Early life stage exposure to cadmium and zinc within hour affected GH/IGF axis, Nrf2 signaling and HPI axis in unexposed offspring of marine medaka Oryzias melastigma.

Information on transgenerational effects of cadmium (Cd) and zinc (Zn) within hour of exposure is scarce. To the end, larvae of marine medaka Oryzias melastigma at 0 day-post-hatching (dph) were subjected to LC50 for 96-h of Cd or Zn for 0.5 and 6 h, and then transferred into clear water for 95 days until the generation of offspring larvae at 25 dph. Growth, antioxidant capacity and stress response in offspring larvae were examined. Exposure to Zn for 0.5 h or Cd for 0.5 h and 6 h promoted growth performance and reduced total antioxidant capacity (TAC) and activities of superoxide dismutase (SOD) and catalase (CAT). Malondialdehyde (MDA) and cortisol levels declined in larvae following Zn exposure for 0.5 h, whereas Cd exposure increased MDA content and did not affect cortisol levels. These physiological changes could be partially explained by transcription of genes in the hormone/insulin-like growth factor-I (GH/IGF) axis, NF-E2-related factor 2 (Nrf2) signaling, and hypothalamus-pituitary-interrenal (HPI) axis. For example, Zn exposure for 0.5 h up-regulated genes encoding growth hormone (gh) and insulin-like growth factor binding protein (igfbp1) and down-regulated mRNA levels of nrf2, Kelch-like-ECH-associated protein 1 gene (keap1a), keap1b, sod1, mineralocorticoid receptor (mr), corticotropin-releasing hormone receptor (crhr1), corticotropin-releasing hormone binding protein (crhbp), cytochrome P450 (cyp11a1, cyp17a1) and hydroxysteroid dehydrogenase (hsd3b1). Cd exposure for 0.5 and 6 h up-regulated growth hormone release hormone (ghrh) and igfbp1, down-regulated nrf2 and keap1a, and did not affect mRNA levels of HPI axis genes. Taken together, this study demonstrated that short-term metal exposure during larvae phase had positive and negative effects on offspring even after a long recovery.

Combined effects of polystyrene microplastics and cadmium on oxidative stress, apoptosis, and GH/IGF axis in zebrafish early life stages.

The toxicological interactions of microplastics (MPs) and heavy metals have been paid much attention in aquatic organism. The mechanisms are not fully clear, particularly in fish early life stages. To the end, zebrafish embryos were exposed to 500 µg/L MPs, 5 µg/L cadmium (Cd), and their combination for 30 days. Body weight, adsorption characteristics of Cd onto MPs, Cd accumulation, oxidative stress, apoptosis, and growth hormone/insulin-like growth factor-I (GH/IGF) axis were examined. Exposure to MPs and Cd alone reduced body weight, which was aggravated by co-exposure. An increase in reactive oxygen species (ROS) levels was observed in larvae exposed to Cd or MPs + Cd, suggesting an induction of oxidative stress. Lipid peroxidation levels were not affected by exposure to MPs and Cd alone but dramatically enhanced by co-exposure, which may be explained by the reduction of total antioxidant capacity (TAOC) and activity levels of Mn-superoxide dismutase (Mn-SOD) and catalase (CAT) after co-exposure. Increased apoptotic cells were observed in the vertebral body of larvae exposed to Cd, the esophagus of larvae exposed to MPs, and both organs of larvae exposed to MPs + Cd, which was further confirmed by changes in the activities of Caspase-3, Caspase-8 and Caspase-9. PCR array on the transcription of genes related to growth, oxidative stress and apoptosis was examined, showing that the combined exposure resulted in greater magnitude of changes than MPs and Cd alone. The results indicate that MPs can enhance the negative effects of Cd on growth, oxidative damage and apoptosis in early life stages of zebrafish. However, the adsorption of Cd onto MPs was not observed and the combined exposure did not increase the Cd content in larvae compared to the single Cd exposure, implying that vector role of MPs in Cd uptake is negligible.

