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A feeding trial with Macrobrachium acanthurus juveniles was performed to determine growth performance and utilization of diets varying in protein, lipid, and carbohydrate level. Twelve diets were formulated with three levels of protein (P) and supplemented with different proportions of lipids (L) and carbohydrates (C): P30‐L20‐C8, P30‐L15‐C19, P30‐L12‐C25, P30‐L10‐C31, P35‐L20‐C3, P35‐L15‐C15, P35‐L10‐C26, P35‐L5‐C38, P40‐L15‐C8, P40‐L10‐C19, P40‐L5‐C31, and P40‐L1‐C40. Lipids and carbohydrates were added allowing an overall energy content limit of 400 kcal per 100 g of diet. Each diet was fed to triplicate groups of juveniles with an initial weight of 60.9 ± 10.9 mg (mean ± SD) for 60 days. Overall growth performance and gene expression of fatty acid synthase (FAS), carnitine palmitoyltransferase 1 (CPT1), glucose‐6‐phosphatase (G6P), and hexokinase (HK) in the hepatopancreas were assessed. Highest weight gain values and specific growth rates were observed in prawns fed diets with 35% of protein inclusion. Expression of FAS was downregulated when fed 30% of protein. Results indicate M. acanthurus use protein as their primary source of energy and when this is low in the diet, lipids are used to spare the energy from proteins. Suggested inclusion of protein, lipids, and carbohydrates in diets for M. acanthurus should be 35%, 15%, and 15%, respectively. [ABSTRACT FROM AUTHOR]

Long-term high-fat feeding results in intramyocellular lipid accumulation, leading to insulin resistance. Intramyocellular lipid accumulation is related to an energy imbalance between excess fat intake and fatty acid consumption. Alternating current electromagnetic field exposure has been shown to enhance mitochondrial metabolism in the liver and sperm. Therefore, we hypothesized that alternating current electromagnetic field exposure would ameliorate high-fat diet-induced intramyocellular lipid accumulation via activation of fatty acid consumption. C57BL/6J mice were either fed a normal diet (ND), a normal diet and exposed to an alternating current electromagnetic field (ND+EMF), a high-fat diet (HFD), or a high-fat diet and exposed to an alternating current electromagnetic field (HFD+EMF). Electromagnetic field exposure was administered 8 hrs/day for 16 weeks using an alternating current electromagnetic field device (max.180 mT, Hokoen, Utatsu, Japan). Tibialis anterior muscles were collected for measurement of intramyocellular lipids, AMPK phosphorylation, FAT/CD-36, and carnitine palmitoyltransferase (CPT)-1b protein expression levels. Intramyocellular lipid levels were lower in the HFD + EMF than in the HFD group. The levels of AMPK phosphorylation, FAT/CD-36, and CPT-1b protein levels were higher in the HFD + EMF than in the HFD group. These results indicate that alternating current electromagnetic field exposure decreases intramyocellular lipid accumulation via increased fat consumption. [ABSTRACT FROM AUTHOR]

The energy stored in fatty acids is essential for several critical activities of insects, such as embryogenesis, oviposition, and flight. Rhodnius prolixus is an obligatory hematophagous hemipteran and vector of Chagas disease, and it feeds infrequently on very large blood meals. As digestion slowly occurs, lipids are synthesized and accumulate in the fat body, mainly as triacylglycerol, in lipid droplets. Between feeding bouts, proper mobilization and oxidation of stored lipids are crucial for survival, and released fatty acids are oxidized by mitochondrial β-oxidation. Carnitine palmitoyl transferase I (CPT1) is the enzyme that catalyzes the first reaction of the carnitine shuttle, where the activated fatty acid, acyl-CoA, is converted to acyl-carnitine to be transported into the mitochondria. Here, we investigated the role of CPT1 in lipid metabolism and in resistance to starvation in Rhodnius prolixus. The expression of the CPT1 gene (RhoprCpt1) was determined in the organs of adult females on the fourth day after a blood meal, and the flight muscle showed higher expression levels than the ovary, fat body, and anterior and posterior midgut. RhoprCpt1 expression in the fat body dramatically decreased after feeding, and started to increase again 10 days later, but no changes were observed in the flight muscle. β-oxidation rates were determined in flight muscle and fat body homogenates with the use of ³H-palmitate, and in unfed females, they were higher in the flight muscle. In the fat body, lipid oxidation activity did not show any variation before or at different days after feeding, and was not affected by the presence of etomoxir or malonyl-CoA. We used RNAi and generated RhoprCPT1-deficient insects, which surprisingly did not show a decrease in measured ³H-palmitate oxidation rates. However, the RNAi-knockdown females presented increased amounts of triacylglycerol and larger lipid droplets in the fat body, but not in the flight muscle. When subjected to starvation, these insects had a shorter lifespan. These results indicated that the inhibition of RhoprCpt1 expression compromised lipid mobilization and affected resistance to starvation. [ABSTRACT FROM AUTHOR]

AIM: To explore the role of chemerin, encoded by retinoic acid receptor responder 2 （Rarres2） gene, in the regulation of skeletal muscle lipid deposition by diet and exercise interventions in mice. METHODS: Eightweek-old wild-type （WT） mice, adipose-specific Rarres2 gene knockout （adipo-Rarres2-/-） mice and global Rarres2 gene knockout （Rarres2-/-） mice were randomly divided into normal diet （ND） and high-fat diet （HFD） groups, namely ND+ WT group, ND+adipo-Rarres2-/- group, ND+Rarres2-/- group, HFD+WT group, HFD+adipo-Rarres2-/- group, and HFD+ Rarres2-/- group, with 6 mice in each group. The mice in HFD groups were divided into 3 groups with 6-week moderate-intensity running （n=6）, namely WT+exercise （Exe） group, adipo-Rarres2-/-+Exe group, and Rarres2-/-+Exe group. Skeletal muscle lipid deposition was analyzed by oil red O staining and quantified by triglyceride （TG） and free fatty acid （FFA） detection. Insulin tolerance and oral glucose tolerance tests were performed to evaluate insulin sensitivity. The protein levels of fatty acid translocase （FAT/CD36）, carnitine palmitoyltransferase 1（ CPT1）, peroxisome proliferator-activated receptor α （PPARα）, stearoyl-coenzyme A desaturase 1 （SCD1） and glucose transporter protein 4 （GLUT4） in skeletal muscles were detected by Western blot. RESULTS: （ 1） In both ND+Rarres2-/- and HFD+Rarres2-/- groups, skeletal muscle lipid deposition was aggravated （P<0. 01） and the insulin sensitivity decreased （P<0. 05）. By contrast, skeletal muscle lipid deposition was significantly attenuated in HFD+adipo-Rarres2-/- group（ P<0. 01）.（ 2） The protein levels of CPT1 and GLUT4 in skeletal muscles decreased in ND+Rarres2-/- and HFD+Rarres2-/- groups（ P<0. 05）, and the SCD1 level increased in HFD+Rarres2-/- group （P<0. 01）. The protein levels of CPT1 and GLUT4 in skeletal muscles increased, and the CD36 protein level decreased in HFD+adipo-Rarres2-/- group（ P<0. 01）.（ 3） The inhibitory effect of exercise on skeletal muscle lipid deposition was weakened in adipo-Rarres2-/- +Exe and Rarres2-/- +Exe groups compared with WT+Exe group, and the effect was more significantly weakened in Rarres2-/-+Exe group. CONCLUSION: Knockout of chemerinencoding Rarres2 gene not only influences skeletal muscle lipid deposition in HFD mice, but also reduces exercise-induced attenuation of lipid deposition in the skeletal muscle of HFD mice. These effects are associated with the changes in glucose and lipid metabolism-related proteins. [ABSTRACT FROM AUTHOR]

