progeny. Milk dry matter and lipid content, as well as plasma total cholesterol and free fatty acid (FFA) concentrations (P < 0.05) were higher in WD than in SD sows. Microbiota activity decreased in both WD sows and 100-d-old piglets (P < 0.05 or P < 0.10, depending on short-chain FAs [SCFAs]). At weaning [postnatal day (PND) 25], WD piglets had increased blood triglyceride and FFA levels (P < 0.01). Both SD and WD piglets consumed more of a known SD than an unknown high-fat and -sucrose (HFS) diet (P < 0.0001), but were quicker to obtain HFS rewards compared with SD rewards (P < 0.01). WD piglets had higher working memory (P = 0.015) and reference memory (P < 0.001) scores, which may reflect better cognitive abilities in the task context and a higher motivation for the food rewards. WD piglets had a smaller hippocampal granular cell layer (P = 0.03) and decreased neurogenesis (P < 0.005), but increased cell proliferation (P < 0.001). A maternal WD during gestation and lactation, even in the absence of obesity, has significant consequences for piglets' blood lipid levels, microbiota activity, gut-brain axis, and neurocognitive abilities after weaning.-Val-Laillet, D., Besson, M., Guérin, S., Coquery, N., Randuineau, G., Kanzari, A., Quesnel, H., Bonhomme, N., Bolhuis, J. E., Kemp, B., Blat, S., Le Huërou-Luron, I., Clouard, C. A maternal Western diet during gestation and lactation modifies offspring's microbiota activity, blood lipid levels, cognitive responses, and hippocampal neurogenesis in Yucatan pigs.

Repeated Prolonged Exercise Decreases Maximal Fat Oxidation in Older Men.

Fat metabolism and muscle adaptation was investigated in six older trained men (age, 61 ± 4 yr; V˙O2max, 48 ± 2 mL·kg·min) after repeated prolonged exercise). A distance of 2706 km (1681 miles) cycling was performed over 14 d, and a blood sample and a muscle biopsy were obtained at rest after an overnight fast before and 30 h after the completion of the cycling. V˙O2max and maximal fat oxidation were measured using incremental exercise tests. HR was continuously sampled during cycling to estimate exercise intensity. The daily duration of exercise was 10 h and 31 ± 37 min, and the mean intensity was 53% ± 1% of V˙O2max. Body weight remained unchanged. V˙O2max and maximal fat oxidation rate decreased by 6% ± 2% (P = 0.04) and 32% ± 8% (P < 0.01), respectively. The exercise intensity that elicits maximal fat oxidation was not significantly decreased. Plasma free fatty acid (FA) concentration decreased (P < 0.002) from 500 ± 77 μmol·L to 160 ± 38 μmol·L. Plasma glucose concentration as well as muscle glycogen, myoglobin, and triacylglycerol content remained unchanged. Muscle citrate synthase and ß-hydroxy-acyl-CoA-dehydrogenase activities were unchanged, but the protein expression of HKII, GLUT4, and adipose triacylglycerol lipase were significantly increased. Overall, the decreased maximal fat oxidation was probably due to lower exogenous plasma fatty acid availability and the muscle adaptation pattern indicates an increased glucose transport capacity and an increased muscle lipolysis capacity supporting an increased contribution of exogenous glucose and endogenous fat during exercise.

Energy metabolism in mobile, wild-sampled sharks inferred by plasma lipids.

Evaluating how predators metabolize energy is increasingly useful for conservation physiology, as it can provide information on their current nutritional condition. However, obtaining metabolic information from mobile marine predators is inherently challenging owing to their relative rarity, cryptic nature and often wide-ranging underwater movements. Here, we investigate aspects of energy metabolism in four free-ranging shark species (n=281; blacktip, bull, nurse, and tiger) by measuring three metabolic parameters [plasma triglycerides (TAG), free fatty acids (FFA) and cholesterol (CHOL)] via non-lethal biopsy sampling. Plasma TAG, FFA and total CHOL concentrations (in millimoles per litre) varied inter-specifically and with season, year, and shark length varied within a species. The TAG were highest in the plasma of less active species (nurse and tiger sharks), whereas FFA were highest among species with relatively high energetic demands (blacktip and bull sharks), and CHOL concentrations were highest in bull sharks. Although temporal patterns in all metabolites were varied among species, there appeared to be peaks in the spring and summer, with ratios of TAG/CHOL (a proxy for condition) in all species displaying a notable peak in summer. These results provide baseline information of energy metabolism in large sharks and are an important step in understanding how the metabolic parameters can be assessed through non-lethal sampling in the future. In particular, this study emphasizes the importance of accounting for intra-specific and temporal variability in sampling designs seeking to monitor the nutritional condition and metabolic responses of shark populations.