Cadmium induced oxidative stress, endoplasmic reticulum (ER) stress and apoptosis with compensative responses towards the up-regulation of ribosome, protein processing in the ER, and protein export pathways in the liver of zebrafish.

The present study identified that exposure to 5, 10, and 20 µg/L Cd for 48 days reduced growth, increased Cd accumulation and levels of reactive oxygen species (ROS) and lipid peroxidation, and induced ER stress and cellular apoptosis in the liver in a dose-dependent manner. However, the survival rate was not affected by Cd. The increased production of ROS might result from reduced catalase (CAT) and copper/zinc-superoxide dismutase (Cu/Zn-SOD) activities, which might trigger ER stress pathways and subsequently induce apoptotic responses, ultimately leading to growth inhibition. Transcriptomic analyses indicated that the differentially expressed genes (DEGs) involved in metabolic pathways were significantly enriched and dysregulated by Cd, suggesting that metabolic disturbances may contribute to Cd toxicity. However, there were increases in glutathione peroxidase (GPX) activity, protein levels of metallothioneins (MTs) and heat shock protein 70 (HSP70), and mRNA levels of sod1, cat, gpx, mt2, and hsp70. Furthermore, DEGs related to ribosome, protein processing in the ER, and protein export pathways were significantly enriched and up-regulated by Cd. These increases may be compensatory responses following oxidative stress, ER stress, and apoptosis to resist negative effects. Taken together, we demonstrated that environmentally relevant levels of Cd induced adaptive responses with compensatory mechanisms in fish, which may help to maintain fish survival at the cost of growth.

Effects of continuous and intermittent cadmium exposure on HPGL axis, GH/IGF axis and circadian rhythm signaling and their consequences on reproduction in female zebrafish: Biomarkers independent of exposure regimes.

Typical biomarkers of cadmium (Cd) pollution have well been confirmed in fish from continuous exposure pattern. However, in a natural environment, fish may be exposed to Cd intermittently. In this study, juvenile female zebrafish were exposed for 48 days to 10 µg/L Cd continuously, 20 µg/L for 1 day in every 2 days or 30 µg/L for 1 day in every 3 days. The toxic effects were evaluated using 8 various physiological and biochemical endpoints like specific growth rate (SGR), 17ß-estradiol (E2) and vitellogenin (VTG) concentrations in plasma, reproductive parameters (gonadosomatic index (GSI), egg-laying amount, spawning percentage, and hatching and mortality rate of embryos). Transcription of 59 genes related to hypothalamic-pituitary-gonadal-liver (HPGL) axis, circadian rhythm signaling and insulin-like growth factor (IGF) system was examined. SGR, spawning percentage, E2 and VTG levels declined in fish exposed to 10 and 20 µg/L Cd but remained relatively stable in fish exposed to 30 µg/L Cd. Exposure to 10, 20 and 30 µg/L Cd significantly reduced GSI, hatching rate and mortality rate. Similarly, mRNA expression of 27 genes were sensitive to both continuous and intermittent Cd exposure. Among these genes, expression levels of 10 genes had more than 5-fold increase or decrease, including mRNA levels of vtg1, vtg2, vtg3, esr1, igf2a, igf2b, igfbp5b, nr1d1, gnrh3 and gnrhr4. The most sensitive molecular biomarker was vtg3 expression with 1500-3100 fold increase in the liver. The present study, for the first time, provides effective candidate biomarkers for Cd, which are independent of exposure regimes.

High salinity acclimatization alleviated cadmium toxicity in Dunaliella salina: Transcriptomic and physiological evidence.

