Search Results (375)

There are currently no approved therapeutic treatments targeting metabolic dysfunction-associated steatotic liver disease (MASLD). Albumin, a liver-produced plasma protein with anti-inflammatory and antioxidant properties, is reduced in advanced liver disease. Considering the role of chronic obesity-induced inflammation in MASLD pathogenesis, we investigated whether albumin administration could prevent disease progression to metabolic dysfunction-associated steatohepatitis (MASH). MASLD was induced in mice using a high-fat and high-cholesterol (PC) treatment for 8 weeks, followed by treatment with bovine serum albumin (BSA; 0.8 mg/kg) every three days for another 8 weeks. This regimen prevented time-dependent weight gain, regardless of diet, with 57% and 27% reductions in mice fed a standard chow (Std Chow) or PC diet, respectively. Further, supplementation reduced nuclear factor kappa B (NF-κB) activation by 2.8-fold (p = 0.0328) in PC-fed mice, consistent with albumin’s known anti-inflammatory properties. Unexpectedly, albumin also reduced hepatic neutral lipid accumulation and circulating non-esterified fatty acids. While PC-fed mice did not exhibit full progression to MASH, albumin treatment significantly increased hepatic matrix metalloproteinase-2 expression, suggesting the inhibition of early fibrotic signalling. While further studies are needed to elucidate the underlying mechanisms, these findings offer new insight into the potential of albumin, either alone or in combination with other therapies, to reduce hepatic steatosis in MASLD. Full article

This study evaluated the effects of dietary supplementation with omega-3 polyunsaturated fatty acids from extruded linseed, alone and combined with Padina pavonica algae extract, on growth performance and metabolic status in fattening rabbits. Sixty New Zealand White rabbits were assigned to three groups, as follows: control (CNT), L (5% linseed), and LPP (3.5% linseed + 0.2% algae extract) from weaning (37 days) to slaughter (85 days). Productive performance was assessed through body weight (BW), average daily gain (ADG), feed conversion ratio (FCR), and feed intake (FI). Blood was sampled at weaning, 60 days, and slaughter and analyzed for insulin, leptin, cortisol, thyroid hormones (T3, T4), glucose, and non-esterified fatty acids (NEFAs). The L group showed significantly higher ADG (41.0 ± 1 g/d) and improved FCR (4.1 ± 0.2) compared to LPP (ADG: 37 ± 1 g/d, FCR: 4.6 ± 0.2; p = 0.001). No differences were observed in final BW or FI among groups (p < 0.001). Insulin peaked at 60 days across all groups (p < 0.001), with the LPP group showing the lowest levels (9.8 ± 0.9 µUI/mL; p = 0.043). T3 and T4 increased significantly with age (p < 0.001), and the T3/T4 ratio varied by diet and time (p = 0.005). Cortisol rose only at slaughter (p < 0.001) and negatively correlated with insulin and thyroid hormones. The results suggest that omega-3-rich nutraceuticals can enhance growth performance without disrupting metabolic balance and may modulate specific hormonal responses due to their bioactive compounds. Full article

Fatty liver is a major metabolic disease in periparturient dairy goats. Protein ubiquitination, a type of dynamic and multifaceted post-translational modification, plays an important role in metabolism by regulating the stability and function of target proteins. However, the hepatic protein ubiquitination profile in dairy goats with fatty liver is yet to be elucidated. In this study, we collected liver and blood samples from healthy dairy goats (Con, n = 3) and dairy goats with fatty liver (FL, n = 3). Then, we analyzed the overall ubiquitination of hepatic proteins in dairy goats with fatty liver through quantitative ubiquitin label-free proteomics and bioinformatics. Proteins showing significantly altered levels of ubiquitination were identified via bioinformatics, and related regulatory pathways were screened. The results showed that the blood levels of beta-hydroxybutyric acid and non-esterified fatty acids were significantly upregulated in dairy goats with fatty liver, and a total of 238 ubiquitination sites across 921 proteins were found to be differentially altered in the fatty liver group. Among them, ubiquitination was upregulated at 351 sites across 93 proteins and downregulated at 570 sites across 145 proteins. In addition, GO and KEGG pathway analysis revealed that the differentially ubiquitinated proteins were enriched in pathways regulating lipid metabolism, such as the PPAR signaling pathway, fatty acid degradation, and peroxisome activity. Notably, by observing the overlap among these three sub-networks, we found that proteins with downregulated ubiquitination—such as ACSL1, ACSL5, EHHADH, and ACAA1—were transcriptionally upregulated in dairy goats with fatty liver. This study reveals the key ubiquitinated proteins in dairy goats with fatty liver and provides a more comprehensive understanding of the pathogenesis of fatty liver in dairy goats. Full article

