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It had been observed that homozygous albumin knockout mice (Alb−/−) exhibit low plasma free fatty acid (FFA) concentration and improved blood glucose regulation. However, it was not yet known to what extent heterozygous albumin knockout (Alb+/−) mice would display a similar phenotype. Alb−/−, Alb+/−, and wild-type (WT) female mice were studied on a low-fat diet (LFD) or high-fat diet (HFD). On both diets, decreased plasma FFA concentration, and improved glucose tolerance test were observed in Alb−/−, but not in Alb+/−, compared to WT. Plasma adiponectin concentration showed greater elevation in Alb−/− than Alb+/−. Consistent with that, adiponectin gene expression was significantly higher in Alb−/− mice than in Alb+/− and WT mice. A dose-dependent response was observed for hepatic Acadl gene expression showing higher Acadl gene expression in Alb−/− mice than in Alb+/− and WT mice. In conclusion, although female Alb+/− mice exhibited some slight differences from WT mice (e.g., increased plasma adiponectin and hepatic Acadl gene expression), Alb+/− mice did not exhibit improved glucoregulation in comparison to WT mice, indicating that a minor suppression of albumin expression is not sufficient to improve glucoregulation. Furthermore, it is now clear that although the response of female mice to HFD might be unique from how males generally respond, still the complete albumin deficiency in Alb−/− mice and the associated FFA reduction is capable of improving glucoregulation in females on this diet. The present results have implications for the role of albumin and FFA in the regulation of metabolism. [ABSTRACT FROM AUTHOR]

Abstract It had been observed that homozygous albumin knockout mice (Alb −/−) exhibit low plasma free fatty acid (FFA) concentration and improved blood glucose regulation. However, it was not yet known to what extent heterozygous albumin knockout (Alb +/−) mice would display a similar phenotype. Alb −/−, Alb +/−, and wild-type (WT) female mice were studied on a low-fat diet (LFD) or high-fat diet (HFD). On both diets, decreased plasma FFA concentration, and improved glucose tolerance test were observed in Alb−/−, but not in Alb +/−, compared to WT. Plasma adiponectin concentration showed greater elevation in Alb −/− than Alb +/−. Consistent with that, adiponectin gene expression was significantly higher in Alb −/− mice than in Alb +/− and WT mice. A dose-dependent response was observed for hepatic Acadl gene expression showing higher Acadl gene expression in Alb −/− mice than in Alb +/− and WT mice. In conclusion, although female Alb +/− mice exhibited some slight differences from WT mice (e.g., increased plasma adiponectin and hepatic Acadl gene expression), Alb +/− mice did not exhibit improved glucoregulation in comparison to WT mice, indicating that a minor suppression of albumin expression is not sufficient to improve glucoregulation. Furthermore, it is now clear that although the response of female mice to HFD might be unique from how males generally respond, still the complete albumin deficiency in Alb −/− mice and the associated FFA reduction is capable of improving glucoregulation in females on this diet. The present results have implications for the role of albumin and FFA in the regulation of metabolism.

The adoption of various practices for higher milk production from the animals is very pertinent, which generally increases peripartum disorders. In the period of transition phase (3 weeks before parturition and 3 weeks after parturition), an animal is in huge demand of energy for the developing fetus, colostrum production, and subsequent milk production for the postnatal development of the calf, and thus animals undergo a complex set of physiological and metabolic adaptations. The transition stress drastically has an impact on immunological function which leads the metabolic disorders in animals. In many experiments, it has been reported that immune dysfunction causes early lactation disorders during the period around the dryoff. The stress and dietary changes occur during the period of transition phase which may affect immunity, metabolic and physio-biochemical changes which finally affect the productive efficiency of animals. Several nutritional strategies and mental strategies have been adopted to minimize the detrimental consequences on the immune system during the transition phase. A suitable environment and a healthy balanced diet should be given to the transition cow to minimize transition phase challenges. Just after parturition, Dry matter (DM) consumption increases more slowly than milk energy output, therefore the animals cannot meet their nutritional needs only through feed consumption. During the last 3 weeks of pregnancy, nutrient demands by the fetal calf and placenta are at their greatest, and in a few animals, DM consumption may decrease by 10 to 30% as compared with consumption during the initial phase of the dry period. In such conditions, animals are exposed to negative energy balance and most of the animals attempt to make up energy balance by lipolysis of stored body fat. This leads to an increase in the non-esterified fatty acid (NEFA) in the blood and further, there is an accumulation of NEFAS in the liver causing fatty liver, which in turn stimulates cytokines. Cytokines activate receptors on different target cells leading to systemic inflammatory reactions resulting in several biochemical changes, such as elevated glucocorticoid and adrenocorticotrophic hormone production, the stimulation of the blood clotting process, decreased serum concentrations of calcium, zinc, copper, iron, and vitamin E. Ascorbic acid and vitamin E are typical antioxidant substances that break the chain of lipid radicals and transform them into more stable metabolites. Cu-Zn superoxide dismutase (SOD) and ceruloplasmin are two enzymes that copper and zinc are involved in, and these enzymes participate in the antioxidant system. In the cytosol, superoxide radicals are transformed into hydrogen peroxide by Cu-Zn SOD. Selenium aids in boosting neutrophil activity. Just before parturition, there is an increase in the level of serum cortisol and estrogen, which suppresses the immunity of animals by reducing the phagocytic index and lymphocyte proliferation in the animals. The animals become immune compromised and under such situations animals used to have different types of metabolic diseases viz, metritis, mastitis and retained placenta. The successful transition phase is of prime importance and concern to animal keepers by reducing macro-mineral deficiencies, lipid mobilization and immune suppression. The animal owner can get rid of transition problems of animals by supplementation of Vit E, Se, Cu, Zn, Chromium and 20-25% additional energy. This supplement may help animals to pass the transition phase successfully with minimal incidence of having metabolic diseases like mastitis, metritis and retained placenta. Further, it improves the quality of colostrums and milk and subsequently promotes the growth and health of newborn calves. [ABSTRACT FROM AUTHOR]

Aim: Non-esterified fatty acids (NEFA) are potential targets for prevention of key cardiometabolic diseases of aging, but their population-level correlates remain uncertain. We sought to identify modifiable factors associated with fasting and post-load NEFA levels in older adults. Methods: We used linear regression to determine the cross-sectional associations of demographic, anthropometric, and lifestyle characteristics and medication use with serum fasting and post-load NEFA concentrations amongst community-dwelling older adults enrolled in the Cardiovascular Health Study (n = 1924). Results: Fasting NEFA levels generally demonstrated a broader set of determinants, while post-load NEFA were more consistently associated with metabolic factors. Waist circumference and weight were associated with higher fasting and post-load NEFA. Cigarette smoking and caffeine intake were associated with lower levels of both species, and moderate alcohol intake was associated with higher fasting levels whereas greater consumption was associated with lower post-load levels. Unique factors associated with higher fasting NEFA included female sex, higher age, loop and thiazide diuretic use and calcium intake, while factors associated with lower fasting levels included higher educational attainment, beta-blocker use, and protein intake. Hours spent sleeping during the daytime were associated with higher post-load NEFA, while DASH score was associated with lower levels. Conclusion: Fasting and post-load NEFA have both common and unique modifiable risk factors, including sociodemographics, anthropometric, medications, and diet. Post-load NEFA were particularly sensitive to metabolic factors, while a broader range of determinants were associated with fasting levels. These factors warrant study as targets for lowering levels of NEFA in older adults.