In the present study, we tested the hypothesis that high salinity acclimatization can mitigate cadmium (Cd) toxicity in the microalga Dunaliella salina. To this end, microalgal cells were subjected to high salinity (60 g/L) for 12 weeks until the growth rate remained stable between generations and were then exposed to 2.5 mg/L of Cd for 4 days. Acute Cd toxicity impaired cell growth by increasing Cd bioaccumulation and lipid peroxidation, which reduced cellular pigment, total protein, and glutathione content. It also significantly weakened photosynthetic efficiency and total antioxidant capacity. However, acclimatization to high salinity alleviated these negative effects under Cd stress. To understand the potential mechanisms behind this phenomenon, 12 cDNA libraries from control, Cd-exposed (Cd), high salinity-acclimated (Salinity), and high salinity-acclimated with Cd exposure (Salinity + Cd) cells were derived using RNA sequencing. A total of 2019, 1799, 2150 and 1256 differentially expressed genes (DEGs) were identified from sample groups Salinity / Control, Cd / Control, Salinity + Cd / Control, and Salinity + Cd / Cd, respectively. Some of these DEGs were significantly enriched in ribosome, photosynthesis, stress defense, and photosynthesis-antenna proteins. Among these genes, 82 ribosomal genes were up-regulated in Salinity / Control (corrected P = 3.8 × 10-28), while 81 were down-regulated in Cd / Control (corrected P = 1.1 × 10-24). Moreover, high salinity acclimatization up-regulated 8 photosynthesis genes and 18 stress defense genes compared with the control. Additionally, 3 photosynthesis genes, 11 stress defense genes and 11 genes encoding light harvesting proteins were up-regulated by high salinity acclimatization under Cd exposure. Overall, high salinity acclimatization mitigated Cd toxicity, possibly by up-regulating the transcription of photosynthesis, stress defense, and ribosomal genes. These results provide new insights on cross-tolerance in microalgae.

Waterborne zinc induced lobe-dependent effect on oxidative stress and energy metabolism in hepatopancreas of Larimichthys crocea.

The study aimed to compare differences in oxidative stress and energy metabolism between the left and right lobe of hepatopancreas in large yellow croaker Larimichthys crocea exposed to 0 (control), 20, and 100 µM Zn for 96 h. Tipical biomarkers were examined including the proportion of white hepatopancreas, lipid content, malondialdehyde (MDA) level, glutathione (GSH) content, activity levels of enzymes (Cu/Zn-superoxide dismutase, Cu/Zn-SOD; catalase, CAT; glutathione peroxidase, GPx; glutathione reductase, GR; mitochondrial ATP synthase, F-ATPase; malate dehydrogenase, MDH; succinate dehydrogenase, SDH; hepatic lipase, HTGL; lipoprotein lipase, LPL), mRNA levels of genes encoding these enzymes (sod1, cat, gpx1a, gr, atp5b, mdh, sdh, htgl, and lpl), and gene expression of signaling molecules the NF-E2-related nuclear factor 2 (nrf2) and Kelch-like ECH-associated protein 1 (keap1). A whitish color in the left lobe of hepatopancreas was observed in the control and Zn-exposed fish. Contrarily, the right lobe of hepatopancreas tended towards red with increasing Zn levels. The phenomenon was further confirmed by that lipid content was reduced in the right lobe and was not significantly affected in the left lobe by Zn. The right lobe showed higher energy consumption than the left lobe as reflected by the up-regulation of activity levels of HTGL, LPL, F-ATPase, MDH, and SDH. Lipid peroxidation declined by 20 µM Zn and was unchanged by 100 µM Zn in both lobes, which could be explained by increased activity levels of Cu/Zn-SOD and GPx. However, the magnitude of increase in Cu/Zn-SOD activity was greater in the right lobe than that in the left one. The difference in enzyme activity between two lobes may be involved in changes in mRNA levels of sod1, gr, atp5b, sdh, htgl, lpl, and nrf2, which was further confirmed by positive relationships between enzyme activity and gene expression. Our data also showed positive correlations between nrf2 expression and mRNA levels of its target genes, suggesting that Nrf2 was required for the protracted induction of these genes. Our results demonstrated the potential molecular mechanism of Zn-induced differences between lobes of hepatopancreas, suggesting that the sampling part of hepatopancreas should be considered with caution when assessing metal contamination.