Background and objectives: This study examined the abrogative role of Terminalia catappa (T. catappa) leaf aqueous extract (TCLAE) on diabetes-induced dyslipidaemia in obese diabetic rats. Methods: Diabetic animals were induced by fat-rich feed for eight weeks and intraperitoneal streptozotocin (STZ, 30 mg/kg bw) injection, while glibenclamide (10 mg/kg bw) and TCLAE-graded doses were administered for four weeks. Then, the biomarkers for diabetes, liver function, lipid profile, cardiovascular indices, and liver histology were investigated, in addition to the hepatic expression of some lipid metabolic genes. Results: TCLAE reduced the diabetes-induced fasting blood glucose, weight loss, insulin, alanine transaminase, bilirubin, cholesterol (CHOL), triglyceride (TRIG), low-density lipoprotein-CHOL and -TRIG, high-density lipoprotein-TRIG, atherogenic, coronary risk, and other studied cardiovascular indices. The increase in high-density lipoprotein-CHOL, the upregulation of peroxisome proliferator-activated receptor alpha (PPAR-a), PPAR delta (PPAR-d), and carnitine palmitoyltransferase 1a, and the downregulation of C-reactive protein hepatic gene expression, in addition to the reversal of damaged liver histology, were observed in diabetic rats treated with TCLAE. Conclusion: T. catappa leaf mitigates diabetes-induced dyslipidaemia in type 2 diabetic rats by ameliorating the altered expression of lipid metabolic genes. [ABSTRACT FROM AUTHOR]

Objective From the perspective of lipid degradation, the effects of bisphenol F (BPF) exposure on lipolysis, fatty acid oxidation, and reactive oxygen species (ROS) levels in HepG2 cells were described. Methods HepG2 cells were used to construct an in vitro exposure model. The effects of BPF on the lipid degradation pathway were observed by realtime quantitative PCR, confocal microscopy, and Western blot. Results BPF exposure reduced the mRNA and protein expression of the rate-limiting enzymes, adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL), in HepG2 cells (P < 0.05). The mRNA and protein expressions of the fatty acid oxidation -related proteins, carnitine palmitoyl transferase 1α (CPT1α) and peroxisome proliferator -activated receptor α (PPAR α), were decreased (P < 0.05), and the ROS level from mitochondria was increased (P < 0.01). This caused the accumulation of lipid droplets. Conclusions BPF exposure reduced lipolysis and fatty acid oxidation in HepG2 cells and increased the level of ROS derived from mitochondria, which may be one of the important reasons for the occurrence of nonalcoholic fatty liver disease (NAFLD)- like changes. [ABSTRACT FROM AUTHOR]

The survival of animals during periods of limited nutrients is dependent on the organism's ability to store lipids during times of nutrient abundance. However, the increased availability of food in modern western society has led to an excess storage of lipids resulting in metabolic diseases. To better understand the genes involved in regulating lipid storage, genome-wide RNAi screens were performed in cultured Drosophila cells and one group of genes identified includes mRNA splicing factor genes. Our lab has previously shown that a group of splicing factors important for intron/exon border recognition known as SR proteins are involved in controlling lipid storage in Drosophila ; however, how these SR proteins are regulated to control lipid storage is not fully understood. Here, we focus on two SR protein kinases (SRPKs) in Drosophila : SRPK and SRPK79D. Decreasing the expression of these genes specifically in the adult fat body using RNAi resulted in lower levels of triglycerides and this is due to a decrease in the amount of fat stored per cell, despite having more fat cells, when compared to control flies. Decreasing SRPK and SRPK79D levels in the fat body leads to altered splicing of the β-oxidation gene, carnitine palmitoyltransferase 1 (CPT1), resulting in increased production of a more active enzyme, which would increase lipid breakdown and be consistent with the lean phenotype observed in these flies. In addition, flies with decreased SRPK and SRPK79D levels in their fat bodies eat less, which may also contribute to the decreased triglyceride phenotype. Together, these findings provide evidence to support that lipid storage is controlled by the phosphorylation of factors involved in mRNA splicing. • Fat body triglyceride storage is regulated by SR proteins in Drosophila. • Whether SR protein kinases (SRPKs) control fat storage in Drosophila is unknown. • SRPK and SRPK79D promote triglyceride storage in the Drosophila fat body. • SRPK and SRPK79D regulate fat body cell number and triglyceride storage. • SRPK and SRPK79D regulate CPT1 splicing and food consumption. [ABSTRACT FROM AUTHOR]

Buffalo milk contains more polyunsaturated fatty acids than bovine milk. However, it is not clear about the effects of buffalo milk and bovine milk on lipid metabolism. In this study, a mouse model was used to explore the effects of buffalo milk and bovine milk on lipid metabolism in mice. The experiment was divided into three groups: a control group on a normal diet; a bovine milk group infused with bovine milk; a buffalo milk group infused with buffalo milk. We fed three groups of mice (n = 6) for 6 weeks. These results showed that bovine milk and buffalo milk had no effect on body weight gain. Bovine milk increased the content of ApoA1, ApoB and glucose in serum, compared with the control group, but buffalo milk has no profound change in serum ApoB. Remarkably, buffalo milk decreased the content of total cholesterol (TC) and triglyceride (TG) in the liver lipid profile, and also downregulated the expression of the carnitine palmitoyltransferase 2 (Cpt2) gene involved in the fatty acid oxidation in the liver. This study also found that bovine milk and buffalo milk did not cause the expression of pro‐inflammatory factors in serum and colon tissues. This experiment proved that buffalo milk has beneficial effects on the regulation of lipid metabolism, and also does not affect the normal growth and pro‐inflammatory response of the colon in mice. It provides a theoretical basis for future in‐depth research on the special functions of buffalo milk and the development of buffalo milk functional foods. [ABSTRACT FROM AUTHOR]

Background: Histologically, cytoplasmic deposits of lipids and glycogen are common in clear cell renal cell carcinoma (ccRCC). Owing to the significance of lipid deposition in ccRCC, numerous trials targeting lipid metabolism have shown certain therapeutic potential. The agonism of peroxisome proliferator-activated receptor-α (PPARα) via ligands, including WY-14,643, has been considered a promising intervention for cancers. Methods: First, the effects of WY-14,643 on malignant behaviors were investigated in ccRCC in vitro. After RNA sequencing, the changes in lipid metabolism, especially neutral lipids and glycerol, were further evaluated. Finally, the underlying mechanisms were revealed. Results: Phenotypically, the proliferation and migration of ccRCC cells treated with WY-14,643 were significantly inhibited in vitro. A theoretical functional mechanism was proposed in ccRCC: WY-14,643 mediates lipid consumption by recognizing carnitine palmitoyltransferase 1 A (CPT1A). Activation of PPARα using WY-14,643 reduces lipid deposition by increasing the CPT1A level, which also suppresses the NF-κB signaling pathway. Spatially, WY-14,643 binds and activates PPARα by targeting Gly335. Conclusion: Overall, WY-14,643 suppresses the biological behaviors of ccRCC in terms of cell proliferation, migration, and cell cycle arrest. Furthermore, its anticancer properties are mediated by the inhibition of lipid accumulation, at least in part, through the PPARα/CPT1A axis by targeting Gly335, as part of the process, NF-κB signaling is also suppressed. Pharmacological activation of PPARα might offer a new treatment option for ccRCC. [ABSTRACT FROM AUTHOR]

