Search Results (62)

Significant differences in reproductive performance exist between meat-type ducks (e.g., Qiangying Duck, QD) and laying-type ducks (e.g., Shaoxing Duck, SD). The molecular mechanisms underlying these differences, particularly concerning ovarian development and function, remain incompletely understood. This study aimed to comprehensively characterize the ovarian transcriptomes of these two duck types, focusing on differential gene expression and post-transcriptional regulatory events. We performed an integrated full-length transcriptome analysis of ovarian tissues from these two breeds using PacBio SMRT and Illumina sequencing. Bioinformatic analyses, including functional annotation, differential expression analysis, and the identification of APA events, were used. We discovered substantial breed-specific differences in alternative polyadenylation (APA), with SD ducks exhibiting significant 3′UTR shortening in 3799 genes and 3′UTR lengthening in 1626 genes compared to QD. The integrated analysis of differential gene expression and APA events highlighted key genes related to steroid hormone synthesis (HMGCS1, DHCR24), lipid metabolism (SCD), signal transduction (HRAS), and antioxidant defense (SOD1). The functional enrichment implicated critical pathways such as mitochondrial energy metabolism, oxidative phosphorylation, and fatty acid degradation. Our study provides a comprehensive atlas of post-transcriptional regulation in the duck ovary and reveals APA as a crucial process of gene regulation. APA may contribute to the differential ovarian function and egg-laying capacity between meat and laying ducks, thus offering valuable targets for genetic selection. Full article

Background/Objectives: Insufficient dietary fiber intake contributes to gut microbiota dysbiosis, systemic inflammation, and the onset of obesity-related metabolic disorders. Agro-industrial by-products have emerged as sustainable sources to restore microbial and metabolic balance. This study aimed to evaluate the effects of a mango bagasse- and peel-based confectionery (MC) on gut microbiota composition, short-chain fatty acids (SCFAs), and hepatic gene expression in Wistar rats fed either a standard diet (STD) or a high-fat diet (HFD). Methods: Twenty-four rats were randomly assigned to four groups (STD, MC-STD, HFD, MC-HFD) and treated for 11 weeks. Eating behavior, body composition, microbiota composition, SCFAs, and hepatic transcriptomics were evaluated. Results: MC supplementation did not significantly alter weight gain or SCFA levels but shifted clustering patterns in principal component analysis, indicating a distinct dietary response. Microbiota analysis revealed a trend toward lower relative abundances of obesogenic species such as Phascolarctobacterium faecium and Ruminococcus torques, while Intestimonas butyriciproducens and Anaerostipes hadrus were modulated according to diet type. Transcriptomic profiling demonstrated consistent downregulation of lipid metabolism–related genes (Cyp4a14, Hmgcs1, Cyp51, Fads1), linked to PPAR signaling pathways. Conclusions: MC supplementation may beneficially modulate the gut–liver axis and highlights the nutritional potential of fruit by-products as functional ingredients to promote metabolic health under high-fat dietary conditions. Full article

Background/Objectives: Ketogenic diets (KDs), defined by very low carbohydrate and high fat content, are widely studied for obesity and metabolic disease. However, KD formulations vary from 60–95% fat, leading to inconsistent induction of ketogenesis and variable outcomes. The fat threshold required for sustained ketosis, and the tissue-specific programs that mediate KD efficacy, remain unclear. Methods: We evaluated multiple KD formulations (80–95% fat) in C57BL/6J wild-type (WT) and diet-induced obese (DIO) mice. Plasma, hepatic, and intestinal β-hydroxybutyrate (BHB) were measured together with expression of ketogenesis and fatty acid oxidation genes. Body weight, adipose distribution, and liver morphology were assessed under both direct feeding and therapeutic settings. Results: In WT mice, only diets exceeding 85% fat induced robust ketogenesis, reflected by elevated BHB and hepatic upregulation of Cd36, Cpt1a, Acat1, and Hmgcs2. Moderate KDs (80–85%) failed to trigger ketosis and resembled high-fat feeding. In obese mice, an 80% KD lowered fasting glucose without reducing body weight, whereas a 90% KD promoted systemic ketosis, weight loss, and adipose reduction. Interestingly, hepatic transcriptional programs for fatty acid oxidation and ketogenesis were suppressed under 90% KD despite elevated BHB, suggesting reliance on substrate availability and peripheral utilization. In contrast, intestinal Hmgcs2 was strongly induced in both WT and DIO mice, with Oxct1 upregulated only in obesity, indicating local ketone production and consumption. Conclusions: These findings identify > 85% dietary fat as a threshold for sustained ketosis and highlight distinct liver–intestine contributions, underscoring ketogenesis as the central driver of KD’s anti-obesity benefits. Full article