Transcriptional and physiological responses of Dunaliella salina to cadmium reveals time-dependent turnover of ribosome, photosystem, and ROS-scavenging pathways.

Effects on short-term (6 h) and long-term (96 h) exposure to cadmium (Cd) at 0.1, 0.5 and 2.5 mg/L in microalga Dunaliella salina were assessed using both physiological end points and gene expression analysis. Different physiological responses between the short-term and long-term exposures were observed. Upon 6 h after Cd exposure, lipid peroxidation and cell ultrastructure remained unchanged, while contents of chlorophyll a, chlorophyll b, carotenoids were increased at 0.5 and 2.5 mg/L Cd. Contrarily, 96 h after Cd exposure, lipid peroxidation levels were increased, while pigments content was decreased, and damaged cell ultrastructure was apparent at 2.5 mg/L Cd. Activities of antioxidant enzymes (APX, SOD, GST, GPX, and GR) changed differently both at 6 h and 96 h after Cd exposure. Upon 6 h after Cd exposure, SOD and GST activity increased at all three doses, GR and GPX activity increased at 0.5 mg/L Cd while APX activity increased at 0.1 mg/L Cd. Contrarily, 96 h after Cd exposure, activities of all the antioxidant enzymes increased both at 0.1 and 0.5 mg/L Cd; but there was a decrease in SOD and GR activity in D. salina exposed to 2.5 mg/L Cd. RNA-seq and qRT-PCR analyses indicated that genes involved in ROS-scavenge, photosystem, and ribosome functions were differentially expressed. The most significantly enriched function was the ribosome, in which more than 30 ribosome genes were up-regulated at 6 h but down-regulated at 96 h after Cd exposure at 2.5 mg/L. Our study indicated for the first time that genes encoding ribosomal proteins are the primary target for Cd in microalgae, which allowed gaining new insights into temporal dynamics of toxicity and adaptive response pathways in microalgae exposed to metals.

Life-cycle exposure to cadmium induced compensatory responses towards oxidative stress in the liver of female zebrafish.

The current study examined effects of waterborne cadmium (Cd) at environmental relevant concentrations (0, 2.5 and 5 µg/L) on growth, survival, histology, ultrastructure, metal homeostasis, and antioxidant responses in female zebrafish from embryos to sexually maturity for 15 weeks. Growth and survival rate were not significantly affected by Cd exposure. There were no significant changes in ultrastructure of cellular organelles, reactive oxygen species (ROS) levels, lipid peroxidation (LPO) in liver. However, Cd exposure increased Cd and lipid accumulation, reduced contents of zinc, copper and reduced glutathione (GSH), and down-regulated activity of copper/zinc-superoxide dismutase (Cu/Zn-SOD) in liver of zebrafish. Contrarily, the mRNA and activity levels of catalase (CAT), the mRNA levels of Cu/Zn-SOD, and the mRNA and protein levels of metallothioneins (MTs) were up-regulated. The transcriptional regulation of Cu and Zn transporters might be a vital mechanism by which fish slow the Zn and Cu uptake. Taken together, our data demonstrated that long-term and low-dose Cd induced adaptive responses with interlinked compensatory mechanism, which may protect fish against oxidative stress.

Heat-induced oxidative stress and inflammation involve in cadmium pollution history in the spleen of zebrafish.

