Browsing by Author "Mei-Ling Zhang"
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Item Atorvastatin remodels lipid distribution between liver and adipose tissues through blocking lipoprotein efflux in fish(American Physiological Society, 2023-03-01) Rui-Xin Li; Ling-Yun Chen; Samwel Mchele Limbu; Bing Yao; Yi-Fan Qian; Wen-Hao Zhou; Li-Qiao Chen; Fang Qiao; Mei-Ling Zhang; Zhen-Yu Du; Yuan LuoThe regulation of cholesterol metabolism in fish is still unclear. Statins play important roles in promoting cholesterol metabolism development in mammals. However, studies on the role of statins in cholesterol metabolism in fish are currently limited. The present study evaluated the effects of statins on cholesterol metabolism in fish. Nile tilapia (Oreochromis niloticus) were fed on control diets supplemented with three atorvastatin levels (0, 12, and 24 mg/kg diet, ATV0, ATV12, and ATV24, respectively) for 4 wk. Intriguingly, the results showed that both atorvastatin treatments increased hepatic cholesterol and triglyceride contents mainly through inhibiting bile acid synthesis and efflux, and compensatorily enhancing cholesterol synthesis in fish liver (P < 0.05). Moreover, atorvastatin treatment significantly inhibited hepatic very-low-density lipoprotein (VLDL) assembly and thus decreased serum VLDL content (P < 0.05). However, fish treated with atorvastatin significantly reduced cholesterol and triglycerides contents in adipose tissue (P < 0.05). Further molecular analysis showed that atorvastatin treatment promoted cholesterol synthesis and lipogenesis pathways, but inhibited lipid catabolism and low-density lipoprotein (LDL) uptake in the adipose tissue of fish (P < 0.05). In general, atorvastatin induced the remodeling of lipid distribution between liver and adipose tissues through blocking VLDL efflux from the liver to adipose tissue of fish. Our results provide a novel regulatory pattern of cholesterol metabolism response caused by atorvastatin in fish, which is distinct from mammals: cholesterol inhibition by atorvastatin activates hepatic cholesterol synthesis and inhibits its efflux to maintain cholesterol homeostasis, consequently reduces cholesterol storage in fish adipose tissue.Item Concentration-dependent effects of 17 β-estradiol and bisphenol A on lipid metabolism, inflammation and antioxidant response in male zebrafish (Danio rerio). Chemosphere, 237: (2019) 124422.(Elsevier, 2019-12) Sheng-Xiang Sun; Yun-Ni Zhang; Dong-Liang Lu; Wei-Li Wang; Samwel Mchele Limbu; Dong-Liang Li; Li-Qiao Chen; Mei-Ling Zhang; Zhen-Yu DuEnvironmental estrogenic compounds are important pollutants, which are widely distributed in natural water bodies. They produce various adverse effects on fish, but their concentration-dependent toxicities in fish metabolism and health are not fully understood. This study investigated the effects of 17β-estradiol (E2) and bisphenol A (BPA) at low and high concentrations on lipid deposition, inflammation and antioxidant response in male zebrafish. We measured fish growth parameters, gonad development, lipid contents and the activities of inflammatory and antioxidant enzymes, as well as their mRNA expressions. All E2 and BPA concentrations used increased body weight, damaged gonad structure and induced feminization in male zebrafish. The exposure of zebrafish to E2 and BPA promoted lipid accumulation by increasing total fat, liver triglycerides and free fatty acid contents, and also upregulated lipogenic genes expression, although they decreased total cholesterol content. Notably, zebrafish exposed to low concentrations of E2 (200 ng/L) and BPA (100 μg/L) had higher lipid synthesis and deposition compared to high concentrations (2000 ng/L and 2000 μg/L, respectively). However, the high concentrations of E2 and BPA increased inflammation and antioxidant response. Furthermore, BPA caused greater damage to fish gonad development and more severe lipid peroxidation compared to E2. Overall, the results suggest that the toxic effects of E2 and BPA on zebrafish are concentration-dependent such that, the relative low concentrations used induced lipid deposition, whereas the high ones caused adverse effects on inflammation and antioxidant response.Item Dietary docosahexaenoic acid reduces fat deposition and alleviates liver damage induced by D-galactosamine and lipopolysaccharides in Nile tilapia (Oreochromis niloticus)(Elsevier, 2023-06) Yi-Chan Liu; Samwel Mchele Limbu; Jin-Gang Wang; Mai Wang; Li-Qiao Chen; Fang Qiao; Yuan Luo; Mei-Ling