Liver Carnitine Palmitoyltransferase Research Articles

A low carbohydrate diet high in fish oil and soy protein delays inflammation, hematopoietic stem cell depletion, and mortality in miR-146a knock-out mice.

Since our previous studies found a low carbohydrate (CHO) diet containing soy protein and fish oil (15%Amylose/Soy/FO) significantly reduced lung and breast cancer in mice we asked herein if this low CHO diet could also delay the onset of myeloid malignancies. To test this we employed a miR-146a knock-out (KO) mouse model and found the 15%Amylose/Soy/FO diet increased their median lifespan by 8.5 month, compared to these mice on a Western diet. This was associated with increased lymphocytes and reduced monocytes, granulocytes, blood glucose and insulin levels. Inflammatory cytokine/chemokine studies carried out with 6-month-old mice, before any signs of illness, revealed the 15%Amylose/Soy/FO diet significantly reduced pro-inflammatory cytokines. This low CHO diet also led to an increase in plasma β-hydroxybutyrate and in liver fatty acid synthase levels. This, together with higher liver carnitine palmitoyltransferase I levels suggested that the 15%Amylose/Soy/FO diet was causing a systemic metabolic shift from glucose to fatty acids as an energy source. Lastly, we found the 15%Amylose/Soy/FO diet resulted in significantly higher numbers of primitive hematopoietic stem cells (HSCs) in the bone marrow of 6-month-old mice than those fed a Western diet. Taken together, these results suggest a 15%Amylose/Soy/FO diet reduces chronic inflammation and increases fatty acid oxidation and that this, in turn, may prevent HSC proliferation and exhaustion, thereby delaying myeloid malignancy-induced death of miR-146a KO mice. We suggest a low CHO diet containing soy protein and fish oil could be beneficial in reducing the risk of myeloid malignancies in patients with low miR-146a levels.

Resistance Exercise Regulates Hepatic Lipolytic Factors as Effective as Aerobic Exercise in Obese Mice

Non-alcoholic fatty liver disease (NAFLD) is associated with obesity. The effect of resistance exercise without dietary restriction on the regulation of hepatic lipolytic factors is unclear. This study aimed to analyze the effects of aerobic and resistance exercise on hepatic lipolytic factors of obese mice. High-fat diet (HFD)-induced obese mice were divided into HFD + sedentary (HF), HFD + aerobic exercise, and HFD + resistance exercise groups. Exercise group mice were subjected to treadmill or ladder climbing exercise for 8 weeks. Fat mass and liver triglycerides were significantly decreased in both aerobic and resistance training groups. In the results of protein levels related to hepatic steatosis, HFD significantly increased liver cannabinoid receptor 1 and sterol-regulatory element binding protein 1 (SREBP-1). Both aerobic and resistance training significantly (p < 0.05) increased liver carnitine palmitoyltransferase-1, phosphor-AMP-activated protein kinase (p-AMPK), and p-AMPK/AMPK and decreased liver SREBP-1. However, the type of exercise did not exert any significant effects on these protein levels. Thus, resistance exercise, similarly to aerobic exercise, effectively regulated hepatic lipolytic factors of obese mice. Therefore, a sustainable type of exercise selected based on the fitness level, disease type, musculoskeletal disorder status, and preference of the patients is the best exercise intervention for alleviating NAFLD.

Merits of probiotic biocatalysis immobilized on wheat bran for the production of functional foods

Dietary incorporation of milk fermented with indigenous probiotic Lactobacillus casei NCDC19 (Lc19) was investigated in mice fed a high-fat and sucrose diet (HFS diet). Epididymal fat mass and adipocyte size were significantly reduced in the group fed HFS diet supplemented with Lc19 compared with the group fed HFS diet only. However, body weight differences were not statistically significant. Fasting blood glucose, serum triglyceride, insulin and homeostatic model assessment of insulin resistance score were found to be significantly decreased in the Lc19 treatment group; liver triglyceride levels remained unaffected. Epididymal fat adiponectin and liver carnitine palmitoyl-transferase 1, peroxisome proliferator-activated receptor α, forkhead box protein A2 and peroxisome proliferator-activated receptor gamma coactivator 1β were significantly up-regulated in the Lc19 group. The influence of Lc19 on the expression of genes related to energy expenditure suggests a possible role of L. casei in gut physiology modulation, which might be affecting the host metabolism.