Zebrafish were exposed to 0, 2.5 and 5 µg/L cadmium (Cd) for 10 weeks, and then each group was exposed to 26 °C(control) and 32 °C (high temperature) for 7 days. 22 indicators were compared between 26 °C and 32 °C in the spleen, including body weight, LPO and NO levels, activity levels of Cu/Zn-SOD, CAT and iNOS, MTs protein levels, and mRNA levels of Nrf2, Cu/Zn-SOD, CAT, HSF1, HSF2, HSP70, MTF-1, MTs, IL-6, IL-10, IL-1ß, TNF-α, iNOS and NF-κB. Most indicators were not significantly affected by heat in fish from no Cd pollution. However, almost all of indicators were responsive to heat in fish pre-exposed to Cd. Several indicators were sensitive to heat in fish pre-exposed to 2.5 µg/L Cd such as iNOS activities, and mRNA levels of iNOS and IL-10. Most other indicators were sensitive to heat in fish pre-exposed to 5 µg/L. The mRNA levels of HSP70 and MTF-1 were up-regulated by heat in fish pre-exposed to 0, 2.5 and 5 µg/L Cd. However, the magnitude of increase was the greatest in fish pre-exposed to 5 µg/L Cd. These differences between control and high temperature would serve as biomarkers to distinguish healthy from Cd-polluted group. The findings imply that metal pollution history should be carefully considered when screening heat biomarkers in fish.

Effects of heat and cadmium exposure on stress-related responses in the liver of female zebrafish: Heat increases cadmium toxicity.

In this study, female zebrafish (Danio rerio) were exposed to 26°C or 34°C, 0 or 197µg/L cadmium (Cd), singly or in combination for 7days. Multiple stress-related indicators were evaluated in the liver. Mortality, lipid peroxidation (LPO) and ultrastructural damage increased significantly by Cd exposure alone, and were not affected by heat alone. Interestingly, the combined exposure increased LPO, ultrastructural damage, and mortality compared with Cd exposure alone. The results indicated that elevated temperature increased Cd toxicity, which could be explained by several reasons. Firstly, Cd-exposed fish failed to activate the antioxidant defense system under heat stress. Secondly, expression levels of heat shock protein 70 (HSP70) were not significantly up-regulated by heat in Cd-exposed fish but increased by 117 times in Cd-free fish. Besides, hypermethylation of heat shock factor (HSF) binding motif in HSP70 promoter was observed during the combined exposure, indicating that simultaneous exposure may have partially suppressed the cytoprotective up-regulation of HSP70. Thirdly, heat induced an immunosuppressive effect in Cd-exposed fish, as reflected by the reduced mRNA and activity levels of nitric oxide synthase (iNOS) and interleukin-1ß (IL-1ß) expression levels. Finally, heat down-regulated Zir-, Irt-like protein 8 (ZIP8) and copper transporter 1 (CTR1) and up-regulated metallothioneins (MTs) in Cd-exposed fish, possibly suggesting Cu and Zn depletion and Cd accumulation. Hence, our data provide evidences that warmer temperatures can potentiate Cd toxicity, involved in the regulation of gene transcription, enzymatic activity, and DNA methylation. We found that heat indicators showed varied sensitivity between normal and Cd-exposed fish, emphasizing that the field metal pollution should be carefully considered when evaluating effects of climate change.

Heat indicators of oxidative stress, inflammation and metal transport show dependence of cadmium pollution history in the liver of female zebrafish.

Environmental stressors such as high temperature and metal exposure may occur sequentially, simultaneously, previously in aquatic ecosystems. However, information about whether responses to high temperature depend on Cd exposure history is still unknown in fish. Zebrafish were exposed to 0 (group 1), 2.5 (group 2) and 5µg/L (group 3) cadmium (Cd) for 10 weeks, and then each group was subjected to Cd-free water maintained at 26°C and 32°C for 7days respectively. 26 indicators were used to compare differences between 26°C and 32°C in the liver of female zebrafish, including 5 biochemical indicators (activity of Cu/Zn-SOD, CAT and iNOS; LPO; MT protein), 8 molecular indicators of oxidative stress (mRNA levels of Nrf2, Cu/Zn-SOD, CAT, HSF1, HSF2, HSP70, MTF-1 and MT), 5 molecular indicators of inflammation (mRNA levels of IL-6, IL-1ß, TNF-α, iNOS and NF-κB), 8 molecular indicators of metal transport (mRNA levels of, ZnT1, ZnT5, ZIP8, ZIP10, ATP7A, ATP7B and CTR1). All biochemical indicators were unchanged in group 1 and changed in group 2 and 3. Contrarily, differences were observed in almost all of molecular indicators of inflammation and metal transport in group 1, about half in group 2, and few in group 3. We also found that all molecular indicators of oxidative stress in group 2 and fewer in group 1 and 3 were significantly affected by heat. Our data indicated that heat indicators of oxidative stress, inflammation and metal transport showed dependence of previous cadmium exposure in the liver of zebrafish, emphasizing metal pollution history should be carefully considered when evaluating heat stress in fish.

