Relationship between types and levels of free fatty acids, peripheral insulin resistance, and oxidative stress in T2DM: A case-control study.

Free Fatty Acids (FFAs) are vital for energy homeostasis and the pathogenesis of a variety of diseases, including diabetes. For the first time, we presumed and investigated the types and levels of FFAs and their links to Insulin Resistance (IR) and Oxidative Stress (OS) in T2DM. A case-control study was conducted on 60 individuals with diabetes, 60 prediabetics with IFG, and 60 control groups. A Gas Chromatography Flame Ionization Detector (GC-FID) was used to estimate FFAs, which were then classified based on length and saturation. Indeed, antioxidant parameters such as TAC, MDA levels, PON-1, SOD-3, and CAT activity were assessed. Higher levels of LCFFA, SFFA, USFFA, and total FFA were found in people with diabetes and prediabetes. These levels were also linked to higher levels of HOMA-IR, BMI, FBS, HbA1C, and MDA, but lower levels of antioxidants. Furthermore, adjusting the above FFAs with age, sex, and antihypertensive medication increased T2DM development. SCFFA and ω3/6 fatty acids had a negative relationship with HOMA-IR, FBS, and insulin and a positive relationship with TAC. Adjusted SCFFA reduces T2DM risk. According to our models, total FFA is utilized to diagnose diabetes (AUC = 83.98, cut-off > 919 µM) and SCFFA for prediabetes (AUC = 82.32, cut-off < 39.56 µM). Total FFA (≥ 776 µM), LCFFA (≥ 613 µM), SFFA (≥ 471 µM), and USFFA (≥ 398 µM) all increase the risk of T2DM by increasing OS, BMI, and HOMA-IR. On the other hand, SCFFAs (≥ 38.7 µM) reduce the risk of T2DM by reducing BMI, HOMA-IR, and OS. SCFFAs and total FFAs can be used for the diagnosis of prediabetes and diabetes, respectively.

Association between non-esterified fatty acids and calcium concentrations at calving with early lactation clinical diseases, fertility and culling in grazing dairy cows in Uruguay.

This study describes the association of non-esterified fatty acids (NEFA) and calcium concentrations at calving with early lactation disease, reproductive performance and culling in 646 dairy cows from 13 commercial grazing dairy herds in Uruguay. During one year, health events were recorded from calving to 30 days in milk (DIM). The first author visited each farm every 20 days. During each visit, body condition score (BCS) was recorded (scale 1-5), defining BCS < 3 as suboptimal and BCS > 3 as optimal, and a blood sample was taken from cows between 0 and 4 DIM for metabolite determination. To evaluate the association between health events (i.e., retained placenta-metritis and clinical mastitis) and risk factors (parity, BCS, high NEFA (> 0.6 mmol/L) and subclinical hypocalcemia (SCH) (< 2.10 mM)) data were analysed using multivariable logistic regression models. To evaluate the association of health events and risk factors with reproductive performance and culling, data were analysed using Cox proportional hazard regression models. A risk factor and an outcome of interest were assumed to be associated at P < 0.05 and a tendency to be associated was defined at P < 0.10. Overall, 47 % (n = 303) of the cows showed elevated NEFA concentration and 77 % (n = 499) had SCH. In addition, 21.5 % (n = 139) of the cows recorded at least one clinical disease. Cumulative incidence was 17 % (n = 109) for clinical mastitis, 4.2 % (n = 27) for retained placenta (RP)-metritis and 1.4 % (n = 7) for lameness. Clinical mastitis was associated with parity, with lower odds in primiparous (PP) cows (OR = 0.42, P < 0.01). Cows in an optimal BCS also tended to have lower odds (OR = 0.66, P = 0.07). Moreover, high NEFA and SCH cows had higher odds of CM (OR = 4.5, P = 0.01 and OR = 1.75, P = 0.04, respectively). Retained placenta-metritis tended to be associated with high NEFA concentration (OR = 2.2, P = 0.06). Primiparous cows with suboptimal BCS showed an increased first insemination rate (HR = 2.34; P < 0.01). The risk of culling was lower in PP cows (HR = 0.19; P < 0.01) and in cows with optimal BCS and low NEFA concentration (HR = 0.38; P = 0.03). Our data show that metabolic challenge (defined as peripartum suboptimal BCS, high NEFA or SCH) is associated with increased odds of clinical mastitis and RP-metritis, decreased probability of insemination and increased hazard of culling. Under grazing conditions, we suggest that farm management to improve the metabolic adaptation to lactation represents an opportunity to enhance cow performance in terms of health, fertility and longevity.

