Search Results (166)

This study investigated choline’s effects on endogenous phospholipid synthesis in Chinese mitten crab (Eriocheir sinensis). Chinese mitten crabs (0.40 g ± 0.03 g) were fed diets supplemented with 0%, 0.2% or 0.4% choline with low phospholipids (low-PL) or normal phospholipids (normal-PL) for eight weeks. Feeding the Chinese mitten crab with 0.4% choline in low-PL diets up-regulated significantly the relative mRNA expressions of neuropathy target enzyme 1 (nte1), phospholipase A2 (pla2) and phospholipase B (plb). Moreover, the crabs fed the 0.4% diet at low-PL diets enhanced hepatopancreatic fatty acid binding protein 3 (fabp3), fatty acid transporter protein 4 (fatp4), carnitine palmitoyltransferase-2 (cpt-2), carnitine acetyltransferase (caat), carnitine palmitoyltransferase-1a (cpt-1a) and carnitine palmitoyltransferase-1b (cpt-1b). However, feeding the mitten crabs 0.2% choline in the normal-PL diets diets up-regulated significantly the relative mRNA expressions of nte1, pla2 and plb. These results indicate that 0.4% choline up-regulates the expressions of genes involving in phospholipids synthesis of Chinese mitten crab fed with low-PL diets, while 0.2% choline improved the genes involved in phospholipid decomposition in normal-PL conditions. Full article

Juvenile hormone (JH) analog insecticides are widely used in pest management because of their ability to disrupt insect growth and metamorphosis; however, the molecular mechanisms linking endocrine disruption to metabolic dysregulation remain incompletely understood. In addition to their established roles in diapause and developmental regulation, JH signaling pathways have also been implicated in carbohydrate and lipid metabolism. In the present study, we investigated the effects of two JH analogs, pyriproxyfen and hydroprene, on the migratory locust, Locusta migratoria, with particular emphasis on lipid metabolic regulation and the function of midgut-enriched fatty acid-binding protein gene (Mg-FABP). Bioassays were performed to evaluate insecticidal activity, and transcriptomic analyses were conducted to identify differentially expressed genes associated with endocrine signaling and lipid metabolism. Functional characterization of Mg-FABP was further performed using RNA interference (RNAi) and Oil Red O staining assays. In addition, the tertiary structure of LmMg-FABP was predicted using AlphaFold 3, and molecular docking analyses were carried out to investigate its interactions with fatty acid ligands. Both pyriproxyfen and hydroprene caused approximately 70% mortality in locust nymphs and induced significant transcriptional changes in pathways related to hormone signaling and lipid metabolism. Transcriptomic analysis revealed pronounced downregulation of Mg-FABP following JH analog exposure. RNAi-mediated silencing of Mg-FABP significantly reduced lipid droplet accumulation in the fat body, indicating that Mg-FABP plays an essential role in lipid transport and metabolic homeostasis in L. migratoria. Structural analyses further demonstrated that LmMg-FABP possesses a conserved tertiary structure highly similar to FABP homologs from other insect species. Molecular docking identified key amino acid residues involved in fatty acid binding and suggested that hydrophobic interactions are critical for ligand stabilization within the binding cavity. Collectively, our findings demonstrate that pyriproxyfen and hydroprene disrupt insect development not only through endocrine imbalance but also through perturbation of Mg-FABP-associated lipid metabolic pathways. This study provides new mechanistic insight into the coordinated interaction between hormonal signaling and lipid metabolism during JH analog exposure and identifies FABP-mediated lipid transport as a potential molecular target for the development of more selective insect growth regulators. Full article