Serum albumin facilitates the transport of free fatty acids (FFAs) from adipose tissue to other organs. It was not known if impeding this process could protect from hepatic steatosis and metabolic dysfunction in obesity. We tested whether albumin knockout (Alb−/−) mice would exhibit a reduction in plasma FFA concentration, reduced hepatic lipid accumulation, and improved glucoregulation as compared to wild-type (WT) mice. Male homozygous albumin knockout mice (Alb−/−) and WT controls were fed a low-fat diet (LFD) or high-fat diet (HFD). Alb−/− mice exhibited a similar body weight gain and body composition as WT on both diets. Despite HFD-induced obesity, Alb−/− mice were protected from various comorbidities. Compared to WT mice on the HFD, Alb−/− exhibited lower plasma FFA levels, lower blood glucose levels during glucose tolerance and insulin tolerance tests, and lower hepatic steatosis and inflammation. Alb−/− mice on HFD also exhibited elevated expression of multiple genes in the liver and adipose tissues, such as peroxisome proliferator-activated receptor α in both tissues, as well as glucose transporter-4 and adiponectin in adipose tissues. The results indicate that albumin's FFA transport function may be involved in the development of hepatic lipid accumulation and dysregulated glucose metabolism in obesity. [ABSTRACT FROM AUTHOR]

Abstract Aims/Introduction Understanding morning–evening variation in metabolic state is critical for managing metabolic disorders. We aimed to characterize this variation from the viewpoints of insulin secretion and insulin sensitivity, including their relevance to the circadian rhythm. Materials and Methods A total of 14 and 10 people without diabetes were enrolled, and underwent a 75‐g oral glucose tolerance test (OGTT) and hyperinsulinemic‐euglycemic clamp study, respectively. Participants completed the OGTT or hyperinsulinemic‐euglycemic clamp at 08.00 hours and 20.00 hours in random order. Before each study, hair follicles were collected. In mice, phosphorylation levels of protein kinase B were examined in the liver and muscle by western blotting. Results Glucose tolerance was better at 08 .00 hours, which was explained by the higher 1‐h insulin secretion on OGTT and increased skeletal muscle insulin sensitivity on hyperinsulinemic‐euglycemic clamp. Hepatic insulin sensitivity, estimated by the hepatic insulin resistance index on OGTT, was better at 20.00 hours. The 1‐h insulin secretion and hepatic insulin resistance index correlated significantly with Per2 messenger ribonucleic acid expression. The change (evening value – morning value) in the glucose infusion rate correlated significantly with the change in non‐esterified fatty acid, but not with clock gene expressions. The change in non‐esterified fatty acid correlated significantly with E4bp4 messenger ribonucleic acid expression and the change in cortisol. In mice, phosphorylation of protein kinase B was decreased in the liver and increased in muscle in the beginning of the active period as, expected from the human study. Conclusions Glucose metabolism in each tissue differed between the morning and evening, partly reflecting lipid metabolism, clock genes and cortisol levels. Deeper knowledge of these associations might be useful for ameliorating metabolic disorders.

Non-esterified fatty acid (NEFA), one of negative energy balance (NEB)'s most well-known products, has a significant impact on cows' reproductive potential. Our study used an in vitro model to investigate the deleterious effects of NEFA on bovine granulosa cells (BGCs) and its underlying molecular mechanism. The results showed that high levels of NEFA led to the accumulation of reactive oxygen species (ROS), increased the expression of apoptosis-related factors such as Bcl2-Associated X/B-cell lymphoma-2 (Bax/Bcl-2) and Caspase-3, and down-regulated steroid synthesis-related genes such as sterol regulatory element binding protein 1 (SREBP-1), cytochrome P450c17 (CYP17), and cytochrome P450 aromatase (CYP19), to promote oxidative stress, cell apoptosis, and steroid hormone synthesis disorders in BGCs. In addition, NEFA significantly inhibited phosphatidylinositol 3-kinase (PI3K) and phosphorylated protein kinase B (p-AKT) activity and increased forkhead box O1 (FoxO1) expression. To further explore the role of the PI3K/AKT/FoxO1 signaling pathway in NEFA, we found that pretreatment with AKT-specific activator SC79 (5 mg/mL) for 2 h or transfection with FoxO1 knockdown siRNA in BGCs could alleviate the negative effects of NEFA treatment by decreasing Bax/Bcl-2 ratio and Caspase-3 expression, and upregulating SREBP-1, CYP17, and CYP19 expression. Meanwhile, SC79 significantly inhibited NEFA-induced dephosphorylation and massive nuclear translocation of FoxO1. Taken together, the NEFA induced oxidative stress, apoptosis, and steroid hormone synthesis disorders in BGCs by inhibiting the PI3K/AKT pathway that regulates FoxO1 phosphorylation and nuclear translocation. Our findings help to clarify the molecular mechanisms underlying the negative effects of high levels of NEFA on BGCs. [ABSTRACT FROM AUTHOR]

Aims/Introduction Understanding morning–evening variation in metabolic state is critical for managing metabolic disorders. We aimed to characterize this variation from the viewpoints of insulin secretion and insulin sensitivity, including their relevance to the circadian rhythm. Materials and Methods A total of 14 and 10 people without diabetes were enrolled, and underwent a 75‐g oral glucose tolerance test (OGTT) and hyperinsulinemic‐euglycemic clamp study, respectively. Participants completed the OGTT or hyperinsulinemic‐euglycemic clamp at 08.00 hours and 20.00 hours in random order. Before each study, hair follicles were collected. In mice, phosphorylation levels of protein kinase B were examined in the liver and muscle by western blotting. Results Glucose tolerance was better at 08.00 hours, which was explained by the higher 1‐h insulin secretion on OGTT and increased skeletal muscle insulin sensitivity on hyperinsulinemic‐euglycemic clamp. Hepatic insulin sensitivity, estimated by the hepatic insulin resistance index on OGTT, was better at 20.00 hours. The 1‐h insulin secretion and hepatic insulin resistance index correlated significantly with Per2 messenger ribonucleic acid expression. The change (evening value – morning value) in the glucose infusion rate correlated significantly with the change in non‐esterified fatty acid, but not with clock gene expressions. The change in non‐esterified fatty acid correlated significantly with E4bp4 messenger ribonucleic acid expression and the change in cortisol. In mice, phosphorylation of protein kinase B was decreased in the liver and increased in muscle in the beginning of the active period as, expected from the human study. Conclusions Glucose metabolism in each tissue differed between the morning and evening, partly reflecting lipid metabolism, clock genes and cortisol levels. Deeper knowledge of these associations might be useful for ameliorating metabolic disorders. [ABSTRACT FROM AUTHOR]

Background and Aim: Many metabolic and immunological changes occur during the transition period. Innate immunity plays an important role against to infections and natural antibodies (NAb) are important in immunity. This study aims to determine a connection between serum NAb titers, beta-hydroxybutyric acid (BHBA), and non-esterified fatty acid (NEFA) concentrations in Tuj and Hemsin sheep during the peripartum period. Materials and Methods: Serum NAb, BHBA, and NEFA levels were determined from the blood samples collected from Tuj and Hemsin sheep on days 30 and 15 before birth, on the day of birth (day 0), and on days 15 and 30 after birth. Results: NAb titers were found to be higher in Tuj than in Hemsin sheep (p0.05). The serum NEFA level was lower in Tuj sheep in the last 15 days of pregnancy compared to Hemsin sheep (p

Background and Aim: Data about dynamics of serum biochemical parameters and negative energy balance (NEB) related conditions differ among geographical areas or farm types. It should be cautious about applying those data to justify control and prevention strategies of NEB problems. Therefore, dynamics of blood biochemical parameters related to NEB condition of peripartum dairy cows raised in either smallholder (SH) or semi-commercial (SC) farms were studied. Materials and Methods: Thirty-two healthy pregnant dry cows were selected from five dairy farms in Western part of Thailand, including 15 and 17 cows from three SH and two SC farms, respectively. Blood samples were collected at 2 weeks before the expected calving date, and 1, 2, 4, and 8 weeks postpartum to determine concentrations of glucose, non-esterified fatty acid (NEFA), and β-hydroxybutyrate (BHBA). Body condition scores (BCSs) and milk yields were also recorded. Results: Dairy cows in both farm types suffered from NEB by elevation of serum NEFA and BHBA, and loss of BCS postpartum. Degrees of elevation in serum NEFA and BHBA were different between farm types. The SC cows showed more BCS loss postpartum, but lower serum NEFA. In the SH cows, even with less BCS loss, the cows showed high serum NEFA concentrations. Conclusion: Dairy cows in our study entered NEB condition even with low milk yields. Moreover, elevation of serum NEFA and BHBA postpartum was higher in our studied cows as compared with other studies in high producing cows of commercial dairy farms in temperate areas.

