Search Results (418)

Cold exposure is an unavoidable stressor in cold regions, leading to growth retardation, oxidative damage, and endocrine disruption. This study investigated changes in blood parameters and antioxidant function in the brown adipose tissue (BAT) of mice exposed to cold. Sixteen naturally mated female mice (aged 70 days) were selected and divided into a control group (CON, n = 8, 25 ± 1 °C) and a cold exposure group (CE, n = 8, 4 ± 1 °C). Each pregnant female gave birth to approximately 12 pups, and the litter (dams and pups co-housed) served as the independent experimental unit, with both euthanized for sampling when the pups reached 20 days of age. Results showed that cold exposure increased ADFI and ADG but decreased the feed conversion rate (FCR) in lactating mice. It also decreased platelet count (PLT) and mean corpuscular hemoglobin concentration (MCHC), elevated lactate dehydrogenase (LDH) activity, and decreased TG and non-esterified fatty acid (NEFA) levels. Hormonal changes included increased adrenocorticotropic hormone (ACTH), apelin 12 (AP12), INS, NE, decreased cortisol (COR), LEP, and thyroid-stimulating hormone (TSH). In pups, cold exposure inhibited growth, reduced PLT, plateletcrit (PCT), red blood cells (RBC), and hemoglobin (HGB), altered lipid profiles, and induced hormonal shifts. Notably, cold exposure enhanced the BAT antioxidant capacity in pups, increasing the total antioxidant capacity (T-AOC) and antioxidant enzyme activities, as supported by gene expression. These findings suggest that, despite growth suppression, mice maintain homeostasis by modulating blood parameters and enhancing BAT antioxidant function to mitigate cold-induced damage. Full article

We previously demonstrated that a clinically relevant dose of pemafibrate (PEM), a selective peroxisome proliferator-activated receptor α (PPARα) modulator (SPPARMα), reduces serum triglyceride (TG) levels in mice via hepatic PPARα activation. However, the specific contribution of hepatocyte PPARα remains unclear. To address this, male Ppara-floxed (Ppara^fl/fl) and hepatocyte-specific Ppara-disrupted (Ppara^ΔHep) mice were fed a diet with or without a clinically relevant dose of PEM (0.00005%) for four weeks. In Ppara^fl/fl mice, PEM significantly reduced circulating TG and non-esterified fatty acid levels by enhancing hepatic fatty acid uptake and β-oxidation. In contrast, these effects were absent in Ppara^ΔHep mice. Notably, PEM did not activate PPARα in extrahepatic tissues, including white/brown adipose tissue, kidney, and skeletal muscle in either genotype. These findings underscore the essential role of hepatocyte PPARα in mediating the pharmacological effects of PEM at clinically relevant doses. Full article

Reproductive efficiency in cattle is critically dependent on embryo quantity and quality, particularly in assisted reproductive technology (ART) programs such as superovulation, embryo transfer, and embryo production. Nutrition is a key determinant of embryo yield through its regulatory effects on metabolic signaling, ovarian function, oocyte competence, and early embryogenesis. This review synthesizes the current evidence describing mechanistic links between nutritional status and embryo production in dairy and beef cattle across both in vivo and in vitro systems. Energy balance, protein supply, micronutrients, and fatty acids influence metabolic hormones including insulin, insulin-like growth factor-1, and leptin, which regulate hypothalamic–pituitary–gonadal axis activity, follicular recruitment, and steroidogenesis. Negative energy balance disrupts endocrine signaling, elevates circulating non-esterified fatty acids, increases oxidative stress, and impairs oocyte mitochondrial function, resulting in reduced embryo yield, compromised blastocyst quality, and diminished cryotolerance. Targeted micronutrients such as selenium, zinc, vitamins A and E, B-complex vitamins, and omega-3 fatty acids enhance antioxidant capacity, membrane integrity, and epigenetic regulation, thereby supporting embryo viability and post-transfer survival. Furthermore, early-life nutrition programs long-term reproductive capacity by influencing ovarian reserve establishment and oocyte epigenetic competence. Strategic nutritional management is therefore essential to optimize ART outcomes and promote sustainable genetic progress in cattle production systems. Full article