The Automatic Checkout (ACO) task aims to accurately generate complete shopping lists from checkout images. Severe product occlusions, numerous categories, and cluttered layouts impose high demands on detection models’ robustness and generalization. To address these challenges, we propose the Edge-Embedded Multi-Feature Fusion Network (E2MF2Net), which jointly optimizes synthetic image generation and feature modeling. We introduce the Hierarchical Mask-Guided Composition (HMGC) strategy to select natural product poses based on mask compactness, incorporating geometric priors and occlusion tolerance to produce photorealistic, structurally coherent synthetic images. Mask-structure supervision further enhances boundary and spatial awareness. Architecturally, the Edge-Embedded Enhancement Module (E3) embeds salient structural cues to explicitly capture boundary details and facilitate cross-layer edge propagation, while the Multi-Feature Fusion Module (MFF) integrates multi-scale semantic cues, improving feature discriminability. Experiments on the RPC dataset demonstrate that E2MF2Net outperforms state-of-the-art methods, achieving checkout accuracy (cAcc) of 98.52%, 97.95%, 96.52%, and 97.62% on Easy, Medium, Hard, and Average mode, respectively. Notably, it improves by 3.63 percentage points in the heavily occluded Hard mode and exhibits strong robustness and adaptability in incremental learning and domain generalization scenarios. Full article

The impact of maternal dietary restriction and hydroxytyrosol (HT) supplementation during the last third of gestation on plasma malondialdehyde (MDA) concentration, total antioxidant capacity (ABTS assay), and peripheral blood gene expression related to antioxidant defence, immune response, and energy metabolism was evaluated in beef cows and calves. Two feeding treatments in late gestation (T100% vs. T60% of nutrient requirements) and two HT levels (Control vs. HT at 180 mg/kg of diet) were evaluated during gestation (n = 46 cows) and lactation (n = 37 cows and calves). In pregnant cows, undernutrition led to inhibition of glucose oxidation (PDK4), decreased lipid synthesis (HMGCS1 and SCD) and TLR signalling; T60% cows showed higher plasma MDA (p < 0.05) with no positive effect of HT on antioxidant capacity. Contrarily, during lactation, earlier HT supplementation upregulated antioxidant capacity and modulated antioxidant gene expression (p < 0.05). In calves, there was an increase in SOD1, CAT, and GPX1, especially in the T60%-HT group (p < 0.05). Interestingly, HT supplementation increased glucose transport (SLC2A1/GLUT1) during pregnancy and lactation (p < 0.05). However, it caused different effects on immunometabolic regulation in both dams and calves, depending on maternal diet. Overall, maternal HT supplementation under restricted nutritional conditions promoted postpartum antioxidant capacity and modulated immune and metabolic gene expression in cows and calves. Full article

