acetyl-CoA Carboxylase mRNA Levels Research Articles

Effects of monochromatic light on hepatic glycogen and lipid synthesis in broilers

Animal growth is closely related to glycolipid metabolism, and the liver is the main organ for glycogen storage and fat synthesis in birds, but whether monochromatic light affects glycogen and lipid synthesis in the liver is unclear. Therefore, in this study, a total of 96 Arbor Acre (AA) broilers at posthatching d 0 (P0) were raised under 4 kinds of light-emitting diode (LED) lights, white light (WL), red light (RL), green light (GL), and blue light (BL), to posthatching d 21 (P21) and 35 (P35). The results showed that the liver, abdominal fat, and abdominal fat indices gradually increased with increasing age under monochromatic light treatments. The liver glycogen and triglyceride (TG) contents also showed an increasing trend. Furthermore, compared with those at P21, the mRNA levels of glycogen synthase (GS), glycogen synthase kinase-3β (GSK-3β), and protein kinase B (AKT1) in the liver were increased in the WL and RL groups at P35, and the mRNA levels of acetyl-CoA carboxylase (ACC) and apolipoprotein B (APOB) increased in all groups at P35. At the same time, the total antioxidant capacity (T-AOC) and liver superoxide dismutase (SOD) contents increased in all groups at P35 compared with those at P21. In addition, at P21, compared with WL, GL and BL promoted the serum glucose (GLU) and TG contents by increasing the mRNA levels of GS, GSK-3β, glucose-6-phosphatase (G6PC), ACC, and fatty acid synthase (FAS), but no effect on the proliferative ability and damage of hepatocytes. At P35, RL promoted the hepatic glycogen and TG contents by increasing GSK-3β, AKT1, ACC, and APOB mRNA levels, and the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were increased than in the WL group. These results suggest that the effects of light color on liver glycogen and lipid synthesis in broilers changed with age, and also provide a theoretical guidance for scientific use of color of light information to improve productive performance in broilers.

A new single-cell protein from Clostridium autoethanogenum as a functional protein for largemouth bass (Micropterus salmoides).

Clostridium autoethanogenum protein (CAP) is a new single-cell protein source originating from inactivated bacteria. An in vitro digestion experiment and an 8-wk growth experiment were conducted to evaluate the molecular weight distribution of the CAP hydrolysate, and the effects of dietary CAP levels on the growth performance, plasma parameters, hepatic and intestinal health, and the diversity of gut-adherent microbiota of largemouth bass (Micropterus salmoides). The fish (initial body weight of 47.99 ± 0.01 g) were fed diets where CAP gradually replaced 0% (CAP0), 12.5% (CAP12.5), 25% (CAP25), 37.5% (CAP37.5) and 50% (CAP50) of low-temperature steam dried anchovy fish meal (LTFM) in the diet. Results showed that the content of peptides below 1,000 Da in the CAP hydrolysate (0.56 mg/mL) was higher than that of the LTFM hydrolysate (0.48 mg/mL). Dietary CAP inclusion had no negative effect on growth performance, while whole-body lipid content significantly reduced in the CAP25 and CAP50 groups (P < 0.05). The plasma alanine aminotransferase activities and triglyceride concentrations in the CAP inclusion groups were significantly lower than those in the CAP0 group (P < 0.05). The plasma aspartate aminotransferase activity was significantly reduced in the CAP37.5 group (P < 0.05). The richness and diversity of the gut-adhesive microbiota and the proportion of Clostridium sensu stricto 12 in the CAP50 group were significantly higher than those in the CAP0 group (P < 0.05). Dietary CAP inclusion inhibited inflammatory responses by down-regulating the mRNA levels of interleukin 1β (IL1β), IL10 and transforming growth factor β1 (P < 0.05) in the liver. The mRNA levels of acetyl-CoA carboxylase 1 were significantly down-regulated in the CAP12.5, CAP25 and CAP37.5 groups (P < 0.05), while that of fatty acid synthase was significantly down-regulated in the CAP50 group (P < 0.05). These results demonstrate that dietary CAP inclusion could improve the hepatic and intestinal health of largemouth bass, and can be helpful to further develop CAP as a functional feed ingredient.

Effects of dietary protein levels on growth and feed utilization in non-transgenic and growth-hormone-gene transgenic common carp (Cyprinus carpio L.)

