Lipid Metabolism In Zebrafish Research Articles

Quantitative assessment and monitoring of microplastics and nanoplastics distributions and lipid metabolism in live zebrafish using hyperspectral stimulated Raman scattering microscopy

Microplastics (MP) and nanoplastics (NP) pollutions pose a rising environmental threat to humans and other living species, given their escalating presence in essential resources that living subjects ingest and/or inhale. Herein, to elucidate the potential health implications of MP/NP, we report for the first time by using label-free hyperspectral stimulated Raman scattering (SRS) imaging technique developed to quantitatively monitor the bioaccumulation and metabolic toxicity of MP/NP within live zebrafish larvae during their early developmental stages. Zebrafish embryos are exposed to environmentally related concentrations (3–60 μg/ml) of polystyrene (PS) beads with two typical sizes (2 μm and 50 nm). Zebrafish are administered isotope-tagged fatty acids through microinjection and dietary intake for in vivo tracking of lipid metabolism dynamics. In vivo 3D quantitative vibrational imaging of PS beads and intrinsic biomolecules across key zebrafish organs reveals that gut and liver are the primary target organs of MP/NP, while only 50 nm PS beads readily aggregate and adhere to the brain and blood vessels. The 50 nm PS beads are also found to induce more pronounced hepatic inflammatory response compared to 2 μm counterparts, characterized by increased biogenesis of lipid droplets and upregulation of arachidonic acid detected in zebrafish liver. Furthermore, Raman-tagged SRS imaging of fatty acids uncovers that MP/NP exposure significantly reduces yolk lipid utilization and promotes dietary lipid storage in zebrafish, possibly associated with developmental delays and more pronounced food dilution effects in zebrafish larvae exposed to 2 μm PS beads. The hyperspectral SRS imaging in this work shows that MP/NP exposure perturbs the development and lipid metabolism in zebrafish larvae, furthering the understanding of MP/NP ingestions and consequent toxicity in different organs in living species.

Vitamin D modulates disordered lipid metabolism in zebrafish (Danio rerio) liver caused by exposure to polystyrene nanoplastics

In this study, zebrafish (Danio rerio) were exposed to polystyrene nanoplastics (PS-NPs, 80 nm) at 0, 15, or 150 μg/L for 21 days and supplied with a low or high vitamin D (VD) diet (280 or 2800 IU/kg, respectively, indicated by – or +) to determine whether and how VD can regulate lipid metabolism disorder induced by PS-NPs. Six groups were created according to the PS-NP concentration and VD diet status: 0−, 0+, 15−, 15+,150−, and 150 +. Transmission electron microscopy showed that PS-NPs accumulated in the livers of zebrafish, which led to large numbers of vacuoles and lipid droplets in liver cell matrices; this accumulation was most prominent in the 150− group, wherein the number of lipid droplets increased significantly by 136.36%. However, the number of lipid droplets decreased significantly by 76.92% in the 150+ group compared with the 150− group. An examination of additional biochemical indicators showed that the high VD diet partially reversed the increases in the triglyceride and total cholesterol contents induced by PS-NPs (e.g., triglycerides decreased by 58.52% in the 150+ group, and total cholesterol decreased by 44.64% in the 15+ group), and regulated lipid metabolism disorder mainly by inhibiting lipid biosynthesis. Untargeted lipidomics analysis showed that exposure to PS-NPs was associated mainly with changes in the lipid molecular content related to cell membrane function and lipid biosynthesis and that the high VD diet reduced the content of lipid molecules related to lipid biosynthesis, effectively alleviating cell membrane damage and lipid accumulation. These findings highlight the potential of VD to alleviate lipid metabolism disorder caused by PS-NP exposure, thereby providing new insights into how the toxic effects of NPs on aquatic organisms could be reduced.

Combined effects of high-fat diet and polystyrene microplastic exposure on microplastic bioaccumulation and lipid metabolism in zebrafish.

