Transcriptomic profiling reveals tetrabromobisphenol A-induced dysregulation of hepatic lipid homeostasis in common carp (Cyprinus carpio).

Effects of NUCB2/nesfatin-1 on lipid metabolism in the hepatopancreas of largemouth bass (Micropterus salmoides)

Introduction: Mn is a trace element essential for growth and development in organisms, and adequate Mn levels are crucial for maintaining normal liver function. This study aimed to investigate the effects of Mn deficiency on the liver and elucidate the underlying mechanisms using transcriptomics. Methods: Weanling mice were fed a Mn-deficient diet, and Mn chloride (MnCl2) was administered intraperitoneally to correct the deficiency. Liver pathological changes were evaluated through histological examination. Liver function and key lipid metabolism markers were assessed using biochemical assays, while hepatic oxidative stress levels were measured via flow cytometry and biochemical kits. Alterations in inflammatory factors were detected using ELISA and qPCR. The mechanisms underlying Mn’s effects on liver function were further explored through Western blot, qPCR, and transcriptome sequencing. Results: Mn deficiency impaired liver morphology and structure. Serum levels of ALT, AST, and ALP were significantly elevated, while ALB decreased, confirming hepatic dysfunction. This dysfunction led to oxidative stress, characterized by increased hepatic ROS and MDA levels, alongside reduced Mn-SOD, GSH-Px, and T-AOC activities. Additionally, Mn deficiency elevated serum TG, TC, and LDL-C levels, indicating abnormal lipid metabolism. Hepatic pro-inflammatory factors (IL-6, IL-1β, and TNF-α) were significantly upregulated. Transcriptomic analysis revealed distinct gene expression patterns under different Mn conditions, with KEGG pathway analysis identifying the PPAR signaling pathway as a key regulatory target. Conclusions: Our findings suggest a potential pathogenic cascade in which manganese deficiency may initially induce hepatic oxidative stress, potentially leading to suppression of the PPAR signaling pathway. This inhibition of PPARα/γ could subsequently orchestrate downstream manifestations of aberrant lipid metabolism and inflammatory responses. Thus, the PPAR signaling pathway is proposed as a plausible central hub for translating oxidative damage into metabolic and inflammatory dysfunction in the manganese-deficient liver.

Hexafluoropropylene oxide dimer acid (HFPO-DA; trade name GenX), as a substitute for perfluorooctanoic acid (PFOA), has been attracting increasing attention. However, its impact and corresponding mechanism on hepatic lipid metabolism are less understood. To investigate the possible mechanisms of GenX for hepatotoxicity, a series of in vivo and in vitro experiments were conducted. In in vivo experiment, male mice were exposed to GenX in drinking water at environmental concentrations (0.1 and 10 μg/L) and high concentrations (1 and 100 mg/L) for 14 weeks. In in vitro experiments, human hepatocellular carcinoma cells (HepG2) were exposed to GenX at 10, 160, and 640 μM for 24 and 48 h. GenX exposure via drinking water resulted in liver damage and disruption of lipid metabolism even at environmental concentrations. The results of triglycerides (TG) and total cholesterol (TC) in this study converged with the results of the population study, for which TG increased in the liver but unchanged in the serum, whereas TC increased in both liver and serum concentrations. KEGG and GO analyses revealed that the hepatotoxicity of GenX was associated with fatty acid transport, synthesis, and oxidation pathways and that Peroxisome Proliferator-Activated Receptor (PPARα) contributed significantly to this process. PPARα inhibitors significantly reduced the expression of CD36, CPT1β, PPARα, SLC27A1, ACOX1, lipid droplets, and TC, suggesting that GenX exerts its toxic effects through PPARα signaling pathway. In general, GenX at environmental concentrations in drinking water causes abnormal lipid metabolism via PPARα signaling pathway.

The antipsychotic drug olanzapine altered lipid metabolism in the common carp (Cyprinus carpio L.): Insight from the gut microbiota-SCFAs-liver axis

AdipoRon ameliorates the progression of heart failure with preserved ejection fraction via mitigating lipid accumulation and fibrosis