High-Fat Feeding Alters Circulating Triglyceride Composition: Roles of FFA Desaturation and ω-3 Fatty Acid Availability.

Hypertriglyceridemia is a risk factor for type 2 diabetes and cardiovascular disease (CVD). Plasma triglycerides (TGs) are a key factor for assessing the risk of diabetes or CVD. However, previous lipidomics studies have demonstrated that not all TG molecules behave the same way. Individual TGs with different fatty acid compositions are regulated differentially under various conditions. In addition, distinct groups of TGs were identified to be associated with increased diabetes risk (TGs with lower carbon number [C#] and double-bond number [DB#]), or with decreased risk (TGs with higher C# and DB#). In this study, we examined the effects of high-fat feeding in rats on plasma lipid profiles with special attention to TG profiles. Wistar rats were maintained on either a low-fat (control) or high-fat diet (HFD) for 2 weeks. Plasma samples were obtained before and 2.5 h after a meal (n = 10 each) and subjected to lipidomics analyses. High-fat feeding significantly impacted circulating lipid profiles, with the most significant effects observed on TG profile. The effects of an HFD on individual TG species depended on DB# in their fatty acid chains; an HFD increased TGs with low DB#, associated with increased diabetes risk, but decreased TGs with high DB#, associated with decreased risk. These changes in TGs with an HFD were associated with decreased indices of hepatic stearoyl-CoA desaturase (SCD) activity, assessed from hepatic fatty acid profiles. Decreased SCD activity would reduce the conversion of saturated to monounsaturated fatty acids, contributing to the increases in saturated TGs or TGs with low DB#. In addition, an HFD selectively depleted ω-3 polyunsaturated fatty acids (PUFAs), contributing to the decreases in TGs with high DB#. Thus, an HFD had profound impacts on circulating TG profiles. Some of these changes were at least partly explained by decreased hepatic SCD activity and depleted ω-3 PUFA.

Metabolic responses to albumin deficiency differ distinctly between partial and full ablation of albumin expression in mice.

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.

Analysis of the relationship between energy balance and properties of rumen fermentation of primiparous dairy cows during the perinatal period.

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.

Excessive free fatty acid sensing in pituitary lactotrophs elicits steatotic liver disease by decreasing prolactin levels.

The pituitary is the central endocrine gland with effects on metabolic dysfunction-associated steatotic liver disease (MASLD). However, it is not clear whether the pituitary responds to free fatty acid (FFA) toxicity, thus dysregulating hepatic lipid metabolism. Here, we demonstrate that decreased prolactin (PRL) levels are involved in the association between FFA and MASLD based on a liver biospecimen-based cohort. Moreover, overloaded FFAs decrease serum PRL levels, thus promoting liver steatosis in mice with both dynamic diet intervention and stereotactic pituitary FFA injection. Mechanistic studies show that excessive FFA sensing in pituitary lactotrophs inhibits the synthesis and secretion of PRL in a cell-autonomous manner. Notably, inhibiting excessive lipid uptake using pituitary stereotaxic virus injection or a specific drug delivery system effectively ameliorates hepatic lipid accumulation by improving PRL levels. Targeted inhibition of pituitary FFA sensing may be a potential therapeutic target for liver steatosis.

Targeted metabolomic analysis of serum free fatty acids: Lipidomics disturbance in patients with superior limbic keratoconjunctivitis.