Serum albumin facilitates the transport of free fatty acids (FFAs) from adipose tissue to other organs. It was not known if impeding this process could protect from hepatic steatosis and metabolic dysfunction in obesity. We tested whether albumin knockout (Alb−/−) mice would exhibit a reduction in plasma FFA concentration, reduced hepatic lipid accumulation, and improved glucoregulation as compared to wild-type (WT) mice. Male homozygous albumin knockout mice (Alb−/−) and WT controls were fed a low-fat diet (LFD) or high-fat diet (HFD). Alb−/− mice exhibited a similar body weight gain and body composition as WT on both diets. Despite HFD-induced obesity, Alb−/− mice were protected from various comorbidities. Compared to WT mice on the HFD, Alb−/− exhibited lower plasma FFA levels, lower blood glucose levels during glucose tolerance and insulin tolerance tests, and lower hepatic steatosis and inflammation. Alb−/− mice on HFD also exhibited elevated expression of multiple genes in the liver and adipose tissues, such as peroxisome proliferator-activated receptor α in both tissues, as well as glucose transporter-4 and adiponectin in adipose tissues. The results indicate that albumin’s FFA transport function may be involved in the development of hepatic lipid accumulation and dysregulated glucose metabolism in obesity.

Non-esterified fatty acid (NEFA), one of negative energy balance (NEB)’s most well-known products, has a significant impact on cows’ reproductive potential. Our study used an in vitro model to investigate the deleterious effects of NEFA on bovine granulosa cells (BGCs) and its underlying molecular mechanism. The results showed that high levels of NEFA led to the accumulation of reactive oxygen species (ROS), increased the expression of apoptosis-related factors such as Bcl2-Associated X/B-cell lymphoma-2 (Bax/Bcl-2) and Caspase-3, and down-regulated steroid synthesis-related genes such as sterol regulatory element binding protein 1 (SREBP-1), cytochrome P450c17 (CYP17), and cytochrome P450 aromatase (CYP19), to promote oxidative stress, cell apoptosis, and steroid hormone synthesis disorders in BGCs. In addition, NEFA significantly inhibited phosphatidylinositol 3-kinase (PI3K) and phosphorylated protein kinase B (p-AKT) activity and increased forkhead box O1 (FoxO1) expression. To further explore the role of the PI3K/AKT/FoxO1 signaling pathway in NEFA, we found that pretreatment with AKT-specific activator SC79 (5 mg/mL) for 2 h or transfection with FoxO1 knockdown siRNA in BGCs could alleviate the negative effects of NEFA treatment by decreasing Bax/Bcl-2 ratio and Caspase-3 expression, and upregulating SREBP-1, CYP17, and CYP19 expression. Meanwhile, SC79 significantly inhibited NEFA-induced dephosphorylation and massive nuclear translocation of FoxO1. Taken together, the NEFA induced oxidative stress, apoptosis, and steroid hormone synthesis disorders in BGCs by inhibiting the PI3K/AKT pathway that regulates FoxO1 phosphorylation and nuclear translocation. Our findings help to clarify the molecular mechanisms underlying the negative effects of high levels of NEFA on BGCs.

Objective The purpose of this study was to determine the effects of feeding ethanol on growth performances, carcass characteristics, and lipid metabolism of finishing Korean cattle (Hanwoo) steers. Methods Thirty (30) Hanwoo steers (average 25.1 months of age, body weight 660.1 kg) were assigned to three treatments: control (0% ethanol), E-3 (1.44% ethanol for 3 months), or E-5 (0.72% ethanol for 2 months followed by 1.44% ethanol for 3 months). The animals were allotted by treatment group into six pens and fed concentrate and perennial ryegrass. Ethanol (30%, v/v) was supplemented into drinking water twice a day to meet final concentrations based on average water consumption of finishing Hanwoo steers. Results There were no statistical differences among the groups in final body weight, average daily gain, or carcass yield grade indices such as cold carcass weight, fat thickness, and loin area. The marbling score tended (p = 0.228) to increase with the highest score (6.7) in the E-5 group followed by 6.3 and 6.0 in E-3 and control groups, respectively. The appearance frequencies of quality grades of 1++ (the best), 1+, 1, and 2, were; 30%, 50%, 0%, and 20% for control, 10%, 80%, 10%, and 0% for E-3, and 10%, 80%, 0%, and 10% for E-5 groups, respectively, indicating improvements of quality grades by feeding ethanol. Concentrations of serum glucose tended to decrease whereas those of insulin and non-esterified fatty acid to increase by feeding ethanol (E-3 and E-5; p>0.05). Conclusion Feeding ethanol directly into drinking water of finishing Hanwoo steers stimulated lipogenesis in intramuscular adipose tissue (marbling) and thereby improved carcass quality grade. The serum metabolites results supported the hypothesis of lipolysis of existing adipose tissue, such as abdominal fats, and lipogenesis in intramuscular adipocytes.

Under current Australian industry pre-slaughter guidelines, lambs may be off feed for up to 48 h before slaughter. The purpose of this study was to examine what proportion of circulating metabolites at slaughter are due to stress and feed deprivation and if this response differs between Merino and Terminal genotypes. In addition the effect of feed deprivation on carcass weight and meat quality was examined. Jugular blood samples were collected from 88 Merino and Terminal sired lambs at rest and at slaughter following 24, 36 and 48 h of feed deprivation and plasma analysed for glucose, lactate, non-esterified fatty acids (NEFA) and β-hydroxybutyrate (BHOB). From the same carcasses hot carcass weight (HCWT) were measured as well as a suite of meat quality traits measured such as M. longissimus lumborum (loin) and M. semitendinosus pH at 24 h postmortem. Loin samples were also analysed for intramuscular fat content and Warner–Bratzer Shear Force. Merino sired lambs had a higher NEFA response compared to Terminal sired lambs at slaughter after 24, 36 and 48 h of feed deprivation, with NEFA levels up to 35% higher than previously reported in the same animals at rest in animal house conditions, whereas BHOB response to feed deprivation was not affected by sire type (P>0.05) and similar to previously reported at rest. In addition to the metabolic effects, increasing feed deprivation from 36 h was associated with a 3% reduction in HCWT and dressing percentage as well as causing increased ultimate pH in the M. semitendinosus in Merino sired lambs. Findings from this study demonstrate that Merino and Terminal sired lambs differ in their metabolic response to feed deprivation under commercial slaughter conditions. In addition, commercial feed deprivation appears to have a negative effect on ultimate pH and carcass weight and warrants further investigation.

Crossbreed F1 Holstein x Gyr cows are proving to be a good alternative for milk production under tropical conditions. In order to contribute to that affirmative, our work focused on clarifying the metabolic patter of F1 Holstein x Gyr dairy cows during the most critical time in the lactation cycle, the transition period, and to compare their performance in two seasons. Blood sampling was performed on 15 cows during summer (January to April) and on 13 cows during winter (May to August), beginning three weeks before the estimated calving date, until 30 days relative to calving. The season had a great influence on the metabolic status. Almost all evaluated metabolites, with exception for aminotransferase (AST), non-esterified fatty acids (NEFA) and beta-hydroxybutyrate (BHBA), that have shown no variation among seasons, demonstrated a different patter between summer and winter. Liver functions were enhanced during the postpartum, with increased liver enzymes activity and increased concentration of cholesterol and BHB. Animals went through negative energy balance (NEB) and an alarming number of animals had experienced subclinical ketosis and high NEFA concentrations.