Extensive use of microplastics (MPs) threatens the safety of aquatic environments and hydrobionts. Increasing the weight of economic fish through high-fat diet (HFD) to increase production is common in aquaculture. However, little is known about the combined effects of MPs and HFD in fish. The aim of this study was to investigate the relationship between adiposity and MP bioaccumulation in fish. Using zebrafish as a vertebrate model, the content of polystyrene (PS) MPs in zebrafish tissues exposed to 5 and 50μm of 1000μg/L PS MPs was detected via confocal Raman spectroscopy in normal diet (ND) and HFD. The content of PS MPs in HFD group was significantly higher than that in ND group. The levels of hepatic lipids were significantly elevated in zebrafish subjected to HFD treatment, and this effect was aggravated by exposure to 5μmPS MPs, and even caused liver injury. Transcriptomic analysis revealed that exposure to PS MPs interferes with hepatic lipid metabolism and energy homeostasis in zebrafish. These results suggests that in addition to controlling the use and performing proper recycling of plastic products in our daily life, we should not blindly increase the weight of fish through HFD. This aids protect the quality of economic fish and prevent MPs from being consumed by humans through the food chain. This study explored the interaction between fish feed culture and environmental pollutants to provide important reference for fish culture.

Exposure to PFOA and its novel analogs disrupts lipid metabolism in zebrafish

Perfluorooctanoic acid (PFOA), a typical perfluoroalkyl group compound, has received worldwide attention due to its significant environmental toxicity. Following regulatory bans on the production and emission of PFOA, concerns have been raised about the potential health risks and the safety of novel perfluoroalkyl analogues. HFPO-DA (trade name Gen-X) and HFPO-TA are two perfluoroalkyl analogues known to be bioaccumulative, whose level of toxicity and whether they are safe alternatives to PFOA remain unclear. In the following study, the physiological and metabolic effects of exposure to PFOA and its novel analogues were explored in zebrafish using 1/3 LC50 (PFOA 100 μM, Gen-X 200 μM, HFPO-TA 30 μM). At the same LC50 toxicological effect, exposure to PFOA and HFPO-TA resulted in abnormal phenotypes such as spinal curvature, pericardial edema and aberrant body length, while Gen-X was little changed. Metabolically, PFOA, HFPO-TA and Gen-X all significantly increased total cholesterol in exposed zebrafish with PFOA and HFPO-TA also increasing total triglyceride levels. Transcriptome analysis showed that the number of differentially expressed genes in PFOA, Gen-X, and HFPO-TA treated conditions compared to control groups were 527, 572, and 3, 933, respectively. KEGG and GO analysis of differentially expressed genes revealed pathways and functions related to lipid metabolism as well as significant activation of the peroxisome proliferators-activated receptor (PPARs) pathway. Furthermore, RT-qPCR analysis identified significant dysregulation in the downstream target genes of PPARα, which is responsible for lipid oxidative catabolism, and the SREBP pathway, which is responsible for lipid synthesis. In conclusion, both perfluoroalkyl analogues HFPO-TA and Gen-X exhibit significant physiological and metabolic toxicity to aquatic organisms and their environmental accumulation should be closely regulated.

Bisphenol A has a sex-dependent disruptive effect on hepatic lipid metabolism in zebrafish

Bisphenol A (BPA) is an endocrine disruptor that has adverse effects on lipid metabolism. However, most of the current studies on the effects of BPA on lipid metabolism in fish have focused on middle- and short-term exposure tests. The aim of this study was to investigate the effects of long-term BPA exposure on liver lipid metabolism in zebrafish. Post-fertilization embryos were exposed to environmentally relevant concentrations of BPA for 120 days, and the changes in triglyceride (TG), total cholesterol (TC) levels, and gene expression related to liver lipid metabolism were investigated in both male and female fish. The results showed that long-term exposure to BPA led to lipid deposition in liver, and there was a sex difference. In the liver of female fish, there was higher lipid transport and synthesis at low concentration of BPA, while overall metabolic levels were increased at high concentration of BPA. In contrast, BPA showed a dose-dependent effect on the lipid deposition in male fish. The expression of mRNA of TG transport-related and lipid synthesis-related genes was significantly up-regulated and the expression of genes related to lipid catabolism, was significantly down-regulated with increasing BPA dose. Taken together, our results indicate that long-term exposure to BPA can increase lipid deposition in a gender-specific manner. This may be due to the different responses of lipid metabolism related genes to BPA in male and female zebrafish. These results will provide a new reference for a deeper understanding of the ecotoxicological effects of BPA on aquatic animals.