This study aimed to identify and quantify free fatty acids (FFAs), secretory phospholipase A2 group IIa (sPLA2-IIa) and cytosolic phospholipase A2 (cPLA2) in serum of superior limbic keratoconjunctivitis (SLK) patients and explored the association between FFAs, sPLA2-IIa and cPLA2 variations and SLK. Targeted metabolomic analysis of FFAs in serum was performed by gas chromatography tandem mass spectrometry (GC-MS/MS) analysis on 16 SLK patients (43.88 ± 7.88 years; female: 62.50%) and 25 healthy controls (43.12 ± 7.88 years; female: 64.00%). Qualitative and absolute quantitative results of FFAs were obtained and classified according to gender and thyroid tests. Differential lipid metabolites, metabolomic pathways and biomarkers were further evaluated. The serum sPLA2-IIa and cPLA2 were determined by enzyme linked immunosorbent assay (ELISA). Among 40 FFAs identified, 6 FFAs showed significant changes (P < 0.05) in SLK patients, including 4 decreased and 2 increased. They were mainly related to unsaturated fatty acid biosynthesis, α-linolenic acid and linoleic acid metabolism, and fatty acid biosynthesis. When dividing the data by gender or abnormal thyroid tests, some comparable FFAs alterations displayed in SLK patients. The ROC analysis revealed that the AUC values of linoleic acid, γ-linolenic acid, cis-8,11,14-eicosatrienoic acid, stearic acid, and palmitic acid, were all greater than 0.8. The serum concentrations of sPLA2-IIa and cPLA2 in patients with SLK were significantly higher than that in healthy controls. Lipidomics disturbance might be the potential mechanism of SLK. Serum FFA biomarkers associated with SLK have potential for the diagnosis and treatment of the disease.

The association between serum free fatty acid levels and neurological outcomes in out-of-hospital cardiac arrest patients: A prospective observational study.

Free fatty acids (FFA) are a known risk factor in the development of sudden cardiac death. However, the relationship between FFA and the outcome of out-of-hospital cardiac arrest (OHCA) patients remains unclear. We aimed to examine the association between FFA and neurological outcomes in OHCA patients. This prospective observational study included adult (≥18 years) OHCA patients between February 2016 and December 2022. We measured serial FFA levels within 1 hour after ROSC and at 6, 12, 24, 48, and 72 hours after the return of spontaneous circulation (ROSC). The primary outcome was neurological outcome at 6 months. A poor neurological outcome was defined by cerebral performance categories 3, 4, and 5. A total of 147 patients were included. Of them, 104 (70.7%) had poor neurological outcomes, whereby the median FFA levels within 1 hour after ROSC (0.72 vs 1.01 mol/L), at 6 hours (1.19 vs 1.90 mol/L), 12 hours (1.20 vs 1.66 mol/L), and 24 hours (1.20 vs 1.95 mol/L) after ROSC were significantly lower than in good outcome group. The FFA levels at 6 hours (odds ratio, 0.583; 95% confidence interval, 0.370-0.919; P = .020), and 12 hours (odds ratio, 0.509; 95% confidence interval, 0.303-0.854; P = .011) after ROSC were independently associated with poor neurological outcomes. The lower FFA levels at 6 hours and 12 hours after ROSC were associated with poor neurological outcomes in patients with OHCA. FFA may reflect oxidative metabolism as well as oxidative stress.

Do concentrations of non-esterified fatty acids change during gestation and lactation in healthy bitches?

During the gestation and lactation period, the energy demand in pregnant and lactating bitches is elevated. Non-esterified fatty acids (NEFAs) are utilized either directly from the fed diet or from body fat storage. High NEFA concentration in the blood plasma leads to an increased risk for diseases. Therefore, measuring blood NEFA concentrations may be an indicator for a period of scarcity. The aim of this study is to explore if serum NEFA concentrations in healthy bitches change during gestation and lactation. Healthy pregnant and lactating bitches were sampled on three appointed dates around parturition. NEFA values were examined with a multiparameter clinical chemistry analyser. All statistical analyses were performed using R. Overall, 38 bitches were enrolled in the study. Twenty-one bitches were sampled on all three appointed dates. The median NEFA concentration antepartum was 0.73 mmol/L (IQR: 0.59, 1.01); during peak lactation, it was 0.57 mmol/L (IQR: 0.44, 0.82); and around weaning, it was 0.58 mmol/L (IQR: 0.46, 0.73). NEFA concentrations rose slightly with litter size in late gestation. Body condition score had no influence on observed NEFA values. We conclude that NEFA concentrations widely remain within reference ranges in well-fed pregnant and lactating bitches. Nevertheless, they may be a valuable parameter to assess the actual metabolic status of malnourished pregnant and lactating bitches.

Differing planes of nutrition alter serum and histotroph amino acid composition in nonpregnant, multiparous beef cows on day 3 of the estrous cycle.