RNA-binding proteins (RBPs) play essential roles in all major steps of RNA processing. Genetic studies in human and mouse models support that many RBPs are crucial for maintaining homeostasis in key tissues/organs, but to what extent the function of RBPs is conserved between humans and mice is not clear. Our recent study using a chimeric humanized liver mouse model found that knocking down human HuR in human hepatocytes resulted in a broad upregulation of human genes involved in fatty acid catabolism. This regulation is human-specific, as the knocking down of mouse HuR in the liver of traditional mouse models did not show these effects. To further study this human-specific role of HuR, we co-overexpressed HuR with PPARα, a master transcription factor that promotes fatty acid catabolism, in cultured cells. We found that HuR suppressed the expression of PPARα-induced fatty acid catabolism genes in human cells but not in mouse cells. We provide evidence supporting that the human-specific suppressive effect of HuR is independent of PPARα expression or location. The regulatory effects of HuR are also independent of its role in regulating mRNA stability. Using the human HMGCS2 gene as an example, we found that the suppressive effect of HuR cannot be explained by decreased promoter activity. We further provide evidence supporting that HuR suppresses the pre-mRNA processing of HMGCS2 gene, leading to accumulated intron/pre-mRNA expression of HMGCS2 gene. Furthermore, overexpression of HuR blocked and knocking down of HuR sensitized PPARα agonist-induced gene expression. By analyzing published RNA-seq data, we found compromised pre-mRNA processing for fatty acid catabolism genes in patients with fatty liver diseases, which was not observed in mouse fatty liver disease models. Our study supports the model that HuR suppresses the expression of fatty acid catabolism genes by blocking their pre-mRNA processing, which may partially explain the mild effects of PPARα agonists in treating fatty liver diseases in humans as compared with studies in mice. Full article

Human mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (HMG-CoA synthase, mHS) synthase is a key enzyme in ketogenesis and is located mainly in the liver, but also in the colon, skeletal muscle, heart, pancreas, and testes. It is an inner mitochondrial membrane-associated protein. Mutations in the HMGCS2 gene, which encodes this enzyme, lead to “mHS deficiency,” a rare, autosomal recessive, inherited metabolic disorder. To date, about 100 patients with this disorder have been described. The disorder usually appears during the first year of life, often after a period of starvation or an intercurrent illness. A total of 77 different DNA mutations has been described that are considered responsible for mHS deficiency, although the mechanisms leading to loss of function are not fully understood. To study how the different missense variants affect the enzymatic activity of the protein on an atomic scale, we used molecular dynamics computational simulation techniques for variants whose activity could be measured “in vitro.” The study included a total of 46 molecular dynamics trajectories of enzyme–substrate/product interaction simulations, each 500 ns long (23 microseconds total). Currently, the atomic and biophysical effects of the mHS variants on their catalyzed reactions have not been studied in detail experimentally. To our knowledge, molecular dynamics simulations are one of the most promising tools for understanding the molecular basis of the phenotypic consequences of these variants. In the present work, molecular dynamics simulations reliably reproduce most experimental enzyme activity measurements, supporting their future application to the study of new mHS mutations. Full article

(1) Objective: This study aimed to systematically elucidate the molecular mechanisms by which gypenosides (GP), a major active component of Gynostemma pentaphyllum, ameliorate hypercholesterolemia by modulating the hepatic steroidogenesis pathway, and to identify key therapeutic targets. (2) Methods: We established a high-fat diet (HFD)-induced hypercholesterolemia (HC) mouse model and performed GP intervention. An integrated multi-omics approach, combining transcriptomics and proteomics, was utilized to comprehensively analyze GP’s effects on the expression of genes and proteins associated with hepatic cholesterol synthesis, transport, and steroid hormone metabolism. (3) Results: HFD induced significant dysregulation, with 48 steroidogenesis pathway-related genes and 35 corresponding proteins exhibiting altered expression in HC mouse livers. GP treatment remarkably reversed these HFD-induced abnormalities, significantly restoring the expression levels of 42 genes and 14 proteins. Multi-omics integration identified seven critical genes/proteins—Cyp3a25, Fdft1, Tm7sf2, Hmgcs1, Fdps, Mvd, and Pmvk—that were consistently and significantly regulated by GP at both transcriptional and translational levels. Furthermore, correlation analyses demonstrated that Cyp3a25 was significantly negatively correlated with serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), whereas Fdft1, Tm7sf2, Hmgcs1, Fdps, Mvd, and Pmvk showed significant positive correlations. (4) Conclusions: GP effectively ameliorates cholesterol dyshomeostasis through a multi-targeted mechanism in the liver. It inhibits endogenous cholesterol synthesis by downregulating key enzymes (Hmgcs1, Fdft1, Pmvk, Mvd, Fdps, Tm7sf2), promotes cholesterol efflux and transport (upregulating Abca1, ApoB), and accelerates steroid hormone metabolism (upregulating Cyp3a11, Cyp3a25). These findings provide robust scientific evidence for the development of GP as a safe and effective novel therapeutic agent for hypercholesterolemia. Full article