Pediococcus pentosaceus PR-1 modulates high-fat-died-induced alterations in gut microbiota, inflammation, and lipid metabolism in zebrafish.

Obesity is a health issue worldwide. This study aimed to evaluate the beneficial effects of Pediococcus pentococcus PR-1 on the modulating of gut microbiota, inflammation and lipid metabolism in high-fat-diet (HFD)-fed zebrafish. Adult zebrafish were fed a commercial (C), high fat (H, 25% fat), probiotic (P, 106 CFU/g), or high fat with probiotic (HP) diets twice daily for 5 weeks. Gut microbiota were analysed using 16S rRNA gene sequencing. Gene expressions of intestinal cytokine, intestinal TJ protein, and liver lipid metabolism were analysed by quantitative real-time polymerase chain reaction. Biochemical and histological analysis were also performed. P. pentosaceus PR-1 reduced body weight and BMI, indicating its anti-obesity effect. The 16S rRNA sequencing results showed HFD induced a distinct gut microbiota structure from C group, which was restored by probiotic. P. pentosaceus PR-1 improved gut health by decreasing the abundance of Ralstonia and Aeromonas which were increased induced by HFD. Moreover, probiotic restored abundance of Fusobacteria, Cetobacterium and Plesiomonas, which were decreased in HFD-fed zebrafish. The results of quantitative real-time polymerase chain reaction showed probiotic suppressed HFD-induced inflammation by decreasing the expressions of IL-1b and IL-6. Levels of hepatic TNF-α, IL-1ß, and IL-6 were reduced by probiotic in HFD-fed zebrafish. Probiotic also ameliorated gut barrier function by increasing the expressions of occludin, Claudin-1, and ZO-1. Probiotic exerted anti-adipogenic activity through regulating the expressions of SREBP1, FAS and LEPTIN. Levels of hepatic triglyceride, total cholesterol, low density lipoprotein were also reduced by probiotic. Histological analysis showed probiotic alleviated liver steatosis and injury induced by HFD. P. pentosaceus PR-1 might be useful as a dietary health supplement, especially for reducing obesity.

Antibiotics disrupt lipid metabolism in zebrafish (Danio rerio) larvae and 3T3-L1 preadipocytes

Antibiotics are emerging environmental contaminants with wide attention due to their high consumption and pseudo-persistence in the environment. They have been shown to induce obesity or obesity-related metabolic diseases in experimental animals, but the underlying toxicological mechanisms remain unclear. Here, the disruptive effects of four commonly used antibiotics, namely doxycycline (DC), enrofloxacin (ENR), florfenicol (FF) and sulfamethazine (SMT) on lipid metabolism were investigated in zebrafish (Danio rerio) larvae and murine preadipocyte cell line. Triglyceride (TG) content was reduced after 1 ng/L DC or ENR exposure but was increased at higher concentrations up to 100 mg/L. FF increased and SMT reduced TG content but did not show any concentration dependence. None of the antibiotics had any significant effect on total cholesterol (TC) content in zebrafish except 100 μg/L SMT. Expression levels of 8 lipid metabolism-related genes were also quantified. SMT was most disruptive by up-regulating six genes, followed by FF which up-regulated four genes and down-regulated one gene, whereas DC and ENR both up-regulated one gene. In 3T3-L1 preadipocytes, ENR, FF, and SMT in general increased TG content, while 100 mg/L FF reduced TG substantially. DC did not show any effect up to 10 mg/L, at which TG increased significantly. FF and SMT increased TC slightly at low concentrations but reduced it at high concentrations, whereas TC, DC and ENR had no effect at any tested concentrations. Gene expression measurement also indicated that SMT was most disruptive, followed by FF, DC, and ENR. Reporter gene assays showed that only SMT inhibited the transcriptional activity of peroxisome proliferator-activated receptor γ (PPARγ). The above experimental results and clustering analysis demonstrate that the four antibiotics exerted disruption on lipid metabolism through different mechanisms, and one of the mechanisms for SMT may be inhibition of PPARγ transcriptional activity.