Background and Aim: Many metabolic and immunological changes occur during the transition period. Innate immunity plays an important role against to infections and natural antibodies (NAb) are important in immunity. This study aims to determine a connection between serum NAb titers, beta-hydroxybutyric acid (BHBA), and non-esterified fatty acid (NEFA) concentrations in Tuj and Hemşin sheep during the peripartum period. Materials and Methods: Serum NAb, BHBA, and NEFA levels were determined from the blood samples collected from Tuj and Hemşin sheep on days 30 and 15 before birth, on the day of birth (day 0), and on days 15 and 30 after birth. Results: NAb titers were found to be higher in Tuj than in Hemşin sheep (p<0.001). No statistically significant difference was found in serum BHBA concentrations of both breeds on all sampling days (p>0.05). The serum NEFA level was lower in Tuj sheep in the last 15 days of pregnancy compared to Hemşin sheep (p<0.05), while no difference was found in samples collected at the other time points. Conclusion: This study indicated that serum NAb titers significantly changed in Tuj and Hemşin sheep during the transition period. Serum BHBA and NEFA concentrations increased during the last stages of pregnancy and decreased after birth. Based on these findings, it is suggested that the immunological status could vary by the breed of sheep or various factors that affect the sheep's metabolic state. [ABSTRACT FROM AUTHOR]

Background and Aim: Data about dynamics of serum biochemical parameters and negative energy balance (NEB) related conditions differ among geographical areas or farm types. It should be cautious about applying those data to justify control and prevention strategies of NEB problems. Therefore, dynamics of blood biochemical parameters related to NEB condition of peripartum dairy cows raised in either smallholder (SH) or semi-commercial (SC) farms were studied. Materials and Methods: Thirty-two healthy pregnant dry cows were selected from five dairy farms in Western part of Thailand, including 15 and 17 cows from three SH and two SC farms, respectively. Blood samples were collected at 2 weeks before the expected calving date, and 1, 2, 4, and 8 weeks postpartum to determine concentrations of glucose, non-esterified fatty acid (NEFA), and ß-hydroxybutyrate (BHBA). Body condition scores (BCSs) and milk yields were also recorded. Results: Dairy cows in both farm types suffered from NEB by elevation of serum NEFA and BHBA, and loss of BCS postpartum. Degrees of elevation in serum NEFA and BHBA were different between farm types. The SC cows showed more BCS loss postpartum, but lower serum NEFA. In the SH cows, even with less BCS loss, the cows showed high serum NEFA concentrations. Conclusion: Dairy cows in our study entered NEB condition even with low milk yields. Moreover, elevation of serum NEFA and BHBA postpartum was higher in our studied cows as compared with other studies in high producing cows of commercial dairy farms in temperate areas. [ABSTRACT FROM AUTHOR]

Purpose: Genetic differences in desaturase genes and consequently fatty acid metabolism have been reported. The aims were to examine ethnic differences in serum fatty acid composition and desaturase indices, and assess the ethnic-specific associations with insulin sensitivity (IS) and liver fat in black and white South African (SA) women.Methods: In this cross-sectional study including 92 premenopausal black (n = 46) and white (n = 46) SA women, serum fatty acid composition was measured in cholesteryl ester (CE) and nonesterified fatty acid (NEFA) fractions. Desaturase activities were estimated as product-to-precursor ratios: stearoyl-CoA desaturase-1 (SCD1-16, 16:1n-7/16:0); δ-5 desaturase (D5D, 20:4n-6/20:3n-6), and δ-6 desaturase (D6D, 18:3n-6/18:2n-6). Whole-body IS was estimated from an oral glucose tolerance test using the Matsuda index. In a subsample (n = 30), liver fat and hepatic IS were measured by 1H-magnetic resonance spectroscopy and hyperinsulinemic euglycemic clamp, respectively.Results: Despite lower whole-body IS (P = .006), black women had higher CE D5D and lower D6D and SCD1-16 indices than white women (P < .01). CE D6D index was associated with lower IS in white women only (r = -0.31, P = .045), whereas D5D index was associated with higher IS in black women only (r = 0.31, P = .041). In the subsample, D6D and SCD1-16 indices were positively and D5D was negatively associated with liver fat (P < .05). Conversely, CE SCD1-16 was negatively associated with hepatic IS (P < .05), but not independently of liver fat.Conclusions: Ethnic differences in fatty acid-derived desaturation indices were observed, with insulin-resistant black SA women paradoxically showing a fatty acid pattern typical for higher insulin sensitivity in European populations. [ABSTRACT FROM AUTHOR]

Background: Fatty acid mobilization and inflammatory response of adipose tissues vary in various depots, hence the response of fat-tailed and thin-tailed sheep breeds to different energy balances was hypothesized to be different due to differences in proportion and metabolism of various adipose depots in these breeds which may affect whole body insulin sensitivity. Objective: Current study aimed to evaluated the changes in plasma metabolites including non-esterified fatty acid (NEFA), glucose, insulin, triglyceride (TG) and tumor necrosis factor-alpha in response to negative and positive energy balances and their correlation with insulin sensitivity indexes in Lori-Bakhtiari fat-tailed and Lori-Bakhtiari × Romanov cross breed thin-tailed lambs. Methods: Thirty-six male lambs (18 fat-tailed and 18 thin-tailed lambs) were placed in individual pens and experienced periods of negative (21 d) and positive (21 d) energy balances. Lambs were bled weekly to measure plasma metabolites. Pearson correlation coefficients among variables were generated using Proc Corr of SAS. Results: In thin-tailed but not fat-tailed lambs, plasma NEFA showed a negative correlation with plasma glucose (R = -0.47; P < 0.0003) and insulin (R = -0.46; P < 0.0005) content. Plasma NEFA negatively correlated with revised quantitative insulin sensitivity check index (RQUICKI) and severity of the correlation was higher in fat-tailed (R = -0.58; P < 0.0001) comparing to thin-tailed (R = -0.40; P < 0.003) lambs. In fat-tailed lambs, plasma NEFA and insulin were the most influential factors on RQUICKI, whereas in thin-tailed lambs, insulin was the main factor affecting RQUICKI. Conclusion: The results of current study demonstrate that despite higher basal and negative energy balance induced plasma NEFA content in thin-tailed lambs, the contribution of plasma NEFA to insulin resistance was higher in fat-tailed lambs, whereas negative correlation between plasma NEFA and insulin content in thin-tailed lambs demonstrate higher sensitivity of insulin secretion capacity to plasma NEFA content.

Plasma free fatty acid (FFA) concentration is elevated in obesity, insulin resistance (IR), non-alcoholic fatty liver disease (NAFLD), type 2 diabetes (T2D), and related comorbidities such as cardiovascular disease (CVD). Furthermore, experimentally manipulating plasma FFA in the laboratory setting modulates metabolic markers of these disease processes. In this article, evidence is presented indicating that plasma FFA is a disease risk factor. Elevations of plasma FFA can promote ectopic lipid deposition, IR, as well as vascular and cardiac dysfunction. Typically, elevated plasma FFA results from accelerated adipose tissue lipolysis, caused by a high adipose tissue mass, adrenal hormones, or other physiological stressors. Reducing an individual’s postabsorptive and postprandial plasma FFA concentration is expected to improve health. Lifestyle change could provide a significant opportunity for plasma FFA reduction. Various factors can impact plasma FFA concentration, such as chronic restriction of dietary energy intake and weight loss, as well as exercise, sleep quality and quantity, and cigarette smoking. In this review, consideration is given to multiple factors which lead to plasma FFA elevation and subsequent disruption of metabolic health. From considering a variety of medical conditions and lifestyle factors, it becomes clear that plasma FFA concentration is a modifiable risk factor for metabolic disease.