Acetate is naturally produced in the rumen through feed degradation and fermentation. It serves as a primary energy source for ruminants and as a key substrate for de novo fatty acid synthesis in the mammary gland. The interaction of exogenous acetate with different animal and dietary factors is an area of growing interest, as it may have significant implications for milk fat synthesis. This study aimed to assess the effect of two diet fermentability levels on the short-term response of lactation to acetate supplementation in dairy cows. Eight ruminally cannulated multiparous European Holstein cows were randomly assigned to treatments in a crossover design that tested the effect of diet fermentability, acetate supply, and their interaction. Using corn silage as the only forage source and a constant forage-to-concentrate ratio, high-fermentability (HF) and low-fermentability (LF) diets were formulated. Acetate supply was investigated by infusing ruminally 10 moles of sodium acetate/d (ACE) or an equimolar infusion of control (CON). Therefore, the treatments were as follows: LF + CON; LF + ACE; HF + CON; and HF + ACE. No interactions between acetate and diet fermentability were found on performance variables. Acetate infusion decreased dry matter intake (DMI), milk yield, and milk protein yield and content but did not affect milk fat yield; however, it increased milk fat concentration, and this response tended to be more pronounced in the HF diet. Acetate infusions increased plasma β-hydroxybutyrate in the HF diet, but not in the LF diet, and increased plasma non-esterified fatty acid, which was likely a lipolysis response to reduced DMI and decreased energy balance. This study demonstrates that acetate availability can be a constraint on mammary lipogenesis, even with adequate dietary fiber. Full article

The transition period is defined as 3 weeks around parturition, involving the rapid increase in the energy demand, promoting adipose mobilization and non-esterified fatty acid (NEFA) release. High NEFA levels might cause oxidative stress and associated health risks, including the disruption of the immune capability of peripheral leukocytes. Nutrient supplementation of choline, which improves cellular lipid metabolism and controls lipid oxidation, potentially maintains the integrity of peripheral leukocytes and alleviates the impacts of increased NEFAs. This study investigated the effects of choline on bovine peripheral blood leukocytes (PBLs) treated with high levels of NEFAs. Peripheral blood mononuclear cells (PBMCs) and polymorphonuclear leukocytes (PMNs) were isolated from dry cows, and treated with 1 mM NEFA in combination with 0, 4, or 12 μM choline. The expression of pro-inflammatory cytokines and oxidative stress indicators was determined. This study demonstrates that 1 mM NEFA induces lipid oxidation and pro-inflammatory cytokine expression in PBLs. Supplementation with 4 μM and 12 μM choline significantly reduced NEFA-induced lipid oxidation; however, it did not affect pro-inflammatory cytokine mRNA expression. In conclusion, choline supplementation may help alleviate NEFA-induced oxidative stress in bovine peripheral blood leukocytes, highlighting its potential as a functional supplement during the transition period. However, it had no observable effect on mitigating pro-inflammatory responses, indicating that additional strategies may be needed to address NEFA-induced immune activation. Full article