Nicotinic acid timed to feeding reverses tissue lipid accumulation and improves glucose control in obese Zucker rats[S

Nicotinic acid (NiAc) is a potent inhibitor of lipolysis, acutely reducing plasma free fatty acid (FFA) concentrations. However, a major FFA rebound is seen during rapid NiAc washout, and sustained exposure is associated with tolerance development, with FFAs returning to pretreatment levels. Our aim was to find a rational NiAc dosing regimen that preserves FFA lowering, sufficient to reverse nonadipose tissue lipid accumulation and improve metabolic control, in obese Zucker rats. We compared feeding-period versus fasting-period NiAc dosing for 5 days: 12 h subcutaneous infusion (programmable, implantable mini-pumps) terminated by gradual withdrawal. It was found that NiAc timed to feeding decreased triglycerides in liver (-47%; P < 0.01) and heart (-38%; P < 0.05) and reduced plasma fructosamine versus vehicle. During oral glucose tolerance test, plasma FFA levels were reduced with amelioration of hyperglycemia and hypertriglyceridemia. Furthermore, timing NiAc to feeding resulted in a general downregulation of de novo lipogenesis (DNL) genes in liver. By contrast, NiAc timed to fasting did not reduce tissue lipids, ameliorate glucose intolerance or dyslipidemia, or alter hepatic DNL genes. In conclusion, NiAc dosing regimen has a major impact on metabolic control in obese Zucker rats. Specifically, a well-defined NiAc exposure, timed to feeding periods, profoundly improves the metabolic phenotype of this animal model.

Glucose tolerance and free fatty acid metabolism in adults with variations in TCF7L2 rs7903146

ObjectiveTCF7L2 variant rs7903146 is associated with increased risk for type 2 diabetes. We investigated the effect of TCF7L2 variant rs7903146 and glucose tolerance on free fatty acid (FFA) metabolism. Research Design and MethodsWe recruited 120 individuals, half homozygous for the major CC allele and half homozygous for the minor TT allele at rs7903146; each underwent a 2-h, 75g oral glucose tolerance test (OGTT). Plasma glucose, insulin and free fatty acid concentrations were measured on blood collected before and during the OGTT. ResultsTotal FFA concentrations and percent FA species during OGTT were not different in CC and TT carriers when males and females were considered together. However, monounsaturated fatty acid (MUFA) concentrations and percentages were greater in TT than CC females during the OGTT. TT carriers with high HOMA-IR had significantly greater fasting FFA concentrations, lower disposition index (DI) and greater AUC of glucose than high HOMA-IR CC carriers, whereas no such differences were observed in the low HOMA-IR group. We found that fasting (826±25 vs. 634±22μmol/L, P<0.0001) and OGTT plasma FFA concentrations were greater in IGT than NGT subjects, and the difference remained after adjusting for sex, age, BMI, and genotype. Finally, IGT subjects had greater MUFA concentrations and percentages than NGT subjects during OGTT. ConclusionsDespite similar fasting insulin and glucose, fasting plasma FFA are greater in IGT than NGT adults. Insulin resistance and sex influence plasma FFA responses amongst carriers of the minor T allele of TCF7L2 rs7903146.

Proliferation and apoptosis in subcutaneous adipose tissue of lactating cows with different genetic merit for milk yield.

The aim of this study was to investigate the adipocyte size and fate in subcutaneous fat (scAT) of cows diverging for genetic merit at mid lactation stage, when anabolic activity increases and animals are in a state of positive energy balance. Twenty mid lactation cows (180±20days in milk) grouped according to the Estimated Breeding Values (EBV) for milk yield in plus (EBVp) and minus (EBVm) variants were selected. Average of adipocytes area, proliferation and apoptotic labelling index as well as DLK-1 expression, a marker of pre-adipocytes, were immunohistochemically evaluated in scAT biopsies. In EBVp cows, the BCS was lower (P<0.01) whereas milk yield, protein, fat yield (P<0.001) and plasma free fatty acid concentration (P<0.05) were higher. The scAT of EBVp cows showed a significantly (P<0.001) higher frequency between 500 and 3000μm2 classes in comparison to EBVm cows, that showed a significantly (P<0.01) higher apoptotic labeling index. The immunohistochemical reaction showed DLK-1 positivity in scAT of EBVp cows. Taking together, the data indicate a link between milk yield genetic merit of cows, scAT morphology and function, suggesting greater dynamics and metabolic flexibility in EBVp cows.