Milk fermented with Lactobacillus casei NCDC19 improves high fat and sucrose diet alters gene expression in obese mice

Dietary incorporation of milk fermented with indigenous probiotic Lactobacillus casei NCDC19 (Lc19) was investigated in mice fed a high-fat and sucrose diet (HFS diet). Epididymal fat mass and adipocyte size were significantly reduced in the group fed HFS diet supplemented with Lc19 compared with the group fed HFS diet only. However, body weight differences were not statistically significant. Fasting blood glucose, serum triglyceride, insulin and homeostatic model assessment of insulin resistance score were found to be significantly decreased in the Lc19 treatment group; liver triglyceride levels remained unaffected. Epididymal fat adiponectin and liver carnitine palmitoyl-transferase 1, peroxisome proliferator-activated receptor α, forkhead box protein A2 and peroxisome proliferator-activated receptor gamma coactivator 1β were significantly up-regulated in the Lc19 group. The influence of Lc19 on the expression of genes related to energy expenditure suggests a possible role of L. casei in gut physiology modulation, which might be affecting the host metabolism.

Liver lipid metabolism disruption in cancer cachexia is aggravated by cla supplementation -induced inflammation

The liver is the main organ regulating metabolism. In spite of that, few studies examine liver metabolism in cachexia, a wasting syndrome associated with increased morbidity and mortality in cancer. Cachexia induces major metabolic disruption, inflammation and fat and lean mass loss. We have previously shown impairment of hepatic lipid metabolism in cancer cachexia that contributes to the aggravation of the symptoms. The present study addresses the effects of Conjugated Linoleic Acid supplementation upon liver lipid metabolism in cachectic rats. Male Wistar rats were randomly assigned to control groups (C) receiving 0.9NaCl (Placebo CP); or to groups supplemented with sunflower oil (CSF), supplemented with CLA (CCLA), or still, to tumour bearing animals (T) receiving NaCl (TP), sunflower oil (TSF), or CLA (TCLA). Supplementation (0.5ml) by gavage was carried out for 14 days. Body weight, dietary intake, glucose, cholesterol and triacylglycerol plasma content, liver glycogen and triacylglycerol content and mRNA expression of liver carnitine palmitoyltransferase I and II (CPT I and II), as well as microsomal triglyceride transfer protein (MTP), liver fatty acid-binding protein (L-FABP), peroxisome proliferator-activated receptor-alpha (PPAR-alpha), and apolipoprotein B (apoB), were assessed. Liver CPT II activity was reduced in all groups, when compared with CP. Hepatic mRNA expression of MTP, apoB and FABP was reduced in TCLA, when compared with all groups. TCLA also presented increased hepatic and plasma triacylglycerol content, when compared with all T groups. Adipose tissue-derived inflammatory factors were assessed. No differences among the groups were observed in regard to Retro Peritoneal Adipose Tissue cytokine (IL-1β, IL-6, and TNF-α) protein content and expression, with the exception of IL-10 in tumour-bearing animals. In the Epididymal Adipose Tissue, the inflammatory cytokines were augmented in TCLA, compared with all other groups. CLA supplementation fails to promote the re-establishment of hepatic lipid metabolism in tumour-bearing animals, and therefore is not recommended in cancer-related cachexia.

Effects of Apelin-13 on expression levels of glucose and lipid metabolism-related genes in the liver and skeletal muscle of diabetic rats