Flower of Citrus aurantium L. var. amara Engl. (CAVA) has been confirmed to have promising anti‐obesity effects. However, the regulation of alkaloid extracts from flower of CAVA (Al) on lipid metabolism remain unknown. In this study, Al was optimized by ultrasound‐assisted extraction using response surface methodology. The optimal conditions were ultrasonic time 72 min, ethanol concentration 78% and liquid/solid ratio 30 ml/g with the maximum alkaloid yield 5.66%. LC–MS assay indicated that the alkaloid compounds were enriched in Al after optimization. Nine alkaloid compounds were identified in Al by LC–MS assay and stachydrine, caffeine and cathine appeared as the major alkaloid compounds. Bioactivity assay showed that Al treatment significantly increased superoxide dismutase (SOD) activity, and reduced malonaldehyde (MDA) and reactive oxygen species (ROS) levels. Al administration also reversed oleic acid‐induced hepatic steatosis in Hep G2 cells by inhibiting the expression of lipogenesis‐signaling genes including fatty acid synthase (FAS), peroxisome proliferator‐activated receptor subtype γ (PPARγ), uncoupling protein 2 (UCP2), and retinol binding protein (RBP4). However, OA‐induced reduction of lipolysis‐related gene carnitine palmitoyl transferase 1A (CPT1A) in Hep G2 cells was not improved by Al supplementation. Moreover, the increased SOD activity and decreased MDA and ROS contents were also observed in Caenorhabditis elegans by Al addition. Al intervention exhibited the ability to inhibit lipid accumulation in C. elegans by suppressing expression of lipid metabolism‐related genes. These results suggested that the alkaloid extracts from the flower of CAVA showed great potential to regulate lipid metabolism. Practical Applications: The extraction of alkaloid extracts from the flower of CAVA was optimized with a maximum yield of 5.66%. The regulatory effects and mechanisms of Al on lipid metabolism of Hep G2 cells and Caenorhabditis elegans were also investigated. More clinical studies are required to evaluate the potential of using alkaloids from the flower of CAVA as therapeutic agents against lipid metabolic disorders. [ABSTRACT FROM AUTHOR]

Inflammation and oxidative stress are well known to induce the biogenesis of lipid droplets (LDs) in various cell types, in which fatty acids are deposited as components of triglycerides (TGs) and/or cholesterol esters. This metabolic shift is critical for cell protection against the toxicity of excess lipids or their oxidative derivatives produced under various stressful exposures, including oxidative stress. The effect of bacterial lipopolysaccharide (LPS) on LD formation in CNS structures was mainly studied on microglial cells, whereas its effect on lipid metabolism in neurons, potentially associated with LD formation, has been studied neither on cell lines nor on primary neuronal cultures. This work was carried out on the PC12 neuronal cell line, which is widely used to explore the mechanisms of neuroinflammation and neurodegeneration, aiming to study the effects of LPS on LD formation, neutral lipid accumulation, and metabolism of major lipid classes, as well as to elucidate the mechanism mediating these effects. PC12 cell incubation with LPS for 24 h led to a significant accumulation of LDs and an increase in the TG level. Etomoxir, a carnitine palmitoyltransferase 1 (CPT1) inhibitor, also induced an increase in an absolute TG content. To elucidate the metabolic pathways of TG accumulation, PC12 cells were preincubated with [3H]-oleic acid and then examined for radioactive label incorporation into major lipid classes. LPS caused an increase the level of TG and free oleic acid radioactivity, accompanied by a significant inhibition of oleic acid oxidation and a decrease the radioactivity of phospholipids. PC12 cell incubation with LPS also caused a decrease in CPT1 expression. Our data indicate that in PC12 cells, LPS suppresses CPT1 expression and fatty acid oxidation, leading to sequestration of excess fatty acids into TG and the formation of LDs. Under conditions of the bacterial pathogen action, this mechanism seems to represent a cell survival strategy that protects from lipotoxicity. [ABSTRACT FROM AUTHOR]

Five isonitrogenous diets were formulated containing five graded levels of lipid (52.0, 81.0, 112.0, 141.0 and 171.0 g/kg). The diets were fed to triplicate groups of juvenile Trachinotus ovatus (10.49 ± 0.23 g) for 8 weeks. Results showed that moderate lipid level in diets significantly increased weight gain rate (WGR), specific growth rate (SGR) and feed efficiency rate (FER) (p <.05). The dietary lipid level affected plasma biochemical indexes containing total cholesterol (TC), triglyceride (TG), high‐density lipoprotein cholesterol (HDL‐c), total lipase (TL) and non‐esterified fatty acid (NEFA) significantly (p <.05). The dietary lipid level also had significant effects on enzymatic activities including alanine aminotransferase (ALT), aspartate aminotransferase (AST), total lipase (TL), fatty acid synthetase (FAS), intestinal lipase (ILPS), adipose triglyceride lipase (ATGL) and hormone‐sensitive lipase (HSL) (p <.05). The relative level of hepatic carnitine palmitoyltransferase I (cpt1) mRNA increased significantly with increasing dietary lipid levels. The mRNA level of hepatic fatty acid synthase (fas) was significantly upregulated with dietary lipid level up to 81.0 g/kg and then decreased (p <.05). Moreover, dietary lipid level influenced microbial community to regulate metabolic capacity of intestine. The optimum dietary lipid level for the optimal growth of juvenile Trachinotus ovatus was 93.6 g/kg. [ABSTRACT FROM AUTHOR]

An eight weeks feeding trial was conducted to investigate the effects of dietary lipid levels on growth performance, lipid metabolism and immune response of Japanese seabass (Lateolabrax japonicus). Five diets were formulated with gradient dietary lipid levels (79.6, 104.4, 129.1, 154.9 and 178.6 g kg−1). Results revealed that growth and feed utilization of fish were significantly lower in group L178.6 than other groups (p < 0.05). Lipid accumulation in whole body, muscle and intraperitoneal were increased with increasing dietary lipid levels. The mRNA levels of adipose triglyceride lipase, carnitine palmitoyl transferase 1, acetyl CoA carboxylase, cholesterol 7 alpha‐hydroxylase and retinoid X receptor in liver were also increased with increasing dietary lipid levels (p < 0.05). The mRNA levels of apolipoprotein A1 and peroxisome proliferator activating receptor α were higher in fish fed L178.6 than those fed other diets. Oxidative stress in plasma and liver were induced when dietary lipid exceed 154.9 g kg−1. L154.9 and L178.6 significantly increased the inflammatory related gene expression of fish. These results suggested that high‐fat diet impaired the growth performance and induced lipid accumulation, inflammation and apoptosis of Japanese seabass. The suitable dietary lipid level of Japanese seabass may not exceed 129.1 g kg−1. [ABSTRACT FROM AUTHOR]