Patients with concurrent non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) exhibit increased susceptibility to non-alcoholic steatohepatitis (NASH), advanced hepatic fibrosis, cirrhosis, and hepatocellular carcinoma. This study investigated the contribution of ketogenesis to T2DM-mediated NAFLD exacerbation and elucidated the therapeutic mechanism of cynaroside in NASH-complicated T2DM. Male C57BL/6J mice were given CDAHFD combined with streptozotocin to establish stage-specific NAFLD with T2DM models. Hepatic HMGCS2 expression was modulated via tail vein injection of adenoviral vectors for HMGCS2 overexpression or knockdown. Cynaroside was administered orally from week 5 to week 8. The results showed that concurrent T2DM accelerated NAFLD progression, accompanied by a dysregulated ketogenesis that was correlated with disease severity. Hepatic HMGCS2 expression paralleled circulating ketone body concentrations, indicating that HMGCS2-mediated ketogenic dysregulation contributed to NAFLD pathogenesis in T2DM contexts. HMGCS2 overexpression in NASH-T2DM models significantly attenuated steatohepatitis progression through the enhancement of ketogenesis. Cynaroside administration ameliorated hepatic pathology in NASH-T2DM mice by (1) reducing hepatocellular injury and lobular inflammation; (2) decreasing intrahepatic lipid accumulation; and (3) suppressing hepatocyte senescence and the secretion of SASP factors. Mechanistically, cynaroside exerted therapeutic effects via HMGCS2-mediated ketogenesis. Our data demonstrated that ketogenic modulation is a viable therapeutic strategy to delay T2DM-NAFLD progression. Full article

The purpose of this study was to determine the effects of essential oil inhalation on body weight, blood lipid profile, and liver and adipose tissue in mice. Middle-aged male mice (C57BL/6J) were exposed to Lavandula angustifolia (LO) and Citrus aurantium (CAO) essential oils for 7 weeks and compared to mice that did not receive essential oil inhalation treatment. Liver, white adipose tissue, and brown adipose tissue were sampled, kept at −80 °C. Although essential oil inhalation increased feed intake and body weight compared to control group, the amount of weight gain per feed intake was lower in the C. aurantium essential oil group. Moreover, relative weight of fat to body weight, liver fat amount, and blood cholesterol was lower, and triglyceride levels were significantly reduced. Reverse transcription polymerase chain reaction (RT-PCR) expression profiling of genes related to lipid metabolism confirmed changes in the regulation of thermogenesis-related gene Ucp1 and the cholesterol synthesis-related genes Hmgcs1 and Hmgcr. The inhalation of C. aurantium essential oil did not reduce the feed intake in mice; however, its effectiveness in suppressing the increases in body weight and fat mass was demonstrated. Full article