The rate of fatty acid (FA) uptake by cells depends on the presence of the CD36 receptor on the cell surface. However, unesterified FAs cannot circulate freely in plasma; they are bound to serum albumin. The molecular mechanisms of FA transfer from albumin to CD36 remain poorly understood. This study used macromolecular docking and molecular dynamics methods to investigate the interaction of the CD36 receptor with human serum albumin (HSA) loaded with oleic acid at the FA1-7 fatty acid-binding sites, with the aim of identifying potential mechanisms of FA transfer from HSA to CD36. The data obtained indicate that the interaction of HSA with CD36 does not result in direct FA transfer, but rather causes a local weakening of the affinity of individual FA sites on HSA. A comparative analysis was performed between the interaction interfaces predicted by macromolecular docking and those generated by AlphaFold 3. To further evaluate the influence of ligand nature, an additional molecular docking of HSA loaded with saturated (palmitic, PALM) and polyunsaturated (arachidonic, ARA) acids to the CD36 receptor was performed. This revealed a marked sensitivity of the protein–protein interface architecture to the type of lipid ligand, with the effect of ARA being more pronounced than PALM. Conversely, an alternative structure prediction using the AlphaFold3 algorithm demonstrated the opposite trend, indicating high geometric invariance and reproducibility of the complex. Ultimately, the proposed dynamic mechanism expands our understanding of the multi-stage processes governing FA transport across the endothelium. Full article

(1) Background: Cardiovascular disease represents the leading cause of morbidity and mortality in patients with autosomal dominant polycystic kidney disease (ADPKD), often developing early in the disease course, even in the presence of preserved renal function. We aimed to evaluate circulating heart-type fatty acid–binding protein (H-FABP) as a marker of subclinical cardiac involvement and cardiorenal interaction in ADPKD. (2) Methods: In this single-center observational study, 80 adult patients with ADPKD receiving tolvaptan therapy were evaluated using echocardiography, renal function parameters, and circulating H-FABP levels. Associations between H-FABP and echocardiographic indices of cardiac structure and function, as well as renal parameters, were assessed using linear regression models. In addition, a composite severity score integrating CKD stage and H-FABP levels was constructed to assess the combined cardiorenal burden. (3) Results: Higher H-FABP concentrations were significantly associated with echocardiographic markers suggestive of subclinical cardiac involvement, particularly parameters related to impaired myocardial relaxation, including lower E/A ratio and reduced tissue Doppler e′ velocities. These associations remained significant after adjustment for renal function and relevant clinical covariates. In parallel, H-FABP levels were also associated with markers of renal disease severity, including lower baseline eGFR and greater total kidney volume. The composite severity score showed a graded association with echocardiographic parameters, with a progressive trend toward less favorable diastolic indices as risk categories increased. These findings suggest a potential complementary role for H-FABP in the integrated evaluation of cardiorenal involvement in ADPKD. Given the cross-sectional design and single-centre setting, these results should be considered hypothesis-generating and require prospective validation in larger, independent cohorts. Full article

Polycystic ovary syndrome (PCOS) is frequently accompanied by visceral obesity, insulin resistance, low-grade chronic inflammation, and metabolic syndrome (MetS). These alterations promote significant dysfunction in adipose tissue and liver metabolism through cytokine production. Growing evidence indicates that the interaction between hepatokines and adipokines plays a central role in the development of metabolic and hepatic abnormalities in women with PCOS. This narrative review was conducted to analyze the relationship between adipose tissue dysfunction and liver metabolic impairment in women with PCOS, emphasizing the involvement of hepatokines and adipokines in insulin resistance, inflammation, hepatic steatosis, hepatic fibrosis and MetS. From this perspective, contemporary clinical, biochemical, and molecular studies were reviewed to evaluate how adipocyte-derived factors and hepatocyte-derived cytokines influence metabolic homeostasis in the liver and adipose tissue in women with PCOS. Increased visceral adiposity in PCOS enhances the release of free fatty acids (FFAs) to the liver, resulting in hepatotoxicity, oxidative stress, and hepatic inflammation. Several hepatokines, including fetuin-A, angiopoietin-like protein 3 (ANGPTL3), selenoprotein P(Sep-P), and hepassocin (HPS), show abnormal circulating levels in PCOS and are strongly associated with insulin resistance, dyslipidemia, and progression to hepatic steatosis. In contrast, fibroblast growth factor 21 (FGF-21), follistatin, and interleukin (IL-6) may exert dual effects. Adipokines, such as resistin, visfatin, apelin, and retinol-binding protein 4 (RBP-4), contribute to chronic inflammation, impaired glucose metabolism, androgen excess, and hepatic steatosis and fibrosis. Some of these adipokines, such as leptin and vaspin, may exert both beneficial and detrimental effects, while others, including chemerin and omentin, appear to play predominantly beneficial roles in metabolism. Reduced adiponectin-to-leptin levels further aggravate metabolic dysfunction. These changes indicate that adipose tissue–liver crosstalk is a key mechanism linking PCOS and MetS. Overall, metabolic disturbances in PCOS are strongly mediated by dysregulated communication between adipose tissue and the liver. Altered hepatokine and adipokine profiles contribute to insulin resistance, liver dysfunction, hypertension and the development of MetS in women with PCOS. Understanding these intricate interactions may support the early identification of high-risk patients and the development of targeted therapeutic strategies. Full article