The effects of dietary stachyose as prebiotic on immunity and antioxidant related genes’ expression and lipid metabolism in zebrafish (Danio rerio)

Abstract An 8-week feeding trial was conducted to examine the efficacy of stachyose as a prebiotic on immune parameters, antioxidant-/immune-related genes’ expression, and lipid metabolism of zebrafish. Three hundred zebrafish (0.45 ± 0.08 g) were fed four diets containing different stachyose levels at 0, 1, 2 and 4 g kg−1, respectively. After eight weeks of the feeding trial, immunity, antioxidant defence and lipid metabolism were tested. It was observed that the addition of stachyose to the diet induced no significant influence (P>0.05) in SOD, GPX, and CAT, gene’s expression, compared to the control diet. The inclusion of stachyose resulted in no significant changes in immune gene expression (Lyz, IL-1, IL-6, and TNF) in zebrafish (P>0.05) compared to the control diet. Total cholesterol, triglyceride and LDL (low-density lipoprotein) significantly (P<0.05) decreased with the addition of 2 and 4 g kg−1 stachyose, while fish fed the control diet and 1 g.kg−1 recorded the highest significant value of LDL (P<0.05). Fish fed diet, either control diet or diet supplemented with 0.5 g kg−1 stachyose, recorded the lowest HDL value (P<0.05) compared to other treatments. In conclusion, stachyose can be potentially used as a feed additive to modulate lipid metabolism. However, this prebiotic did not benefit immune parameters and antioxidant defence.

Fluorene-9-bisphenol exposure decreases locomotor activity and induces lipid-metabolism disorders by impairing fatty acid oxidation in zebrafish

AimsFluorene-9-bisphenol (BHPF), as a substitute for bisphenol A, is used in many industries in daily life. Many studies have clarified its effects as an endocrine disruptor on organisms, but its effect on lipid metabolism of zebrafish larvae is not clear. Patients with non-alcoholic fatty liver disease (NAFLD) are more susceptible to external pollutants. It is not clear how BHPF perturbs lipid metabolism or promotes NAFLD progression. Main methodsWe explored the biological effects of BHPF on locomotor activity, inflammatory response, endoplasmic reticulum (ER) stress and lipid metabolism in zebrafish, especially in the mechanism of lipid homeostasis disorder. In addition, the role of BHPF in the progression of non-alcoholic fatty liver disease (NAFLD) was further explored. Key findingsWe found that high concentration (100 nmol/L) BHPF caused retarded growth, mild lipid accumulation and reduced the locomotive activity of zebrafish larvae, accompanied by a decrease in endogenous cortisol level. At the same time, it caused the full activation of inflammation and ER stress. Rescue experiments by 25(OH)D3 demonstrated that high concentration of BHPF caused defects in 1,25(OH)2D3 metabolic pathway through downregulation of cyp2r1, which further damaged pgc1a-mediated fatty acid oxidation and mitochondrial function, resulting in lipid accumulation. In summary, exposure to BHPF could damage lipid homeostasis and worsen the diet-induced NAFLD. SignificanceOur findings provide new insights into the role of BHPF in development of overweight and obesity and also improve understanding of its toxicological mechanism. Our results play a warning role in the administration of environmental pollutants.

Dietary Nitrate Supplementation Alters Protein and Lipid Metabolism in Zebrafish (Danio rerio) Livers

ObjectivesDietary nitrate supplementation shows protective effects against cardio-metabolic disease, decreases pulmonary oxygen uptake, and improves exercise performance in animal models and humans. However, the biological effect of nitrate on energy metabolism in the liver is not well understood. The objective of this study was to elucidate changes in liver metabolism associated with nitrate treatment and exercise. MethodsFish were exposed to sodium nitrate (606.9 mg/L), or control water, for 21 days and analyzed at intervals during a strenuous exercise test. We utilized untargeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis to determine the effect of nitrate treatment and exercise on the liver metabolome. We measured gene expression of 31 genes linked to energy metabolism and redox signaling. ResultsIn the absence of exercise, nitrate treatment upregulated expression of genes central to nutrient sensing (pgc1a and sirt3), protein synthesis (mtor) and purine metabolism (pnp5a and ampd1) and downregulated expression of genes involved in mitochondrial fat oxidation (acaca, cpt2 and hadh). Upregulation of these genes was associated with an increased abundance of metabolites involved in endogenous nitric oxide metabolism, dopamine biosynthesis, branched chain amino acid metabolism, and lipid metabolism in nitrate-treated livers at rest, compared to rested controls. As expected, the availability of these metabolites was diminished in nitrate-treated livers relative to rested controls. We found no significant change in gene of metabolites directly linked to glycolysis. ConclusionsThe main novel finding of this study was that sub-chronic nitrate treatment altered dopamine biosynthesis, protein synthesis and lipid metabolism in zebrafish liver without exercise. This is significant because dietary nitrate is emerging as an interesting therapeutic modality for metabolic syndrome and non-alcoholic fatty liver disease by preventing lipid accumulation in the liver. Funding SourcesCelia Strickland and G. Kenneth Austin III Endowment and National Institutes of Health.