Acetyl-CoA carboxylase (ACC) plays a regulatory role in both fatty acid synthesis and oxidation, controlling the process of lipid deposition in the liver. Given that existing studies have shown a close relationship between low phosphorus (P) and hepatic lipid deposition, this study was conducted to investigate whether ACC plays a crucial role in this relationship. Zebrafish liver cell line (ZFL) was incubated under low P medium (LP, P concentration: 0.77 mg/L) or adequate P medium (AP, P concentration: 35 mg/L) for 240 h. The results showed that, compared with AP-treated cells, LP-treated cells displayed elevated lipid accumulation, and reduced fatty acid β-oxidation, ATP content, and mitochondrial mass. Furthermore, transcriptomics analysis revealed that LP-treated cells significantly increased lipid synthesis (Acetyl-CoA carboxylases (acc), Stearyl coenzyme A dehydrogenase (scd)) but decreased fatty acid β-oxidation (Carnitine palmitoyltransferase I (cptI)) and (AMP-activated protein kinase (ampk)) mRNA levels compared to AP-treated cells. The phosphorylation of AMPK and ACC, and the protein expression of CPTI were significantly decreased in LP-treated cells compared with those in AP-treated cells. After 240 h of LP treatment, PF-05175157 (an ACC inhibitor) was supplemented in the LP treatment for an additional 12 h. PF-05175157-treated cells showed higher phosphorylation of ACC, higher protein expression of CPTI, and lower protein expression of FASN, lower TG content, enhanced fatty acid β-oxidation, increased ATP content, and mitochondrial mass compared with LP-treated cells. PF-05175157 also relieved the LP-induced oxidative stress and inflammatory response. Overall, these findings suggest that ACC is a promising target for treating LP-induced elevation of lipid deposition in ZFL, and can alleviate oxidative stress and inflammatory response. • Low phosphorus induces lipid deposition in ZFL. • Inhibition of Acetyl-CoA carboxylase (ACC) alleviates LP-induced lipid deposition. • Inhibiting ACC enhances antioxidant ability and reduces inflammatory responses. [ABSTRACT FROM AUTHOR]

This study was conducted to evaluate the effect of dietary lipid levels on growth, body composition and liver oxidative stress of largemouth bass, Micropterus salmoides. Fish were fed isonitrogenous (crude protein 45%) practical diets with five lipid levels (3.3%，8.2%，13.2%，18.1% and 23.3%, respectively) for 60 days. The results showed that weight gain (WG) and protein efficiency ratio (PER) were all significantly improved by dietary lipid levels up to 18.1% and then levelled off beyond this level. Both feed intake (FI) and feed conversion ratio (FCR) showed a decreasing trend with dietary lipid increased. Body lipid content, liver lipid content, total n-3 and n-6 PUFA content in muscle, and triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) contents in plasma significantly increased with increasing dietary lipid levels. However, body protein content, and HDL-C/TC and HDL-C/LDL-C values significantly reduced. The carnitine palmitoyltransferase I (CPT-1), lipoprtein lipase (LPL), glucose-6-phosphatase (G6Pase), phosphoenolpyruvate carboxykinase (PEPCK) and fructose-1,6-bisphosphatase (FBPase) activities in liver increased significantly as dietary lipid levels increased, whereas both fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC) activities showed the opposite trend. Moreover, higher superoxide dismutase (SOD), catalase (CAT) and oxide synthase (NOS) activities, and nitric oxide (NO) concent in liver were recorded in fish fed diets with 18.1% lipid, while the malondialdehyde (MDA) content in liver increased as dietary lipid levels increased. Results indicated that high dietary lipid level (23.3%) inhibit weight gain and induce oxidative stress, which affect the health status of largemouth bass. Based on WG, a dietary lipid level of 18.42% was optimal for growth performance of juvenile largemouth bass. • The lipid levels may affect growth performance of M. salmoides. • The largemouth bass can achieve a well growth performance with dietary lipid level at 18.42%. • Excess dietary lipid could increase the lipid deposition in liver of M.salmoides juveniles. • Excess dietary lipid could result in oxidative stress of the fish. • Excess dietary lipid could suppress metabolic enzyme activities of the fish. [ABSTRACT FROM AUTHOR]

The carnitine palmitoyltransferase (CPT) family includes CPT 1 and CPT 2 that transport long-chain fatty acids into the mitochondrial compartment for β-oxidation. In this study, three isoforms (CPT 1α, CPT 1β and CPT 2) of the CPT family were cloned from Chinese mitten crab (Eriocheir sinensis) and their complete coding sequences (CDS) were obtained. Sequence analysis revealed deduced amino acid sequences of 915, 775 and 683 amino acids, respectively. Gene expression analysis revealed a broad tissue distribution for all three isoforms, with high CPT 1α and CPT 2 mRNA levels in the hepatopancreas of males and females. In males, CPT 1β was highly expressed in gill, heart, brain ganglia and muscle, while in females, CPT 1β-mRNA levels were relatively high in muscle, hepatopancreas and ovary tissue. The effects of dietary fish oil replacement on the expression of the three CPT isoforms in the hepatopancreas during gonadal development were investigated using five experimental diets formulated with replacement of 0, 25, 50, 75 and 100% fish oil by 1:1 rapeseed oil: soybean oil. The results showed that Diets 2# and 5# yielded higher CPT 1α and CPT 2 mRNA expression in males (P < 0.05), while in females, expression of all three CPT isoforms increased then declined in the hepatopancreas with increasing dietary fish oil replacement. The observed changes in CPT gene expression varied in different isoforms and gender, suggesting the three CPT genes might play different roles in fatty acid β-oxidation in E. sinensis. [ABSTRACT FROM AUTHOR]

It has been suggested that some cancer cells rely upon fatty acid oxidation (FAO) for energy. Here we show that when FAO was reduced approximately 90% by pharmacological inhibition of carnitine palmitoyltransferase I (CPT1) with low concentrations of etomoxir, the proliferation rate of various cancer cells was unaffected. Efforts to pharmacologically inhibit FAO more than 90% revealed that high concentrations of etomoxir (200 μM) have an off-target effect of inhibiting complex I of the electron transport chain. Surprisingly, however, when FAO was reduced further by genetic knockdown of CPT1, the proliferation rate of these same cells decreased nearly 2-fold and could not be restored by acetate or octanoic acid supplementation. Moreover, CPT1 knockdowns had altered mitochondrial morphology and impaired mitochondrial coupling, whereas cells in which CPT1 had been approximately 90% inhibited by etomoxir did not. Lipidomic profiling of mitochondria isolated from CPT1 knockdowns showed depleted concentrations of complex structural and signaling lipids. Additionally, expression of a catalytically dead CPT1 in CPT1 knockdowns did not restore mitochondrial coupling. Taken together, these results suggest that transport of at least some long-chain fatty acids into the mitochondria by CPT1 may be required for anabolic processes that support healthy mitochondrial function and cancer cell proliferation independent of FAO. [ABSTRACT FROM AUTHOR]