Zhang; Zhen-Yu DuLiver health is important to maintain survival and growth of fish. Currently, the role of dietary docosahexaenoic acid (DHA) in improving fish liver health is largely unknown. This study investigated the role of DHA supplementation in fat deposition and liver damage caused by D-galactosamine (D-GalN) and lipopolysaccharides (LPS) in Nile tilapia (Oreochromis niloticus). Four diets were formulated as control diet (Con), Con supplemented with 1 % DHA, 2 % DHA and 4 % DHA diets, respectively. The diets were fed to 25 Nile tilapia (2.0 ± 0.1 g, average initial weight) in triplicates for four weeks. After the four weeks, 20 fish in each treatment were randomly selected and injected with a mixture of 500 mg D-GalN and 10 μL LPS per mL to induce acute liver injury. The results showed that the Nile tilapia fed on DHA diets decreased visceral somatic index, liver lipid content and serum and liver triglyceride concentrations than those fed on the Con diet. Moreover, after D-GalN/LPS injection, the fish fed on DHA diets decreased alanine aminotransferase and aspartate transaminase activities in the serum. The results of liver qPCR and transcriptomics assays together showed that the DHA diets feeding improved liver health by downregulating the expression of the genes related to toll-like receptor 4 (TLR4) signaling pathway, inflammation and apoptosis. This study indicates that DHA supplementation in Nile tilapia alleviates the liver damage caused by D-GalN/LPS through increasing lipid catabolism, decreasing lipogenesis, TLR4 signaling pathway, inflammation, and apoptosis. Our study provides novel knowledge on the role of DHA in improving liver health in cultured aquatic animals for sustainable aquaculture.Item Dietary L-carnitine alleviates the adverse effects caused by reducing protein and increasing fat contents in juvenile largemouth bass (Micropterus salmoides)(2022-05-06) Yi-Chan Liu; Samwel Mchele Limbu; Jin-Gang Wang; Jiong Ren; Fang Qiao; Mei-Ling Zhang; Zhen-Yu DuProtein ingredients for formulation of fish feeds are expensive and have limited availability. Therefore, reducing dietary protein while increasing dietary fat content is a common practice in rearing carnivorous fish species. However, the ability of dietary L-carnitine to alleviate adverse effects in such diets is currently unknown. This study investigated the role of L-carnitine supplementation in alleviating adverse effects on growth performance, energy metabolism, antioxidant capacity, and inflammation response in juvenile largemouth bass (Micropterus salmoides) fed on a low protein and high fat diet. Three diets were formulated to contain low protein and high fat (LPHF: 420 g kg-1 protein and 150 g kg-1 lipid), LPHF supplemented with L-carnitine (LPHFC: 420 g kg-1 protein and 150 g kg-1 lipid), and a control diet (CON: 480 g kg-1 protein and 130 g kg-1 lipid). The diets were fed to 30 largemouth bass (g) juveniles in triplicates for eight weeks. The results showed that the fish feed on LPHF diet increased hepatosomatic index, visceral somatic index, mesenteric fat index, whole-body crude fat content, serum and liver triglyceride concentrations, and serum non-esterified fatty acid level than those fed on CON diet. Moreover, the fish fed on LPHF diet increased serum alanine aminotransferase activity and liver malondialdehyde content and reduced superoxide dismutase (SOD) activities in the serum and liver. Furthermore, the fish fed on LPHF diet reduced the whole-body crude protein content. Interestingly, feeding the fish on the LPHFC diet decreased fat deposition and liver damage by downregulating the expression of genes related to lipogenesis, inflammation, and increased SOD activity. This study indicates that L-carnitine supplementation in largemouth bass alleviates the adverse effects caused by LPHF diet by decreasing lipogenesis and increasing lipid catabolism. Our study provides novel knowledge on strategies to improve utilization of LPHF diet in cultured aquatic animals.Item Dietary L-carnitine supplementation recovers the increased pH and hardness in fillets caused by high-fat diet in Nile tilapia (Oreochromis niloticus)(Elsevier, 2022-07-15) Zhi-Yong Zhang; Samwel Mchele Limbu; Si-Han Zhao; Li-Qiao Chen; Yuan Luo; Mei-Ling Zhang; Fang Qiao; Zhen-Yu DuThe wide use of high-fat diet (HFD) causes negative effects on flesh quality in farmed fish. l-carnitine, a lipid-lowering additive, enhances mitochondrial fatty acid β-oxidation. However its roles in alleviating the effects of HFD