Investigating the functional interactions between rumen microbial fermentation and epithelial mitochondrial dynamics/energy metabolism in Tibetan sheep at different altitudes, this study examined ultrastructural changes in rumen epithelial tissues, expression levels of mitochondrial dynamics-related genes (fusion: Mfn1, Mfn2, OPA1, Mic60; fission: Drp1, Fis1, MFF), and ketogenesis pathway genes (HMGS2, HMGCL) in Tibetan sheep raised at three altitudes (TS 2500m, TS 3500m, TS 4500m). Correlation analysis was performed between rumen microbiota/metabolites and mitochondrial energy metabolism. Results: Ultrastructural variations were observed across altitudes. With increasing altitude, keratinized layer became more compact; desmosome connections between granular layer cells increased; mitochondrial quantity and distribution in spinous and basal layers increased. Mitochondrial dynamics regulation: Fission genes (FIS1, DRP1, MFF) showed significantly higher expression at TS 4500m (p < 0.01); fusion genes (Mfn1, OPA1) exhibited altitude-dependent upregulation. Energy metabolism markers: Pyruvate (PA) decreased significantly at TS 3500m/TS 4500m (p < 0.01); citrate (CA) increased with altitude; NAD⁺ peaked at TS 3500m but decreased significantly at TS 4500m (p < 0.01); Complex II (SDH) and Complex IV (CO) activities decreased at TS 4500m (p < 0.01). Ketogenesis pathway: β-hydroxybutyrate increased significantly with altitude (p < 0.01); acetoacetate peaked at TS 2500 m/TS 4500 m; HMGCS2 expression exceeded HMGCL, showing altitude-dependent upregulation at TS 4500m (p < 0.01). Microbiome–metabolism correlations: Butyrivibrio_2 and Fibrobacter negatively correlated with Mic60 (p < 0.01); Ruminococcaceae_NK4A214_Group positively correlated with Mfn1/OPA1 (p < 0.05); WGCNA identified 17 metabolite modules, with MEturquoise module positively correlated with DRP1/Mfn2/MFF (p < 0.05). Conclusion: Altitude-induced ultrastructural adaptations in rumen epithelium correlate with mitochondrial dynamics stability and ketogenesis upregulation. Mitochondrial fission predominates at extreme altitudes, while microbiota–metabolite interactions suggest compensatory energy regulation mechanisms. Full article

Ketogenesis, a mitochondrial metabolic pathway, occurs primarily in liver, but kidney, colon and retina are also capable of this pathway. It is activated during fasting and exercise, by “keto” diets, and in diabetes as well as during therapy with SGLT2 inhibitors. The principal ketone body is β-hydroxybutyrate, a widely recognized alternative energy source for extrahepatic tissues (brain, heart, muscle, and kidney) when blood glucose is sparse or when glucose transport/metabolism is impaired. Recent studies have identified new functions for β-hydroxybutyrate: it serves as an agonist for the G-protein-coupled receptor GPR109A and also works as an epigenetic modifier. Ketone bodies protect against inflammation, cancer, and neurodegeneration. HMGCS2, as the rate-limiting enzyme, controls ketogenesis. Its expression and activity are regulated by transcriptional and post-translational mechanisms with glucagon, insulin, and glucocorticoids as the principal participants. Loss-of-function mutations occur in HMGCS2 in humans, resulting in a severe metabolic disease. These patients typically present within a year after birth with metabolic acidosis, hypoketotic hypoglycemia, hepatomegaly, steatotic liver damage, hyperammonemia, and neurological complications. Nothing is known about the long-term consequences of this disease. This review provides an up-to-date summary of the biological functions of ketone bodies with a special focus on HMGCS2 in health and disease. Full article

Maintaining the normal biological rhythms of livestock is of great significance for reflecting the environmental suitability and welfare level of animals. Mistimed feeding can interfere with the circadian rhythms of both humans and animals, resulting in disorders of lipid metabolism, obesity, and metabolic syndrome. Low-temperature environment stimulates increased appetite and decreased physical activity, resulting in higher energy intake than consumption and thus facilitating fat deposition and even obesity. In this study, growing rabbits were randomly allocated to the daytime feeding (DF) group and nighttime restricted feeding (NRF) group. Our research demonstrated that, during winter, the DF regimen disrupted the behavioral rhythms of rabbits and accelerated weight gain without changing overall feed intake. The underlying reason was that DF disturbed the lipid metabolism rhythms, promoted hepatic lipid synthesis regulated by DGAT1 and lipid synthesis of adipose tissues regulated by GPAM, thus triggering fat deposition. In contrast, the NRF regimen enhanced thermogenesis regulated by T3 and elevated body temperature and facilitated ketogenesis mediated by HMGCS2, increasing energy consumption. However, it had no significant impact on the fat content within muscle. This study offers a theoretical foundation for the refinement of feeding management and healthy raising of rabbits. Full article