Objective: The performance of chrono-impedance measurement, a novel electrochemical method for determining free fatty acids (FA), was evaluated in a real-world clinical setting. Methods: Patients presenting to the emergency department with chest pain or discomfort were included. Routine diagnostic tests were performed in accredited laboratories. Chrono-impedance was measured using a screen-printed carbon electrode connected to a dedicated potentiostat. Serum total free-FA levels were determined by gas chromatography with flame ionization detection. Results: Among 104 patients, 21 received a specific diagnosis, while the remaining 83 patients were discharged with non-specific pain. Mean free-FA level was 0.9 ± 0.6 mM. Palmitic, linoleic, stearic, oleic, and arachidonic acids accounted for 74.9% of total free FAs. Impedance plots showed a characteristic logarithmic increase over time for all patients. When instantaneous impedance values at four different time points (10, 100, 376.6, and 500 s) were examined, a significantly strong correlation was observed between impedance and FA molarity (r = 0.8312, 0.9897, 0.9947, and 0.9951) and FA weight (r = 0.9572, 0.9878, 0.9996, and 0.9998), respectively. Conclusions: Chrono-impedance demonstrated a very high correlation with total free-FA levels in real patient samples. Full article

Obesity is a complex metabolic disorder characterized by excessive accumulation of adipose tissue, resulting from an imbalance between energy intake and expenditure. It is associated with an increased risk of chronic diseases such as type 2 diabetes, cardiovascular disease, and cancer. Kefiran is a water-soluble exopolysaccharide produced by lactic acid bacteria, Lactobacillus kefiranofaciens, in kefir grains, composed primarily of glucose and galactose. It has garnered scientific interest due to its antioxidant, anti-inflammatory, and antimicrobial properties. Rice Kefiran (RK) is a functional food made with culturing L. kefiranofaciens in a medium containing rice. It is standardized to contain at least 5 mg/g of kefiran. This study investigated the anti-obesity effect of RK on a high-fat diet (HFD)-induced obese mouse model. HFD-fed mice exhibited marked increases in body weight gain (10.3 g vs. 2.0 g in controls) and adipose tissue mass (2.4 g vs. 0.4 g in controls). RK administration significantly attenuated weight gain to 8.3 g and 6.0 g at doses of 10 and 50 mg/kg, respectively, and reduced adipose tissue mass to 2.2 g (RK10) and 1.7 g (RK50). Oral glucose tolerance testing revealed impaired glucose clearance in HFD-fed mice, with blood glucose levels of 403.5 mg/dL at 15 min and 314.6 mg/dL at 120 min, compared with 348.8 mg/dL and 232.2 mg/dL in controls. RK treatment improved glucose tolerance, particularly at 50 mg/kg, reducing glucose levels to 359.0 mg/dL at 15 min and 263.8 mg/dL at 120 min. Biochemical analyses demonstrated that RK significantly reduced serum total cholesterol (213.6 mg/dL in HFD vs. 178.0 and 184.0 mg/dL in RK10 and RK50), triglycerides (379.0 mg/dL in HFD vs. 228.8 and 234.6 mg/dL), and non-esterified fatty acids (0.89 mEq/mL in HFD vs. 0.54 and 0.35 mEq/mL), while phospholipid levels remained unchanged. Furthermore, RK increased serum nicotinamide phosphoribosyltransferase (NAMPT) levels from 15.8 ng/mL in HFD-fed mice to 30.0 and 50.0 ng/mL in the RK10 and RK50 groups, respectively, and restored hepatic NAD⁺/NADH ratios toward control levels (1.78 µmol/L in HFD vs. 1.90 µmol/L and 2.07 µmol/L in RK10 and RK50). Gene expression analysis showed that RK increased Nampt mRNA expression and decreased the mRNA expression of adipogenic and lipogenic genes, including Srebp-1c, Acc-1, and Fas. These findings suggest that RK may ameliorate obesity-related metabolic disturbances and its associated metabolic dysfunctions by modulating lipid metabolism, glucose tolerance, and NAD⁺ biosynthesis pathways. Full article