on flesh quality in fish are unknown. We fed Nile tilapia with medium-fat diet (MFD, 6% dietary lipid), high-fat diet (HFD, 12% dietary lipid) and HFCD supplemented with l-carnitine (HFCD + 400 mg/kg l-carnitine) for 10 weeks. The HFD-fed fish had higher fat deposition, pH value, myofiber density and flesh hardness than those fed on MFD. However, feeding the fish with the HFCD improved lipid catabolism, which increased significantly lactic acid content and myofiber diameter in muscle, thus reduced pH and hardness values. HFCD also reduced endoplasmic reticulum stress and myofiber apoptosis caused by HFD in the fish. Our study suggests that dietary l-carnitine supplementation alleviates the negative effects of HFD on flesh quality of farmed fish.Item Dietary sodium acetate improves high-fat diet utilization through promoting differential nutrients metabolism between liver and muscle in Nile tilapia (Oreochromis niloticus)(Elsevier, 2023-02-25) Wen-Hao Zhou; Samwel Mchele Limbu; Rui-Xin Li; Yuan Luo; Jiong Ren; Fang Qiao; Mei-Ling Zhang; Zhen-Yu Duigh-fat diet (HFD) often causes many negative effects and impairs fish growth. Short-chain fatty acids (SCFAs) such as acetates modify metabolic disorders and regulate body homeostasis. However, the effects of sodium acetate on alleviating HFD in fish is currently unknown. This study investigated the role of using dietary sodium acetate to alleviate adverse effects caused by HFD in fish. Three replicates (thirty fish each) of 4.8 ± 0.30 g Nile tilapia (Oreochromis niloticus) were fed with control diet (Con), high-fat diet (HFD) or HFD containing sodium acetate diet (HFD + NaAc) for eight weeks. After the feeding trial, Nile tilapia fed with HFD increased significantly tissue lipid deposition, reduced insulin sensitivity and suppressed glucose and lipid metabolism in both liver and muscle, accompanied with signs of metabolic disorders and liver damage. Moreover, HFD feeding inhibited muscle protein synthesis and impaired fish growth performance. However, the fish fed on HFD + NaAc improved significantly oxidative stress, inflammation, apoptosis and injury in liver compared to those fed on HFD. More importantly, dietary sodium acetate supplementation enhanced insulin sensitivity, promoted glucose catabolic utilization and protein synthesis in muscle through activation of insulin and mTOR signaling pathways, respectively, and markedly improved the growth performance. In contrast, dietary sodium acetate promoted hepatic pentose phosphate pathway, hepatic glycogen accumulation, and activated lipid catabolism to alleviate hepatic lipid deposition. Our study illustrates that sodium acetate alleviates differentially the adverse effects induced by feeding Nile tilapia with HFD in muscle and liver. SCFAs such as acetate may be used for improving HFD utilization in fish nutrition.Item Different effects of two dietary levels of tea polyphenols on the lipid deposition, immunity and antioxidant capacity of juvenile GIFT tilapia (Oreochromis niloticus) fed a high-fat diet. Aquaculture, 542: 736896. https://doi.org/10.1016/j.aquaculture.2021.736896(Elsevier, 2021-05-11) Yu-Cheng Qian; Xue Wang; Jiong Ren; Jie Wang; Samwel Mchele Limbu; Rui-Xin Li; Wen-Hao Zhou; Fang Qiao; Mei-Ling Zhang; Zhen-Yu DuLong-term feeding of fish with a high-fat diet (HFD) causes excess fat deposition and an impairment of immune function. In the present study, we aimed to determine whether dietary tea polyphenols (TPs) would ameliorate the adverse effects of HFD-feeding in GIFT tilapia. Juvenile GIFT tilapias (5.4 ± 0.9 g) were raised in twelve 200-L tanks (three tanks per diet, 20 fish per tank) and fed a control diet (6% fat, 36% protein), an HFD (12% fat, 36% protein), or an HFD supplemented with 50 mg/kg or 200 mg/kg TP for 8 weeks. The fish were hand-fed 5% of their body weight per day in three feeds, and maintained at 28 ± 1 °C under a 14-h light/10-h dark cycle. The fish in each tank were bulk weighed and counted fortnightly, and the daily feed amount was adjusted accordingly. At the end of the trial, the cumulative survival rate was calculated, and the weight gain and feed conversion ratio were calculated according to the bulk weight of fish in each tank. Tissues were collected from nine fish per diet, their organs were weighed, and biochemical and molecular indices were subsequently measured. HFD-feeding significantly increased lipid deposition, reduced cumulative survival from 96% to 75%, reduced hepatic alkaline phosphate activity (AKP) and serum