The aim of this study is to evaluate the effects of patulin on hepatic lipid metabolism and mitochondrial oxidative function and elucidate the underlying molecular mechanisms. The effects of patulin on hepatic lipid accumulation were evaluated in free fatty acid-treated AML12 or HepG2 cells through oil red O staining, triglyceride assay, real-time polymerase chain reaction, and western blotting. Alteration of mitochondrial oxidative capacity by patulin treatment was determined using Seahorse analysis to measure the oxygen consumption rate. The increased amounts of lipid droplets induced by free fatty acids were significantly reduced by patulin treatment. Patulin markedly activated the CaMKII/AMP-activated protein kinase (AMPK)/proliferator-activated receptor-γ coactivator (PGC)-1α signaling pathway in hepatocytes, reduced the expression of sterol regulatory element binding protein 1c (SREBP-1c) and lipogenic genes, and increased the expression of genes related to mitochondrial fatty acid oxidation. In addition, patulin treatment enhanced the mitochondrial consumption rate and increased the expression of mitochondrial oxidative phosphorylation proteins in HepG2 hepatocytes. The effects of patulin on anti-lipid accumulation; SREBP-1c, PGC-1α, and carnitine palmitoyltransferase 1 expression; and mitochondrial oxidative capacity were significantly prevented by compound C, an AMPK inhibitor. Patulin is a potent inducer of the AMPK pathway, and AMPK-mediated mitochondrial activation is required for the efficacy of patulin to inhibit hepatic lipid accumulation. This study is the first to report that patulin is a promising bioactive compound that prevents the development and worsening of fatty liver diseases, including non-alcoholic fatty liver disease, by improving mitochondrial quality and lipid metabolism. [Display omitted] [ABSTRACT FROM AUTHOR]

Inhibiting fatty acid oxidation is one approach to lowering glucose levels in diabetes. Skeletal muscle specific Carnitine Palmitoyltransferase 1b knockout mice (Cpt1bm-/-) comprise a model of impaired fat oxidation; and have decreased fat mass and enhanced glucose disposal and muscle oxidative capacity compared to controls. However, unfavorable effects occur relative to controls when Cpt1bm-/- mice are fed a 25% fat diet, including decreased activity and fat free mass and increased intramuscular lipid and serum myoglobin. In this study we explore if a low fat, high carbohydrate diet can ablate the unfavorable effects while maintaining the favorable phenotype in Cpt1bm-/- mice. Mice were fed either 10% fat (low fat) or 25% fat (chow) diet. Body composition was measured biweekly and indirect calorimetry was performed. Low fat diet abolishes the decreased activity, fat, and fat free mass seen in Cpt1bm-/- mice fed chow diet. Low fat diet also reduces serum myoglobin levels in Cpt1bm-/- mice and diminishes differences in IGF-1 seen between Cpt1bm-/- mice and control mice fed chow diet. Glucose tolerance tests reveal that glucose clearance is improved in Cpt1bm-/- mice relative to controls regardless of diet, and serum analysis shows increased levels of muscle derived FGF21. Electron microscopic analyses and measurements of mRNA transcripts show increased intramuscular lipids, FGF21, mitochondrial and oxidative capacity markers regardless of diet. The favorable metabolic phenotype of Cpt1bm-/- mice therefore remains consistent regardless of diet; and a combination of a low fat diet and pharmacological inhibition of CPT1b may offer remedies to reduce blood glucose. [ABSTRACT FROM AUTHOR]

Clear cell renal cell carcinoma (ccRCC) is histologically defined by its lipid and glycogen-rich cytoplasmic deposits. Alterations in the VHL tumor suppressor stabilizing the hypoxiainducible factors (HIFs) are the most prevalent molecular features of clear cell tumors. The significance of lipid deposition remains undefined. We describe the mechanism of lipid deposition in ccRCC by identifying the rate-limiting component of mitochondrial fatty acid transport, carnitine palmitoyltransferase 1A (CPT1A), as a direct HIF target gene. CPT1A is repressed by HIF1 and HIF2, reducing fatty acid transport into the mitochondria, and forcing fatty acids to lipid droplets for storage. Droplet formation occurs independent of lipid source, but only when CPT1A is repressed. Functionally, repression of CPT1A is critical for tumor formation, as elevated CPT1A expression limits tumor growth. In human tumors, CPT1A expression and activity are decreased versus normal kidney; and poor patient outcome associates with lower expression of CPT1A in tumors in TCGA. Together, our studies identify HIF control of fatty acid metabolism as essential for ccRCC tumorigenesis. [ABSTRACT FROM AUTHOR]

The discovery of active brown adipose tissue (BAT) in adult humans and the fact that it is reduced in obese and diabetic patients have put a spotlight on this tissue as a key player in obesity-induced metabolic disorders. BAT regulates energy expenditure through thermogenesis; therefore, harnessing its thermogenic fat-burning power is an attractive therapeutic approach. We aimed to enhance BAT thermogenesis by increasing its fatty acid oxidation (FAO) rate. Thus, we expressed carnitine palmitoyltransferase 1AM (CPT1AM), a permanently active mutant form of CPT1A (the rate-limiting enzyme in FAO), in a rat brown adipocyte (rBA) cell line through adenoviral infection. We found that CPT1AM-expressing rBA have increased FAO, lipolysis, UCP1 protein levels and mitochondrial activity. Additionally, enhanced FAO reduced the palmitate-induced increase in triglyceride content and the expression of obese and inflammatory markers. Thus, CPT1AM-expressing rBA had enhanced fat-burning capacity and improved lipid-induced derangements. This indicates that CPT1AM-mediated increase in brown adipocytes FAO may be a new approach to the treatment of obesity-induced disorders. [ABSTRACT FROM AUTHOR]

Adipose tissue, dietary lipids and de novo lipogenesis are sources of hepatic free fatty acids (FFAs) that are stored in lipid droplets (LDs) as triacylglycerols (TAGs). Destiny of TAGs stored in LDs is determined by LD proteomic equipment. When adipose triglyceride lipase (ATGL) localizes at LD surface the lipid mobilization is stimulated. In this work, an in vitro model of cultured rat hepatocytes mimicking a mild steatosis condition was used to investigate the direct lipid-lowering action of iodothyronines, by focusing, in particular, on LD-associated proteins, FFA oxidation and lipid secretion. Our results demonstrate that in "steatotic" hepatocytes iodothyronines reduced the lipid excess through the recruitment of ATGL on LD surface, and the modulation of the LD-associated proteins Rab18 and TIP47. As an effect of ATGL recruitment, iodothyronines stimulated the lipid mobilization from LDs then followed by the up-regulation of carnitine-palmitoyl-transferase (CPT1) expression and the stimulation of cytochrome-c oxidase (COX) activity that seems to indicate a stimulation of mitochondrial function. The lipid lowering action of iodothyronines did not depend on increased TAG secretion. On the basis of our data, ATGL could be indicated as an early mediator of the lipid-lowering action of iodothyronines able to channel hydrolyzed FFAs toward mitochondrial beta-oxidation rather than secretion. [ABSTRACT FROM AUTHOR]

Fatty acids cause endothelial dysfunction involving increased ROS (reactive oxygen species) and reduced NO (nitric oxide) bioavailability. We show that in MAECs (mouse aortic endothelial cells), the PPARβ/δ (peroxisomeproliferator- activated receptor β/δ) agonist GW0742 prevented the decreased A23187-stimulated NO production, phosphorylation of eNOS (endothelial nitric oxide synthase) at Ser1177 and increased intracellular ROS levels caused by exposure to palmitate in vitro. The impaired endothelium-dependent relaxation to acetylcholine in mouse aorta induced by palmitate was restored by GW0742. In vivo, GW0742 treatment prevented the reduced aortic relaxation, phosphorylation of eNOS at Ser1177, and increased ROS production and NADPH oxidase in mice fed on a high-fat diet. The PPARβ/δ antagonist GSK0660 abolished all of these protective effects induced by GW0742. This agonist enhanced the expression of CPT (carnitine palmitoyltransferase)-1. The effects of GW0742 on acetylcholineinduced relaxation in aorta and on NO and ROS production in MAECs exposed to palmitate were abolished by the CPT-1 inhibitor etomoxir or by siRNA targeting CPT-1. GW0742 also inhibited the increase in DAG (diacylglycerol), PKCα/βII (protein kinase Cα/βII) activation, and phosphorylation of eNOS at Thr495 induced by palmitate in MAECs, which were abolished by etomoxir. In conclusion, PPARβ/δ activation restored the lipid-induced endothelial dysfunction by up-regulation of CPT-1, thus reducing DAG accumulation and the subsequent PKC-mediated ROS production and eNOS inhibition. [ABSTRACT FROM AUTHOR]