Background: Curcumin, a bioactive polyphenol derived from turmeric, has demonstrated potential therapeutic effects in metabolic dysfunction-associated steatotic liver disease (MASLD) by modulating inflammation, oxidative stress, hepatic fat accumulation, and fibrosis. Objective: To evaluate the efficacy of curcumin in reducing hepatic steatosis and liver stiffness in patients with MASLD. Methods: In this randomized, double-blind, placebo-controlled trial, 78 patients with type 2 diabetes mellitus (T2DM) and MASLD were randomly assigned to receive either curcumin (1500 mg/day) or placebo for 12 months. The primary outcome was the change in tumor necrosis factor (TNF) levels. Secondary outcomes included changes in interleukin-1 beta (IL-1β), interleukin-6 (IL-6), antioxidant enzyme activities (glutathione peroxidase, superoxide dismutase), the oxidative stress marker malondialdehyde, non-esterified fatty acids, and hepatic parameters (hepatic steatosis and liver stiffness). Assessments were conducted at baseline and at 3, 6, 9, and 12 months. Results: All participants completed the study (curcumin group: n = 39; placebo group: n = 39). Curcumin significantly reduced TNF levels at all follow-up points compared to placebo (p < 0.001). IL-1β, IL-6, and malondialdehyde levels also declined significantly (p < 0.001), while antioxidant enzyme activities, including glutathione peroxidase and superoxide dismutase, increased significantly (p < 0.001), indicating improved oxidative balance. Furthermore, curcumin led to significant reductions in non-esterified fatty acids, total body fat, BMI, hepatic steatosis, and liver stiffness compared to placebo. Conclusions: Twelve months of curcumin supplementation improved glycemic control, reduced systemic inflammation and oxidative stress, and significantly improved hepatic steatosis and liver stiffness in patients with MASLD. These findings support curcumin as a promising adjunctive therapy for MASLD management. Full article

Forty multiparous Nellore cows, with an average body weight, body condition score, and gestation days of 533 ± 32 kg, 5.7 ± 0.4 points, and 198 days, respectively, were managed under continuous grazing on a Urochloa decumbens pasture and either received or did not receive 1 kg/day of supplement varying in the levels of inclusion of dried distillers grains (DDG) (Control, 0% DDG, 42% DDG, or 84% DDG) during the last trimester of gestation. The objective was to evaluate the effects of prepartum DDG supplementation on performance, reproduction, fetal development, and calf performance. A quadratic effect of supplementation on BW variation pre- and postpartum was observed (p < 0.05), with cows treated with 42% DDG showing higher BW gain prepartum and low BW loss postpartum. Cows supplemented with 42% DDG had lower levels of non-esterified fatty acids and β-hydroxybutyrate prepartum (p < 0.05). However, body weight-related metrics, such as condition score, carcass traits, and metabolic indicators, varied only by measurement day (p < 0.05). No effect of supplementation was observed on fetal development, calf metabolic profile, milk yield, or postnatal calf performance (p > 0.05). It is recommended to include up to 42% DDG in supplements for beef cows during late gestation grazing on low-quality tropical forage conditions. Full article

Metabolic and inflammatory stress during early lactation poses significant risks to dairy cow health and productivity. This study aimed to assess the physiological, metabolic, and inflammatory differences between dairy cows producing low (LL; <4.5%) and high (HL; ≥4.5%) milk lactose, focusing on C-reactive protein (CRP), liver function markers, iron metabolism, and reticulorumen health. A total of 71 clinically healthy lactating multiparous cows (20–30 days postpartum) were monitored using real-time physiological sensors, milk composition analysis, blood biomarkers and continuous reticulorumen pH measurement (every 10 min). Cows in the LL group showed significantly higher aspartate transaminase (AST) activity (p = 0.042), lower serum iron (Fe) concentration (p = 0.013), and reduced reticulorumen pH (p = 0.03). Although CRP concentrations did not differ significantly between groups, correlation analysis revealed positive associations with non-esterified fatty acids (NEFA) (r = 0.335, p = 0.043), reticulorumen pH (r = 0.498, p = 0.002), and body temperature (r = 0.372, p = 0.023). Receiver operating characteristic (ROC) analysis identified gamma-glutamyl transferase (GGT) (AUC = 0.66), AST (AUC = 0.63), and NEFA (AUC = 0.58) as moderate predictors of low milk lactose levels. Conversely, Fe (AUC = 0.66) and reticulorumen pH (AUC = 0.64) showed moderate ability to predict higher lactose content. These results support the integration of milk lactose, liver enzymes, and inflammatory biomarkers into precision health monitoring protocols. The combined use of CRP and milk lactose as complementary biomarkers may enhance the early identification of metabolic stress and support more targeted dairy herd health management. Full article