Objective To investigate the effects of exogenous Apelin-13 on the expression of glucose and fatty acid metabolism-related genes in the liver and skeletal muscle of diabetic rats. Methods Forty male Wister rats were randomly divided into a control group (n=8) and an experimental group (n=32). In the experimental group, a rat model of type 2 diabetes mellitus was established by a high-glucose and high-fat diet and intraperitoneal injection of streptozotocin (STZ). The diabetic rats were randomized into a diabetic model group and an Apelin-13 treatment group with 14 rats in each group.Rats in the Apelin-13 treatment group were intraperitoneally injected with 0.1 μmol·kg·d-1 Apelin-13 for 10 weeks, while the control group and the diabetic model group were injected with an equal volume of 0.9% NaCl solution for 10 weeks.At the end of the 10 week treatment, fasting blood glucose values in each group were measured.Levels of mRNA expression of glucose-6-phosphate (G-6-P), phosphoenolpyruvate carboxykinase (PEPCK), peroxisome proliferator-activated receptor alpha (PPAR-α), acy1-CoA synthetase long-chain family member1 (ACSL1), and carnitine palmitoyltransferase1 (CPT1) in the liver and levels of mRNA expression of PPAR-α and glucose transporter type 4 (GLUT4) in skeletal muscle were detected by real-time fluorescence quantitative polymerase chain reaction (PCR). Results Levels of mRNA expression of liver PPAR-α, liver ACSL1, liver CPT1, and GLUT4 in skeletal muscle were lower in the diabetic model group (0.309±0.073, 0.508±0.056, 0.389±0.118 and 0.289±0.066, respectively) than in the control group (0.971±0.028, 0.990±0.015, 0.987±0.015 and 0.994±0.009, respectively) (all P 0.05). Conclusions Apelin-13 increases the expression of the PPAR, ACSL1, and CPT1 genes in the liver and, to a certain extent, improves fatty acid oxidation metabolism in the liver in type 2 diabetic rats.It also increases the expression of the G-6-P and PEPCK genes, promotes gluconeogenesis in the liver, and may be related to the development of type 2 diabetes.In skeletal muscle, Apelin-13 increases GLUT4 gene expression, moderately improves skeletal muscle metabolism and may play a role in the regulation of oxidative stress. Key words: Diabetes mellitus; Carbohydrate metabolism; Lipid metabolism; Apelin-13

Branched-chain amino acid ratios in low-protein diets regulate the free amino acid profile and the expression of hepatic fatty acid metabolism-related genes in growing pigs.

Liver metabolism is affected by nutrients. The aim of this study was to explore the effects of low-protein diets (17% crude protein, CP) supplemented with branched-chain amino acids (BCAAs), including leucine (Leu), isoleucine (Ile) and valine (Val), on hepatic amino acid profile and lipid metabolism in growing pigs. The ratio of Leu:Ile:Val in all groups was 1:0.51:0.63 (20% crude protein, CP), 1:1:1 (17% CP), 1:0.75:0.75 (17% CP), 1:0.51:0.63 (17% CP) and 1:0.25:0.25 (17% CP) respectively. Results revealed that compared to the positive control group (1:0.51:0.63, 20% CP), the low-protein diets significantly augmented the concentrations of most essential amino acids and non-essential amino acids (p<.05), with the greatest values observed in the 1:0.25:0.25 group. Moreover, relative to the control, the low-protein diets with the Leu:Ile:Val ratio ranging from 1:0.75:0.75 to 1:0.25:0.25 markedly downregulated the mRNA abundance of acetyl-CoA carboxylase (ACC), lipoprotein lipase (LPL) and fatty acid-binding protein 4 (FABP-4) (p<.05), and upregulated the mRNA expression of hormone-sensitive lipase (HSL), peroxisome proliferator-activated receptor-g coactivator-1α (PGC-1α), uncoupling protein 3 (UCP3) and liver carnitine palmitoyltransferase 1 (L-CPT-1) (p<.05). Therefore, our data suggest that protein-restricted diets supplemented with optimal BCAA ratio, that is, 1:0.75:0.75-1:0.25:0.25, induce a shift from fatty acid synthesis to fatty acid oxidation in the liver of growing pigs. These effects may be associated with increased mitochondrial biogenesis.

Long-term administration of DHEA prevents fat deposition in rats fed a high-fat diet

The effects of dehydroepiandrosterone (DHEA) on lipid metabolism and lipogenic gene mRNA expression in rats subjected to a high-fat diet were determined. Totally 75 rats were randomly divided into 5 groups: control group 1 fed a normal diet (NCG), and groups 2–5 fed a high-fat diet with 0 (HCG), 25 (HLG), 50 (HMG), 100 (HHG) mg DHEA per kg body weight via gavage once a day for 8 weeks, respectively. DHEA significantly decreased body weight in HMG group as compared with HCG group (P < 0.05). Hepatic triglyceride and total cholesterol contents were decreased in HMG and HHG groups (P < 0.05), and hepatic lipase activity in HMG group was higher (P < 0.01) than in HCG group. Fatty acid synthesis (FAS) mRNA level was decreased in HLG and HHG groups (P < 0.01), and sterol response element binding protein-1 (SREBP-1) mRNA level was decreased in HMG and HHG groups when compared with HCG group (P < 0.01). Acyl-CoA oxidase (ACO) and liver carnitine palmitoyl transferase-1 (LCPT-1) mRNA abundance was decreased in HLG and HHG groups (P < 0.01), whereas hormone sensitive lipase (HSL) mRNA level was increased in HMG group as compared with HCG group (P < 0.05). These results indicated that long-term administration of DHEA reduced the synthesis of endogenous triglycerides by inhibiting SREBP-1 and FAS expression, and augmented the lipolysis of exogenous triglycerides through enhancing HSL expression, which eventually led to reduced fat deposition in rats fed a high-fat diet.