BackgroundIn vitro studies have shown that acylation stimulating protein (ASP) stimulates triglyceride (TG) synthesis and storage in adipocytes. We have previously demonstrated that intraperitoneal (i.p.) injection of ASP in C57BL/6J mice accelerated TG clearance following an orally-administered fat load as well as reducing postprandial glucose levels.ResultsIn the present study, we first examined the effect of i.p. and intracerebroventricular (i.c.v.) injection of ASP on food intake in Sprague-Dawley rats. Intraperitoneal injection resulted in a short-term increase in food intake (maximum increase 29.3% within the first hour, P

Short-chain fatty acids (SCFAs) produced in the rumen are key factors affecting dairy cows' energy balance (EB). This study aimed to quantitatively evaluate the effects of SCFAs production on EB in dairy cows. Primiparous dairy cows were divided into high non-esterified fatty acid (NEFA; group H) and low NEFA (group L) groups based on their blood NEFA levels at week 3 postpartum, which served as an indicator of EB. The amounts of SCFAs produced in the rumen, including acetate, propionate, and butyrate (SCFAsP), were calculated using the predicted rumen volume. Because there were no differences between the groups in SCFAsP/dry matter intake, whereas 4% fat-corrected milk (FCM)/SCFAsP was significantly higher in group H, it was suggested that more body fat was mobilized for milk production in group H. However, group L, which showed better EB, had propionate dominant and lower FCM/SCFAsP and milk energy/SCFAs energy at 3 and 7 weeks postpartum, indicating that group L had a better energy supply for milk production. These results suggest that SCFAsP produced by rumen fermentation and the composition of SCFAs in the rumen affect milk production and EB., (© 2024 Japanese Society of Animal Science.)

Under current Australian industry pre-slaughter guidelines, lambs may be off feed for up to 48 h before slaughter. The purpose of this study was to examine what proportion of circulating metabolites at slaughter are due to stress and feed deprivation and if this response differs between Merino and Terminal genotypes. In addition the effect of feed deprivation on carcass weight and meat quality was examined. Jugular blood samples were collected from 88 Merino and Terminal sired lambs at rest and at slaughter following 24, 36 and 48 h of feed deprivation and plasma analysed for glucose, lactate, non-esterified fatty acids (NEFA) and β -hydroxybutyrate (BHOB). From the same carcasses hot carcass weight (HCWT) were measured as well as a suite of meat quality traits measured such as M. longissimus lumborum (loin) and M. semitendinosus pH at 24 h postmortem. Loin samples were also analysed for intramuscular fat content and Warner–Bratzer Shear Force. Merino sired lambs had a higher NEFA response compared to Terminal sired lambs at slaughter after 24, 36 and 48 h of feed deprivation, with NEFA levels up to 35% higher than previously reported in the same animals at rest in animal house conditions, whereas BHOB response to feed deprivation was not affected by sire type (P> 0.05) and similar to previously reported at rest. In addition to the metabolic effects, increasing feed deprivation from 36 h was associated with a 3% reduction in HCWT and dressing percentage as well as causing increased ultimate pH in the M. semitendinosus in Merino sired lambs. Findings from this study demonstrate that Merino and Terminal sired lambs differ in their metabolic response to feed deprivation under commercial slaughter conditions. In addition, commercial feed deprivation appears to have a negative effect on ultimate pH and carcass weight and warrants further investigation. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: The blood triacylglycerol level is one of the main determinants of blood Mg2+ concentration in individuals with type 2 diabetes. Hypomagnesaemia (blood Mg2+ concentration <0.7 mmol/l) has serious consequences as it increases the risk of developing type 2 diabetes and accelerates progression of the disease. This study aimed to determine the mechanism by which triacylglycerol levels affect blood Mg2+ concentrations.Methods: Using samples from 285 overweight individuals (BMI >27 kg/m2) who participated in the 300-Obesity study (an observational cross-sectional cohort study, as part of the Human Functional Genetics Projects), we investigated the association between serum Mg2+ with laboratory variables, including an extensive lipid profile. In a separate set of studies, hyperlipidaemia was induced in mice and in healthy humans via an oral lipid load, and blood Mg2+, triacylglycerol and NEFA concentrations were measured using colourimetric assays. In vitro, NEFAs harvested from albumin were added in increasing concentrations to several Mg2+-containing solutions to study the direct interaction between Mg2+ and NEFAs.Results: In the cohort of overweight individuals, serum Mg2+ levels were inversely correlated with triacylglycerols incorporated in large VLDL particles (r = −0.159, p ≤ 0.01). After lipid loading, we observed a postprandial increase in plasma triacylglycerol and NEFA levels and a reciprocal reduction in blood Mg2+ concentration both in mice (Δ plasma Mg2+ −0.31 mmol/l at 4 h post oral gavage) and in healthy humans (Δ plasma Mg2+ −0.07 mmol/l at 6 h post lipid intake). Further, in vitro experiments revealed that the decrease in plasma Mg2+ may be explained by direct binding of Mg2+ to NEFAs. Moreover, Mg2+ was found to bind to albumin in a NEFA-dependent manner, evidenced by the fact that Mg2+ did not bind to fatty-acid-free albumin. The NEFA-dependent reduction in the free Mg2+ concentration was not affected by the presence of physiological concentrations of other cations.Conclusions/interpretation: This study shows that elevated NEFA and triacylglycerol levels directly reduce blood Mg2+ levels, in part explaining the high prevalence of hypomagnesaemia in metabolic disorders. We show that blood NEFA level affects the free Mg2+ concentration, and therefore, our data challenge how the fractional excretion of Mg2+ is calculated and interpreted in the clinic. [ABSTRACT FROM AUTHOR]

The effect of quantity of nutrients on rumen fermentation and the level of metabolic markers in blood serum were simultaneously analysed in groups of dairy cows 21 days before and 21 days after parturition with aim to diagnose disorders in milk production in the transition period of dairy cows. Results of analysis of health disorders confirmed the following: low energy concentration in the diet insufficiently saturated with fibrous carbohydrates, followed with rapid change to concentrate type of diet after delivery resulted in insufficient adaptation of the rumen metabolism before and after rapid transition to production feeding rations after calving; the level indicative of acidification of the rumen environment. Investigation of intermediary metabolism confirmed pre- and post-partum lipomobilization, with increased values of NEFA in 68 % and 54 % of animals respectively, with liver load manifestation in 37 % and 69 % of animals, respectively.

The transition period is a central moment in dairy cows breeding because metabolic disorders may occur in relation to a dramatic increase in energy demand. This research aimed to identify new biomarkers for the diagnosis of hyperketonemia in bovine in early lactation phase with different value of plasmatic non-esterified fatty acid (NEFA). The profile of plasma fatty acids (FAs) divided into four lipid classes was evaluated using thin layer chromatography and gas chromatographic techniques (TLC-GC). A group of 60 multiparous Holstein–Friesian dairy cows were recruited in the present study. Blood samples were collected from the coccygeal vein and NEFA and the β-hydroxybutyrate (BHB) were evaluated. All animals were divided in 2 groups based on NEFA, NEFA0 group had as mean value 0.24 ± 0.12 mEq/L and NEFA1 group had as mean value 0.87 ± 0.23 mEq/L. Plasma FA concentrations were analyzed separately in free fatty acids, cholesterol esters, phospholipids and triglycerides. Six FAs demonstrated a predictive value in the hyperketonemic dairy cows. In the free fatty acid class, the predictive FAs were C14:0 (AUC = 0.77), C18:1 ω 9 (AUC = 0.72), C18:1 ω 7 (AUC = 0.70) and C18:3 ω 3 (AUC = 0.68). In the phospholipids class the predictive parameters were C12:0 (AUC = 0.78) and C8:0 (AUC = 0.73). In cholesterol, esters and triglycerides lipidic classes no FA had a predictive function.