Per- and polyfluoroalkyl substances (PFAS) are persistent chemicals with substantial bioaccumulation potential, but their distribution between blood and urine in humans remains poorly characterized. In this review, we assessed the urine-to-blood concentration ratio (UtBCR) as a potential indicator of PFAS bioaccumulation by integrating evidence from human biomonitoring studies and protein-binding data. We summarized PFAS concentrations in human serum and urine across general and highly exposed populations and identified clear compound-specific differences in blood–urine partitioning. We further examined the associations of UtBCR with carbon chain length, biological half-life, and binding-related parameters for human serum albumin (HSA), liver fatty acid-binding protein (L-FABP), and several renal transporters. Pairwise correlation analysis and partial least squares regression indicated that UtBCR was closely associated with major toxicokinetic determinants, particularly protein-binding affinity, carbon chain length, and biological half-life. Parameters related to FABP, HSA, urate transporter 1 (URAT1), and organic anion transporter 4 (OAT4) showed more consistent associations with UtBCR than those related to organic anion transporters 1(OAT1) and organic anion transporter 3 (OAT3), suggesting that plasma/tissue binding and tubular reabsorption may contribute more than active tubular secretion to PFAS blood–urine partitioning. Overall, UtBCR appears to be a useful toxicokinetic metric for comparing the relative bioaccumulation potential of PFAS. Full article

We previously demonstrated that fatty acid-binding protein 3 (FABP3) is significantly upregulated in ischemic neurons, and its inhibition mitigates ischemic brain injury in mice and attenuates mitochondrial damage under rotenone-induced oxidative stress. These findings suggest a potential role for FABP3 in mitochondrial dysfunction in ischemic neurons, although the underlying mechanism remains unclear. In this study, we further investigated the role of FABP3 in mitochondrial injury and apoptosis in ischemic neurons. Our findings indicated that FABP3 deficiency significantly decreased infarct volume following middle cerebral artery occlusion/reperfusion (MCAO/R) in mice, improved cognitive and spontaneous activity deficits, and suppressed BAX activation and mitochondrial translocation, caspase-3 activation, and cytochrome c release. In HT22 cells subjected to oxygen-glucose deprivation/reoxygenation (OGD/R), FABP3 deficiency increased cell viability, reduced apoptosis, and alleviated the loss of mitochondrial membrane potential. Conversely, FABP3 overexpression further exacerbated mitochondrial dysfunction and apoptosis, effects that were partially reversed by the BAX inhibitor BAI1. Furthermore, FABP3 overexpression promoted abnormal mitochondrial lipid accumulation and increased lipid peroxidation. Both the mitochondria-targeted antioxidant MitoQ and the ferroptosis inhibitor Ferrostatin-1 alleviated FABP3 overexpression-induced mitochondrial damage and apoptotic signaling. Collectively, our findings suggest that FABP3 is an important promoter of cerebral ischemia–reperfusion injury. FABP3 may aggravate ischemic neuronal injury by promoting abnormal mitochondrial lipid accumulation and lipid peroxidation, thereby enhancing BAX-dependent mitochondrial apoptotic signaling. Targeting FABP3 may provide a potential therapeutic strategy for neuroprotection in ischemic stroke. Full article