Cyprinus carpio is a significant freshwater species with substantial nutritional and economic value. Rice-carp co-culture represents one of its principal cultivation methods. However, in the system, the optimal farming density for carp and the impact of high stocking density on their muscle nutritional composition have yet to be explored. Thus, the objective of the current study was to investigate the influences of stocking density on the muscle nutrient profiles and metabolism of C. carpio in rice-fish co-culture systems. Common carp were cultured at three stocking densities, low density (LD), medium density (MD), and high density (HD), over a period of 60 days. Following this, comprehensive analyses incorporating physiological, biochemical, and multi-omics sequencing were conducted on the muscle tissue of C. carpio. The results demonstrated that HD treatment led to a reduction in the antioxidant capacity of C. carpio, while resulting in elevated levels of various fatty acids in muscle tissue, including saturated fatty acids (SFAs), omega-3 polyunsaturated fatty acids (n-3 PUFAs), and omega-6 polyunsaturated fatty acids (n-6 PUFAs). The metabolome analysis showed that HD treatment caused a marked reduction in 43 metabolites and a significant elevation in 30 metabolites, primarily linked to lipid and amino acid metabolism. Additionally, transcriptomic analysis revealed that the abnormalities in lipid metabolism induced by high-stocking-density treatment may be associated with significant alterations in the PPAR signaling pathway and adipokine signaling pathway. Overall, our findings indicate that in rice-fish co-culture systems, high stocking density disrupted the balance of antioxidant status and lipid metabolism in the muscles of C. carpio.

Simple SummaryDietary lipids are the main source of energy for the development of fish larvae, and an adequate supply of essential fatty acids is essential for rapidly growing larvae. Mirror carp (Cyprinus carpio) has been cultivated widely because of its advantages of a fast growth rate, strong disease resistance, and high feed conversion rate. In this study, mirror carp larvae were fed iso-nitrogen (approximately 33% dietary protein) diets with different lipid levels (3%, 5%, 7%, 9%, 11%, and 13%), and the weight gain rate, serum lipid-related indices, muscle amino acid and fatty acid contents, liver lipid deposition, antioxidant enzyme activity, and expression of genes related to growth and fat metabolism were determined in different experimental groups. The optimal dietary lipid requirement of the mirror carp cultivar (6.86 ± 0.95 g) was 9%. This study provides data for improving the breeding of new common carp varieties with unsaturated fatty acids.In fish, increasing the crude lipid level of feed can save protein and improve feed utilization. Mirror carp (Cyprinus carpio) is one of the most widely farmed fish species in the world. In this study, mirror carp larvae were fed isonitrogenous diets with different lipid levels (3%, 5%, 7%, 9%, 11%, and 13%). The rearing trial lasted for eight weeks. The results revealed that when the fat content was 9%, the AWGR, WGR, and FCR were highest, whereas FCR was lowest. The AWGR was correlated with the dietary lipid level, and the regression equation was y = −2.312x2 + 45.01x + 214.49. Compared with those in the control group, the T-CHO and TG contents were significantly greater in the 13% lipid content groups and significantly lower in the 9% lipid content groups (p < 0.05). In terms of muscle quality, the contents of MUFAs, PUFAs, and DHA + EPA were significantly greater than those in the other experimental groups (p < 0.05). Oil red O staining revealed a lipid content of 13% with severe fat deposition. In addition, the results of the analysis of antioxidant enzyme activity revealed that the activities of GSH, CAT and T-AOC were significantly greater at the 9% lipid content, and that the MDA content was significantly greater at the 13% lipid content (p < 0.05). Similarly, the mRNA levels of GH, IGF-I, FAS, and LPL were significantly highest at a lipid level of 9% (p < 0.05). The above results revealed that the optimal dietary lipid requirement for the fast growth of mirror carp (6.86 ± 0.95 g) was 9.74% on the basis of nonlinear regression analysis of the AWGR. The dietary lipid level (9%) improved the growth, stress resistance, and lipid utilization of mirror carp to a certain extent.

Transcriptomic analysis reveals that selenium-enriched Lactobacillus plantarum alleviates high -salinity stress in common carp through lipid metabolism and ferroptosis signalling pathways.

UV filter ethylhexyl salicylate affects cardiovascular development by disrupting lipid metabolism in zebrafish embryos

Black rice bran improved lipid metabolism in hyperlipidemia mice via steroid hormone biosynthesis and PPAR signaling pathway.