Endometrial-derived uterine histotroph is a critical component of nutrient supply to a growing conceptus throughout gestation; however, the effect of nutritional plane on histotroph nutrient composition remains unknown in multiparous cows. We hypothesized that differing planes of nutrition would alter histotroph and serum nutrient composition in beef cattle. Thus, we evaluated serum and histotroph amino acid and glucose composition, and serum non-esterified fatty acids (NEFA) and blood urea nitrogen (BUN) in cows individually fed to maintain body weight (BW; 0 kd/d, n = 9; CON) compared with those losing moderate BW (-0.7 kg/d, n = 9; NEG). After 49 d of differing nutritional planes, cows were subjected to the 7-d CoSynch + controlled internal drug release device estrus synchronization protocol and then slaughtered on day 62. Blood serum (days 0 and 62) and uterine histotroph [day 62; from uterine horns ipsilateral and contralateral to the corpus luteum (CL)] were collected and analyzed for concentrations of amino acids, glucose, and NEFA. Performance characteristics, body composition via ultrasound (days 0 and 62), and carcass characteristics were collected. Body condition score, change in BW, average daily gain, dry matter intake, and gain:feed were decreased (P ≤ 0.05) in NEG vs. CON cows. There were no differences in body composition or carcass characteristics, except an increase (P ≤ 0.05) in dressing percentage in NEG cows due to differences in gut fill, consistent with study design. Serum NEFA increased (P ≤ 0.05) in the NEG group, but there were no differences between NEG vs. CON in glucose or BUN. Serum histidine increased (P ≤ 0.05) and alanine, isoleucine, and tryptophan decreased (P ≤ 0.05) in NEG vs. CON cows. Compared with that of the uterine horn ipsilateral to the CL, histotroph from the uterine horn contralateral to the CL had increased (P ≤ 0.05) isoleucine, asparagine, and proline concentrations in NEG cows, and decreased (P ≤ 0.05) tryptophan as a proportion of essential and total amino acids. There were no differences in glucose concentrations of histotroph contralateral or ipsilateral to the CL. Cow nutritional plane does alter serum and histotroph amino acid composition, although the presence of an embryo may be necessary to fully elucidate these changes. Differences in serum and histotroph tryptophan should be given consideration in future studies due to its importance as an essential amino acid in protein synthesis and bioactive affects.

Amino acids are important in protein synthesis and bioactive affects. Maternal diet could impact histotroph amino acid composition which serves as a nutrient supply to the conceptus throughout pregnancy and is especially critical during early pregnancy, before the placenta is fully functional. Cows were subjected to their diets for 62 d, resulting in decreased body condition, average daily gain, dry matter intake, G:F, and a greater change in body weight (BW) among moderate loss cows. These data demonstrate our model for moderate BW loss was successful. Moderate BW loss cows exhibited alterations in serum and histotroph amino acid composition in the uterine horn contralateral to the corpus luteum (CL). However, in the present study, histotroph amino acid alterations were in the uterine horn contralateral to the CL, which would be opposite of the developing conceptus. Nevertheless, because the 2 uterine horns communicate via the common uterine body, the pre-implantation conceptus should have access to the histotroph from the contralateral uterine horn. Thus, future studies are needed to fully elucidate effects of nutritional plane on histotroph nutrient composition, and its potential impact on pregnancy.

Effects of angiotensin receptor-neprilysin inhibitor on ketone body metabolism in pre-heart failure/heart failure patients.

Recently, a mild elevation of the blood ketone levels was found to exert multifaceted cardioprotective effects. To investigate the effect of angiotensin receptor neprilysin inhibitors (ARNIs) on the blood ketone body levels, 46 stable pre-heart failure (HF)/HF patients were studied, including 23 who switched from angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) to ARNIs (ARNI group) and 23 who continued treatment with ACE inhibitors or ARBs (control group). At baseline, there were no significant differences in the total ketone body (TKB) levels between the two groups. Three months later, the TKB levels in the ARNI group were higher than the baseline values (baseline to 3 months: 71 [51, 122] to 92 [61, 270] µmol/L, P < 0.01). In the control group, no significant change was observed between the baseline and 3 months later. A multiple regression analysis demonstrated that the initiation of ARNI and an increase in the blood non-esterified fatty acid (NEFA) levels at 3 months increased the percentage changes in the TKB levels from baseline to 3 months (%ΔTKB level) (initiation of ARNI: P = 0.017, NEFA level at 3 months: P < 0.001). These results indicate that ARNI administration induces a mild elevation of the blood TKB levels in pre-HF/HF patients.

Milk components as potential indicators of energy status in early lactation Holstein dairy cows from two farms.