In this paper, we review the literature regarding metformin’s action on blood lipid concentrations in metformin-treated diabetic patients. Published data indicate that metformin reduces serum total cholesterol (T-C), LDL-cholesterol (LDL-C) and triacylglycerol (TAG) concentrations and raises serum HDL-cholesterol (HDL-C) concentrations in diabetic patients. The beneficial effect of metformin on serum lipid profiles in diabetic patients can result from (a) its action on AMP-activated protein kinase, which inhibits lipogenesis and cholesterol synthesis and stimulates fatty acid oxidation; (b) decreased plasma TAG concentrations, via promoting VLDL-TAG clearance by brown adipose tissue; (c) the inhibition of nuclear factor erythroid 2-related factor 2 (Nrf2) gene expression, affecting lipid profile in diabetic patients; (d) the inhibition of the expression of genes encoding proprotein convertase subtilisin/kexin 9 (PCSK9) and lipogenic enzymes; (e) the downregulation of carbohydrate-response element-binding protein (ChREBP), which affects liver TAG and cholesterol synthesis from acetate formed by gut microbiota; (f) the inhibition of angiopoietin-like 3 protein (ANGPTL3) gene expression, and consequent effects on plasma TAG concentrations; (g) the activation of AMPK, which inhibits LXRα activity; and (h) reverse cholesterol transport. In conclusion, one can assume that beyond its primary antihyperglycemic effect, metformin exerts pleiotropic effects that modulate lipid metabolism and blood lipid profile in T2D patients. These beneficial effects of metformin on blood lipid profile may play a role in the reduction in cardiovascular risk in diabetic patients. Full article

Background: Peripheral artery disease (PAD) impacts more than 200 million individuals globally. Despite its prevalence, management remains suboptimal, partly due to the lack of reliable blood-based biomarkers. The ankle–brachial index (ABI), the current gold-standard test for PAD, is limited by inter-operator variability, misinterpretation, and reduced accuracy in patients with diabetes. Fatty acid binding protein 3 (FABP3) has emerged as a potential biomarker for PAD; however, its prognostic performance relative to ABI remains unclear. This study compared FABP3 and ABI for predicting PAD outcomes using statistical and machine learning approaches. Methods: A total of 1001 participants were prospectively recruited, including 644 patients with PAD and 357 without PAD. The primary outcome was 2-year major adverse limb event (MALE), defined as a composite of vascular intervention, major amputation, or acute limb ischemia. At enrollment, plasma FABP3 was quantified using a validated multiplex immunoassay. Kaplan–Meier analysis of MALE-free survival was performed across pre-specified FABP3 tertiles (high [>3.55 ng/mL], moderate [1.55–3.55 ng/mL], and low [<1.55 ng/mL]) and ABI tertiles (severe [<0.40], moderate [0.40–<0.70], and mild [0.70–0.90]), with curve separation assessed using log-rank tests. Multivariable Cox proportional hazards modelling was used to evaluate the independent relationships of FABP3 and ABI with 2-year MALE after adjustment for baseline demographic and clinical covariates. To assess predictive performance for 2-year MALE, an extreme gradient boosting (XGBoost) classification model incorporating 10-fold cross-validation was trained using a combination of clinical covariates, plasma FABP3 levels, and ABI. Discriminatory performance was assessed using the area under the receiver operating characteristic curve (AUC). Results: The average participant age was 68 years (SD 12), and 34% (n = 340) were women. Mean ABI was 0.75 ± 0.25 and mean FABP3 concentration was 2.97 ± 2.06 ng/mL. Among the 644 participants with PAD, 558 (86.6%) had complete time-to-event data for MALE status, FABP3, and ABI. Over the median follow-up period of 2 years, 140 (25.1%) participants with PAD experienced MALE. Kaplan–Meier analyses demonstrated significant separation in MALE-free survival across FABP3 tertiles (log-rank p < 0.001). At 24 months, MALE-free survival was 100.0% in the FABP3 < 1.55 group, compared with 71.1% in the FABP3 1.55–3.55 group and 67.7% in the FABP3 > 3.55 group. In contrast, ABI severity groups showed less pronounced separation, with 24-month MALE-free survival rates of 80.3% for mild ABI, 73.2% for moderate ABI, and 71.3% for severe ABI, without a statistically significant overall difference (p = 0.170). In adjusted Cox proportional hazards models, FABP3 demonstrated strong prognostic performance for 2-year MALE. A 1 SD increase in log-transformed FABP3 was independently associated with a higher risk of 2-year MALE (HR 1.90, 95% CI 1.60–2.25; p < 0.001), with minimal change after additional adjustment for ABI (HR 1.90, 95% CI 1.60–2.24; p < 0.001). Machine learning analyses similarly favored FABP3 over ABI, with the FABP3-based model achieving an AUC of 0.773 compared to 0.686 for the ABI-based model. Adding ABI to the FABP3 model did not improve discrimination. Conclusions: Circulating plasma levels of FABP3 are strongly associated with PAD outcomes. Specifically, FABP3 demonstrated a stronger and more robust association with 2-year MALE compared to ABI. This study validates the prognostic value of FABP3 for PAD outcomes in comparison to ABI. Full article