A 48 days growth trial investigated the effects of dietary protein on growth, feed utilization in non-transgenic and GH (growth hormone gene) transgenic common carp (Cyprinus carpio L.). Transgenic common carp (TG fish) and non-transgenic (NT fish) were fed with seven diets of different protein levels (20%, 24%, 28%, 32%, 36%, 40%, 44%). The results showed that, TG fish obtained higher growth and feed utilization. NT fish showed higher whole-body protein and lipid. Compared to NT fish, the lower whole-body lipid of TG fish was mainly achieved by reducing fat synthesis and promoting fatty acid β-oxidation, including down-regulation of mRNA levels of acetyl-CoA carboxylase 1 (acc1), acyl-CoA desaturase 1 (scd1) and fatty-acid synthase (fas), upregulation of mRNA level of carnitine palmitoyl transferase 1a (cpt-1a). Plasma glucose levels were found higher in TG fish than NT fish, which might be caused by the inhibition of glycolysis (pfk, p < 0.01). With increased dietary protein, both TG fish and NT fish showed increased growth and decreased body lipid. High dietary protein levels inhibit glycolysis, fat synthesis and fatty acid β-oxidation. In conclusion, TG fish exhibited better growth performance, and lower glycolysis, lipid synthesis and better fatty acid oxidation than the NT fish.

Effect of all-trans retinoic acid on casein and fatty acid synthesis in MAC-T cells.

ObjectiveCaseins and fatty acids of milk are synthesized and secreted by the epithelial cells of the mammary gland. All-trans retinoic acid (ATRA), an active metabolite of vitamin A, has been shown to promote mammary development. This study was conducted to determine the effect of ATRA on casein synthesis and fatty acid composition in MAC-T cells.MethodsMAC-T cells were allowed to differentiate for 4 d, treated with ATRA (0, 1.0, 1.5, and 2.0 μM), and incubated for 3 d. We analyzed the fatty acid composition, the mRNA expression of casein and fatty acid synthesis-related genes, and the phosphorylation of casein synthesis-related proteins of MAC-T cells by gas chromatography, quantitative polymerase chain reaction, and western blotting, respectively.ResultsIn MAC-T cells, ATRA increased the mRNA levels of αS1-casein and β-casein, janus kinase 2 (JAK2) and E74-like factor 5 of the signal transducer and activator of transcription 5 β (STAT5-β) pathway, ribosomal protein S6 kinase beta-1 (S6K1) and eukaryotic translation initiation factor 4E binding protein 1 of the mammalian target of rapamycin (mTOR) pathway, inhibited the mRNA expression of phosphoinositide 3-kinase and eukaryotic initiation factor 4E of the mTOR pathway, and promoted the phosphorylation of STAT5-β and S6K1 proteins. Additionally, ATRA increased the de novo synthesis of fatty acids, reduced the content of long-chain fatty acids, the ratio of monounsaturated fatty acids to saturated fatty acids (SFA), the ratio of polyunsaturated fatty acids (PUFA) to SFA, and the ratio of ω-6 to ω-3 PUFA. The mRNA levels of acetyl-CoA carboxylase 1, fatty acid synthase, lipoprotein lipase, stearoyl-CoA desaturase, peroxisome proliferator-activated receptor gamma, and sterol regulatory element-binding protein 1 (SREBP1) were enhanced by ATRA.ConclusionATRA promotes the synthesis of casein by regulating JAK2/STAT5 pathway and downstream mTOR signaling pathway, and it improves the fatty acid composition of MAC-T cells by regulating SREBP1-related genes.

Prostate cancer chemoprevention by sulforaphane in a preclinical mouse model is associated with inhibition of fatty acid metabolism.