NAMPT-Mediated NAD+ Biosynthesis in Adipocytes Regulates Adipose Tissue Function and Multi-organ Insulin Sensitivity in Mice

Obesity is associated with adipose tissue dysfunction and multi-organ insulin resistance. However, the mechanisms of such obesity-associated systemic metabolic complications are not clear. Here, we characterized mice with adipocyte-specific deletion of nicotinamide phosphoribosyltransferase (NAMPT), a rate-limiting NAD(+) biosynthetic enzyme known to decrease in adipose tissue of obese and aged rodents and people. We found that adipocyte-specific Nampt knockout mice had severe insulin resistance in adipose tissue, liver, and skeletal muscle and adipose tissue dysfunction, manifested by increased plasma free fatty acid concentrations and decreased plasma concentrations of a major insulin-sensitizing adipokine, adiponectin. Loss of Nampt increased phosphorylation of CDK5 and PPARγ (serine-273) and decreased gene expression of obesity-linked phosphorylated PPARγ targets in adipose tissue. These deleterious alterations were normalized by administering rosiglitazone or a key NAD(+) intermediate, nicotinamide mononucleotide (NMN). Collectively, our results provide important mechanistic and therapeutic insights into obesity-associated systemic metabolic derangements, particularly multi-organ insulin resistance.

Postprandial Inflammatory Responses and Free Fatty Acids in Plasma of Adults Who Consumed a Moderately High-Fat Breakfast with and without Blueberry Powder in a Randomized Placebo-Controlled Trial

Background: Saturated fatty acids (FAs) released from triglyceride-rich lipoproteins (TGRLs) activate Toll-like receptor 2 (TLR-2) and induce the expression of proinflammatory cytokines in monocytes. Certain plant polyphenols inhibit TLR-mediated signaling pathways.Objective: We determined whether plasma free FAs (FFAs) after a moderately high-fat (MHF, 40% kcal from fat) breakfast modulate the inflammatory status of postprandial blood, and whether blueberry intake suppresses FFA-induced inflammatory responses in healthy humans.Methods: Twenty-three volunteers with a mean ± SEM age and body mass index (in kg/m2) of 30 ± 3 y and 21.9 ± 0.4, respectively, consumed an MHF breakfast with either a placebo powder or 2 or 4 servings of blueberry powder in a randomized crossover design. The placebo powder was provided on the first test day and the blueberry powder doses were randomized with a 2-wk washout period. Plasma concentrations of lipids, glucose, and cytokines were determined. To determine whether FFAs derived from TGRL stimulate monocyte activation, and whether this is inhibited by blueberry intake, whole blood was treated with lipoprotein lipase (LPL).Results: The median concentrations of FFAs and cytokines [tumor necrosis factor-α, interleukin (IL)-6 and IL-8] in postprandial plasma (3.5 h) decreased compared with fasting plasma regardless of the blueberry intake (P < 0.001 for FFAs and P < 0.05 for cytokines). However, concentrations of FFAs and cytokines including IL-1β increased in LPL-treated whole blood compared with untreated blood samples from participants who consumed the placebo powder. Blueberry intake suppressed IL-1β and IL-6 production in LPL-treated postprandial blood compared with the placebo control when fasting changes were used as a covariate.Conclusions: The plasma FFA concentration may be an important determinant affecting inflammatory cytokine production in blood. Supplementation with blueberry powder did not affect plasma FFA and cytokine concentrations; however, it attenuated the cytokine production induced by ex vivo treatment of whole blood with LPL. This trial was registered at clinicaltrials.gov as NCT01594008.

Association of Temperament and Acute Stress Responsiveness with Productivity, Feed Efficiency, and Methane Emissions in Beef Cattle: An Observational Study.