Preheating mitigates cadmium toxicity in zebrafish livers: Evidence from promoter demethylation, gene transcription to biochemical levels.

The working hypothesis for this study was that moderate heat stress would alleviate the deleterious effects of subsequent cadmium (Cd) exposure on fish. Thus, zebrafish (Danio rerio) were subjected to water maintained at 26°C and 34°C for 4days, and then exposed to 0 or 200µg/L Cd for 1 week at 26°C. Multiple indicators were measured from livers of zebrafish at different levels, including DNA, RNA, protein and enzymatic activity associated with oxidative stress, inflammation and metal transport. The ameliorative effect of preheatinging on Cd toxicity was demonstrated. In the Cd-exposed groups, preheating decreased mortality and lipid peroxidation, increased activity levels of catalase (CAT) and copper/zinc-superoxide dismutase (Cu/Zn-SOD), and up-regulated mRNA levels of heat shock protein 70 (HSP70) and heat shock factor 2 (HSF2). Preheating also mitigated Cd-induced increases in protein and mRNA levels of metallothioneins (MTs), and mRNA levels of several inflammation-related genes. Furthermore, preheating alone dramatically up-regulated mRNA levels of genes related to antioxidant and immune defenses, zinc and copper transporters, protein folding, and reduced methylation levels in the HSF binding motif of the HSP70 promoter. Overall, preheating-induced accumulation of transcripts via demethylation might support the rapid defense responses at post-transcriptional levels caused by subsequent Cd exposure, indicating an adaptive mechanism for organisms exposed to one mild stressor followed by another.

Immunosuppressive effects and associated compensatory responses in zebrafish after full life-cycle exposure to environmentally relevant concentrations of cadmium.

In natural environments, fish survive in polluted water by cadmium (Cd) throughout their whole life cycle. However, little information is available on Cd toxicity considering a life cycle assessment. The present study investigated effects of environmental levels of cadmium (0, 2.5, and 5µg/L) on immune responses in liver and spleen of zebrafish for 15 weeks, from embryos to sexually maturity. Nitric oxide (NO) levels and iNOS activity declined in liver and spleen of zebrafish exposed to 5µg/L Cd, suggesting an immunosuppressive effect. The result was further supported by the decreased transcriptional levels of proinflammatory cytokines by Cd, such as interleukin-6 (IL-6), interleukin-10 (IL-10), interleukin-1ß (IL-1ß), and tumour necrosis factor-α (TNF-α) in liver. However, a sharp increase in the mRNA levels of these cytokines was observed in spleen of zebrafish exposed to Cd. The increased mRNA expression of these proinflammatory cytokines may be the secondary effect following immunosuppression and just reflect a compensatory mechanism for coping with the decreased immunity, which may explain an increase in mRNA levels and a decrease in iNOS activity in spleen of zebrafish exposed to Cd. In liver, the down-regulated mRNA levels of iNOS paralleled with the decreased iNOS activity, suggesting a synchronous response from a molecular level to a biochemical level. Positive correlations between mRNA expression levels of nuclear transcription factor κB (NF-κB) and proinflammatory cytokines were also observed, suggesting that NF-κB might be required for the protracted induction of inflammatory genes. The corresponding changes in the mRNA levels of the inhibitor of κBα (IκBαa and IκBαb) may form a feedback loop to restore transcriptional activity of NF-κB. Furthermore, splenic ROS levels were increased by 5µg/L Cd, possibly activating NF-κB pathway. Taken together, immunosuppressive effects and tissue-dependent compensatory responses were demonstrated in zebrafish after full life-cycle exposure to environmental levels of Cd, indicating a compromise between survival and immunity.