Negative energy balance (NEB) is a serious problem in most dairy cows. It occurs most frequently after calving, when cows are unable to consume sufficient DM to meet their energy requirements during early lactation. During NEB, the breakdown of fat stores releases non-esterified fatty acids (NEFAs) into the bloodstream. High blood concentrations of NEFAs cause health problems such as ketosis, fatty liver syndrome, and enhanced susceptibility to infections. These issues may substantially increase premature culling from the herd. Serum NEFA concentrations are often used as a direct marker of energy metabolism. However, because the direct measurement of serum NEFAs is difficult under commercial conditions, alternative indicators, such as milk components, have been increasingly investigated for their use in estimating energy balance. The objectives of this study were to (1) evaluate the relationships between serum NEFA concentrations and selected milk components in cows from two farms during the first 5 weeks of lactation, and to (2) develop a model valid for both herds for predicting serum NEFA concentrations using milk components. A total of 121 lactating Holstein cows from two different farms were included in the experiment. Blood samples were collected for NEFA analysis on days 7 (± 3), 14 (± 3), 21 (± 3), and 35 (± 3) after calving. Composite milk samples were collected during afternoon milking on the same days as blood sampling. Concentrations of fat, protein, lactose, and milk fatty acids (FAs) were determined using Fourier-transform IR spectroscopy analysis. The strongest correlations (r > 0.43) were recorded between serum NEFAs and milk long-chain FAs, monounsaturated FAs, C18:0, and C18:1 within each farm and for both farms combined. Two prediction models for serum log(NEFA) using milk components as predictors were developed by stepwise regression. The prediction model with the best fit (R2 = 0.52) included days in milk, fat-to-protein ratio, and C18:1, C18:12 and C14:0 expressed as g/100 g of milk fat. An essential finding is that, despite different concentrations of NEFAs, and of most milk components observed in the evaluated herds, there were no significant interactions between farm and any of the FAs, so the same regression coefficients could be used for the prediction models in both farms. Validation of these findings in a greater number of herds would allow for the use of milk FAs to identify energy-imbalanced cows in herds under different farm conditions.

The abnormalities of free fatty acid metabolism in patients with hypertrophic cardiomyopathy, a single-center retrospective observational study.

BACKGROUND: Previous studies have shown the importance of energy deficiency and malfunctioning mitochondria in the pathophysiology of hypertrophic cardiomyopathy (HCM). There has been a little research into the relationship between plasma free fatty acids (FFA), one of the heart's main energy sources, and HCM. We evaluated its clinical importance in HCM to see if there was a link between plasma FFA metabolism and HCM. METHODS: In a single-center retrospective observational study, we investigated 420 HCM patients diagnosed at Beijing Anzhen Hospital between January 1, 2018, and December 31, 2022. Meanwhile, 1372 individuals without HCM (non-HCM) were recruited. 391 non-HCM patients were chosen as controls via a propensity score matching (PSM) study with a 1:1 ratio. RESULTS: FFA in HCM patients showed statistically significant correlations with creatinine (r = 0.115, p = 0.023), estimated GFR (r=-0.130, p = 0.010), BNP (r = 0.152, p = 0.007), LVEF (r=-0.227, p < 0.001), LVFS (r=-0.160, p = 0.002), and LAD (r = 0.112, p = 0.028). Higher FFA levels were found in HCM patients who had atrial fibrillation and NYHY functional classes III or IV (p = 0.015 and p = 0.022, respectively). In HCM patients, multiple linear regression analysis revealed that BNP and LVEF had independent relationships with increasing FFA (Standardized = 0.139, p = 0.013 and =-0.196, p < 0.001, respectively). CONCLUSIONS: Among HCM patients, the plasma FFA concentration was lower, and those with AF and NYHY functional class III or IV had higher FFA levels, and LVEF and BNP were independently associated with increasing FFA. The findings of the study should help inspire future efforts to better understand how energy deficiency contributes to hypertrophic cardiomyopathy (HCM) development.

Feed restriction affects milk performances and decreases milk lipolysis in dairy ewes.