Negative energy balance (NEB) during the perinatal period can affect dairy cow follicular development and reduce the fecundity. Non-esterified fatty acid (NEFA) concentration is elevated during NEB, and is known to be toxic for multiple cell types. In the ovary, NEB increased NEFA, and may influences follicular growth and development. However, the effect and mechanism of NEFA on granulosa cells (GCs) in vitro remains unknown. In this study, we found that NEFA dose-dependently induced apoptosis in primary cultured granulosa cells. Mechanistically, our data showed that NEFA significantly increased reactive oxygen species (ROS) levels, resulting in the activation of endoplasmic reticulum stress (ERS) and eventually cell apoptosis in GCs. Moreover, NEFA also increased the phosphorylation levels of ERK1/2 and p38MAPK pathways, upregulated the expression of p53 and potentially promoted its translocation to the nuclear, thus transcriptionally activated Bax, a downstream gene of this pathway. NEFA also promoted nuclear factor E2 (Nrf2) expression and its level in the nuclear. To elucidate the mechanism of NEFA action, N-acetyl-l-cysteine (NAC), a ROS scavenger was used to verify the role of ROS in NEFA induced apoptosis of GCs. NAC pretreatment reversed the NEFA-induced ERS-related protein and apoptosis-related protein levels. Meanwhile, NAC pretreatment also blocked the phosphorylation of ERK1/2 and p38 induced by NEFA, and the nucleation of Nrf2 and p53, suggesting that ROS plays a crucial role in regulating the NEFA-induced apoptosis of GCs. Together, these findings provide an improved understanding of the mechanisms underlying GCs apoptosis, which could potentially be useful for improving ovarian function.

Aim: Non-esterified fatty acids (NEFA) are potential targets for prevention of key cardiometabolic diseases of aging, but their population-level correlates remain uncertain. We sought to identify modifiable factors associated with fasting and post-load NEFA levels in older adults., Methods: We used linear regression to determine the cross-sectional associations of demographic, anthropometric, and lifestyle characteristics and medication use with serum fasting and post-load NEFA concentrations amongst community-dwelling older adults enrolled in the Cardiovascular Health Study (n = 1924)., Results: Fasting NEFA levels generally demonstrated a broader set of determinants, while post-load NEFA were more consistently associated with metabolic factors. Waist circumference and weight were associated with higher fasting and post-load NEFA. Cigarette smoking and caffeine intake were associated with lower levels of both species, and moderate alcohol intake was associated with higher fasting levels whereas greater consumption was associated with lower post-load levels. Unique factors associated with higher fasting NEFA included female sex, higher age, loop and thiazide diuretic use and calcium intake, while factors associated with lower fasting levels included higher educational attainment, beta-blocker use, and protein intake. Hours spent sleeping during the daytime were associated with higher post-load NEFA, while DASH score was associated with lower levels., Conclusion: Fasting and post-load NEFA have both common and unique modifiable risk factors, including sociodemographics, anthropometric, medications, and diet. Post-load NEFA were particularly sensitive to metabolic factors, while a broader range of determinants were associated with fasting levels. These factors warrant study as targets for lowering levels of NEFA in older adults., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Abstract: The aim of this study was to investigate the changes in hepatic oxidative phosphorylation (OXPHOS) complexes (COs) in patients and cows with non‐alcoholic steatohepatitis (NASH) and to investigate the mechanism that links mitochondrial dysfunction and hepatic insulin resistance induced by non‐esterified fatty acids (NEFAs). Patients and cows with NASH displayed high blood NEFAs, TNF‐α and IL‐6 concentrations, mitochondrial dysfunction and insulin resistance. The protein levels of peroxisome proliferator‐activated receptor‐γ coactivator‐1α (PGC‐1α), mitofusin‐2 (Mfn‐2) and OXPHOS complexes (human: COI and COIII; cow: COI‐IV) were significantly decreased in patients and cows with NASH. NEFA treatment significantly impaired mitochondrial function and, increased reactive oxygen species (ROS) production, and excessive ROS overactivated the JNK and p38MAPK pathways and induced insulin resistance in cow hepatocytes. PGC‐1α and Mfn‐2 overexpression significantly decreased the NEFA‐induced ROS production and TNF‐α and IL‐6 mRNA expressions, reversed the inhibitory effect of NEFAs on mitochondrial function and attenuated the overactivation of the ROS‐JNK/p38MAPK pathway, alleviated insulin resistance induced by NEFAs in cow hepatocytes and HepG2 cells. These findings indicate that NEFAs induce mitochondrial dysfunction and insulin resistance mediated by the ROS‐JNK/p38MAPK pathway. PGC‐1α or Mfn‐2 overexpression reversed the lipotoxicity of NEFAs on mitochondrial dysfunction and insulin resistance. Our study clarified the mechanism that links hepatic mitochondrial dysfunction and insulin resistance in NASH. [ABSTRACT FROM AUTHOR]

Background: As a frequent subclinical disease, fatty liver disease (FLD) is associated with a severe negative energy balance (NEB) during the early lactation period, and usually cause of economic loss to dairy farmers. Liver biopsy is the gold standard for the assessment of FLD. However, as an invasive procedure, liver biopsy has several limitations and such procedures are not readily available to dairy farmers. To further evaluate FLD in dairy cows, a FLD model of lactating sheep was developed by simulation of the state of negative energy balance (NEB). Materials, Methods & Results: Fourteen pregnancy thin-tail ewes were divided into control group (CG, n = 4), non-lamb restrained feeding group (NRG, n = 4) and single birth restrained feeding group (SRG, n = 6). After lambing, NRG and SRG ewe were received a feed restrained diet for 16 days. Liver biopsies and blood was collected on days 1, 4, 7, 10, 13, and 16, and biochemical parameters were analyzed. With restricted feeding and lactation administration, ewes in SRG showed increased liver fat concentrations (LFC) from days 4 post-administration and severe LFC was detected at day 13. Compared with CG, SRG sheep showed significant lower concentration of serum glucose (Glu) from days 7-13 and higher non-esterified fatty acid (NEFA) from days 4-16, ƒÀ-hydroxybutyric acid (BHBA) from days 4-16, triglyceride from days 4-16, low-density lipoprotein cholesterol from days 4-16, lactate dehydrogenase (LDH) from days 13-16, aspartate aminotransferase (AST) at days 16. While, ewes in NRG showed normal LFC levels, and high concentration of serum Glu and insulin from days 4-16 were detected than CG and SRG ewes. With restricted feeding, ewes in NRG and SRG showed significant low level of revised quantitative insulin sensitivity check index from days 4-16 and high level of liver total cholesterol (TC) at day 16. Liver pathological characteristics showed LFC of NEB sheep was first detected around the liver portal area. Discussion: In this study, a model of FLD in lactating thin-tail sheep was developed by restricted feeding. Serum glucose concentrations were sharply decreased in SRG sheep Cthat was due to the large energy requirements for lactation and low energy provided by a restricted diet. While non-lactating NRG sheep demonstrated lower fat mobilization, which was considered to contribute to the high concentrations of serum glucose, as compared to SRG sheep. Meanwhile, in a state of NEB, oxaloacetic acid, which is generated by glycolysis and glycogenic amino acids, tends to be used for gluconeogenesis, that a generous amount of NEFA is incompletely oxidized to generate ketone body in SRG sheep, which is a major component of BHBA. Liver TC concentrations were significantly higher in NRG sheep than those in the SRG sheep, while liver triglyceride was significantly lower. The high level of liver TC in NRG sheep was considered to induce removal of triglyceride from the liver in the form of VLDL. Compared with CG sheep, although higher levels of liver TC were detected in SRG sheep on postpartum day 16, these levels were considered too low to induce significant depletion of triglycerides from the liver. In this study, the increase in serum AST and LDH was considered to cause by oxidative stress in mitochondria, and LDH concentrations was considered more sensitively than AST for LFC caused by NEB. Liver pathological characteristics showed that FLD caused by NEB had a major impact on reduced LFC, although no significant liver fibrosis was detected. While different from FLD caused by high-fat diet, TG was first accumulates around the hepatic lobules and LFC of NEB sheep was first detected around the liver portal area. It was considered that high concentrations of NEFA are prioritized for oxygenation in the liver portal area, which results in triglyceride accumulation. [ABSTRACT FROM AUTHOR]