Apolipoprotein E isoforms disrupt long-chain fatty acid distribution in the plasma, the liver and the adipose tissue of mice

Evidences suggest that omega-3 fatty acid (n-3 PUFA) metabolism is imbalanced in apolipoprotein E epsilon 4 isoform carriers (APOE4). This study aimed to investigate APOE genotype-dependant modulation of FA profiles, protein and enzyme important to fatty acid (FA) metabolism in the adipose tissue, the liver and the plasma using human APOE-targeted replacement mouse-model (N=37). FA transport (FATP) and binding (FABP) protein levels in tissues and concentrations of liver carnitine palmitoyltransferase 1 (CPT1) were performed. N-3 PUFA concentration was >45% lower in the adipose tissue and liver of APOE4 mice compared to APOE3 mice. In APOE4 mice, there were higher levels of FATP and FABP in the liver and higher FATP in the adipose tissue compared to APOE2 mice. There was a trend towards higher CPT1 concentrations in APOE4 mice compared to APOE3 mice. Therefore, since APOE-isoform differences were not always in line with the unbalanced n-3 PUFA profiles in organs, other proteins may be involved in maintaining n-3 PUFA homeostasis in mice with different APOE-isoforms.

Silkworm pupae powder ingestion increases fat metabolism in swim-trained rats.

[Purpose]Many researchers are trying to solve the metabolic syndrome by utilizing a variety of nutritional control and exercise. Of those, silkworm pupae peptides are known to inhibit the synthesis of fat. Therefore, we examine the effect of fat metabolism by supplying silkworm pupae (SP) for 5-week in swim-trained rats.[Methods]Animals were divided into four groups as a group (n = 32) fed a normal diet (CO) with exercise training (CE); a group fed a silkworm pupa diet (SPC) with an exercise training (SPE), respectively.[Results]Abdominal fat pads (abdominal and epididymal) weight were lowest in SPE. The serum triglyceride, total cholesterol concentrations were lower in the SP and the SPE. HDL-cholesterol, however, was not different between groups. Liver AMPK (AMP-activated protein kinase) was increased in the CE and the SPE. Liver PPAR-α (Peroxisome proliferator-activated receptor alpha) was increased in the SPC and SPE. L-FABP (liver fatty acids binding protein) was increased by SP ingestion. Liver CPT-1 (carnitine palmitoyltransferase-1) protein expression was increased by exercise training only.[Conclusion]In the present study showed that the silkworm pupae intake and/or swimming exercise training activates fat metabolism to reduce the concentration of serum lipids. Thus, the silkworm pupae intake leads to a reduction in fat storage, this is considered to be effective in the inhibition of the metabolic syndrome.

Mice do not accumulate muscle lipid in response to dietary conjugated linoleic acid1

Dietary CLA decreases body fat in several species and in pigs this is accompanied by increased muscle lipid. Our objective was to determine 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 determined that thigh muscle lipid content 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 palmitoyltransferase (CPT) enzyme activity, so less fatty acid oxidation 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-γ in the thigh muscle to the level of SO-fed mice, indicating that intramuscular adipocyte differentiation may be increasing. 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.