total antioxidant capacity (T-AOC); and reduced the hepatic expression of immunoglobulin M (IgM), transforming growth factor-beta (TGF-β) and glutathione-S-transferase (GST) genes versus the control diet. The addition of TPs at 50 or 200 mg/kg both ameliorated the HFD-induced increase in lipid droplets in the liver (50 mg/kg TP from 40.83% to 17.27%; 200 mg/kg TP to 25.33%), and increased the cumulative survival rate of the tilapia. The addition of 50 mg/kg TP had a marked effect increasing cumulative survival to 90%, and increasing the activities of serum acid phosphatase (ACP), T-AOC; and IgM, TGF-β, nuclear factor-κB (NF-κB), superoxide dismutase (SOD), and GST gene expression to the highest level of the HFD-fed groups. The 50 mg/kg TP-containing diet also significantly increased the hepatic expression of carnitine palmitoyltransferase 1 alpha (CPT1α) versus the control diet. In contrast, the tilapia fed an HFD supplemented with 200 mg/kg TPs had the lowest expression of adipose triglyceride lipase, hormone-sensitive lipase, CPT1α, fatty acid synthase and acetyl-CoA carboxylase alpha genes of any of the groups, which implies that the lower and higher levels of TP supplementation have differing effects on lipid metabolism. The 200 mg/kg supplement had lower cumulative survival rate (82%), and smaller effects on serum ACP and hepatic AKP activities than the 50 mg/kg dose, and had no significant effect on serum T-AOC or the expression of IgM, TGF-β, GST, or NF-κB genes in the tilapia. These results indicate that the beneficial effects of TPs on the lipid metabolism and health of fish fed an HFD are dose-related. Moreover, they are likely to be largely mediated through lipid catabolism.Item Environmental estrogen exposure converts lipid metabolism in male fish to a female pattern mediated by AMPK and mTOR signaling pathways. Journal of Hazardous Materials, 394: 122537.(Elsevier, 2020-07-15) Sheng-Xiang Sun; Jun-Lin Wu; Hong-Bo Lv; Hai-Yang Zhang; Jing Zhang; Samwel Mchele Limbu; Fang Qiao; Li-Qiao Chen; Yi Yang; Mei-Ling Zhang; Zhenyu DuEnvironmental estrogens, including bisphenol A (BPA) and 17β-estradiol (E2), which are widely used in industries and medicine, pose a severe ecological threat to fish due to feminization induction. However, the related metabolic basis for reproductive feminization in male fish has not been well addressed. We first found that female zebrafish exhibited higher lipid accumulation and lipogenesis activity than males. Next, we exposed male and female zebrafish to E2 (200 ng/L) or BPA (100 μg/L) for six weeks, and observed an early-phase reproductive feminization in males, accompanied with reduced spermatids, significant fat deposition and lipogenic gene expressions that mimicked female patterns. Cellular signaling assays revealed that, E2 or BPA modulated lipid metabolism in males mainly through lowering 5′ AMP-activated protein kinase (AMPK) and upregulating the lipogenic mechanistic target of rapamycin (mTOR) pathways. For the first time, we show that environmental estrogens could alter lipid metabolism in male fish to a female pattern (metabolic feminization) prior to gonad feminization in male fish, to allows males to accumulate efficiently lipids to harmonize with the feminized gonads. This study suggests that negative effects of environmental estrogens, as hazardous materials, on vertebrate health are more complicated than originally thought.Item High cholesterol intake remodels cholesterol turnover and energy homeostasis in Nile tilapia (Oreochromis niloticus)(2023-02-16) Rui-Xin Li; Ling-Yun Chen; Samwel Mchele Limbu; Yu-Cheng Qian; Wen-Hao Zhou; Li-Qiao Chen; Yuan Luo; Fang Qiao; Mei-Ling Zhang· · ·The roles of dietary cholesterol in fish physiology are currently contradictory. The issue reflects the limited studies on the metabolic consequences of cholesterol intake in fish. The present study investigated the metabolic responses to high cholesterol intake in Nile tilapia (Oreochromis niloticus), which were fed with four cholesterol-contained diets (0.8, 1.6, 2.4 and 3.2%) and a control diet for eight weeks. All fish-fed cholesterol diets showed increased body weight, but accumulated cholesterol (the peak level was in the 1.6% cholesterol group). Then, we selected 1.6% cholesterol and control diets for further analysis. The high cholesterol diet impaired liver function and reduced mitochondria number in fish. Furthermore, high cholesterol intake triggered protective adaptation via (1) inhibiting endogenous cholesterol