The aim of this study was to assess individual differences in temperament and stress response and quantify their impact on feed efficiency, performance, and methane (CH4) emissions in beef cattle. Eighty-four steers (castrated males) (Charolais or Luing) were used. Temperament was assessed using two standardized tests: restlessness when restrained [crush score (CS)] and flight speed (FS) on release from restraint. Over a 56-day period individual animal dry matter intake (DMI) and weekly body weight was measured. Ultrasound fat depth was measured at the end of 56 days. Average daily gain (ADG), feed conversion ratio (FCR), and residual feed intake (RFI) were calculated. After the 56-day test period, animals were transported in groups of six/week to respiration chamber facilities. Blood samples were taken before and 0, 3, 6, and 9 h after transport. Plasma cortisol, creatine kinase (CK), glucose, and free fatty acids (FFA) were determined to assess physiological stress response. Subsequently, CH4 emissions were measured over a 3-day period in individual respiration chambers. CS (1.7 ± 0.09) and FS (1.6 ± 0.60 m/s) were repeatable (0.63 and 0.51, respectively) and correlated (r = 0.36, P < 0.001). Plasma cortisol, CK, and FFA concentrations increased after transport (P = 0.038, P = 0.006, and P < 0.001, respectively). Temperament (CS) and CK concentration were correlated (r = 0.29; P = 0.015). The extreme group analysis reveals that excitable animals (FS; P = 0.032) and higher stress response (cortisol, P = 0.007; FFA, P = 0.007; and CK, P = 0.003) were associated with lower DMI. ADG was lower in more temperamental animals (CS, P = 0.097, and FS, P = 0.030). Fat depth was greater in steers showing calmer CS (P = 0.026) and lower plasma CK (P = 0.058). Temperament did not show any relationship with RFI or CH4 emissions. However, steers with higher cortisol showed improved feed efficiency (lower FCR and RFI) (P < 0.05) and greater CH4 emissions (P = 0.017). In conclusion, agitated temperament and higher stress responsiveness is detrimental to productivity. A greater stress response is associated with a reduction in feed intake that may both increase the efficiency of consumed feed and the ratio of CH4 emissions/unit of feed. Therefore, temperament and stress response should be considered when designing strategies to improve efficiency and mitigate CH4 emissions in beef cattle.

Transgenic Overexpression of Them1 in WAT Promotes Inflammation but not Insulin Resistance

BackgroundIn the setting of obesity, inflammation in white adipose tissue (WAT) may contribute to insulin resistance through the liberation of free fatty acids (FFA) and production of inflammatory cytokines. Thioesterase superfamily member 1 (Them1) is a fatty acyl‐CoA thioesterase that converts long chain fatty acyl‐CoAs to FFA and CoASH. It is highly expressed in brown adipose tissue (BAT), where it functions to suppress energy expenditure. Although basal levels in WAT are minimal, Them1 is upregulated in response to high fat feeding, suggesting a pathogenic role in insulin resistance. Them1−/−mice are resistant to high fat diet‐induced obesity and diabetes, exhibiting improved insulin sensitivity, an absence of macrophage infiltration in WAT and blunted inflammatory cytokine production. Whether these beneficial effects are primarily due to increased energy expenditure in BAT or the absence of Them1 in WAT is unknown.AimThis study was designed to assess whether transgenic overexpression of Them1 in WAT is sufficient to promote inflammation and insulin resistance.MethodsWe previously designed conditional Them1 transgenic (c‐Them 1Tg) mice with Cre recombinase‐dependent Them1 overexpression. Adipose‐specific Them1 transgenic (A‐Them 1Tg) mice were generated by breeding with Adiponectin‐cre mice on the same genetic background. Littermate c‐Them 1Tg were used as controls. Adipose‐specific overexpression of Them1 expression in WAT and BAT was confirmed by immunoblot analysis. Mice were fed chow or a high fat (60% of kcal) diet for 14 w. Body composition was determined by magnetic resonance spectroscopy. For tolerance tests (n=10 mice/group) to insulin (ITT) and glucose (GTT), plasma glucose concentrations were determined after fasting (6 h for ITT, 16 h for GTT) and periodically up to 120 min after i.p. injection of insulin (0.75 U/kg bw) or glucose (1 – 2 mg/g bw). Mice were allowed to recover for 7 d between tolerance tests. WAT was embedded in paraffin and subjected to H&amp;E or immunostaining using an F4/80 antibody. mRNA levels were determined by quantitative real‐time PCR and plasma concentrations of TNFα were determined by ELISA.ResultsWhereas total body weights and compositions did not differ in A‐Them 1Tg mice compared with c‐Them 1Tg controls on chow diet, high fat feeding increased body weights, as well as fat and lean body mass more for A‐Them 1Tg mice. Increased macrophage infiltration was observed in both chow and high fat fed A‐Them 1Tg mice, an effect supported by increased F4/80 mRNA expression and immunostaining. Whereas plasma FFA concentrations did not differ, TNFα concentrations were higher in chow fed A‐Them 1Tg mice. No differences were observed for GTT and ITT between A‐them 1Tg and c‐Them 1Tg mice fed either diet.ConclusionAdipose tissue specific overexpression of Them 1 in WAT is sufficient to promote inflammation, but not insulin resistance. These findings suggest that Them1 promotes obesity‐associated insulin resistance primarily by suppressing energy expenditure in BAT.Support or Funding InformationNIH DK056626 and DK103046