Effect of Hypoxic Training on Fatty Acid Oxcidation in Obese Rats

ObjectiveTo study the effects of hypoxic training on fatty acid oxcidation of obese rats.Method130 obese rats were divided into 13 groups at random:control group, normoxic training 1,2,3,4 week group, hypoxia sedentary1,2,3,4 week group, and hypoxic training 1,2,3,4 week group. The rats in training groups ran on a treadmill for 60 min a day at 26 m/min in normoxia or 21 m/min in hypoxia(13.6%), 6 days a week for 1–4 weeks. After corresponding week, Real‐time quantitative PCR was adopted to test the expression of carnitine palmitoyl transferase (CPT‐1mRNA) in gastrocnemius and liver. Lipoprotein lipase in gastrocnemius (LPLm) and adipose (LPLa) were measured using ELISA.Results1)Hypoxic training 4 week significantly reduced CPT‐1mRNA in liver more than control, and even more than normoxic training (P&lt;0.05) ;2) CPT‐1mRNA in gastrocnemius of obese rats was increased in 3–4 week (P&gt;;0.05), and in 4th week, CPT‐1mRNA was significantly higher in hypoxic training group compared with normoxic training and hypoxia sedentary (P&lt; 0.05) ;3) After 4 weeks, LPLa/ LPLm was lower in hypoxic training group than normoxic training group (P&lt;0.05).Conclusion1)Hypoxic training increased fatty acid oxcidation of skeletal muscle more than normoxic training. 2)Hypoxic training decreased fatty acid oxcidation of liver and even more than normoxic training.(Supported by NSFC: Grant No. 30971415)

An iTRAQ Proteomic Study Reveals an Association between Diet-Induced Enhanced Fatty Acid Metabolism and the Development of Glucose Intolerance in Prediabetic Mice

High-fat diet (HFD)-induced glucose intolerance and insulin resistance increases the chances of developing type-2 diabetes and cardiovascular disease. To study the mechanism(s) by which a HFD impairs glucose tolerance, we used a quantitative proteomic platform that integrated pI-based OFFGEL fractionation and iTRAQ labeling to profile the temporal changes in adipose membrane protein expression in mice fed a HFD for up to 8 months. Within 2 months of starting the diet, the mice adipose and liver tissues accumulated fat droplets, which contributed to subsequent insulin resistance and glucose intolerance within 6 months. The membrane proteomic delineation of such phenotypic expression resulted in quantification of 1713 proteins with 266, 343, and 125 differentially expressed proteins in 2-, 6-, and 8-month HFD-fed versus control mice, respectively. Pathway analysis of these differentially expressed proteins revealed the interplay between upregulation of fatty acid metabolism and downregulation of glucose metabolism. Substantial upregulation of adipose and liver carnitine palmitoyltransferase (Cpt) 1, the rate-limiting enzyme in the transport of long-chain fatty acids into mitochondria, occurred by 2 months. The increase in hepatic Cpt 1a expression was associated with a progressive decrease in glucose uptake as evidenced by downregulation of the liver glucose transporter protein (Glut) 2. Loss of glycogen storage was found in those hepatocytes full of fat droplets. Intriguingly, skeletal muscle Cpt 1b expression was unaltered by the HFD, whereas skeletal muscle Glut 4 and tyrosine phosphoryated insulin receptor substrate 1 (p-IRS1) were substantially upregulated at the same time as abnormal glucose metabolism developed in adipose and liver tissues. This study defines some of the molecular mechanisms as well as the relationship among adipose tissue, liver and skeletal muscle during development of HFD-induced glucose intolerance in vivo and identifies Cpt 1 as a potential drug target for the control or prevention of diabetes.

Mitochondrial Long Chain Fatty Acid Oxidation Related Enzyme Changes in Different Preeclampsia-Like Mouse Models

Background: Long-chain Free Fatty Acids (FFA) and long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) are related to some preeclampsia. We studied the relationship between LCHAD, carnitine palmitoyltransferase (CPT) I and II and FFA in different preeclampsia-like models. Methods: Classic preeclampsia models with Nw-nitro-L-arginine-methyl ester (L-NA) or Lipopolysaccharide (LPS) injection, antiphospholipid syndrome model with β2 glycoprotein I (β2GPI) injection, and ApoC3 mice with abnormal fatty acid metabolism (ApoC3+NS and ApoC3+L-NA) were used. Controls were saline injected. At days 14 and 18 of pregnancy, serum FFA levels were compared and placental and hepatic LCHAD, CPT I and II mRNA and protein were detected using real-time quantitative PCR and western blot. Results: Serum FFA levels increased significantly except in LPS, compared to controls (P<0.05). CPT I mRNA and protein increased significantly in the liver and placenta of L-NA and β2GPI and liver of ApoC3+L-NA (P<0.05). CPT II mRNA and protein increased significantly in the liver and placenta of L-NA and the liver of ApoC3+L-NA and β2GPI (P<0.05). LCHAD mRNA and protein increased significantly in the liver and placenta of ApoC3+NS, ApoC3+L-NA and β2GPI, and decreased significantly in L-NA (P<0.05). Serum FFA levels positively correlated with liver CPT I mRNA and protein in all groups (P<0.05) and negatively correlated with liver LCHAD mRNA and protein expression in all groups except in β2GPI group (P<0.05). Conclusions: Changes and correlations in FFA levels and LCHAD, CPT I and II were different according to preeclampsia-like models. β-oxidation disorders may occur at different stages.