Sustainable development of the largemouth bass industry is hindered by limited freshwater resources. Consequently, the expansion of farming space by brackish and saline water aquaculture has become imperative. Largemouth bass is an economically important freshwater fish species. However, there is presently a lack of germplasm resources with the capacity to adapt to hypertonic environments and maintain rapid growth. A genome-wide association study is a technique used for the detection of genetic variants associated with specific phenotypic traits. In this study, we firstly applied this technique to explore the potential single-nucleotide polymorphism (SNP) locus and candidate genes associated with rapid growth and adaptation to the hypertonic environment of largemouth bass. A total of 10 potential growth-related SNPs were obtained on chromosome 16, and SNP16:4120214 was a significant SNP peak. Based on these SNPs, 23 candidate genes were annotated in the genome, including Nkcc1, Mapkap1, Hmgcs1, Slc27a6, and Shroom3. Shroom3 expression was significantly higher in individuals enriched for the most growth-advantageous genotypes. Shroom3 upregulation is beneficial for fish growth in hyperosmotic environments. This study provides insight into the genetic basis of rapid growth in hypertonic environments and foundational information for the future breeding of salt-tolerant largemouth bass. Full article

Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency (HMGCS2D) is a rare metabolic disorder that impairs the body’s ability to produce ketone bodies and regulate energy metabolism. Diagnosing HMGCS2D is challenging because patients typically remain asymptomatic unless they experience fasting or illness. Due to the absence of reliable biochemical markers, genetic testing has become the definitive method for diagnosing HMGCS2D. This study included 19 patients from 14 unrelated families diagnosed with HMGCS2D in our department between October 2018 and October 2024. The clinical presentations, biochemical findings, molecular characteristics, and management strategies were systematically summarized and analyzed. Of the 19 cases studied, 16 were symptomatic, and 3 were asymptomatic. The onset of the first acute episode occurred between 10 days and 28 months of age. Triggers for the initial crisis in the symptomatic cases included poor feeding (93.8%), vomiting (56.3%), diarrhea (25.0%), and fever (18.8%). Clinical manifestations during the first episode were lethargy/coma (81.3%), rapid breathing (68.8%), hepatomegaly (56.3%), shock (37.5%), and seizures (18.8%). The biochemical abnormalities observed included elevated plasma transaminases (100%), metabolic acidosis (75%), hypoglycemia (56.3%), and elevated plasma ammonia levels (31.3%). Additionally, low free carnitine levels were found in seven cases, elevated C2 levels were found in one case, dicarboxylic aciduria was found in two cases, and ketonuria was found in two cases. Abnormal brain MRI findings were detected in three patients. Genetic analysis revealed seven HMGCS2 gene variants across the 19 cases. Notably, a novel variant, c.407A>T (p.D136V), was identified and has not been reported in any existing databases. Two common variants, c.559+1G>A and c.1090T>A (p.F364I), were present in 11 out of 19 cases (57.9%) and 10 out of 19 cases (55.5%), respectively. The implementation of a high glucose infusion and proactive management strategies—such as preventing prolonged fasting and providing enteral carbohydrate/glucose infusion during illness—effectively reduced the rate of acute relapses following accurate diagnosis. Currently, all 19 patients are alive, with ages ranging from 5 months to 14 years, and exhibit normal physical development. To the best of our knowledge, this study represents the first reported cases of HMGCS2D in Vietnamese patients. Our findings contribute to a broader understanding of the clinical phenotype and expand the known spectrum of HMGCS2 gene variants, enhancing current knowledge of this rare metabolic disorder. Full article