Effects of dry period length and dietary energy source on milk yield, energy balance, and metabolic status of dairy cows over 2 consecutive years: Effects in the second year

The objective of the current study was to evaluate the effect of dry period (DP) length on milk yield, energy balance (EB), and metabolic status in cows fed a lipogenic or glucogenic diet in the second year after implementation of DP and dietary treatments. Holstein-Friesian dairy cows (n=167) were assigned randomly to 1 of 3 DP lengths (0, 30, or 60d) and 1 of 2 early lactation diets (glucogenic or lipogenic) for 2 consecutive years. Results of the first year were reported previously. In the second year, 19 cows in the 0-d DP group were attributed to a new group (0→67d DP) because these cows had a milk yield of <4kg/d at least 30d before expected calving date and were dried off. Milk yield was recorded and EB was calculated from wk –8 to 9 relative to calving. Blood samples were taken weekly from wk –3 to 8 relative to calving. Liver samples were taken in wk –2, 2, and 4 relative to calving. At the onset of lactation, cows with a 0-d or 0→67-d DP had greater body condition score (BCS) than cows with a 60-d DP. During the first 9wk, cows with a 0- or 30-d DP produced 5.0 and 4.3kg less milk per day, respectively, but had similar EB compared with cows with a 60-d DP. Cows with a 0- or 30-d DP produced additional milk precalving, which could compensate milk yield losses in the first 9wk postcalving. Cows with a 0-d DP did not have milk yield losses or improve EB in the second year as much as in the first year. Cows with a 0-d DP had greater plasma insulin and insulin-like growth factor-I (IGF-I) and lower liver triacylglycerol concentrations than cows with other DP lengths. Cows with a 0→67-d DP had lower EB, and greater plasma free fatty acids (FFA) and β-hydroxybutyrate (BHB) concentrations than cows with other DP lengths. Feeding a glucogenic diet increased plasma glucose, IGF-I, and insulin concentrations, and decreased plasma FFA, BHB, and urea concentrations compared with a lipogenic diet, independent of DP length. In conclusion, omitting the DP or feeding a glucogenic diet improved metabolic status in early lactation of the second year after implementation of DP length and dietary treatments, although effects of omitting the DP were less pronounced in the second year than in the first year. The less pronounced improvement of EB in the second year was related to the high BCS at the onset of lactation and reduced milk yield losses in cows with a 0-d DP.

Maternal Glucose and Fatty Acid Kinetics and Infant Birth Weight in Obese Women With Type 2 Diabetes.

The objectives of this study were 1) to describe maternal glucose and lipid kinetics and 2) to examine the relationships with infant birth weight in obese women with pregestational type 2 diabetes during late pregnancy. Using stable isotope tracer methodology and mass spectrometry, maternal glucose and lipid kinetic rates during the basal condition were compared in three groups: lean women without diabetes (Lean, n = 25), obese women without diabetes (OB, n = 26), and obese women with pregestational type 2 diabetes (OB+DM, n = 28; total n = 79). Glucose and lipid kinetics during hyperinsulinemia were also measured in a subset of participants (n = 56). Relationships between maternal glucose and lipid kinetics during both conditions and infant birth weight were examined. Maternal endogenous glucose production (EGP) rate was higher in OB+DM than OB and Lean during hyperinsulinemia. Maternal insulin value at 50% palmitate Ra suppression (IC50) for palmitate suppression with insulinemia was higher in OB+DM than OB and Lean. Maternal EGP per unit insulin and plasma free fatty acid concentration during hyperinsulinemia most strongly predicted infant birth weight. Our findings suggest maternal fatty acid and glucose kinetics are altered during late pregnancy and might suggest a mechanism for higher birth weight in obese women with pregestational diabetes.