Background/Objective: Peripheral arterial disease (PAD) is a widespread but underdiagnosed manifestation of systemic atherosclerosis, associated with high morbidity and mortality. Traditional diagnostic methods such as the ankle-brachial index (ABI) have limited sensitivity in certain populations, highlighting the need for reliable blood-based biomarkers. Fatty Acid Binding Protein 3 (FABP3) has emerged as a robust biomarker with diagnostic utility in PAD. To evaluate the diagnostic performance of FABP3 when used in combination with traditional clinical risk factors for PAD in patients presenting to vascular surgery clinics. Methods: A retrospective analysis was conducted on 657 patients presenting to ambulatory vascular surgery clinics at St. Michael’s Hospital. Two logistic regression models were compared: (1) Model A: Included standard clinical risk factors (calf pain, age, smoking, diabetes, hypertension, hypercholesterolemia, coronary artery disease, and signs of chronic limb-threatening ischemia); and (2) Model B: Included the same factors as Model A, plus FABP3 levels. Diagnostic metrics including area under the curve (AUC), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy were assessed. Results: Among 657 patients, 423 had PAD and 234 did not. Model B (FABP3-integrated model) outperformed Model A, with a higher AUC (0.86 vs. 0.82), sensitivity (96% vs. 81%), specificity (84% vs. 67%), PPV (92% vs. 81%), NPV (94% vs. 65%), and diagnostic accuracy (93% vs. 76%). FABP3 also improved detection in asymptomatic PAD patients (84% detected vs. 0%). Conclusions: Integrating FABP3 with standard clinical risk factors significantly improves PAD diagnosis, especially in asymptomatic and borderline cases. These findings support the potential role of FABP3 in routine PAD screening, warranting further prospective studies for validation. Full article

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by dysbiosis of the gut microbiota. Helminth infections are known to modulate host immunity and intestinal microbial composition; however, the therapeutic use of live parasites poses safety challenges. The recombinant Fasciola hepatica fatty acid-binding protein Fh15 is a helminth-derived molecule with anti-inflammatory effects in models of septic shock and dextran sulfate sodium (DSS)-induced colitis. Whether Fh15 also influences gut microbial composition during colitis remains unknown. Male C57BL/6 mice received 4% DSS in drinking water for 7 days to induce colitis and were treated intraperitoneally with Fh15 (2 mg/kg) on days 1, 3, and 5. Fecal samples were collected on days 2, 4, and 7 for 16S rRNA gene sequencing. Standard microbiota pipelines were used to evaluate community diversity. Acute DSS treatment disrupted gut microbial diversity and community structure compared with non-colitic controls. Fh15 treatment partially restored early microbial balance by shifting microbial composition toward that of healthy mice and reducing microbial dispersion, indicating enhanced community stability despite severe dysbiosis. Although alpha diversity did not return to control levels, Fh15 mitigated the expansion of pro-inflammatory genera (Enterococcus and Turicibacter) and preserved beneficial taxa, including Adlercreutzia. Full article