Carnitine palmitoyltransferase IB (CPT1B) and adrenoceptor beta-3 (ADRB3) are critical regulators of fat metabolism. CPT1B transports free acyl groups into mitochondria for oxidation, and ADRB3 triggers lipolysis in adipocytes, and their respective polymorphisms E531K and W64R have been identified as indicators of obesity in population studies. It is therefore important to understand the effects of these mutations on ADRB3 and CPT1B function in adipose and skeletal muscle tissue, respectively. This study aimed to analyze the rate of lipolysis of plasma indicators (glycerol, free fatty acids, and beta hydroxybutyrate) and fat oxidation (through the non-protein respiratory quotient). These parameters were measured in 37 participants during 30 min of aerobic exercise at approximately 62% of maximal oxygen uptake, followed by 30 min of recovery. During recovery, mean respiratory quotient values were higher in K allele carriers than in non-carriers, indicating low post-exercise fatty acid oxidation rates. No significant differences in lipolysis or lipid oxidation were observed between R and W allele carriers of ADRB3 at any time during the aerobic load. The substitution of glutamic acid at position 531 by lysine in the CPT1B protein decreases the mitochondrial beta-oxidation pathway, which increases the non-protein respiratory quotient value during recovery from exercise. This may contribute to weight gain or reduced weight-loss following exercise. [ABSTRACT FROM AUTHOR]

Lipid metabolism in the ventromedial hypothalamus (VMH) has emerged as a crucial pathway in the regulation of feeding and energy homeostasis. Carnitine palmitoyltransferase (CPT) 1A is the rate-limiting enzyme in mitochondrial fatty acid β-oxidation and it has been proposed as a crucial mediator of fasting and ghrelin orexigenic signalling. However, the relationship between changes in CPT1A activity and the intracellular downstream effectors in the VMH that contribute to appetite modulation is not fully understood. To this end, we examined the effect of long-term expression of a permanently activated CPT1A isoform by using an adeno-associated viral vector injected into the VMH of rats. Peripherally, this procedure provoked hyperghrelinemia and hyperphagia, which led to overweight, hyperglycemia and insulin resistance. In the mediobasal hypothalamus (MBH), long-term CPT1AM expression in the VMH did not modify acyl-CoA or malonyl-CoA levels. However, it altered the MBH lipidomic profile since ceramides and sphingolipids increased and phospholipids decreased. Furthermore, we detected increased vesicular γ-aminobutyric acid transporter (VGAT) and reduced vesicular glutamate transporter 2 (VGLUT2) expressions, both transporters involved in this orexigenic signal. Taken together, these observations indicate that CPT1A contributes to the regulation of feeding by modulating the expression of neurotransmitter transporters and lipid components that influence the orexigenic pathways in VMH. [ABSTRACT FROM AUTHOR]

High-fat diets may promote growth, partly through their protein-sparing effects. However, high-fat diets often lead to excessive fat deposition, which may have a negative impact on fish such as poor growth and suppressive immune. Therefore, this study investigated the effects of a fat-rich diet on the mechanisms of fat deposition in the liver. Three-hundred blunt snout bream (Megalobrama amblycephala) juveniles (initial mass 18.00±0.05 g) were fed with one of two diets (5% or 15% fat) for 8 weeks. β-Oxidation capacity and regulation of rate-limiting enzymes were assessed. Large fat droplets were present in hepatocytes of fish fed the high-fat diet. This observation is thought to be largely owing to the reduced capacity for mitochondrial and peroxisomal β-oxidation in the livers of fish fed the high-fat diet, as well as the decreased activities of carnitine palmitoyltransferase (CPT) I and acyl-CoA oxidase (ACO), which are enzymes involved in fatty-acid metabolism. Study of CPT I kinetics showed that CPT I had a low affinity for its substrates and a low catalytic efficiency in fish fed the high-fat diet. Expression of both CPT I and ACO was significantly down-regulated in fish fed the high-fat diet. Moreover, the fatty-acid composition of the mitochondrial membrane varied between the two groups. In conclusion, the attenuated β-oxidation capacity observed in fish fed a high-fat diet is proposed to be owing to decreased activity and/or catalytic efficiency of the rate-limiting enzymes CPT I and ACO, via both genetic and non-genetic mechanisms. [ABSTRACT FROM AUTHOR]

CB1 (also known as CNR1), a main receptor for cannabinoids acting at PPARs, can enhance fat deposition. Carnitine palmitoyltransferase-1 ( CPT1), an enzyme responsible for the transport of long-chain fatty acids for β-oxidation, is closely related to fat deposition. Whether CB1 can regulate intramuscular adipocytes lipid accumulation through regulation of CPT1 is unclear. Based on the investigation of tissue- and breed-specific CPT1A and CPT1 B m RNA expression levels in Jinhua and Landrace pigs, we studied the effects of CB1 on lipid accumulation and CPT1 B expression by treating porcine intramuscular adipocytes with CB1 antagonist Δ9- THC and antagonist SR141716. Results showed that muscle CPT1 m RNA was expressed at higher levels in the longissimus dorsi and subcutaneous fat. Liver CPT1 A m RNA expression levels were higher in the pancreas, duodenum and liver. Compared with Landrace pigs, CPT1 A and CPT1 B in the longissimus dorsi of Jinhua pigs were significantly higher and positively correlated with intramuscular fat content. However, for subcutaneous fat, CPT1 levels were significantly lower and negatively correlated with body fat percentage. Δ9- THC significantly increased CB1 m RNA levels and lipid accumulation but decreased CPT1 A and CPT1 B m RNA levels. Conversely, SR141716 reduced CB1 m RNA levels but increased CPT1 A and CPT1 B m RNA levels, resulting in decreased lipid accumulation. The CPT1 antagonist etomoxir did not affect CB1 expression, suggesting that CB1 is likely upstream of CPT1 A and CPT1 B. Meanwhile, PPARA expression was greatly decreased when CPT1A and CPT1B were inhibited and enhanced when CPT1A and CPT1B were activated. Taken together, these data indicate that CB1 can affect intramuscular fat deposition by regulating both CPT1 A and CPT1 B m RNA expression, with the PPARA signal pathway likely playing a major role in this process. [ABSTRACT FROM AUTHOR]