The transition from energy sufficiency to deficiency triggers complex metabolic and immune adaptations that have traditionally been viewed through a reductionist pathological lens. During early lactation, coordinated mobilization of adipose tissue, muscle protein, and bone minerals supports milk synthesis, with ketogenesis specifically arising from hepatic oxidation of non–esterified fatty acids. This review introduces the Keto–Inflammatory Network (KIN), a novel framework positioning ketonemia as an evolutionarily conserved adaptive response rather than inherent metabolic dysfunction. The KIN integrates β–hydroxybutyrate (BHB) signaling with immune modulation, epigenetic regulation, circadian rhythms, and microbiota interactions. Through mechanisms including NLRP3 inflammasome inhibition, HDAC–mediated epigenetic modifications, and HCAR2 receptor activation, ketone bodies orchestrate anti–inflammatory responses while maintaining metabolic flexibility. Building upon important precedent work recognizing beneficial roles of ketones in ruminant metabolism, this review synthesizes recent advances in immunometabolism and systems biology into an integrated framework. The KIN encompasses calcium–ketone integration through the Calci–Keto–Inflammatory Code (CKIC), temporal regulation via the Ketoinflammatory Clock, and trans–kingdom signaling through microbiota interactions. In dairy cattle, this perspective reframes periparturient ketonemia as existing on a continuum from adaptive to pathological, with biological meaning determined by integrated metabolic–inflammatory patterns rather than absolute ketone concentrations. The CKIC paradigm, while requiring prospective validation, suggests novel therapeutic approaches leveraging ketone signaling for inflammatory diseases, autoimmune conditions, and metabolic disorders while challenging traditional threshold–based ketosis management strategies. This systems–level understanding opens new avenues for precision interventions that work with, rather than against, evolved adaptive mechanisms refined through millions of years of mammalian evolution. By distinguishing ketonemia (measurable ketone elevation) from pathological ketosis (dysregulated ketone accumulation), and by integrating evidence from both ruminant and monogastric models, this review provides a comprehensive framework for next–generation metabolic medicine. Full article

Sunite sheep are well-adapted to the cold Mongolian steppe, exhibiting robust metabolic flexibility in which adipose tissue contributes significantly to energy homeostasis. Proteomics analysis of scapular fat in Sunite sheep during winter and summer identified 432 upregulated and 493 downregulated differentially expressed proteins (DEPs). These DEPs were notably enriched in essential biological functions such as energy metabolism, lipogenesis, and thermogenesis. Furthermore, they exhibited significant enrichment of signaling pathways such as oxidative phosphorylation and fatty acid metabolism. Meanwhile, the precursor protein of asprosin (ASP),profibrillin-1 (pFBN1), showed a marked decrease during winter. Given that ASP had been demonstrated to exert metabolic regulatory effects promoting lipid synthesis and suppressing thermogenesis in model animals, it was hypothesized that the seasonal downregulation of pFBN1 might drive adaptive thermogenesis through ASP. Therefore, this study focused on functional validation of the ASP-encoding gene FBN1 (fibrillin-1). In Adipose-Derived Mesenchymal Stem Cells (ADMSCs), FBN1 was specifically downregulated through overexpressing of its regulatory factor miR-29b-1. The results indicated that downregulation of the FBN1 led to the inhibition of adipogenesis in ADMSCs. This was reflected by a reduction in the number of lipid droplets, a decrease in the expression of adipogenesis marker genes, and a significant drop in triglyceride levels. Furthermore, the reduction in FBN1 levels enhanced the thermogenic function of differentiated adipocytes derived from ADMSCs, as evidenced by enhanced expression of thermogenic marker genes, along with a notable rise in both uncoupling protein 1 (UCP1) and non-esterified fatty acid (NEFA) levels. Full article