33. 肝臓Carnitine Palmitoyltransferase 1及び2活性に及ぼすホルモン及び発生的因子の影響

33. 肝臓Carnitine Palmitoyltransferase 1及び2活性に及ぼすホルモン及び発生的因子の影響

Acute Liver Carnitine Palmitoyltransferase I Overexpression Recapitulates Reduced Palmitate Oxidation of Cardiac Hypertrophy

Muscle carnitine palmitoyltransferase I is predominant in the heart, but the liver isoform (liver carnitine palmitoyltransferase I [L-CPT1]) is elevated in hearts with low long chain fatty acid oxidation, such as fetal and hypertrophied hearts. This work examined the effect of acute L-CPT1 expression on the regulation of palmitate oxidation and energy metabolism in intact functioning rat hearts for comparison with findings in hypertrophied hearts. L-CPT1 was expressed in vivo in rat hearts by coronary perfusion of Adv.cmv.L-CPT1 (L-CPT1, n=15) vs. phosphate-buffered saline (PBS) infusion (PBS, n=7) or empty virus (empty, n=5). L-CPT1 was elevated 5-fold at 72 hours after Adv.cmv.L-CPT1 infusion (P<0.05), but muscle carnitine palmitoyltransferase I was unaffected. Despite similar tricarboxylic acid cycle rates, palmitate oxidation rates were reduced with L-CPT1 (1.12 ± 0.29 μmol/min per gram of dry weight, mean±SE) vs. PBS (1.6 ± 0.34). Acetyl CoA production from palmitate was reduced with L-CPT1 (69 ± 0.02%; P<0.05; PBS=79 ± 0.01%; empty=81 ± 0.02%), similar to what occurs in hypertrophied hearts, and with no difference in malonyl CoA content. Glucose oxidation was elevated with L-CPT1 (by 60%). Surprisingly, L-CPT1 hearts contained elevated atrial natriuretic peptide, indicating induction of hypertrophic signaling. The results link L-CPT1 expression to reduced palmitate oxidation in a nondiseased adult heart, recapitulating the phenotype of reduced long chain fatty acid oxidation in cardiac hypertrophy. The implications are that L-CPT1 expression induces metabolic remodeling hypertrophic signaling and that regulatory factors beyond malonyl CoA in the heart regulate long chain fatty acid oxidation via L-CPT1.

Dietary sea cucumber cerebroside alleviates orotic acid-induced excess hepatic adipopexis in rats

BackgroundNonalcoholic fatty liver disease (NAFLD) is a prevalent chronic liver disease in industrialized countries. The present study was undertaken to explore the preventive effect of dietary sea cucumber cerebroside (SCC) extracted from Acaudina molpadioides in fatty liver rats.MethodsMale Wistar rats were randomly divided into four groups including normal control group, NAFLD model group, and two SCC-treated groups with SCC at 0.006% and 0.03% respectively. The fatty liver model was established by administration of 1% orotic acid (OA) to the rats. After 10d, serum and hepatic lipid levels were detected. And the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were also determined. Besides, to gain the potential mechanism, the changes of key enzymes and gene expressions related to the hepatic lipid metabolism were measured.ResultsDietary SCC at the level of 0.006% and 0.03% ameliorated the hepatic lipid accumulation in fatty liver rats. SCC administration elevated the serum triglyceride (TG) level and the ALT, AST activities in OA-fed rats. The activities of hepatic lipogenic enzymes including fatty acid synthase (FAS), malic enzyme (ME) and glucose-6-phosphatedehydrogenase (G6PDH) were inhibited by SCC treatment. And the gene expressions of FAS, ME, G6PDH and sterol-regulatory element binding protein (SREBP-1c) were also reduced in rats fed SCC. However, dietary SCC didn't affect the activity and mRNA expression of carnitine palmitoyltransferase (CPT) in liver. Besides, suppression of microsomal triglyceride transfer protein (MTP) activity was observed in SCC-feeding rats.ConclusionsThese results suggested that dietary SCC could attenuate hepatic steatosis due to its inhibition of hepatic lipogenic gene expression and enzyme activity and the enhancement of TG secretion from liver.