Purpose: To study the time course of the differentiation process and its regulatory networks in primary limbal epithelial cells (pLECs) using serum-free, low calcium Keratocyte growth medium 3 (KGM3) and CnT-2D differentiation medium. Methods: pLECs were isolated from corneoscleral rims from healthy donors and cultured in serum-free low calcium (0.06 mM Ca²⁺) KGM3. Differentiation was induced by supplementation with CnT-2D differentiation medium, while control cells were maintained in low-calcium KGM3 medium. Gene and protein expression analyses were performed using qPCR and Western blotting, respectively, at 72 h and at 5, 7, 10, and 14 days post-supplementation to determine the optimal time course of differentiation induction. Results: CnT-2D differentiation medium supplementation resulted in a significant upregulation of differentiation-associated markers, including desmoglein 1 (DSG1), paired box domain 6 (PAX6), keratin 3 (KRT3), fatty acid binding protein 5 (FABP5), cellular retinoic acid binding protein 2 (CRABP2), alcohol dehydrogenase 7 (ADH7), aldehyde dehydrogenase 1A1 (ALDH1A1), with the most pronounced changes observed at day 10 post-supplementation (p ≤ 0.05). Conclusions: CnT-2D differentiation medium effectively initiates differentiation of limbal epithelial cells in vitro. The gradual increase in the expression of key differentiation markers, including DSG1, KRT3, and PAX6, indicates that CnT-2D medium successfully induces differentiation in 2D cultured primary limbal epithelial cells. However, subcellular localization of these markers, epithelial barrier function, and differentiation in 3D models were not assessed and remain to be investigated. Full article

Milk fat synthesis in dairy cows is a complex process affected by ruminal fermentation, systemic metabolism, and mammary gland activity. To explore the metabolic interplay across these systems, a multi-tissue metabolomics approach (rumen fluid, plasma, and milk) using ultra-high-performance liquid chromatography–mass spectrometry was used to identify metabolic differences between Chinese Holstein cows with high (H-MF, 5.82 ± 0.41%) and low (L-MF, 3.60 ± 0.12%) milk fat content under the same diet. The bovine mammary epithelial cells (BMECs) were also cultured to evaluate the impact of a key metabolite, malic acid (MA), on lipid metabolism. Our findings reveal distinct metabolic profiles across rumen fluid, plasma, and milk, with 96, 109, and 79 differential metabolites, respectively, between the L-MF and H-MF groups. In rumen fluid, H-MF cows showed higher levels of lauric acid and succinic acid, linked to fatty acid biosynthesis, while the L-MF cows had elevated citraconic and orotic acids, associated with amino acid metabolism and liver stress. Plasma from the H-MF cows contained higher β-hydroxybutyric acid, methionine sulfoxide, and phosphatidylcholine, supporting lipogenesis, whereas L-MF plasma showed increased 3-hydroxy-L-proline, indicating tissue catabolism. In milk, the L-MF cows had higher MA, while the H-MF cows exhibited elevated L-carnitine, linked to fatty acid β-oxidation. Metabolite trend analysis during rumen fluid–plasma–milk showed that 211 metabolites were classified into 8 profiles. Profile 1 had the largest number of metabolites whose levels were down-regulated from rumen to plasma and enriched in lipid metabolism. Profile 3 (mainly related to amino acid metabolism) and profile 4 (mainly related to energy metabolism) exhibited opposite trends from plasma to milk. In vitro, 200 μM of MA reduced the triglyceride content in BMECs and down-regulated lipogenic genes and their protein expression levels (fatty acid synthase, stearoyl-CoA desaturase and sterol regulatory element binding protein 1). These results highlight how rumen fluid, plasma, and milk metabolites collectively influence milk fat synthesis, with MA acting as a key regulator of lipid metabolism in mammary epithelial cells. Full article