Background: This study evaluated the effects of rumen-protected choline (RUPCHOL) supplementation in dairy cows from 21 days before calving to 28 days postpartum. The objective was to determine how RUPCHOL influences metabolic status, milk composition, and subsequent calf growth until weaning. Methods: Twenty-seven pregnant Holstein cows were assigned to a Control group (n = 13) or an RUPCHOL group (n = 14), both receiving a total mixed ration (TMR), with the RUPCHOL group supplemented with 15 g/day of choline chloride. Cows were monitored during prepartum, calving, and postpartum periods for body weight, body condition score, dry matter intake, rectal temperature, milk yield and composition, and blood metabolites. Results: RUPCHOL supplementation tended to reduce serum aspartate aminotransferase and lowered concentrations of non-esterified fatty acids and β-hydroxybutyrate, indicating improved metabolic status. Milk total solids, fat, and protein percentages were higher in RUPCHOL-fed cows, suggesting enhanced milk quality. Maternal supplementation did not affect colostrum immunoglobulin G (IgG) content or calf body weight and body measurements (heart girth, wither height, hip height, and body length) from birth to weaning. Conclusions: In summary, RUPCHOL supplementation improved indicators of metabolic health and milk composition of dairy cows during the peripartum period without altering calf growth outcomes. Full article

Background: Structured lipids, composed of re-esterified triacylglycerols containing eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and medium-chain fatty acids, may influence metabolism and endurance performance. This trial aimed to evaluate the effects of eight weeks of structured lipid supplementation on substrate utilization, erythrocyte fatty acid content, and endurance performance in healthy untrained men. Methods: In a double-blind, placebo-controlled, randomized design, 36 participants (18 per group) received either structured lipids or placebo supplementation for eight weeks. Pre- and post-supplementation assessments included maximal oxygen uptake, time to exhaustion, substrate oxidation during exercise at 65% VO_2max, and erythrocyte membrane fatty acid content. Non-parametric statistical methods were used to analyze within- and between-group differences. Results: After supplementation, the structured lipids group showed statistically significant within-group changes in substrate utilization, including lower respiratory exchange ratio and higher percentage fat oxidation, total fat oxidation, and mean fat oxidation rate. Statistically significant increases were also observed in erythrocyte EPA + DHA content and time to exhaustion. Compared with the placebo group, the structured lipids group showed statistically significant post-intervention differences in substrate oxidation, erythrocyte EPA + DHA levels, and time to exhaustion. Conclusions: Eight weeks of structured lipid supplementation increased erythrocyte membrane EPA and DHA and enhanced fat oxidation during moderate-intensity exercise in untrained men. Although endurance performance improved, the change was within natural variability and showed substantial interindividual differences. Further rigorously controlled studies are needed to determine whether these metabolic adaptations yield meaningful functional benefits. Full article

During the periparturient period, negative energy balance (NEB) in dairy cows leads to increased concentrations of non-esterified fatty acids (NEFA) in the blood, which can induce fatty liver disease and ketosis. Forkhead box protein A3 (FOXA3) is a key transcription factor that regulates liver metabolism; however, its specific role in the pathogenesis of fatty liver in dairy cows remains unclear. This study aimed to investigate the mechanism by which FOXA3 regulates hepatic lipid metabolism. We collected liver samples from dairy cows with fatty liver (n = 10) and from healthy cows (n = 10). Bovine primary hepatocytes were isolated from the liver tissue of calves (n = 5), followed by NEFA treatment, and we utilized FOXA3 overexpression, immunofluorescence, and RNA sequencing (RNA-seq) to conduct our analysis. Our results demonstrated that FOXA3 expression in the livers of cows with fatty liver was significantly lower than in healthy cows. NEFA treatment resulted in the downregulation of FOXA3 protein levels in hepatocytes, promoting triacylglycerol (TAG) accumulation and the expression of lipogenesis-related genes. Conversely, FOXA3 overexpression mitigated NEFA-induced lipid accumulation, inhibited the expression of lipogenesis-related genes and proteins—particularly SREBP1—and affected cell proliferation, and the intracellular localization of FOXA3 and SREBP1. RNA-seq analysis suggested that FOXA3 may influence hepatic lipogenesis through pathways such as PI3K-Akt and the cell cycle. In summary, FOXA3 mitigates NEFA-induced hepatic lipid accumulation through a dual mechanism: regulating SREBP1 expression and inhibiting cellular proliferation. These findings highlight FOXA3′s potential as a novel target for the prevention and treatment of fatty liver disease in dairy cows. Full article