New insights into bisphenols induced obesity in zebrafish (Danio rerio): Activation of cannabinoid receptor CB1

Bisphenols (BPs), as widely used plastic additives, penetrate into our daily lives. BPs are considered endocrine disruptors and could potentially induce obesity. In this study, the effects of bisphenol A (BPA) and tetrabromobisphenol A (TBBPA) on food intake and lipid metabolism in zebrafish were determined. Moreover, the impact of BPA and TBBPA on the endocannabinoid system (ECS) of zebrafish was further explored by metabolomics, transcriptomics, and molecular docking analysis. Here we show that exposure to BPA and TBBPA at concentrations commonly found in the environment (20, 100, and 500 μg/L) led to hyperphagia and obesity in adult male zebrafish. Metabolomics and histopathological analysis revealed significant lipid accumulation in the liver of zebrafish exposed to BPA and TBBPA. The expression of ECS-related genes, in conjunction with RNA-Seq results, further indicated that BPA and TBBPA increased appetite and induced obesity by activating cannabinoid receptor type 1(CB1). Furthermore, molecular docking revealed that six representative BPs including BPA and TBBPA could bind to the CB1 receptor. Collectively, these findings indicate that CB1 may be a potential target for BPs to induce obesity.

Unraveling the mechanism of long-term bisphenol S exposure disrupted ovarian lipids metabolism, oocytes maturation, and offspring development of zebrafish

Bisphenol S (BPS) acts as a xenoestrogen and disturbs the female reproductive system; however, the underlying mechanism has not been elucidated. In this study, the effect of chronic BPS exposure (1 μg/L and 100 μg/L) on ovarian lipid metabolism in zebrafish was investigated to determine its influence on adult reproductive capacity and offspring development. The results showed that long-term (240 days) exposure to BPS induced lipid accumulation in the ovaries by promoting the transport of more lipids from the circulation to the ovaries and by upregulating triacylglycerol synthesis-related genes. Significantly increased expression of cpt2, acadm, acadl, and pparα, which are involved in β-oxidation in the ovarian mitochondria, indicated that more energy was provided for oocyte maturation in exposed zebrafish ovaries. Thus, the proportion of full-grown stage oocytes in ovaries and egg reproduction were elevated at an accelerated rate, which earlier than normal reproductive cycle (8–10 days posts pawning). Moreover, the maternally BPS-exposed F1 embryos (2 h post-spawning, hpf) showed higher neutral lipid levels, impaired hatching capacity, and increased occurrence of larval deformities. All these findings demonstrated that stimulated lipid synthesis and β-oxidation in zebrafish ovaries significantly contribute to BPS-induced oocyte precociousness with subsequent effects on the development of unexposed offspring. This study provides new insight into the impact of xenoestrogens on oviparous reproduction in females and offspring development from the perspective of ovarian lipid metabolism.

Zebrafish as an Emerging Model for Dyslipidemia and Associated Diseases.

Dyslipidemia related diseases such as hyperlipidemia and atherosclerosis are the leading cause of death in humans. While cellular and molecular basis on the pathophysiology of dyslipidemia has been extensively investigated over decades, we still lack comprehensive understanding on the etiology of dyslipidemia due to the complexity and the innate multimodality of the diseases. While mouse has been the model organism of choice to investigate the pathophysiology of human dyslipidemia, zebrafish, a small freshwater fish which has traditionally used to study vertebrate development, has recently emerged as an alternative model organism. In this review, we will provide comprehensive perspective on zebrafish as a model organism for human dyslipidemia; we will discuss the attributes of zebrafish as a model, and compare the lipid metabolism in zebrafish and humans. In addition, we will summarize current landscape of zebrafish-based dyslipidemia research.