Spontaneous lipolysis results in the breakdown of milk fat by the lipoprotein lipase (EC: 3.1.1.34), an enzyme present in milk. Free fatty acids (FFAs) and by-products released in milk during lipolysis can alter both the organoleptic value of milk (off-flavors release) and technological properties of dairy products (decrease in creaming capabilities). Current climate change is having significant impacts on the feeding of grazing animals, with negative consequences on the availability and quality of grass. We and others have demonstrated that dietary restriction increases milk lipolysis in the cow species. However, no data about the impact of feed restriction on milk lipolysis is available in the ewe species. Thus, this paper aims to investigate the effect of feed restriction on milk characteristics with regard to lipolysis values in dairy ewes. Two groups of 24 multiparous Lacaune ewes in mid-lactation received a "non-restricted" control diet (100% of ad libitum DM intake) or a "restricted" (RESTR) diet (65% of ad libitum DM intake) according to a 2 × 2 crossover design. Milk gross composition together with lipolysis analyses were performed. Blood samples were also screened for metabolites or hormone concentrations. The RESTR treatment induced a decrease in milk production (- 21% compared with control treatment) and a modification of the metabolism of dairy ewes characterized by an increase in plasma non-esterified fatty acids (NEFAs), which represents the balance between adipose tissue mobilization and the use of NEFA by other tissues (+153%), cholesterol (+17%) and ß-hydroxybutyrate (+4 %) levels. As a result, a decrease in BW of dairy ewes was observed (-7%). Feed restriction also resulted in a decrease in milk lipolysis estimated by the milk FFA measured by the copper-soap method (-63 and -62%, respectively, for morning and evening milking) or by the reference Bureau of Dairy Industry method (-51 and -57%, respectively, for morning and evening milking). The decrease in milk spontaneous lipolysis under feed restriction was not associated with a decrease in lipoprotein lipase activity in ewes. These results will be completed with proteomic and lipidomic studies in milk samples to better understand mechanisms initiated in the ewe species specifically with regard to lipolysis in milk.

Relationship of postprandial fibroblast growth factor 21 with lipids, inflammation and metabolic dysfunction-associated fatty liver disease during oral fat tolerance test.

Introduction: Metabolic dysfunction-associated fatty liver disease (MAFLD) is closely associated with serum fibroblast growth factor (FGF) 21; however, previous studies have typically focused on the static fasting state, and the relationships between postprandial FGF21 levels, postprandial metabolic status, and MAFLD remain unclear. Therefore, we measured postprandial lipids, inflammatory factors, and FGF21 levels in MAFLD and further analyzed their relationship using an oral fat tolerance test (OFTT). Patients and methods: In total, 103 non-diabetic adult volunteers, including 46 patients with MAFLD, were included in this study. All participants underwent the OFTT. Venous blood samples were collected at 0, 2, 4, and 6 h. Circulating total cholesterol (TC), triglyceride (TG), free fatty acid (FFA), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), interleukin-6(IL-6), tumor necrosis factor-α(TNF-α), hypersensitive-C reactive protein(hs-CRP) and FGF21 were assessed. Results: Serum FGF21 significantly increased in the fasting state (P < 0.05) and showed a biphasic change of first decreasing and then increasing in MAFLD during the OFTT. The postprandial levels of TG, TC, LDL-C, FFA, IL-6, TNF-α and hs-CRP were significantly increased in MAFLD (P < 0.05). After adjusting for multiple factors, the FGF21 incremental area under the curve (iAUC) was linearly correlated with the FFA iAUC, TG iAUC, and IL-6 iAUC (P < 0.05) and was an independent factor for MAFLD (P < 0.05, OR=1.403). Conclusion: Dyslipidemia and excessive inflammation in MAFLD are associated to FGF21 levels in the postprandial period. An abnormal postprandial FGF21 response may be an important mechanism of MAFLD.

Variations of blood metabolites in single- and multiple-bearing Ossimi ewes during the transition period.