synthesis, (2) elevating the expression of genes related to cholesterol esterification and efflux, and (3) promoting chenodeoxycholic acid synthesis and efflux. Accordingly, high cholesterol intake reshaped the fish gut microbiome by increasing the abundance of Lactobacillus spp. and Mycobacterium spp., both of which are involved in cholesterol and/or bile acids catabolism. Moreover, high cholesterol intake inhibited lipid catabolic activities through mitochondrial β-oxidation, and lysosome-mediated lipophagy, and depressed insulin signaling sensitivity. Protein catabolism was elevated as a compulsory response to maintain energy homeostasis. Therefore, although high cholesterol intake promoted growth, it led to metabolic disorders in fish. For the first time, this study provides evidence for the systemic metabolic response to high cholesterol intake in fish. This knowledge contributes to an understanding of the metabolic syndromes caused by high cholesterol intake or deposition in fish.Item Inhibition of pyruvate dehydrogenase kinase increases carbohydrate utilization in Nile tilapia by regulating PDK2/4-PDHE1α axis and insulin sensitivity(Elsevier, 2022-06-24) Yuan Luo; Wen-Hao Zhou; Rui-Xin Li; Samwel Mchele Limbu; Fang Qiao; Li-Qiao Chen; Mei-Ling Zhang; Zhen-Yu DuPyruvate dehydrogenase kinases (PDKs)-pyruvate dehydrogenase E1α subunit (PDHE1α) axis plays an important role in regulating glucose metabolism in mammals. However, the regulatory function of PDKs-PDHE1α axis in the glucose metabolism of fish is not well known. This study determined whether PDKs inhibition could enhance PDHE1α activity, and improve glucose catabolism in fish. Nile tilapia fingerlings (1.90 ± 0.11 g) were randomly divided into 4 treatments in triplicate (30 fish each) and fed with control diet without dichloroacetate (DCA0) (38% protein, 7% lipid and 45% corn starch) and the control diet supplemented with DCA, which inhibits PDKs through binding the allosteric sites, at 3.75 (DCA3.75), 7.50 (DCA7.50) and 11.25 g/kg (DCA11.25), for 6 wk. The results showed that DCA3.75, DCA7.50 and DCA11.25 significantly increased weight gain, carcass ratio and protein efficiency ratio (P < 0.05) and reduced feed efficiency (P < 0.05) of Nile tilapia. To investigate the effects of DCA on growth performance of Nile tilapia, we selected the lowest doseDCA3.75 for subsequent analysis. Nile tilapia fed on DCA3.75 significantly reduced the mesenteric fat index, serum and liver triglyceride concentration and total lipid content in whole fish, and down-regulated the expressions of genes related to lipogenesis (P < 0.05) compared to the control. The DCA3.75 treatment significantly improved glucose oxidative catabolism and glycogen synthesis in the liver, but significantly reduced the conversion of glucose to lipid (P < 0.05). Furthermore, the DCA3.75 treatment significantly decreased the PDK2/4 gene and protein expressions (P < 0.05), accordingly stimulated PDHE1α activity by decreasing the phosphorylated PDHE1α protein level. In addition, DCA3.75 treatment significantly increased the phosphorylated levels of key proteins involved in insulin signaling pathway and glycogen synthase kinase 3β (P < 0.05). Taken together, the present study demonstrates that PDK2/4 inhibition by using DCA promotes glucose utilization in Nile tilapia by activating PDHE1α, and improving insulin sensitivity. Our study helps to understand the regulatory mechanism of glucose metabolism for improving dietary carbohydrate utilization in farmed fish.Item Lipolysis and lipophagy play individual and interactive roles in regulating triacylglycerol and cholesterol homeostasis and mitochondrial form in zebrafish(Elsevier, 2021-06-08) Si-Lan Han; Yu-Cheng Qian; Samwel Mchele Limbu; Jing Wang; Li-Qiao Chen; Mei-Ling Zhang; Zhen-Yu DuNeutral lipases-mediated lipolysis and acid lipases-moderated lipophagy are two main processes for degradation of lipid droplets (LDs). However, the individual and interactive roles of these metabolic pathways are not well known across vertebrates. This study explored the roles of lipolysis and lipophagy from the aspect of neutral and acid lipases in zebrafish. We established zebrafish strains deficient in either adipose triglyceride lipase (atgl−/−; AKO fish) or lysosomal acid lipase (lal−/−; LKO fish) respectively, and then inhibited lipolysis in the LKO fish and lipophagy in the AKO fish by feeding diets supplemented with the corresponding inhibitors Atglistatin and 3-Methyladenine, respectively. Both the AKO and LKO