This experiment investigated the effects of dietary Artemisia ordosica Krasch. (AOK) supplementation on the n3-polyunsaturated fatty acid (n3-PUFA) profile of subcutaneous adipose tissue (SADT) in Arbas cashmere goats and explored the underlying transcriptional mechanisms. Forty healthy, weaned kids (120 ± 10 days of age; similar body weight) were randomly allocated to two groups (n = 20): a control group (CON, basal diet) and an AOK group (AOK, basal diet with 3% of the roughage replaced by AOK). The feeding trial spanned 104 days, consisting of a 14-day adaptation period and 90 days of data acquisition. Compared with the CON group, AOK significantly reduced the content of saturated fatty acids (SFAs) and n6-polyunsaturated fatty acids (n6-PUFAs)/n3-PUFAs (n6/n3). In contrast, the levels of n3-PUFAs in the SADT of cashmere goats increased markedly (p < 0.05). Compared with the CON group, AOK exhibited significantly higher activities of hormone-sensitive lipase (HSL) (p = 0.027), adenylyl cyclase 2 (ADCY2) (p = 0.010), adenylyl cyclase 5 (ADCY5) (p = 0.046), cluster of differentiation 36 (CD36) (p = 0.013), solute carrier family 27 member 4 (SLC27A4) (p = 0.021), and fatty acid binding protein 4 (FABP4) (p = 0.040), along with significantly lower activities of fatty acid synthase (FAS) (p = 0.002), lipoprotein lipase (LPL) (p = 0.048), and stearoyl-coa desaturase (SCD) (p = 0.026) in SADT. Compared with the CON group, the activities of superoxide dismutase (SOD) (p = 0.032), catalase (CAT) (p = 0.010), glutathione peroxidase (GSH-PX) (p = 0.029), and total antioxidant capacity (T-AOC) (p = 0.002) were significantly increased in the AOK group. Transcriptomic profiling revealed that AOK supplementation downregulated mRNA levels of ADCY2, ADCY5, LPL, FAS, SCD, stearoyl-CoA desaturase 1 (SCD1), stearoyl-CoA desaturase 2 (SCD2), glycogen synthase 1 (GYS1), acyl-CoA oxidase 1 (ACOX1), acetyl-CoA carboxylase (ACC), diacylglycerol acyltransferase 1 (DGAT1), fatty acid desaturase 1 (FADS1), solute carrier family 27 member 2 (SLC27A2), erythroblastic leukemia viral oncogene homolog 4 (ERBB4), and carnitine palmitoyltransferase 1B (CPT1B) (p < 0.05). It also markedly induced acyl-CoA synthetase long-chain family member 4 (ACSL4) (p < 0.01) in SADT. Genes significantly enriched in the adenosine-monophosphate-activated protein kinase (AMPK) signaling pathway included LPL, SCD1, CPT1B, and GYS1 (p = 0.010). Genes significantly enriched in the phosphatidylinositol 3-kinase-akt (PI3K-Akt) signaling pathway included GYS1 and ERBB4 (p = 0.015). CPT1B, ADCY2, and GYS1 were identified as the genes significantly enriched in the insulin resistance signaling pathway (p = 0.048). LPL was the only gene significantly enriched in the cholesterol metabolism pathway (p = 0.049). Genes showing a tendency toward significant enrichment in the peroxisome-proliferator-activated receptor (PPAR) signaling pathway included ACSL4, CPT1B, SCD1, and LPL (p = 0.051). These interconnected cascades improve insulin sensitivity, stimulate triglyceride (TG) hydrolysis, and modulate n3-PUFA levels. Supplementation with AOK enhances n3-PUFA content by accelerating TG breakdown while simultaneously restraining FA oxidation in SADT. Consequently, AOK supplementation can be effectively used to enhance the nutritional value of cashmere goat meat through improved n3-PUFA deposition in SADT. Full article

Objectives: Obesity remains a global health challenge, and promoting white adipose tissue browning has emerged as a promising anti-obesity strategy. This study aimed to investigate the anti-obesity effects of denatonium benzoate (DB) and elucidate its underlying mechanisms. Methods: In order to study the anti-obesity effects of DB and its mechanisms, we used in vivo and in vitro obesity models to study whether DB has anti-obesity effects by participating in fat browning. We investigated the role of DB in high-fat diet (HFD)-induced obese C57BL/6J mice using 36 male animals (8 weeks old, 25 ± 2 g), and evaluated the expression of the adipogenic marker genes Fatty acid-binding protein 4 (Fabp4) and Peroxisome Proliferator-Activated Receptor gamma (PPAR-γ); the thermogenic genes uncoupling protein 1 (Ucp1), Transcription Factor A, Mitochondrial (TFAM), Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-Alpha (Pgc1α), and Adrenergic receptor beta 3 (Adrb3); as well as the adipose browning marker genes Deiodinase, Iodothyronine, Type II (Dio2), PR domain containing 16 (PRDM16), and Peroxisome Proliferator-Activated Receptor alpha (PPAR-α) in 3T3-L1 cells and primary adipocytes with DB treatment. Conclusions: These results indicate that the anti-obesity effects of DB may be related to the browning of white fat, providing a novel potential candidate for anti-obesity drug development. Full article