Increased de novo synthesis of fatty acids is a rather unique and targetable mechanism of human prostate cancer. We have shown previously that oral administration of sulforaphane (SFN) significantly inhibits the incidence and/or burden of prostatic intraepithelial neoplasia and well-differentiated adenocarcinoma in TRansgenic Adenocarcinoma of Mouse Prostate (TRAMP) mice. The present study used cellular models of prostate cancer and archived plasma/adenocarcinoma tissues and sections from the TRAMP study to demonstrate inhibition of fatty acid synthesis by SFN treatment in vitro and in vivo. Treatment of androgen-responsive (LNCaP) and castration-resistant (22Rv1) human prostate cancer cells with SFN (5 and 10 μM) resulted in downregulation of protein and mRNA levels of acetyl-CoA carboxylase 1 (ACC1) and fatty acid synthase (FASN), but not ATP citrate lyase. Protein and mRNA levels of carnitine palmitoyltransferase 1A (CPT1A), which facilitates fatty acid uptake by mitochondria for β-oxidation, were also decreased following SFN treatment in both cell lines. Immunohistochemistry revealed a significant decrease in expression of FASN and ACC1 proteins in prostate adenocarcinoma sections of SFN-treated TRAMP mice when compared with controls. SFN administration to TRAMP mice resulted in a significant decrease in plasma and/or prostate adenocarcinoma levels of total free fatty acids, total phospholipids, acetyl-CoA and ATP. Consistent with these results, number of neutral lipid droplets was lower in the prostate adenocarcinoma sections of SFN-treated TRAMP mice than in control tumors. Collectively, these observations indicate that prostate cancer chemoprevention by SFN in TRAMP mice is associated with inhibition of fatty acid metabolism.

Transcriptome analysis of Helicoverpa armigera male hairpencils: Alcohol biosynthesis and requirement for mating success

Many female animals use different strategies to assess male quality to increase their own reproductive fitness. In moths, females usually use chemical signals (sex pheromones) to attract males from a distance. Once males approach a female, they release close range pheromones from hairpencils to facilitate female acceptance. However, detailed mechanisms involved in male sex pheromone biosynthesis and its action in promoting female acceptance have not yet been fully characterized. This study screened a series of candidate genes via a transcriptome analysis of the male hairpencil of Helicoverpa armigera. Using pharmacological inhibitor and RNAi-mediated knockdown assays, we demonstrated that Ca2+ and cyclic-AMP were involved in pheromone biosynthesis activating neuropeptide (PBAN)-induced male sex pheromone biosynthesis. The functional analysis of candidate enzymes involved in the male sex pheromone biosynthesis pathway demonstrated that a decreased mRNA levels of acetyl-CoA carboxylase, Δ11-desaturase, and fatty-acyl reductase 2 by RNAi-mediated knockdown led to a significant decrease in the production of fatty acyl alcohols and the efficacy of female acceptance. Our results demonstrated the important role of the fatty acyl alcohol biosynthetic pathway in a PBAN-induced male sex pheromone biosynthesis and the importance of hairpencil compounds in female mating acceptance.

Reciprocal regulation of acetyl-CoA carboxylase 1 and senescence in human fibroblasts involves oxidant mediated p38 MAPK activation

We sought to explore the fate of the fatty acid synthesis pathway in human fibroblasts exposed to DNA damaging agents capable of inducing senescence, a state of irreversible growth arrest. Induction of premature senescence by doxorubicin or hydrogen peroxide led to a decrease in protein and mRNA levels of acetyl-CoA carboxylase 1 (ACC1), the enzyme that catalyzes the rate-limiting step in fatty-acid biosynthesis. ACC1 decay accompanied the activation of the DNA damage response (DDR), and resulted in decreased lipid synthesis. A reduction in protein and mRNA levels of ACC1 and in lipid synthesis was also observed in human primary fibroblasts that underwent replicative senescence.We also explored the consequences of inhibiting fatty acid synthesis in proliferating non-transformed cells. Using shRNA technology, we knocked down ACC1 in human fibroblasts. Interestingly, this metabolic perturbation was sufficient to arrest proliferation and trigger the appearance of several markers of the DDR and increase senescence associated β-galactosidase activity. Reactive oxygen species and p38 mitogen activated protein kinase phosphorylation participated in the induction of senescence. Similar results were obtained upon silencing of fatty acid synthase (FAS) expression. Together our results point towards a tight coordination of fatty acid synthesis and cell proliferation in human fibroblasts.

Dietary Niacin Supplementation Suppressed Hepatic Lipid Accumulation in Rabbits.