Effects of difenoconazole on hepatotoxicity, lipid metabolism and gut microbiota in zebrafish (Danio rerio)

In current study, larvae and adult zebrafish were exposed to difenoconazole to assess its effect on hepatotoxicity, lipid metabolism and gut microbiota. Results demonstrated that difenoconazole could induce hepatotoxicity in zebrafish larvae and adult, 0.400, 1.00, 2.00 mg/L difenoconazole caused yolk retention, yolk sac edema or liver degeneration after embryos exposure for 120 h, hepatocyte vacuolization and neoplasm necrosis were observed in adult liver after 0.400 mg/L difenoconazole exposure for 21 d. RNA sequencing showed that the 41 and 567 differentially expressed genes in zebrafish larvae and liver induced by 0.400 mg/L difenoconazole, were concentrated in pathways related to protein digestion and absorption, pancreatic secretion, steroid biosynthesis, and different metabolic pathways including galactose or sugar metabolism. Difenoconazole exposure caused lipid accumulation in larval yolk sac, and the elevated triglyceride (TG), malondialdehyde (MDA) and reactive oxygen species (ROS) levels in larvae and liver, which further confirmed the lipid metabolism disorders induced by difenoconazole. The results further showed that difenoconazole increased the abundance of gut microbiota such as Firmicutes, Aeromonas, Enterobacteriaceae and Bacteroides, further suggested that gut microbiota might participate in lipid metabolism and hepatotoxicity during zebrafish development. These findings advanced the field of the difenoconazole-induced developmental toxicity in larvae and adult zebrafish, and the imbalance of gut microbiota provided the plausible mode of action for the liver damage and disordered lipid metabolism in zebrafish.

Evaluation of growth performance and lipid metabolism in zebrafish fed fructooligosaccharide using RNA sequencing

Evaluation of growth performance and lipid metabolism in zebrafish fed fructooligosaccharide using RNA sequencing

Corrigendum: Depletion of Myostatin b Promotes Somatic Growth and Lipid Metabolism in Zebrafish.

[This corrects the article DOI: 10.3389/fendo.2016.00088.].

Sex-specific alterations of lipid metabolism in zebrafish exposed to polychlorinated biphenyls

Polychlorinated biphenyls (PCBs) are persistent organic pollutants (POPs) mixtures exerting environmental health risk. In mammals, PCBs have been shown to disrupt metabolic state, especially lipid metabolism, and energy balance, but their effects on lipid metabolism in fish are largely unknown. The zebrafish were selected as model and both male and female adult zebrafish were exposed to different concentrations of PCBs at gradient concentrations of 0.2, 2.0 and 20.0 μg/L for 6 weeks. PCB exposure did not affect survival, but a significant inhibition of growth was observed in the males after exposure to 20.0 μg/L. The lower concentrations of 0.2 and 2.0 μg/L increased hepatic lipid accumulation to a greater extent in male fish, but the higher concentration of 20.0 μg/L did not cause significant fat accumulation in either male or female fish. In males, the expression of genes related to lipogenesis and lipid catabolism was upregulated in a concentration-dependent manner in the liver and visceral mass without liver and gonad; the effects of exposure on lipid metabolism-related genes in female fish were less pronounced. PCB exposure did not induce significant oxidative stress, but did upregulate the expression of stress- and apoptosis-related genes, mostly in male fish. The low concentrations of PCBs (0.2 μg/L and 2.0 μg/L) exerted sex-specific effects on zebrafish lipid metabolism, and male fish were more sensitive to the exposure. This study provides new mechanistic insights into the complex interactions between PCBs, lipid metabolism, and sex in zebrafish, and may contribute to a future systematic assessment of the effects of PCBs on aquatic ecosystems.