Introduction: The objective was to determine the relationship between the serum concentrations of Calcium (Ca2+), non-esterified fatty acids (NEFA), and insulin 10 days prepartum with losses in milk yield (MY) at 10 and 20 days of lactation. Method: Two hundred forty-three Holstein-Friesian cows (780 ± 36 kg PV, with more than two lactations) were sampled by coccygeal puncture several times before, during and after parturition. Results: When Ca2+ levels were low 10 days before parturition and were related to MY at 10 days postpartum, it was observed that 77.11% of the cows lost 2.20 kg of milk; while on day 20, 66.41% of the cows lost 1.40 kg animal-1 day-1. In contrast, when NEFA were high 10 days before calving and were related to MY, 67.40% of cows showed a risk of losing 0.80 kg, whereas at 20 days postpartum, 22.00% of cows lost approximately 0.90 kg cow-1 day-1. The determination of low prepartum insulin and MY on days 10 and 20 of lactation indicated that 6.02% of cows lost 0.80 and 0.70 kg of milk-1 animal-1 day-1 for days 10 and 20 of lactation. Conclusion: In conclusion, low blood levels of calcium, high levels of NEFA, and low insulin 10 days before parturition were associated with milk yield losses at 10 and 20 days after parturition. It was also observed that low calcium could cause greater milk losses than excesses of nonesterified fatty acids and serum low insulin concentrations. [ABSTRACT FROM AUTHOR]

Aim: Diabetes mellitus is reported to be a risk factor for dementia. We evaluated the cognitive function in elderly diabetic patients and estimated the prevalence of patients with cognitive impairment and looked for any related clinical factors. Subjects and methods: Using 281 elderly (65 years of age or older) Japanese patients with type 2 diabetes mellitus who were free of clinically evident cognitive impairment, we evaluated their cognitive function with the Mini Mental State Examination (MMSE). Results: The MMSE score of all the participants was 27.3 ± 2.4 with 31.3% of them being in the abnormal range (tentatively defined normal range as having an MMSE score of 27-30). Multiple regression analysis disclosed that fasting serum non-esterified fatty acid (NEFA), estimated glomerular filtration ratio (eGFR) and insulin treatment were significantly related factors for the MMSE score, in addition to age and schooling history, which are extremely strong factors. Conclusions: We revealed that approximately one-third of elderly type 2 diabetic patients who were free of clinically evident cognitive impairment had impaired cognitive function, demonstrating that the MMSE score was significantly correlated with fasting NEFA level, renal function, insulin treatment, age and schooling history. [ABSTRACT FROM AUTHOR]

Objective To explore the regulation of lipid metabolism by exogenous hydrogen sulfide (H2S) in mice serum. Methods Mice were divided into a normal group (n=10), a model group (n=10) and three treatment groups (n=15) of NaHS (25, 50 and 100 μmol·kg-1·d-1) as exogenous H2S donor. The normal group was given a normal feed. The diet-induced obesity (DIO) model group mice were induced by using high-fat diet for 12 weeks. Treatment groups received different concentrations of NaHS in saline solution by daily intra peritoneal injection for 6 weeks since the 18th week. Finally, at the end of treatment period, we measured the weight of epididymis adipose and perirenal fat after killing mice of treatment groups. Then the content of non-esterified fatty acid (NEFA) was measured by automatic biochemical analyzer and resistin level was measured with ELISA kit in mice serum. Results Compared with the normal group, the body weight, epididymis adipose weight and perirenal fat weight had obvious increase (P<0.05), but the levels of NEFA and resistin did not change significantly in model group; Compared with model group mice, the weight of epididymis adipose and perirenal fat and the level of NEFA had significant decrease in mice of treatment groups (P<0.05), but the content of resistin had no obvious change. Conclusions Hydrogen sulfide could obviously reduce the fat accumulation of DIO mice and significantly decrease the serum level of NEFA in treatment groups, but its regulation on resistin was not obvious. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine the effect of butaphosphan and cyanocobalamin (BTPC) supplementation on plasma metabolites and milk production in postpartum dairy cows. A total of fifty-two Holstein cows were randomly assigned to receive either: (1) 10 ml of saline (NaCl 0.9%, control group); (2) 1000 mg of butaphosphan and 0.5 mg of cyanocobalamin (BTPC1 group); and (3) 2000 mg of butaphosphan and 1.0 mg of cyanocobalamin (BTPC2 group). All cows received injections every 5 days from calving to 20 days in milk (DIM). Blood samples were collected every 15 days from calving until 75 DIM to determine serum concentration of glucose, non-esterified fatty acids (NEFA), β-hydroxybutyrate (BHB), cholesterol, urea, calcium (Ca), phosphorus (P), magnesium (Mg), aminotransferase aspartate (AST) and γ-glutamyltransferase (GGT). The body condition score (BCS) and milk production were evaluated from calving until 90 DIM. Increasing doses of BTPC caused a linear reduction in plasma concentrations of NEFA and cholesterol. Supplementation of BTPC also reduced concentrations of BHB but it did not differ between the two treatment doses. Milk yield and milk protein had a linear increase with increasing doses of BTPC. A quadratic effect was detected for milk fat and total milk solids according to treatment dose, and BTPC1 had the lowest mean values. Concentrations of glucose, urea, P, Mg, AST, GGT, milk lactose and BCS were not affected by treatment. These results indicate that injections of BTPC during the early postpartum period can reduce NEFA and BHB concentrations and increase milk production in Holstein cows.

Growth hormone (GH) increases phosphorylation and mRNA levels of hormone-sensitive lipase (HSL) in the livers of some marine teleosts. The hepatic GH-HSL axis appears to play important roles in fasting-induced lipolysis. However, it is not known whether GH exerts similar effects on HSL in fish adipose tissues. Functional differentiation of two fish-specific HSL isoforms (HSL1 and HSL2) also remains unclear. The present study seeks to address two unanswered questions about fish lipolysis using red seabream ( Pagrus major ): (1) Does GH increase phosphorylation and mRNA levels of HSL in adipose tissue? (2) How do GH and fasting affect mRNA levels of two HSL isoform genes in the liver and adipose tissue? To this end, we first cloned HSL1 and HSL2 cDNAs and investigated their tissue distribution. Transcripts of both HSLs and HSL1 proteins were abundant in the visceral adipose tissue, gonads, and liver, suggesting the important role of HSL in adipose tissue lipolysis. HSL2 transcript levels were 20–65% those of HSL1 except in the skin, and HSL2 proteins were not detected by our in-house antisera. Ex vivo administration of GH increased HSL1 phosphorylation, non-esterified fatty acid (NEFA) release, and levels of HSL1 and HSL2 mRNA in both the liver and visceral adipose tissue. Hepatic HSL2 mRNA was particularly sensitive to GH administration and sometimes exceeded HSL1 mRNA levels with up to 13-fold induction. In contrast, fasting for 4 and 7 d increased HSL1 mRNA levels, but had only marginal effects on HSL2 mRNA levels in both adipose tissue or liver. We concluded that GH would increase HSL mRNAs during adipose tissue lipolysis in red seabream; however, GH and fasting result in different induction ratio of two HSL isoform genes, suggesting that other hormone(s) also contributes to fasting-induced lipolysis. [ABSTRACT FROM AUTHOR]