Elevated non-esterified fatty acid (NEFA) levels are closely associated with metabolic disorders in dairy cattle, yet their direct effects on adipocyte physiology remain poorly understood. In this study, we demonstrate that high NEFA concentrations significantly impair bovine adipocyte function by simultaneously inhibiting proliferation/differentiation (p < 0.01) and promoting pathological lipid deposition. Through integrated transcriptomic and functional analyses, we identified NDUFAB1 as a central metabolic regulator that counteracts NEFA-induced adipocyte dysfunction. Mechanistically, NDUFAB1 activation attenuates the cytotoxic effects of excessive NEFA exposure. These findings provide both fundamental insights into energy metabolism regulation and a potential therapeutic target (NDUFAB1) for preventing bovine metabolic diseases. Full article

Serum beta-hydroxybutyrate (BHB) and non-esterified fatty acids (NEFAs) are biomarkers of situations of negative energetic balance in bovine. However, knowledge about their possible measurement and use in saliva is limited. In this report, two commercially available methods for the measurement of BHB and NEFAs were validated for use in bovine saliva. Both methods showed good precision and accuracy. The BHB concentrations were correlated between the saliva and the serum, but not the NEFA concentrations. The cows with hyperketonemia (n = 17) had increased salivary BHB compared to the cows with no clinical signs and no hyperketonemia (n = 34) and those with clinical signs of metritis (n = 17). The salivary NEFA concentration increased in newborn calves (n = 10) on days 1 and 2 of life compared to the day of birth before colostrum intake. The calves with symptomatic bovine respiratory disease complex (BRD, n = 7) showed higher salivary NEFA concentrations than those without clinical symptoms (n = 6). Thus, BHB and NEFAs can be reliably measured in bovine saliva using easily automatable colorimetric methods. Salivary BHB increased in hyperketonemia and could be a potential biomarker of this condition. Further studies should be undertaken to clarify the mechanism and possible use of salivary NEFAs as biomarkers. Full article

Our study investigated the growth-related metabolic changes and microbial community dynamics during the early feeding stage of bullfrog (Lithobates catesbeiana) tadpoles. In this research, we examined the changes in fat accumulation patterns, as well as the levels of biochemical and enzymatic indicators and genes mRNA expression related to lipid metabolism across the endogenous, mixed, and exogenous nutritional stages of bullfrog tadpoles from a single mating pair. Simultaneously, we characterized the community structures of intestines, excreta, and water bodies during these stages using 16S rRNA high-throughput sequencing technology. Our findings reveal that fat accumulation in tadpole tissues gradually increases with the onset of feeding. Levels of alanine aminotransferase, aspartate aminotransferase, triacylglycerol, total cholesterol, non-esterified fatty acid, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol show a significant increase in exogenous nutritional stages. The mRNA levels of lipid synthesis-related genes and lipid degradation-related genes increased gradually with the changes of nutritional stage. Significant differences were observed in microbial community characteristics among intestines, excreta, and water bodies across nutritional stages. Specifically, gut microbiota exhibited a lower similarity to water body microbiota but a higher similarity to excreta microbiota. Notably, the phyla Firmicutes and Actinobacteriota, and the genus Cetobacterium within the gut microbiota, increased with nutritional changes. A Spearman correlation analysis highlighted a significant correlation between gut microbiota composition and lipid metabolism markers, particularly a strong positive association between Cetobacterium and lipid-related parameters. These insights provide a theoretical foundation for nutritional interventions aimed at enhancing tadpole growth and survival rates. Full article

Selenium-binding protein 1 (SeBP1) is an anticancer factor that affects lipid metabolism in mouse kidneys via the peroxisome proliferator-activated receptor-alpha (PPARA) pathway. However, its physiological role in the liver is difficult to explain because of the presence of the highly homologous selenium-binding protein 2 (SeBP2). To investigate the role of these proteins in the liver, we generated SeBP1 and SeBP2 double-knockout mice (SeBP1/2-DK). SeBP1/2 deletion did not significantly alter the mice phenotypic compared to that of the wild-type strain. Then, we identified the genes involved in hepatic lipid metabolism. The double knockout did not affect fatty acid and cholesterol synthesis, but inhibited fatty acid oxidation and cholesterol efflux. Furthermore, transfection of HepG2 cells with human selenium-binding protein 1 (hSeBP1) positively regulated PPARA and the genes controlled by it. Overexpression of hSeBP1 reduced the levels of non-esterified fatty acids in the culture medium. The serum levels of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides were significantly different among the three groups. In summary, we elucidated the potential signaling pathways of SeBP1 and SeBP2 in fatty acid oxidation and hepatic cholesterol efflux. Our findings provide insights relevant for developing new strategies to prevent and treat lipid metabolism disorders. Full article