Evaluation of the metabolic profile indices allows early detection and treatment of various metabolic disorders during the transition period in ewes. This study aimed to determine the variations in the blood metabolites around lambing in Ossimi ewes. The blood metabolites were investigated in ewes with single (n = 27) and multiple (n = 9) lambs at 3- and 1-week pre-lambing and 3-week post-lambing. The plasma concentrations of glucose were higher in single-bearing ewes than those in multiple-bearing ewes (p < .05), moreover, its lowest value was measured at 1-week prepartum in both groups. Throughout the study period, the serum concentrations of non-esterified fatty acids (NEFA) were significantly increased in ewes with multiple lambs compared to ewes with single lambs (p < .05), and the highest value was found at 1-week before parturition in both groups. In addition, the serum level of beta-hydroxybutyric acid (BHBA) was higher at 3-week postpartum, and it was significantly increased in multiple-bearing ewes than that in single-bearing ones (p < .05) at 3-week pre-lambing. In both groups, the lowest values of total proteins were determined 1-week before lambing, and its concentrations, at 3- and 1-week prepartum, were higher in ewes with single lambs than those with multiple lambs (p < .05). In contrast, the serum concentrations of albumin were significantly lowered 1-week postpartum (p < .05), and without significant differences between both groups (p > .05). The serum activities of aspartate aminotransferase (AST) and gamma-glutamyltransferase (GGT) were significantly increased at 1-week after parturition in both groups (p < .05). Furthermore, the serum activities of AST were higher in multiple-bearing ewes than those in single-bearing ones at 3-week pre-lambing and 3-week post-lambing (p < .05). Variable positive and negative correlations were determined among the blood metabolites. In conclusion, physiological adaptations are associated with the fluctuation of the blood metabolites around lambing. The higher the number of foetuses the higher the metabolic variations in Ossimi ewes. Therefore, regular metabolic profiling for health monitoring may be necessary to avoid disease development during the transition period.

[Relationship between body condition of dairy cows in the peripartum period and selected metabolic parameters in consideration of different breeds]. / Zusammenhänge zwischen Körperkondition von Milchkühen im peripartalen Zeitraum und ausgewählten Stoffwechselparametern unter Berücksichtigung verschiedener Rassen.

OBJECTIVE: The results of this study describe the relationship between the body condition of dairy cows and selected metabolic parameters during the peri- and post-partum period with special consideration of 3 local dairy cow breed in Upper Bavaria and the Allgau. MATERIAL AND METHODS: Three local dairy cattle breeds (Swiss Brown (BV), Simmental (FL), Holstein Friesian (HF)) were examined on 68 farms in southern Germany for 7 consecutive weeks. In dry cows as well as lactating cows (5.-65. day in milk), following blood parameters were investigated: beta-hydroxybutyrate (BHB), non-esterified fatty acids (NEFA), creatinine, aspartate aminotransferase, gamma-glutamyltransferase, glutamate dehydrogenase, total protein, albumin, creatine kinase. In addition, body condition (body condition score [BCS] and back fat thickness [BFT]) were recorded. Exploratory and descriptive statistics were used for data analysis. RESULTS: Concerning the difference in condition before and after calving, the FL showed the smallest difference in RFD. For FL and BV a trend towards higher BFT values could be seen in first lactating cows. For FL and HF, the NEFA values of the later lactating cows were below those of the first lactating cows. The higher lactating cows of BV and FL had higher BHB values. The correlation between BFT and BCS showed the highest R2 (0.53) in the HF cows. BV and FL were below at 0.42 and 0.37. BCS and BFT could not be predicted by the variables NEFA, BHB and liver enzymes. BHB levels of all 3 breeds increased at weeks 2-4 post-partum. The NEFA values for all 3 breeds increased primarily in the 1st-3rd week p.p. in parallel to when the BFT p.p. decreased. NEFA values were highest when body condition declined and therefore when fat mobilization peaked. In BV and HF, there was a constant increase in GLDH when the p.p. BCS difference was there. CONCLUSION AND CLINICAL RELEVANCE: Body condition assessment (BCS at herd and animals` level, BFT at animal level) is an important tool for animal health monitoring. Due to the recognizable breed specificity, the dairy herds can be dealt with more explicitly. The aim is to optimally influence the energy balance of the cow during early lactation in order maintain the health of the animal and its organ systems.

Mediating effect of adiponectin between free fatty acid and tumor necrosis factor-α in patients with diabetes.