This study aimed to collaboratively investigate the mechanism of variations in intramuscular fat (IMF) content in Wandong cattle using transcriptomics and metabolomics techniques. Longissimus dorsi (LD) muscle samples were collected from thirteen free-range Wandong cattle in Fengyang County, Anhui Province, China. From this initial cohort, eight animals closely matched in age and body weight were selected. Based on IMF content measured by Soxhlet extraction, these eight cattle were divided into two groups: the high-IMF (HF, n = 4) and low-IMF (LF, n = 4) groups. Subsequent analyses were performed on integrated datasets comprising the transcriptome, metabolome, and fatty acid profile. The results revealed a significant increase in IMF in the HF group compared to the LF group (p < 0.05). Specifically, α-linolenic acid (C18:3n3) and γ-linolenic acid (C18:3n6) were significantly more abundant in the LF group compared to the HF group (p < 0.05), whereas oleic acid (C18:1n9c) and cis-9-palmitoleic acid (C16:1) predominated in the HF group. However, saturated fatty acids (SFAs), such as myristic acid (C14:0), palmitic acid (C16:0), stearic acid (C18:0), and Margaric acid (C17:0), did not show significant differences (p > 0.05). A total of 9164 differentially expressed genes (DEGs) were identified via transcriptome analysis, with 2202 genes upregulated and 6962 genes downregulated in the HF group compared to the LF group. The expression profiles exhibited a distinct pattern, characterized by the upregulation of genes such as FABP1, SREBF1, and LIPE, while genes including SCD, PPARGC1A, and LEP were downregulated. GO enrichment analysis demonstrated that the majority of DEGs were predominantly abundant across 25 distinct functional categories distributed across the three primary ontologies. KEGG pathway analysis further identified 341 significantly enriched signaling pathways in the HF group (p < 0.05), predominantly involving metabolic pathways, FoxO, AMPK, and PPAR signaling pathways. Untargeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) metabolomics analysis revealed 404 differential accumulated metabolites (DAMs), with 187 in positive ion mode and 217 in negative ion mode (p < 0.05). These DAMs were notably enriched in pathways such as glycerophospholipid metabolism, terpene and steroid biosynthesis, fatty acid degradation, and fatty acid metabolism. Notably, C16:1, C18:1n9c, arachidonic acid (peroxide free) (C20:4n6), oleoyl-L-carnitine, and linoleoyl-carnitine were identified as key players in lipid metabolism. Integrating transcriptomics with metabolomics data unveiled significant associations between DAMs linked to lipid metabolism and DEGs. Specifically, C18:1n9c exhibited a positive correlation with LPIN3, while C16:1 showed negative associations with PPAP2B, PPAP2A, CDS2, HADHA, LPL, HSD17B12, ELOVL5, ACSL1, and ACOX1, and positive correlations with PLA2G15, CDIPT, AGPSBG1, and GPD1. In summary, the variation in IMF content in Wandong cattle is co-regulated by key genes (SREBF1, ACSL1, SCD) via the AMPK, PPAR, and FoxO signaling pathways, coupled with alterations in specific fatty acid metabolites such as C18:1n9c, C16:1, and C20:4n6. These findings provide critical molecular insights for the genetic selection and breeding of Wandong cattle, which are renowned for their superior meat quality.

Multi-omics and random forest reveal lipid metabolism disruption and biomarkers in grass carp (Ctenopharyngodon idellus) exposed to 2-methylisoborneol.

Transcriptomic and metabolomic profile changes in the liver of Sprague Dawley rat offspring after maternal PFOS exposure during gestation and lactation

Liver transcriptome response to avian pathogenic Escherichia coli infection in broilers with corticosterone treatment.

Phthalic acid esters (PAEs), commonly used as plasticizers, are pervasive in the environment, leading to widespread human exposure. The association between phthalate exposure and metabolic disorders has been increasingly recognized, yet the precise biological mechanisms are not well-defined. In this study, we explored the effects of monoethylhexyl phthalate (MEHP) and monocyclohexyl phthalate (MCHP) on glucose and lipid metabolism in human hepatocytes and adipocytes. In hepatocytes, MEHP and MCHP were observed to enhance lipid uptake and accumulation in a dose-responsive manner, along with upregulating genes involved in lipid biosynthesis. Transcriptomic analysis indicated a broader impact of MEHP on hepatic gene expression relative to MCHP, but MCHP particularly promoted the expression of the gluconeogenesis key enzymes G6PC and FBP1. In adipocytes, MEHP and MCHP both increased lipid droplet formation, mimicking the effects of the Peroxisome proliferator-activated receptor γ (PPARγ) agonist rosiglitazone (Rosi). Transcriptomic analysis revealed that MEHP predominantly altered fatty acid metabolism pathways in mature adipocytes (MA), whereas MCHP exhibited less impact. Metabolic perturbations from MEHP and MCHP demonstrate shared activation of the PPARs pathway in hepatocytes and adipocytes, but the cell-type discrepancy might be attributed to the differential expression of PPARγ. Our results indicate that MEHP and MCHP disrupt glucose and lipid homeostasis in human liver and adipose through mechanisms that involve the PPAR and adenosine monophosphate-activated protein kinase (AMPK) signaling pathways, highlighting the nuanced cellular responses to these environmental contaminants.