The transition period, spanning approximately three weeks before and after parturition, represents one of the most critical physiological windows in dairy production. Profound metabolic, endocrine, and immune adaptations occur as the cow shifts from gestation to lactation, predisposing high-yielding cows to oxidative stress, inflammation, and metabolic imbalance. Negative energy and metabolisable protein balances stimulate extensive lipolysis and the accumulation of non-esterified fatty acids (NEFAs) and β-hydroxybutyrate (BHBA), which can impair hepatic function and postpartum performance. This review integrates recent advances in the understanding of metabolic and immunometabolic regulation during transition, emphasising the interplay among energy metabolism, oxidative stress, and immune dysregulation. It critically re-evaluates current nutritional interventions including controlled-energy and negative DCAD diets, rumen-protected polyunsaturated fatty acids, and methyl donor amino acids while highlighting the emerging potential of injectable trace minerals as adjunct strategies to improve metabolic resilience. The review concludes by outlining remaining knowledge gaps and proposing a framework linking physiological mechanisms with targeted nutritional management. Full article

The purpose of this study was to investigate the effect of capsaicin (CAP) on lipid metabolism in weaned piglets and its related mechanisms. Twenty-four weaned piglets with an initial body weight of 9.00 ± 0.30 kg were randomly divided into three groups, with eight replicates in each group. The control (CON) and lipopolysaccharide (LPS) groups were fed a basal diet, while the LPS and capsaicin group (LCA) received the basal diet supplemented with 4 mg/kg pure capsaicin (delivered via 800 mg/kg additive) for 35 days. About 4 h before sampling, piglets in the LPS and LCA groups were intraperitoneally injected with LPS at a dose of 100 μg/kg body weight, while those in the CON group were intraperitoneally injected with the same dose of normal saline. In this study, we found that the addition of 800 mg/kg CAP to the diet of piglets significantly reduced the accumulation of serum triglyceride (TG), non-esterified fatty acids (NEFA), and liver fat, and that CAP up-regulates expression of genes and proteins in the PPARα pathway, consistent with enhanced fatty acid oxidation. The intervention with 4 mg/kg CAP was also found to down-regulate cholesterol synthesis precursors (such as mevalonate, MVA), reduce pro-inflammatory phospholipids (such as phosphatidic acid–phosphatidylcholine, PA–PC), and modulate bile acid metabolism, thereby beneficially regulating blood lipid profiles (TC, TG, LDL-C) and disrupting the “lipid metabolism–inflammation” interaction cycle. Furthermore, CAP promoted fatty acid β-oxidation and bile acid metabolism by activating the TRPV1 channel, which alleviated hepatic lipid accumulation. These findings indicated that CAP has potential application value in improving lipid metabolism, intestinal health, and immune function in weaned piglets. However, its long-term safety and dose-dependent effects require further investigation. Full article