Angiotensin-(1−7) is a biologically active product of the renin-angiotensin system cascade and exerts inhibitory effects on inflammation, vascular and cellular growth mechanisms signaling through the G protein-coupled Mas receptor. The major purpose of the present study was to investigate the use of glucose and fatty acids by cardiac tissue in Mas knockout mice models. Serum levels of glucose, lipids, and insulin were measured in Mas -deficient and wild-type FVB/N mice. To investigate the cardiac use of lipids, the lipoprotein lipase, the gene expression of peroxisome proliferator-activated receptor alpha; carnitine palmitoyltransferase I and acyl-CoA oxidase were evaluated. To investigate the cardiac use of glucose, the insulin signaling through Akt/GLUT4 pathway, glucose-6-phosphate (G-6-P) and fructose-6-phosphate (F-6-P) glycolytic intermediates, in addition to ATP, lactate and the glycogen content were measured. Despite normal body weight, cholesterol and insulin, Mas -Knockout mice presented hyperglycemia and hypertriglyceridemia, impaired insulin signaling, through reduced phosphorylation of AKT and decreased translocation of GLUT4 in response to insulin, with subsequent decrease of the cardiac G-6-P and F-6-P. Lactate production and glycogen content were not altered in Mas -KO hearts. Mas -KO presented reduced cardiac lipoprotein lipase activity and decreased translocation of CD36 in response to insulin. The expression of peroxisome proliferator-activated receptor alpha and carnitine palmitoyltransferase I genes were lower in Mas -KO animals compared to wild-type animals. The ATP content of Mas -KO hearts was smaller than in wild-type. The present results suggest that genetic deletion of Mas produced a devastating effect on cardiac use of glucose and lipids, leading to lower energy efficiency in the heart. • The renin-angiotensin system modulates the use of fatty acids and glucose cardiac. • Genetic deletion of the Mas receptor in mice decreases cardiac energy efficiency. • Genetic deletion of the Mas receptor inhibits insulin-induced Akt activation. • Mas -KO hearts present reduced LPL and expression of the CD36 at cardiac membrane. [ABSTRACT FROM AUTHOR]

Dietary CLA decreases body fat in several species and in pigs this is accompanied by increased mus-cle lipid. Our objective was to detennine if mice could be used as a model for CLA-induced increased marbling in pigs. We used our model of enhanced CLA response, where mice fed coconut oil (CO) lose more body fat than mice fed soy oil (SO). Mice (21 d old; Imprinting Control Region [ICR]) were fed SO or CO diets for 6 wk followed by 12 d of 0 or 0.5% mixed isomer CLA. Ether extraction detennined that thigh muscle lipid con-tent was reduced by both CLA and CO (P = 0.007 and P = 0.006, respectively). Conjugated linoleic acid also caused a reduction (P = 0.016) in carnitine palmitoyl-transferase (CPT) enzyme activity, so less fatty acid oxi-dation appeared to be occurring. Lumbar muscle, which is more similar to the longissimus dorsi tested in pigs, did not differ in lipid content between mice (56 d old; ICR) fed SO or SO+CLA for 14 d. Therefore, CLA-fed mice do not appear to be accumulating excess lipid in their muscle. However, CLA addition to CO diets increased (P = 0.007) the mRNA expression of PPAR-y in the thigh muscle to the level of SO-fed mice, indicating that intramuscular adipocyte differentiation may be increas-ing. On the other hand, liver lipid was increased (P < 0.0001) by CO and tended to be increased (P = 0.099) by CLA. Liver CPT activity was decreased (P = 0.018) in SO+CLA-fed mice but not CO+CLA. It appears that mice may accumulate lipid in their livers preferentially over muscle when fed CLA and therefore are not a good model for CLA-induced muscle lipid accumulation. [ABSTRACT FROM AUTHOR]

The aim of the present study was to examine the effects of 8 weeks of exercise training on the fatty acid composition of phospholipids (PL) and triacylglycerols (TG) in rat liver, skeletal muscle (gastrocnemius medialis), and adipose tissue (epididymal and subcutaneous fat). For this purpose, the relevant tissues of 11 trained rats were compared to those of 14 untrained ones. Training caused several significant differences of large effect size in the concentrations and percentages of individual fatty acids in the aforementioned lipid classes. The fatty acid composition of liver PL, in terms of both concentrations and percentages, changed with training. The TG content of muscle and subcutaneous adipose tissue decreased significantly with training. In contrast to the liver, where no significant differences in the fatty acid profile of TG were found, muscle underwent more significant differences in TG than PL, and adipose tissue only in TG. Most differences were in the same direction in muscle and adipose tissue TG, suggesting a common underlying mechanism. Estimated fatty acid elongase activity was significantly higher, whereas ?9-desaturase activity was significantly lower in muscle and adipose tissue of the trained rats. In conclusion, exercise training modified the fatty acid composition of liver PL, muscle PL and TG, as well as adipose tissue TG. These findings may aid in delineating the effects of exercise on biological functions such as membrane properties, cell signaling, and gene expression. [ABSTRACT FROM AUTHOR]

Stearoyl-CoA desaturase (SCD) has recently been shown to be a critical control point of lipid partitioning and body weight regulation. Lack of SCD1 function significantly increases insulin sensitivity in skeletal muscles and corrects the hypometabolic phenotype of leptin-deficient ob/ob mice, indicating the direct antilipotoxic action of SCD1 deficiency. The mechanism underlying the metabolic effects of SCD1 mutation is currently unknown. Here we show that SCD1 deficiency reduced the total ceramide content in oxidative skeletal muscles (soleus and red gastrocnemius) by ∼40%. The mRNA levels and activity of serine palmitoyltransferase (SPT), a key enzyme in ceramide synthesis, as well as the incorporation of [14C]palmitate into ceramide were decreased by ∼50% in red muscles of SCD1-/- mice. The content of fatty acyl-CoAs, which contribute to de novo ceramide synthesis, was also reduced. The activity and mRNA levels of carnitine palmitoyltransferase I (CPT I) and the rate of β-oxidation were increased in oxidative muscles of SCD1-/- mice. Furthermore, SCD1 deficiency increased phosphorylation of AMP-activated protein kinase (AMPK), suggesting that AMPK activation may be partially responsible for the increased fatty acid oxidation and decreased ceramide synthesis in red muscles of SCD1-/- mice. SCD1 deficiency also reduced SPT activity and ceramide content and increased AMPK phosphorylation and CPT I activity in muscles of ob/ob mice. Taken together, these results indicate that SCD1 deficiency reduces ceramide synthesis by decreasing SPT expression and increasing the rate of βoxidation in oxidative muscles. [ABSTRACT FROM AUTHOR]

The efficiency of five dietary lipid sources (fish oil as control—C; canola oil—CO; poultry fat—PF; pork lard—PL; and oleine oil—OO) were evaluated in juvenile brown trout (58.4±0.7 g) in an experiment conducted over 70 days at 14.6±0.4 °C. The best growth was observed in fish fed the C diet whereas the PL diet fed fish had the best feed utilization. Significant differences in carcass and muscle proximate composition, but not in liver, were noted among fish fed the different dietary treatments. The fatty acid composition of muscle largely reflected that of the diets, while total cholesterol was not affected. The atherogenicity and the thrombogenicity qualities of the trout flesh were modified by the lipid sources. Sensory analysis did not show any significant differences among the cooked fillets with respect to dietary treatments, while in uncooked products, some significant differences were observed. The carnitine palmitoyltransferase I and II (CPT-I and CPT-II) activities of liver and white muscle were assayed for a better understanding of the potential β-oxidation capability of the different dietary lipid sources. The hepatic, but not white muscle CPT-I and CPT-II activities were affected by dietary treatments. This study showed that alternative lipid sources could be used effectively for oil coating extruded diets for brown trout. [Copyright &y& Elsevier]