An experiment was conducted to investigate the effect of niacin supplementation on hepatic lipid metabolism in rabbits. Rex Rabbits (90 d, n = 32) were allocated to two equal treatment groups: Fed basal diet (control) or fed basal diet with additional 200 mg/kg niacin supplementation (niacin). The results show that niacin significantly increased the levels of plasma adiponectin, hepatic apoprotein B and hepatic leptin receptors mRNA (p<0.05), but significantly decreased the hepatic fatty acid synthase activity and adiponectin receptor 2, insulin receptor and acetyl-CoA carboxylase mRNA levels (p<0.05). Plasma insulin had a decreasing tendency in the niacin treatment group compared with control (p = 0.067). Plasma very low density lipoproteins, leptin levels and the hepatic adiponectin receptor 1 and carnitine palmitoyl transferase 1 genes expression were not significantly altered with niacin addition to the diet (p>0.05). However, niacin treatment significantly inhibited the hepatocytes lipid accumulation compared with the control group (p<0.05). In conclusion, niacin treatment can decrease hepatic fatty acids synthesis, but does not alter fatty acids oxidation and triacylglycerol export. And this whole process attenuates lipid accumulation in liver. Besides, the hormones of insulin, leptin and adiponectin are associated with the regulation of niacin in hepatic lipid metabolism in rabbits.

Preventing non-alcoholic fatty liver disease through Lactobacillus johnsonii BS15 by attenuating inflammation and mitochondrial injury and improving gut environment in obese mice.

The increasing prevalence of obesity worldwide is associated with a parallel increase in non-alcoholic fatty liver disease (NAFLD). To investigate the effect of Lactobacillus johnsonii BS15 on NAFLD, 120 male ICR mice were randomly divided into four groups and administrated with BS15 (2 × 10(7) cfu/0.2 mL or 2 × 10(8) cfu/0.2 mL) or phosphate buffered saline (PBS) throughout a 17-week experimental period. The mice were fed with normal chow diet (NCD) 5 weeks before the experimental period. Afterward, with the exception of the PBS group, NCD was changed into high-fat diet (HFD) for the remaining experimental period. Results showed that BS15-treated HFD mice were protected from hepatic steatosis and hepatocyte apoptosis. BS15 exhibited a positive effect on liver lipid peroxidation through an anti-oxidative stress activity by enhancing the liver antioxidant defense system. In addition, BS15 inhibited the insulin resistance; decreased the mRNA levels of acetyl-CoA carboxylase 1, fatty acid synthase, and peroxisome proliferator-activated receptor γ; and increased the expression of the fasting-induced adipose factor in livers. Meanwhile, BS15 attenuated mitochondria abnormalities when the content of uncoupling protein-2 decreased and cytochrome c increased in NAFLD mice. BS15 also reduced the level of serum lipopolysaccharide in NAFLD mice by lowering the intestinal permeability and adjusting gut flora, followed by the downregulation of the TNFα mRNA level in liver and the serum level of C-reactive protein. These findings suggest that BS15 may be effective in preventing NAFLD induced by HFD.

Dexamethasone-induced hepatic lipogenesis is insulin dependent in chickens (Gallus gallus domesticus)

Hepatic lipogenesis-induced de novo by glucocorticoids (GCs) is associated with the development of obesity and diabetes mellitus. The interaction of GCs and insulin in the regulation of hepatic lipogenesis remains unclear. The effect of exogenous GC administration on hepatic lipogenesis and fat deposition was studied in broiler chickens (Gallus gallus domesticus), and the role of insulin in the effect of GCs on hepatic lipogenesis was evaluated. Dexamethasone (DEX, 2 mg/kg body mass (BM)) administration for 3-d resulted in BM loss and increased liver and cervical adipose tissue mass compared to control and pair-fed counterparts. DEX treatment significantly (P < 0.05) increased plasma level of insulin in either the fed or fasting state, whereas plasma glucose level was only increased in the fed state. In fasted chickens, DEX treatment significantly (P < 0.01) upregulated the hepatic mRNA levels of acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS). In the fed state, the mRNA levels of ACC and FAS were not significantly influenced by DEX treatment, nor was FAS activity. In cultured primary hepatocytes, combined DEX and insulin significantly upregulated the transcription of the genes for FAS (1.34-fold) and malic enzyme (1.72-fold). By contrast, the expression of sterol response element-binding protein-1 (SREBP-1) was significantly upregulated by insulin (1.67-fold) regardless of DEX. In abdominal adipose tissue, DEX treatment had no significant (P>0.05) effect on the activities and transcription of FAS. The expressions of lipoprotein lipase and peroxisome proliferator-activated receptor-γ were not significantly (P>0.05) affected by DEX treatment in either the fasting or fed state. The results indicate that DEX increased hepatic de novo lipogenesis via the increased activity and expression of lipogenic enzymes. Insulin-activated gene expression for SREBP-1 is suggested to be involved in stress-augmented hepatic lipogenesis.