Background: Bariatric surgery is an increasingly common option for control of type 2 diabetes (T2D) and obesity. Mechanisms underlying rapid improvement of T2D after different types of bariatric surgery are not clear. Caloric deprivation and altered levels of non-esterified fatty acid (NEFA) have been proposed. This study examines how sleeve gastrectomy (SG), Roux-en-Y gastric bypass (GBP) or matched hypocaloric diet (DT) achieves improvements in T2D by characterising components of the glucose metabolism and NEFA levels before and 3 days after each intervention. Methods: Plasma samples at five time points during oral glucose tolerance test (OGTT) from subjects with T2D undergoing GBP ( N = 11) or SG ( N = 12) were analysed for C-peptide, insulin and glucose before surgery and 3-day post-intervention or after DT ( N = 5). Fasting palmitic, linoleic, oleic and stearic acid were measured. C-peptide measurements were used to model insulin secretion rate (ISR) using deconvolution. Results: Subjects who underwent GBP surgery experienced the greatest improvement in glycaemia (median reduction in blood glucose (BG) from basal by 29 % [IQR −57, −18]) and the greatest reduction in all NEFA measured. SG achieved improvement in glycaemia with lower ISR and reduction in all but palmitoleic acid. DT subjects achieved improvement in glycaemia with an increase in ISR, 105 % [IQR, 20, 220] and stearic acid. Conclusions: GBP, SG and DT each improve glucose metabolism through different effects on pancreatic beta cell function, insulin sensitivity and free fatty acids. [ABSTRACT FROM AUTHOR]

Obesity has become an important global health issue. Over the last few decades, the increasing burden of obesity has resulted in ever increasing prevalence of metabolic and cardiovascular complications. Both insulin resistance and inflammation play an important role in linking obesity with cardiovascular disease (CVD). In obese people, adipose tissue undergoes substantial remodeling including hypertrophy, possibly hampering the normal physiological functions. These hypertrophic adipocytes produce an increase amount of non-esterified fatty acids (NEFAs), hormones and inflammatory cytokines that are strongly involved in the pathogenesis of CVD. Early diagnosis and lifestyle modifications including weight loss, healthy diet intake and increased physical activity could of great importance in management and prevention of these disorders. [ABSTRACT FROM AUTHOR]

Non-esterified and triacylglyceride fatty acid quantification in plasma is important in order to know fatty acid plasma availability and the nutritional status. A reliable method to determine free, triacylglycerol, phospholipid, and cholesterol ester fatty acids in human plasma samples by combining two types of fatty acid isolation and enzymatic and chromatographic methods has been developed and made safer by avoiding diazomethane derivatization. Lipoprotein lipase was used to obtain hydrolyzed fatty acids from triacylglycerides, and chromatography performed with an active carbon column was used to isolate free fatty acids. Posterior safe derivatization to methylated fatty acids by transesterification, with m-trifluoromethylphenyl trimethylammonium hydroxide reagent (Meth-Prep™ II) and gas chromatography enabled us to identify and quantify a wide spectral range of non-esterified and triacylglyceride fatty acids in plasma. Additionally, the method allows the fatty acids of the phospholipid and cholesterol ester fraction to be determined after the determination of total plasma fatty acids. Determining the individual fatty acid recovery with respect to the C17:0 internal standard makes it possible to calculate the individual fatty acid concentration in each fraction of plasma. The method optimizes the derivatization reagent and chromatographic conditions and enables quantification of additional fatty acids such as omega-3 and omega-6 of the C18:3 fatty acid and C20:1n9, C22:0, and C22:6n3 fatty acids. The procedure can be safely used to analyze a large number of samples. [ABSTRACT FROM AUTHOR]

Objective: Perioperative nutritional assessment is critically important to reflect nutritional management because liver transplantation (LTx) often is undertaken in patients with poor nutritional status. The aim of this study was to evaluate nutritional status, including the non-protein respiratory quotient (npRQ), resting energy expenditure (REE), nitrogen balance, and blood biochemical parameters in patients before and after LTx. Methods: Fourteen patients undergoing LTx and 10 healthy controls were enrolled in this study. The npRQ and REE were measured using indirect calorimetry before LTx and at 2, 3, and 4 wk after the procedure. Blood biochemistry and nitrogen balance calculated by 24-h urine collection were performed concurrently with indirect calorimetric measurement; the results were compared between the two groups. Results: Before LTx, npRQ was significantly lower and serum non-esterified fatty acid levels were significantly higher in the patients than in the controls. Furthermore, a negative nitrogen balance was observed in the patients. These, however, improved significantly at 4 wk after LTx. REE did not significantly increase compared with the preoperative values in recipients. Blood biochemistry showed gradually increasing levels of serum cholinesterase and albumin. These failed to reach to normal levels by 4 wk post-transplant. Conclusions: The findings revealed that improvement of nutritional metabolism after LTx may require 4 wk. Additional nutritional strategies, therefore, may be needed to minimize catabolic state during the early post-transplant period. Adequate, individualized nutritional guidance before and after LTx should be performed in these patients. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the relationship between concentration of non-esterified fatty acid and ketone bodies in blood of dairy cows, and to evaluate these concentrations for the detection of prevalence of subclinical ketosis. The second aim was to compare the concentration of β-hydroxybutyric acid determined by an electronic handheld meter Precision Xtra® with serum concentration of β-hydroxybutyric acid analysed in laboratory with izotachometric and photometric method, respectively. Blood samples were collected from jugular vein 4-6 h after morning feeding in three groups of Holstein cows (n = 909) according to the lactation phase from 51 different herds with similar husbandry characteristics. High lipomobilization (non-esterified fatty acid ≥ 0.35 mmol·l-1, mean concentration 0.34 ± 0.15 mmol·l-1) was detected in 30.3% of antepartum cows, while increased concentrations of β-hydroxybutyric acid (≥ 1.0 mmol·l-1, prevalence of subclinical ketosis) were detected in 18.5% and 14.1% of the early lactation and mid lactation cows, respectively. The correlation coefficient (r = 0.84, P < 0.001; r = 0.93, P < 0.001) was found between measurements of whole blood β-hydroxybutyric acid of 60 and 38 dairy cows determined with the Precision Xtra® test and plasma or serum β-hydroxybutyric acid concentration determined by isotachophoresis and photometrical method, respectively. Our results show that the monitoring of changes in the blood concentration of β-hydroxybutyric acid in high-yielding cows in the early postpartum period by the electronic handheld meter Precision Xtra® may be effective in reducing the incidence of ketosis and health problems associated with ketosis in dairy cattle herds. [ABSTRACT FROM AUTHOR]

Increased blood non-esterified fatty acid (NEFA) concentrations might be implicated as a factor that plays a role in the pathogenesis of gastrointestinal motility disorder, such as abomasal displacement. We sought to elucidate possible effects of high concentrations of NEFA on primary cultured bovine abomasal smooth muscle cells (BSMC). BSMC treated with high concentrations of NEFA resulted in decrease of cell viability and increase of cell apoptosis rate. NEFA treatment induced oxidative stress, as revealed by increased levels of ROS and MDA, while decreased the antioxidative abilities (SOD, CAT, GSH, and GSSG) in BSMC. Meanwhile, high concentrations of NEFA induced BSMC mitochondrial apoptotic cell death. Mitochondrial membrane potential decrease, increased Bax and decreased Bcl-2, cytochrome c release, caspases activation, and apoptosis inducing factor (AIF) translocation were observed in NEFA-treated cells. Pretreatment with the antioxidant N-acetylcysteine (NAC) effectively reversed these NEFA-induced events. In conclusion, these results show that NEFA induce BSMC apoptosis mainly via a ROS-dependent mechanism involving the mitochondrial pathway. [ABSTRACT FROM AUTHOR]