Inhibition of diacylglycerol acyltransferase 1 (DGAT1) is an alternative therapeutic strategy for treating fatty liver in mammals. However, the effects of DGAT1 inhibition in fish remain unclear. Here, we found that inhibition of DGAT1 significantly reduced triglyceride (TAG) levels and lipid droplet formation in hepatocytes of large yellow croaker (Larimichthys crocea). Meanwhile, there were no significant effects of DGAT1 specific inhibitors on the cell viability. In addition, inactivation of DGAT1 significantly suppressed the mRNA expression of sterol regulatory element binding protein 1 (srebp1) and fatty acid synthase (fas), and promoted carnitine palmitoyltransferase 1 α (cpt1α) mRNA expression in croaker hepatocytes. After treated with DGAT1 specific inhibitor, expression of catalase (cat) was significantly decreased in hepatocytes under the condition of lipid overload, while glutathione peroxidase (gpx) was significantly increased. However, inhibition of DGAT1 had no significant effects on genes expression related to inflammatory response in croaker hepatocytes. Finally, injection of DGAT1 specific inhibitor into large yellow croaker juveniles showed statistically significant decrease in hepatic TAG contents induced by high fat diet. These results showed that DGAT1 inhibition could significantly alleviate the abnormal deposition of TAG in liver induced by lipid overload in large yellow croaker, which may provide novel therapeutic target for improving the quality control of fish. • DGAT1 inhibition significantly decreased lipid contents induced by lipid overload in hepatocytes of large yellow croaker. • DGAT1 inhibition had no significant effects on the cell viability and inflammatory response in croaker hepatocytes. • Inhibition of DGAT1 significantly reduced fatty acid synthesis and promoted β-oxidation under lipid overload. [ABSTRACT FROM AUTHOR]

Berteroin (5-methylthiopentyl isothiocyanate) is a naturally occurring sulforaphane analog containing a non-oxidized sulfur atom in cruciferous vegetables. The objectives of the present study were to determine the effects of berteroin on lipid metabolism in hepatocytes and adipocytes and to elucidate the mechanisms involved. The effect of berteroin on lipid metabolism were evaluated in liver X receptor α agonist-stimulated HepG2 cells and adipocyte differentiation-induced 3T3-L1 cells using MTT assay, western blot, real time polymerase chain reaction, oil red O staining, and triglyceride assay. T0901317 treatment increased the expression of sterol regulatory element binding protein (SREBP)-1c, a major transcription factor that mediates lipogenesis, and berteroin pretreatment significantly inhibited the expressions of T0901317-induced SREBP-1c and lipogenic genes. Especially, berteroin had a greater inhibitory effect on T0901317-induced SREBP-1c activation than sulforaphane, AICAR, or metformin. Berteroin also markedly suppressed lipid droplet formations and triglyceride accumulations caused by both T0901317 stimulation in HepG2 hepatocytes and differentiation induction in 3T3-L1 preadipocytes. However, berteroin significantly increased the expression of mitochondrial fatty acid oxidation-related genes (carnitine palmitoyltransferase 1 (CPT-1) and peroxisome proliferator-activated receptor gamma coactivator-1α) and the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) in HepG2 cells. Interestingly, effects of berteroin on the expressions of SREBP-1c protein and CPT-1 mRNA were remarkably prevented by compound C (an AMPK inhibitor). Our results suggest berteroin-inhibited hepatic lipid accumulation and adipocyte differentiation might be mediated by AMPK activation and that berteroin might be useful for the prevention, amelioration, and treatment of metabolic diseases, including hepatic steatosis. [ABSTRACT FROM AUTHOR]

Long-chain fatty acid oxidation disorders (lc-FAOD) are a group of diseases affecting the degradation of long-chain fatty acids. In order to investigate the disease specific alterations of the cellular lipidome, we performed undirected lipidomics in fibroblasts from patients with carnitine palmitoyltransferase II, very long-chain acyl-CoA dehydrogenase, and long-chain 3-hydroxyacyl-CoA dehydrogenase. We demonstrate a deep remodeling of mitochondrial cardiolipins. The aberrant phosphatidylcholine/phosphatidylethanolamine ratio and the increased content of plasmalogens and of lysophospholipids support the theory of an inflammatory phenotype in lc-FAOD. Moreover, we describe increased ratios of sphingomyelin/ceramide and sphingomyelin/hexosylceramide in LCHAD deficiency which may contribute to the neuropathic phenotype of LCHADD/mitochondrial trifunctional protein deficiency. [ABSTRACT FROM AUTHOR]

An experiment was conducted to test the hypothesis that Cu hydroxychloride (IntelliBond CII, Micronutrients, LLC, Indianapolis, IN) improves growth performance by upregulating the mRNA transcription of genes involved in lipid metabolism of pigs. Thirty-two pigs (15.05 ± 0.98 kg) were allotted to 2 dietary treatments with 2 pigs per pen for a total of 8 replicate pens per treatment. Pigs were fed a control diet based on corn, soybean meal, and distillers dried grains with solubles that included Cu to meet the requirement. A second diet was formulated by adding 150 mg Cu/kg from Cu hydroxychloride to the control diet. On the last day of the experiment, one pig per pen was sacrificed and samples from liver, skeletal muscle, and subcutaneous adipose tissue were collected to analyze relative mRNA abundance of genes involved in lipid metabolism. Data were analyzed using SAS with pen as the experimental unit. Diet was the fixed effect and replicate was the random effect. Results indicated that overall average daily gain and gain:feed were greater (P < 0.05) for pigs fed the diet containing Cu hydroxychloride compared with pigs fed the control diet (Table 1). Pigs fed the diet supplemented with Cu hydroxychloride had increased (P < 0.05) abundance of cluster of differentiation 36 in liver and increased (P < 0.05) abundance of fatty acid binding protein 4 and lipoprotein lipase in subcutaneous adipose tissue. Inclusion of Cu hydroxychloride also tended to increase (P < 0.10) abundance of fatty acid binding protein 1, peroxisome proliferator-activated receptor alpha, and carnitine palmitoyl transferase 1 B in liver, skeletal muscle, and subcutaneous adipose tissue, respectively. In conclusion, supplementation of Cu hydroxychloride to the control diet improved growth performance and may affect signaling pathways associated with lipid metabolism by upregulating abundance of some genes involved in postabsorptive metabolism of lipids. [ABSTRACT FROM AUTHOR]

GH (growth hormone) secretion/action is modulated by alterations in energy homeostasis, such as malnutrition and obesity. Recent data have uncovered the mechanism by which hypothalamic neurons sense nutrient bioavailability, with a relevant contribution of AMPK (AMP-activated protein kinase) and mTOR (mammalian Target of Rapamycin), as sensors of cellular energy status. However, whether central AMPK-mediated lipid signaling and mTOR participate in the regulation of pituitary GH secretion remains unexplored. We provide herein evidence for the involvement of hypothalamic AMPK signaling, but not hypothalamic lipid metabolism or CPT-1 (carnitine palmitoyltransferase I) activity, in the regulation of GH stimulatory responses to the two major elicitors of GH release in vivo, namely GHRH (growth hormone–releasing hormone) and ghrelin. This effect appeared to be GH-specific, as blocking of hypothalamic AMPK failed to influence GnRH (gonadotropin-releasing hormone)-induced LH (luteinizing hormone) secretion. Additionally, central mTOR inactivation did not alter GH responses to GHRH or ghrelin, nor this blockade affected LH responses to GnRH in vivo. In sum, we document here for the first time the indispensable and specific role of preserved central AMPK, but not mTOR, signaling, through a non-canonical lipid signaling pathway, for proper GH responses to GHRH and ghrelin in vivo. [ABSTRACT FROM AUTHOR]