fish showed reduced growth, swimming activity, and oxygen consumption. The AKO fish did not show phenotypes in adipose tissue, but mainly accumulated triacylglycerol (TAG) in liver, also, they had large LDs in the hepatocytes, and did not stimulate lipophagy as a compensation response but maintained basal lipophagy. The LKO fish reduced total lipid accumulation in the body but had high cholesterol content in liver; also, they accumulated small LDs in the hepatocytes, and showed increased lipolysis, especially Atgl expression, as a compensatory mechanism. Simultaneous inhibition of lipolysis and lipophagy in zebrafish resulted in severe liver damage, with the potential to trigger mitophagy. Overall, our study illustrates that lipolysis and lipophagy perform individual and interactive roles in maintaining homeostasis of TAG and cholesterol metabolism. Furthermore, the interactive roles of lipolysis and lipophagy may be essential in regulating the functions and form of mitochondria.Item Mitochondrial fatty acid β-oxidation inhibition promotes carbohydrate catabolism and protein deposition through energy homeostasis remodelling. The Journal of Nutrition, nxaa187, https://doi.org/10.1093/jn/nxaa187.(Oxford University Press, 2019-09) Ling-Yu Li; Jia-Min Li; Li-Jun Ning; Dong-Liang Lu; Yuan Luo; Qiang Ma; Samwel Mchele Limbu; Dong-Liang Li; Li-Qiao Chen; Irfan J. Lodhi; Pascal Degrace; Mei-Ling Zhang; Zhen-Yu DuBackground Fish cannot use carbohydrate efficiently and instead utilize protein for energy supply, thus limiting dietary protein storage. Protein deposition is dependent on protein turnover balance, which correlates tightly with cellular energy homeostasis. Mitochondrial fatty acid β-oxidation (FAO) plays a crucial role in energy metabolism. However, the effect of remodeled energy homeostasis caused by inhibited mitochondrial FAO on protein deposition in fish has not been intensively studied. Objectives This study aimed to identify the regulatory role of mitochondrial FAO in energy homeostasis maintenance and protein deposition by studying lipid, glucose, and protein metabolism in fish. Methods Carnitine-depleted male Nile tilapia (initial weight: 4.29 ± 0.12 g; 3 mo old) were established by feeding them with mildronate diets (1000 mg/kg/d) for 6 wk. Zebrafish deficient in the carnitine palmitoyltransferase 1b gene (cpt1b) were produced by using CRISPR/Cas9 gene-editing technology, and their males (154 ± 3.52 mg; 3 mo old) were used for experiments. Normal Nile tilapia and wildtype zebrafish were used as controls. We assessed nutrient metabolism and energy homeostasis–related biochemical and molecular parameters, and performed 14C-labeled nutrient tracking and transcriptomic analyses. Results The mitochondrial FAO decreased by 33.1–88.9% (liver) and 55.6–68.8% (muscle) in carnitine-depleted Nile tilapia and cpt1b-deficient zebrafish compared with their controls (P < 0.05). Notably, glucose oxidation and muscle protein deposition increased by 20.5–24.4% and 6.40–8.54%, respectively, in the 2 fish models compared with their corresponding controls (P < 0.05). Accordingly, the adenosine 5′-monophosphate–activated protein kinase/protein kinase B–mechanistic target of rapamycin (AMPK/AKT-mTOR) signaling was significantly activated in the 2 fish models with inhibited mitochondrial FAO (P < 0.05). Conclusions These data show that inhibited mitochondrial FAO in fish induces energy homeostasis remodeling and enhances glucose utilization and protein deposition. Therefore, fish with inhibited mitochondrial FAO could have high potential to utilize carbohydrate. Our results demonstrate a potentially new approach for increasing protein deposition through energy homeostasis regulation in cultured animals.Item More simple more worse: Simple carbohydrate diets cause alterations in glucose and lipid metabolism in Nile tilapia (Oreochromis niloticus).