Redox-responsive nanocarriers for drug and gene co-delivery based on chitosan derivatives modified mesoporous silica nanoparticles.

Stimuli-responsive nanocarriers for anticancer drug and gene co-delivery are promising strategy in cancer therapy. The ultimate goal is to deliver high local concentration of therapeutic agents with no premature release and result in synergistic effects for combination therapies. In this work, we developed a redox stimuli-responsive and synergistic co-delivery system for anticancer drug DOX and p53 gene for potential cancer therapy. A dendronized chitosan derivative (CP) as a "gatekeeper" to control release the drug was used to modify MSNs via a disulfide linker and improve the gene transfection efficiency. Stimulus-induced release of the DOX was studied in the presence of glutathione (GSH), which showed that polymer shell was shed and accelerated the release of embedded drugs inside the tumor cells under a GSH-rich environment. The obtained nanoparticles showed good gene delivery ability in vitro by inducing an obvious increase in p53 protein expression in Hela cells. Apoptosis analysis confirmed that DOX and p53 could be co-delivered to the Hela cells by MSN-SS-CP nanocarriers and induced significant cell apoptosis. These results demonstrated that the dual delivery system resulted in synergistic effects and lead to an effective cancer cell apoptosis, which may be promising for cancer therapeutic application.

Differential effect of waterborne cadmium exposure on lipid metabolism in liver and muscle of yellow catfish Pelteobagrus fulvidraco.

The present study was conducted to investigate the effect of waterborne cadmium (Cd) exposure on lipid metabolism in liver and muscle of juvenile yellow catfish Pelteobagrus fulvidraco. Yellow catfish were exposed to 0 (control), 0.49 and 0.95 mg Cd/l, respectively, for 6 weeks, the lipid deposition, Cd accumulation, the activities and expression level of several enzymes as well as the mRNA expression of transcription factors involved in lipid metabolism in liver and muscle were determined. Waterborne Cd exposure reduced growth performance, but increased Cd accumulation in liver and muscle. In liver, lipid content, the activities and the mRNA expression of lipogenic enzymes (6-phosphogluconate dehydrogenase (6PGD), glucose-6-phosphate dehydrogenase (G6PD), fatty acid synthetase (FAS)) and lipoprotein lipase (LPL) activity increased with increasing waterborne Cd concentrations. However, the mRNA expressions of LPL and peroxisome proliferators-activated receptor (PPAR) α were down-regulated by Cd exposure. Carnitine palmitoyltransferase 1 (CPT1) activity as well as the mRNA expressions of CPT1 and PPARγ showed no significant differences among the treatments. In muscle, lipid contents showed no significant differences among the treatments. The mRNA expression of 6PGD, FAS, CPT1, LPL, PPARα and PPARγ were down-regulated by Cd exposure. Thus, our study indicated that Cd triggered hepatic lipid accumulation through the improvement of lipogenesis, and that lipid homeostasis in muscle was probably conducted by the down-regulation of both lipogenesis and lipolysis. Different variation patterns of lipid metabolism to waterborne Cd exposure indicated the tissue-specific regulatory effect of lipid metabolism under waterborne Cd exposure. To our knowledge, the present study provides, for the first time, evidence that waterborne chronic Cd exposure can disturb the normal processes of lipid metabolism at both the enzymatic and molecular levels, and in two tissues (the liver and muscle).