BACKGROUND/OBJECTIVES: Increased free fatty acid (FFA) promotes adiponectin secretion in healthy subjects and induces inflammation in diabetes. Given the potential pro-inflammatory role of adiponectin in "adiponectin paradox", we performed this study in patients with type 2 diabetes mellitus (T2DM) to assess the association of FFA with adiponectin and to investigate whether adiponectin mediates FFA-related inflammation. METHODS: This cross-sectional study consisted of adult patients with T2DM. FFA, adiponectin, and tumor necrosis factor-α (TNF-α) were assayed from fasting venous blood after overnight fasting for at least 8 h. Multivariable linear regression analysis and restricted cubic splines (RCS) analysis were performed to identify the association between FFA and adiponectin. Mediation analysis was performed to determine the mediating effect of adiponectin on the association between FFA and TNF-α. RESULTS: This study included 495 participants, with 332 males (67.1%) and a mean age of 47.0 ± 11.2 years. FFA was positively associated with adiponectin (b = 0.126, 95%CI: 0.036-0.215, P = 0.006) and was the main contributor to the increase of adiponectin (standardized b = 0.141). The RCS analysis demonstrated that adiponectin increased with FFA when FFA was less than 0.7 mmol/L but did not further increase thereafter (Poverall < 0.001 and Pnon-linear < 0.001). In addition, adiponectin mediated the association between FFA and TNF-α. The mediating effect was 0.08 (95%CI: 0.03-0.13, P = 0.003) and the mediating effect percentage was 26.8% (95%CI: 4.5-49.2, P = 0.02). CONCLUSIONS: In patients with T2DM, FFA was positively associated with adiponectin when FFA was less than 0.7 mmol/L. Elevated adiponectin mediated FFA-related inflammation. This study may provide insights into the pro-inflammatory effect of adiponectin in T2DM.

Similar insulin regulation of splanchnic FFA and VLDL-TG in men with nonalcoholic hepatic steatosis and steatohepatitis.

This study aimed to determine whether obese men with nonalcoholic fatty liver disease (NAFLD) display differences between those with simple steatosis versus steatohepatitis (NASH) in splanchnic and hepatic FFA and VLDL-triglycerides (VLDL-TG) balances. The study involved 17 obese men with biopsy-proven NAFLD (9 with NASH and 8 with simple steatosis). We used hepatic vein catheterization in combination with [3H]palmitate and [14C]VLDL-TG tracers to measure splanchnic palmitate and VLDL-TG uptake and release rates during basal and hyperinsulinemic conditions. Indocyanine green was used to measure splanchnic plasma flow. Splanchnic palmitate uptake was similar in the two groups and significantly reduced during hyperinsulinemia (NASH: 62 (48-77) versus 38 (18-58) µmol/min; simple steatosis: 62 (46-78) versus 45 (25-65) µmol/min, mean (95% CI), basal versus clamp periods, respectively, P = 0.02 time-effect). Splanchnic palmitate release was also comparable between groups and nonsignificantly diminished during hyperinsulinemia. The percent palmitate delivered to the liver originating from visceral adipose tissue lipolysis was similar and unchanged by hyperinsulinemia. Splanchnic uptake and release of VLDL-TG were similar between groups. Hyperinsulinemia suppressed VLDL-TG release (P <0.05 time-effect) in both groups. Insulin-mediated glucose disposal was similar in the two groups (P = 0.54). Obese men with NASH and simple steatosis have similar splanchnic uptake and release of FFA and VLDL-TG and a similar proportion of FFA from visceral adipose tissue lipolysis delivered to the liver. These results demonstrate that the splanchnic balances of FFA and VLDL-TG do not differ between obese men with NASH and those with simple steatosis.

Metabolic Responses to High-Fat Feeding and Chronic Psychological Stress Combination.

INTRODUCTION: High-fat diet (HFD) consumption and being exposed to daily psychological stress, common environmental factors in modern lifestyle, play an important role on metabolic disorders such as glucose homeostasis impairment. The aim of this study was to investigate the effects of high-fat diet (HFD) and psychological stress combination on metabolic response to chronic psychological stress in male rats. METHOD: Male Wistar rats were divided into HFD, and normal diet (ND) groups and then into stress and nonstress subgroups. The diets were applied for 5 weeks, and psychological stress was induced for 7 consecutive days. Then, blood samples were taken to measure glucose, insulin, free fatty acids (FFA), and leptin and corticosterone concentrations. Subsequently, glucose-stimulated insulin release from pancreatic isolated islets was assessed. RESULTS: HFD did not significantly change fasting plasma glucose, insulin and corticosterone levels, whereas increased plasma leptin (7.05 ± 0.33) and FFA (p < 0.01) levels and impaired glucose tolerance. Additionally, HFD and stress combination induced more profound glucose intolerance associated with increased plasma corticosterone (p < 0.01) and leptin (8.63 ± 0.38) levels. However, insulin secretion from isolated islets did not change in the presence of high-fat diet and/or stress. CONCLUSION: HFD should be considered as an intensified factor of metabolic impairments caused by chronic psychological stress.