A crucial component of small ruminant production, particularly where intensive systems are becoming more prevalent, is determining the forage-to-concentrate (F:C) ratio in their daily diets. The effects of the F:C ratio in lambs and goat kids’ daily diets on growth, stereotypical behavior, and blood biochemical parameters were investigated. Eighteen Tahirova sheep lambs and 18 Turkish Saanen goat kids were used, divided into three groups using the following F:C ratios: 20:80, 60:40, and 80:20. Growth rates, weight gains, and feed conversion ratios were determined. Urea nitrogen, glucose, non-esterified fatty acids, creatine kinase, and cortisol hormones were measured in blood samples. In lambs, growth remained consistent across F:C groups. In goat kids, however, the 20:80 group showed superior growth and weight gain. Based on the F:C ratios, behavioral differences were found in forage feeding, rumination, water consumption, and standing activities. Similarly, the 20:80 group displayed higher rates of bar biting, crib biting, and wool biting in lambs, as well as bar biting, crib biting, bucket biting, and chain chewing in goat kids. Cortisol levels were significantly higher in the 80:20 group than in the 20:80 group for both species. Insufficient forage can cause abnormal stereotypical behaviors, which negatively impact animal welfare. Full article

Background: Cannabidiol (CBD) exerts diverse metabolic effects, yet its influence on intestinal lipid metabolism remains unclear. Methods: In this study, we investigated whether short-term (one-week) CBD treatment affects lipid absorption and transport through the lymphatic system using a validated lymph fistula model. Results: CBD treatment significantly enhanced the transport of radiolabeled triglycerides through the lymphatic system. This effect appeared specific, as CBD did not substantially alter cholesterol output in the lymph. Chemical assays indicated that CBD treatment did not significantly alter total triglycerides, cholesterol, phospholipids, or non-esterified fatty acid levels in the lymph. However, it significantly enhanced the lymphatic output of apolipoprotein A4 (ApoA4) and apolipoprotein A1 (ApoA1). Additionally, gene expression analysis revealed a downregulation of vascular endothelial growth factor receptor 1 (Flt1) in the small intestine, leading to increased lymphatic lacteal permeability and altered lipid transport dynamics. Conclusions: These findings indicate that short-term CBD treatment modulates lymphatic lipid composition and apolipoprotein secretion by regulating lymphatic lacteal function, thereby influencing lipid transport and metabolism. This study provides novel insights into CBD’s role in facilitating TG-rich lipoprotein transport via the lymphatic system, highlighting its potential therapeutic applications in lipid-related disorders. Full article

Postpartum dairy cows often face significant challenges due to metabolic disorders. Danggui Buxue Tang (DBT), a botanical drug composed of Astragali radix and Angelica sinensis radix in a 5:1 ratio, has been recognized for its potential to alleviate metabolic disorders. Its regulatory mechanisms on livestock metabolic health have remained unexplored. This study integrated the analyses of serum pharmacochemistry, network pharmacology, serum metabolomics, and fecal microbiota to investigate the regulatory effects of DBT on metabolic adaptation in postpartum dairy cows. Following the oral administration of DBT, levels of blood non-esterified fatty acids and beta-hydroxybutyrate were decreased in multiparous dairy cows one week after calving. Five absorbed prototype metabolites of DBT were identified, specifically formononetin and nicotinic acid, both of which play roles in the regulation of lipid metabolic homeostasis. Furthermore, DBT modified the composition of the gut microbial community and glycerophospholipid levels. Decreases in serum phosphatidylethanolamine and phosphatidylcholine levels were closely correlated with the relative abundance of Bacillus and the concentration of circulating beta-hydroxybutyrate. These findings suggest that DBT contributes positively to metabolic health in postpartum dairy cows by regulating the gut microbiota and glycerophospholipid metabolism, providing new insights into strategies for promoting metabolic adaptation in dairy cows. Full article