(Elsevier, 2022-03-15) Wen-Hao Zhou; Chen-Chen Wu; Samwel Mchele Limbu; Rui-Xin Li; Li-Qiao Chen; Fang Qiao; Yuan Luo; Mei-Ling Zhang; Tao Han; Zhen-Yu DuDietary carbohydrates are widely used in aquafeeds as cheap energy source and improve quality of feeds. However, comprehensive assessment of the effects of dietary carbohydrate complexity on fish metabolism and liver health is currently lacking. This study investigated the effect of replacing 50% of starch by using sucrose, fructose and glucose. Four isonitrogenic (400 g/kg protein) and isolipidic (60 g/kg fat) feeds containing starch (polysaccharide), sucrose (disaccharide) and fructose and glucose (monosaccharides) were fed to three replicates of 4.5 ± 0.30 g Nile tilapia (Oreochromis niloticus) for eight weeks. Afterwards, growth performance, feed utilization efficiency, glucose and lipid metabolism and liver health were evaluated. The results showed that the Nile tilapia fed on monosaccharide diets had significantly lower growth and feed utilization efficiency than those fed on disaccharide and polysaccharide diets. The Nile tilapia fed on monosaccharide diets reduced significantly lipid deposition, hepatosomatic index (HSI), serum alanine transaminase (ALT) and aspartate aminotransferase (AST) and expression of lipid metabolism genes than those fed on polysaccharide diet. The Nile tilapia fed on disaccharide diet increased significantly the serum insulin, muscle glycogen, and muscle glycogen synthase (gs) gene expression compared with those fed on polysaccharide diet. Interestingly, the Nile tilapia fed on monosaccharide diets reduced significantly the glycogen content while they increased insulin, glucose and the expression of liver gluconeogenesis genes such as glucose-6-phosphatase (g6pase) and phosphoenolpyruvate carboxykinase (pepck) than those fed on polysaccharide diet. Contrary, the Nile tilapia fed on disaccharide diet downregulated liver glucose catabolism and lowered serum triglyceride (TG) levels than those fed on polysaccharide but enhanced muscle peroxisome proliferator activated receptor alpha (pparα) and carnitine palmitoyltransferase 1a (cpt1a) gene expression, liver gluconeogenesis and pentose phosphate pathways. These results indicate that Nile tilapia utilizes better dietary polysaccharides and disaccharides than monosaccharides. Feeding Nile tilapia on monosaccharide diets caused insulin resistance and glucose metabolism disorders manifested by hyperinsulinism and hyperglycemia, respectively. The carbohydrate complexity affects the nutritional metabolism and liver health of fish.Item Reduced fatty acid β-oxidation improves glucose catabolism and liver health in Nile tilapia (Oreochromis niloticus) juveniles fed a high-starch diet. Aquaculture, 535 (2021) 736392. https://doi.org/10.1016/j.aquaculture.2021.736392(Elsevier, 2021-03-30) Ling-Yu Li; Yue Wang; Samwel Mchele Limbu; Jia-Min Li; Fang Qiao; Li-Qiao Chen; Mei-Ling Zhang; Zhen-Yu DuFish are poor users of dietary carbohydrates and often display prolonged hyperglycemia and fat deposition after feeding high digestible carbohydrate diets. Recently, fatty acid β-oxidation (FAO) inhibition has been reported to increase glucose oxidation in fish. Therefore, this study tested the assumption that the inhibition of FAO with mildronate (MD, a carnitine synthesis inhibitor) might also increase glucose utilization and alleviate adverse effects induced by high starch diet (HSD) in Nile tilapia, Oreochromis niloticus. Nile tilapia juveniles (6.13 ± 0.11 g) were cultured in nine 200-L tanks (30 fish per tank) and divided into three groups (three tanks per group). The fish were fed twice a day (9:00 and 18:30) at 4% body weight by using a normal starch diet (NSD, 30% corn starch), a HSD (45% corn starch), or a HSD supplemented with MD (25 g/kg of diet, HSD + MD) for eight weeks. These three feeds contained approximately 35.8% protein and 6.4% lipid. The fish each tank were weighed every two weeks, and the feeding amount was adjusted accordingly. After the feeding trial, the fish fed on HSD showed higher hepatosomatic index (HSI), visceral somatic index (VSI), serum triglyceride concentration and whole-body and tissue (liver and muscle) lipid contents than those fed on NSD. The fish fed on HSD also had higher relative area of vacuolation in the liver, hepatic malondialdehyde (MDA) content, and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities in the serum than those fed on NSD. Moreover, the fish fed on HSD increased serum glucose and insulin concentrations, and hepatic lactate, pyruvate and glycogen contents, but reduced whole-body protein content and dietary protein utilization than those fed on NSD, indicating that HSD induced fat deposition, liver damage, glucose intolerance and lowered protein-sparing effect. However, the fish fed on HSD + MD decreased hepatic carnitine content and FAO activity, attenuated the indexes related to fat deposition and liver damage, improved blood glucose clearance and whole-body protein deposition than those fed on HSD, suggesting that the adverse effects caused by HSD were reversed after FAO inhibition. Furthermore, the fish fed on