Plasma Free Fatty Acid as a Risk Factor for Cardiac Arrhythmias in Cases of Stable Angina and Acute Myocardial Infarction

Acute myocardial infarction carries a high mortality among cardiac patients. The discovery of the fact that certain enzymes like CPK, LDH liberated into circulation following necrosis of the myocardial cells came as boon for physicians and patients. There has been a constant search of different parameters for the diagnosis and management of Coronary Artery Diseases (CAD). The present study was undertaken to investigate a possible relation between the changes in plasma free fatty acid (FFA) concentration and incidence of cardiac arrhythmia in patients with coronary artery disease. Fifty cases (25 males and 25 females) of acute myocardial infarction were selected for the present study. All the patients were in the age group of 40–70 years. For the control group fifty (25 male and 25 female) subjects of same age group were selected from patient's relatives and friends. Plasma free fatty acid concentration was estimated by Titrametric method of Trout et al. (1960), a modified version of Dole (1956). Statistical Analysis: The statistical analysis of the data of the present study was done by using SPSS, version 14.0.1 was used. Our study showed that the patients with a striking elevation (above 1200 μeq/L) had an increased prevalence of serious arrhythmias and disorder of conduction. On the basis of present study, it is worth to say that in all cases with high level of serum free fatty acid should be closely monitored for early and timely detection of development of various cardiac arrhythmias.

Lauric Acid Stimulates Ketone Body Production in the KT-5 Astrocyte Cell Line.

Coconut oil has recently attracted considerable attention as a potential Alzheimer's disease therapy because it contains large amounts of medium-chain fatty acids (MCFAs) and its consumption is thought to stimulate hepatic ketogenesis, supplying an alternative energy source for brains with impaired glucose metabolism. In this study, we first reevaluated the responses of plasma ketone bodies to oral administration of coconut oil to rats. We found that the coconut oil-induced increase in plasma ketone body concentration was negligible and did not significantly differ from that observed after high-oleic sunflower oil administration. In contrast, the administration of coconut oil substantially increased the plasma free fatty acid concentration and lauric acid content, which is the major MCFA in coconut oil. Next, to elucidate whether lauric acid can activate ketogenesis in astrocytes with the capacity to generate ketone bodies from fatty acids, we treated the KT-5 astrocyte cell line with 50 and 100 μM lauric acid for 4 h. The lauric acid treatments increased the total ketone body concentration in the cell culture supernatant to a greater extent than oleic acid, suggesting that lauric acid can directly and potently activate ketogenesis in KT-5 astrocytes. These results suggest that coconut oil intake may improve brain health by directly activating ketogenesis in astrocytes and thereby by providing fuel to neighboring neurons.

Free fatty acid as an outcome predictor of atrial fibrillation-associated stroke.

We investigated whether baseline plasma free fatty acid (FFA) concentration is associated with any (ischemic/hemorrhagic) stroke, ischemic stroke/systemic embolism (ISSE), or ischemic stroke among stroke survivors with atrial fibrillation (A-fib). Moreover, we compared the outcome predictability of FFA with previously adopted models, including the CHADS2 and CHA2 DS2 -VASc scoring systems. We analyzed data from 279 stroke patients with A-fib and investigated the association between plasma FFA concentration and outcomes using Cox regression models with competing risk analyses. Median follow-up period was 17.5 months. During the study period, any stroke, ISSE, and ischemic stroke occurred in 22, 21, and 17 patients, respectively. The cumulative risk for any stroke, ISSE, and ischemic stroke were 5.1%, 4.7%, and 4.2% at the end of the first year and 14.8%, 12.1%, and 10.8% at the end of the third year, respectively. After adjusting covariates (model 1), baseline FFA concentration was associated with recurrence of any stroke (hazard ratio [HR] = 1.774, 95% confidence interval [CI] = 1.124-2.801, per 1mEq/l increment of FFA). FFA showed a trend association with ISSE (HR = 1.569, 95% CI = 0.950-2.592) and ischemic stroke (HR = 1.630, 95% CI = 0.967-2.746). In adjusted models including CHADS2 or CHA2 DS2 -VASc score as a covariate, (models 2 and 3) FFA was still shown to be an independent predictor of any stroke and ischemic stroke. There was a significant or trend association between FFA and ISSE. FFA may be a potential biomarker that predicts outcome events in stroke with A-fib along with the CHADS2 and CHA2 DS2 -VASc scoring systems.