Thifluzamide affects lipid metabolism in zebrafish (Danio reio)

Thifluzamide, a succinate dehydrogenase inhibitor (SDHI) fungicide, has been widely used in rice fields throughout the world and causes hepatotoxicity in zebrafish (Danio reio). This study was conducted to investigate the effect of thifluzamide on lipid metabolism in zebrafish after exposure to a control or, 0.019, 0.19, or 1.90mg/L thifluzamide for 28days. Following exposure, pathological changes in the liver were evaluated. Total cholesterol (TCHO) level, and triglyceride (TG) levels as well as hepatic lipase (HL), lipoprotein lipase (LPL), fatty acid synthetase (FAS) and carnitine palmitoyltransferase (CPT-I) activities were measured. In addition, the expression levels of genes related to lipid metabolism were quantified. No obvious accumulation of lipid droplets was detected in the liver following any of the thifluzamide treatments. TCHO and TG levels were significantly decreased. FAS activity was markedly decreased, and CPT-I activity was significantly increased in the 0.19 and 1.90mg/L groups. However, no apparent changes in HL and LPL activities were observed in any of the treatment groups. Additionally, the expression of genes related to lipid metabolism showed corresponding changes. The results suggest that altered gene expression and enzyme activities might be responsible for the changes in lipid metabolism, as evidenced by the decreased TCHO and TG levels. Overall, thifluzamide altered lipid metabolism and led to events that might contribute to developmental toxicity in exposed zebrafish.

Lipophilic phosphorescent iridium(III) complexes as one- and two-photon selective bioprobes for lipid droplets imaging in living cells

Lipid droplets (LDs) have been the focus of intense research in recent years due to their deep involvement in lipid metabolism and association with diverse diseases. Compared with conventional organic fluorescent LD probes, metal-based phosphorescent probes have some unique advantages. In this study, two lipophilic neutral phosphorescent Ir(III) complexes (Ir1: [Ir(mtq)2(acac)] and Ir2: [Ir(mtq)2(dpm)], where mtq is 4-methyl-2-(thiophen-2-yl)quinolone, acac is acetylacetone and dpm is dipropionylmethane) have been investigated for their LD-specific imaging properties in detail. Complex Ir1 was demonstrated to selectively accumulate in cellular LDs with high specificity, good biocompatibility and excellent photostability. Moreover, complex Ir1 can be utilized to observe LDs by two-photon phosphorescence lifetime imaging microscopy (PLIM), which is a great benefit for phosphorescent bioprobes. Further studies reveal that probe Ir1 can be utilized to analyze LDs accumulation in living cells and visualize in vivo lipid metabolism in zebrafish. Overall, complexes Ir1 and Ir2 are promising alternative phosphorescent probes for LD analysis in LD-related scientific research. Our work also provides useful clues for the construction of highly specific phosphorescent LD probes through rational structural modification of phosphorescent metal complexes.

Bisphenol S induces obesogenic effects through deregulating lipid metabolism in zebrafish (Danio rerio) larvae

It has been suggested that dramatic increase in obesity may be caused by growing exposure to environmental chemicals. In vitro data has suggested bisphenol S (BPS), a compound widely used in polycarbonate plastic production, can induce lipid accumulation in preadipocytes. However, the mechanisms responsible for BPS-induced obesity in vivo remain unclear. In this study, we used translucent zebrafish (Danio rerio) larvae as a model to investigate the effect of environmentally relevant BPS exposure (1, 10, and 100 μg/L from 2 h to 15 d post fertilization) on lipid accumulation, triacylglycerol (TAG) and lipoproteins content, and mRNA expression of genes involved in the regulation of lipid synthesis, transport, degradation, and storage. We also analyzed activities of two enzymes critical to TAG metabolism: lipoprotein lipase and diglyceride acyltransferase. Overfed, obese larvae were used as positive control. The results indicated that BPS-treated and overfed larvae had much higher TAG levels and visceral fat accumulation compared with control. BPS exhibited obesogenic effects by interfering with lipid metabolism as evidenced by (a) upregulation of the mRNA expression of fasn, acc1, and agpat4 genes encoding enzymes involved in the de novo synthesis of TAG in the liver, (b) downregulation of apolipoprotein expression, which should reduce TAG transport from the liver, and (c) increase in rxrα expression, which should promote visceral fat accumulation. Our study is the first to demonstrate that the obesogenic effects of BPS in zebrafish are related to the disruption of TAG metabolism.