Differences in metabolic traits between traditional and modern pig breeds may influence their physiological responses to stress hormones. This study evaluated the in vivo metabolic effects of an acute adrenaline challenge in Iberian (obese, slow-growing) and Landrace (lean, fast-growing) pigs (Sus scrofa domesticus). Four Iberian and five Landrace barrows (≈50 kg body weight; BW) fitted with a carotid catheter received an injection of adrenaline (3 µg/kg BW), and serial blood samples were collected for 105 min. Adrenaline transiently increased plasma glucose (p < 0.001) and lactate (p < 0.001) concentrations, both peaking at 5 min post-injection. Iberian pigs showed higher plasma lactate (1.26 vs. 1.03 mM; p = 0.002), triglycerides (0.34 vs. 0.27 mM; p < 0.001), and non-esterified fatty acids (NEFA; 0.38 vs. 0.29 mM; p = 0.021), but lower glucose (4.80 vs. 5.03 mM; p = 0.010) than Landrace pigs, while cholesterol remained unaffected (p > 0.10). No breed × time interaction was detected for any metabolite. The relative increase in glucose reached +47% in Iberian and +27% in Landrace pigs, whereas lactate rose +140% and +113%, respectively, indicating stronger glycolytic activation in Iberian pigs. Despite the limited sample size, the results provide physiologically relevant evidence supporting increased metabolic flexibility in Iberian pigs, characterized by a heightened sensitivity to adrenergic stimulation and associated with enhanced lipolytic and glycolytic responses; however, these conclusions should be interpreted within the specific experimental conditions under which the study was conducted. These findings demonstrate that Iberian pigs have higher metabolic sensitivity to adrenergic stimulation, with enhanced lipolytic and glycolytic activity. In conclusion, breed-dependent differences in stress-related metabolism suggest that Iberian pigs are furnished with increased metabolic flexibility to face short-term stress. Full article

This study investigated the metabolic mechanisms driving physiological functional remodeling in RFM by analyzing plasma biochemical parameters and metabolomic profiles at key peripartum timepoints (21 and 7 d prepartum and 4 h postpartum), integrated with placental and fetal membrane metabolic characteristics. The results revealed that RFM cows exhibited significant negative energy balance (NEB) as early as 21 days before parturition, characterized by elevated plasma levels of non-esterified fatty acids, β-hydroxybutyrate, and malondialdehyde, alongside reduced activity of antioxidant enzymes (GSH-Px, CAT) (p ≤ 0.05). Metabolomic analysis demonstrated persistent lipid metabolism dysregulation, amino acid imbalance, and nucleotide metabolism disturbances in RFM cows from 21 days prepartum to 4 h postpartum, indicating premature mobilization of adipose and muscle tissues. Further metabolomic analyses of the placenta and fetal membranes confirmed that metabolic dysfunction compromises energy supply during parturition, adversely affecting immune homeostasis and extracellular matrix degradation in the placenta and fetal membranes of RFM dairy cows. These physiological dysfunctions have the potential to impede the timely expulsion of fetal membranes after calving. In conclusion, RFM is closely associated with early-onset metabolic dysfunction during the periparturient period, where insufficient energy supply due to NEB, oxidative stress, and immune-endocrine disruptions collectively impair normal fetal membrane detachment. Full article

Background/Objectives: Variants in the lipoprotein lipase (LPL) gene have been associated with lipid level variability and obesity; however, their role in energy homeostasis remains unclear. The aim of this study was to investigate the association of LPL single-nucleotide variants (SNVs) with lipid parameters and leptin concentrations in a cohort of prepubertal children. The sample population comprised 635 boys and 631 girls, with available information on lipid profiles and leptin levels. Methods: Five LPL SNVs (rs258, rs316, rs326, rs320, and rs328) were genotyped by Real-Time PCR using predesigned TaqMan™ Genotyping Assays. Results: An association of the LPL SNV rs258 was found with non-esterified fatty acid (NEFA) levels in males and with leptin concentrations in both sexes. On the other hand, an association of the LPL SNV rs326 was observed with low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (Apo-B) levels, displaying opposite trends in males and females. No significant associations with any of the parameters under study were observed for the remaining LPL SNVs. Conclusions: These results suggest that functional differences among LPL SNVs may either be related to an enhancement of catalytic activity or modulation of lipoprotein binding affinity, influencing the efficiency of remnant lipoprotein clearance. Full article