HSD down-regulated the expression of genes associated with glucose uptake, glycolysis, FAO process, and lipolysis compared to those fed on HSD + MD and NSD, yet up-regulated lipogenic and proteolytic genes. These data suggested that inhibition of FAO improved glucose utilization and alleviated the HSD-induced adverse effects in Nile tilapia. This work demonstrates that, modifying mitochondrial FAO activity regulates the ability of fish to adapt to HSD intake through remodeling energy homeostasis. Our study provides new insights into improving carbohydrate utilization in aquatic animals.Item The reduction of lipid-sourced energy production caused by ATGL inhibition cannot be compensated by activation of HSL, autophagy, and utilization of other nutrients in fish. Fish Physiology and Biochemistry, 47: 173–188(Springer, 2021-02) Si-Lan Han; Yan Liu; Samwel Mchele Limbu; Li-Qiao Chen; Mei-Ling Zhang; Zhen-Yu DuThe adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL)–mediated lipolysis play important roles in lipid catabolism. ATGL is considered the central rate-limiting enzyme in the mobilization of fatty acids in mammals. Currently, severe fat accumulation has been commonly detected in farmed fish globally. However, the ATGL-mediated lipolysis and the potential synergy among ATGL, HSL, and autophagy, which is another way for lipid breakdown, have not been intensively understood in fish. In the present study, we added Atglistatin as an ATGL-specific inhibitor into the zebrafish diet and fed to the fish for 5 weeks. The results showed that the Atglistatin-treated fish exhibited severe fat deposition, reduced oxygen consumption, and fatty acid β-oxidation, accompanied with increased oxidative stress and inflammation. Furthermore, the Atglistatin-treated fish elevated total and phosphorylation protein expressions of HSL. However, the free fatty acids and lipase activities in organs were still systemically reduced in the Atglistatin-treated fish, and the autophagy marker LC3 was also decreased in the liver. On the other hand, glycogenolysis was stimulated but blood glucose was higher in the Atglistatin-treated fish. The transcriptomic analysis also provided the hint that the protein turnover efficiency in Atglistatin-treated fish was likely to be accelerated, but the protein content in whole fish was not affected. Taken together, ATGL plays crucial roles in energy homeostasis such that its inhibition causes loss of lipid-sourced energy production, which cannot be compensated by activation of HSL, autophagy, and utilization of other nutrients.Item Vitellogenin 1 is essential for fish reproduction by transporting DHA-contained phosphatidylcholine from liver to ovary(Elsevier, 2023-04) Sheng-Xiang Sun; Yi-Chan Liu; Samwel Mchele Limbu; Dong-Liang Li; Li-Qiao Chen; Mei-Ling Zhang; Zhan Yin; Zhen-Yu DuVitellogenins (Vtgs) are essential for female reproduction in oviparous animals, yet the exact roles and mechanisms remain unknown. In the present study, we knocked out vtg1, which is the most abundant Vtg in zebrafish, Danio rerio via the CRISPR/Cas 9 technology. We aimed to identify the roles of Vtg1 and related mechanisms in reproduction and development. We found that, the Vtg1-deficient female zebrafish reduced gonadosomatic index, egg production, yolk granules and mature follicles in ovary compared to the wide type (WT). Moreover, the Vtg1-deficient zebrafish diminished hatching rates, cumulative survival rate, swimming capacity and food intake, but increased malformation rate, and delayed swim bladder development during embryo and early-larval phases. The Vtg1-deficiency in female broodstock inhibited docosahexaenoic acid-enriched phosphatidylcholine (DHA-PC) transportation from liver to ovary, which lowered DHA-PC content in ovary and offspring during larval stage. However, the Vtg1-deficient zebrafish increased gradually the total DHA-PC content via exogeneous food intake, and the differences in swimming capacity and food intake returned to normal as they matured. Furthermore, supplementing Vtg1-deficient zebrafish with dietary PC and DHA partly ameliorated the impaired female reproductive capacity and larval development during early phases. This study indicates that, DHA and PC carried by Vtg1 are crucial for female fecundity, and affect embryo and larval development through maternal-nutrition effects. This is the first study elucidating the nutrient and physiological functions of Vtg1 and the underlying biochemical mechanisms in fish reproduction and development.