Dexamethasone facilitates lipid accumulation in chicken skeletal muscle

The effects of glucocorticoid on lipid metabolism of broiler chicken (Gallus gallus domesticus) skeletal muscle were investigated. Male Arbor Acres chickens (35 days old) were subjected to dexamethasone treatment for 3 days. We found that dexamethasone retards body growth while facilitating lipid accumulation. In M. pectoralis major (PM), dexamethasone increased the expression of glucocorticoid receptor (GR), fatty acid transport protein 1 (FATP1), heart fatty acid-binding protein (H-FABP) and long-chain acyl-CoA dehydrogenase (LCAD) mRNA and decreased the expression of liver carnitine palmitoyltransferase 1 (L-CPT1), adenosine-monophosphate-activated protein kinase (AMPK) α2 and lipoprotein lipase (LPL) mRNA. LPL activity was also decreased. In M. biceps femoris (BF), the levels of GR, FATP1 and L-CPT1 mRNA were increased. AMPKα (Thr172) phosphorylation and CTP1 activity of skeletal muscle were decreased by dexamethasone. In fed chickens, dexamethasone enhanced very low-density lipoprotein receptor (VLDLR) expression and AMPK activity in muscle, but it impaired the expression of LPL and L-CPT1 mRNA and LPL activity in PM and augmented the expression of GR, LPL, H-FABP, L-CPT1, LCAD and AMPKα2 mRNA in BF. Adipose triglyceride lipase (ATGL) protein expression was not affected by dexamethasone. In conclusion, in the fasting state, dexamethasone-induced-retarded fatty acid utilisation may be involved in the augmented intramyocellular lipid accumulation in both glycolytic (PM) and oxidative (BF) muscle tissues. In the fed state, dexamethasone promoted the transcriptional activity of genes related to lipid uptake and oxidation in muscles. Unmatched lipid uptake and utilisation are suggested to be involved in the augmented intramyocellular lipid accumulation.

Derivatives of R-Aminocarnitine without Ammonium Moiety as Liver Carnitine Palmitoyltransferase I (L-CPT I) Inhibitors

Derivatives of R-Aminocarnitine without Ammonium Moiety as Liver Carnitine Palmitoyltransferase I (L-CPT I) Inhibitors

L-carnitine ameliorates cancer cachexia in mice by regulating the expression and activity of carnitine palmityl transferase

Cancer cachexia is characterized by progressive weight loss with the depletion of adipose tissue and skeletal muscle. Impaired fatty acid oxidation mainly resulting from the decrease of carnitine palmitoyltransferase I and II activities in the liver is an important factor that contributes to cancer cachexia . Although recent studies suggest a potential application of L-carnitine in treatment of cancer cachexia, the underlying mechanisms are unknown. In the present study, we aim to assess the effects of L-carnitine on the activity and expression of CPT I and II in the liver of cachectic cancer mice. Our results show that the inoculation of colon-26 adenocarcinoma cells into mice led to cancer cachexia characterized by notable decreases in food intake, gastrocnemius muscle and epididymus fat weight. In addition, the mRNA level and activity of liver carnitine palmitoyltransferase (CPT) I and II, and serum levels of free carnitine and acetylcarnitine were markedly decreased in cachectic mice, accompanied by marked increases in serum levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). A continuous oral treatment with L-carnitine at 18 mg/kg per day increased dietary uptake, gastrocnemius muscle weight and epididymus fat weight, increased blood glucose and serum albumin levels, and decreased total cholesterol level in cancer cachectic mice, but did not affect tumor growth. These effects of L-carnitine on cancer cachexia mice were accompanied by the upregulation of mRNA level of CPT I and II and increased enzyme activity of CPT I in the liver, as well as the downregulation of serum TNF-α and IL-6 levels. Moreover, free carnitine levels were negatively correlated with serum TNF-α or IL-6 level. These results indicate that L-carnitine ameliorates cancer cachexia by regulating serum TNF-α and IL-6 levels and modulating the expression and activity of CPT in the liver.