Fibroblast Growth Factor 19 Treatment Ameliorates Disruption of Hepatic Lipid Metabolism in Farnesoid X Receptor (Fxr)-Null Mice

Human fibroblast growth factor 19 (FGF19) is an enterohepatic hormone that is involved in the regulation of hepatic metabolism of bile acids, lipids, and glucose. Farnesoid X receptor (Fxr)-null mice exhibit steatosis-like symptoms, showing higher hepatic lipid levels than with the wild-type mice. We investigated the influence of FGF19 treatment on hepatic lipogenesis in Fxr-null mice. Recombinant FGF19 treatment (400 µg/kg/d) for 3 d prevented the accumulation of lipid droplets and decreased serum alanine aminotransferase activity and hepatic lipid levels, including those of triglycerides and free fatty acids. The treatment significantly decreased the hepatic mRNA levels of acetyl-CoA carboxylase 1 (Acc1), Cd36, and sterol regulatory element-binding protein-1c (Srebp-1c) as well as those of acetyl-CoA carboxylase 2 (Acc2), stearoyl CoA desaturase 1 (Scd1), and Cyp7a1. FGF19 treatment (4 µg/kg/d) for 3 d also decreased the hepatic free fatty acid levels and mRNA levels of Acc1, Cd36, and Srebp-1c. These results indicate that FGF19-mediated signaling ameliorates disrupted hepatic lipogenesis in Fxr-null mice.

24 S-hydroxycholesterol effects on lipid metabolism genes are modeled in traumatic brain injury

Membrane damage during traumatic brain injury (TBI) alters the brain homeostasis of cholesterol and other lipids. Cholesterol 24 S-hydroxylase (Cyp46) is a cholesterol metabolic enzyme that is increased after TBI. Here, we systematically examined the effects of the enzymatic product of Cyp46, 24 S-hydroxycholesterol, on the cholesterol regulatory genes, SREBP-1 and 2, their posttranslational regulation, and their effects on gene transcription. 24 S-hydroxycholesterol increased levels of SREBP-1 mRNA and full-length protein but did not change levels of cleaved SREBP-1, consistent with the role of 24-hydroxycholesterol as an LXR agonist. In contrast, 24 S-hydroxycholesterol decreased levels of LXR-independent SREBP-2 mRNA, full-length protein, and SREBP-2 active cleavage product. We examined the downstream effects of changes to these lipid regulatory factors by studying cholesterol and fatty acid synthesis genes. In neuroblastoma cells, 24 S-hydroxycholesterol decreased mRNA levels of the cholesterol synthesis genes HMG CoA reductase, squalene synthase, and FPP synthase but did not alter levels of the mRNA of fatty acid synthesis genes acetyl CoA carboxylase or fatty acid synthase. After TBI, as after 24 S-hydroxycholesterol treatment in vitro, SREBP-1 mRNA levels were increased while SREBP-2 mRNA levels were decreased. Also similar to the in vitro results with 24 S-hydroxycholesterol, HMG CoA reductase and squalene synthase mRNA levels were significantly decreased. Fatty acid synthase mRNA levels were not altered but acetyl CoA carboxylase mRNA levels were significantly decreased. Thus, changes to transcription of cholesterol synthesis genes after TBI were consistent with increases in Cyp46 activity, but changes to fatty acid synthesis genes must be regulated by other mechanisms.

Sheep and goats differences in CLA and fatty acids milk fat content in relation with mRNA stearoyl-CoA desaturase and lipogenic genes expression in their mammary gland

An experiment was conducted with 12 lactating dairy ewes and 12 goats with the objective to determine whether, under the same dietary treatments, the differences in their fatty acid (FA) profile with emphasis on cis-9 trans-11 CLA milk fat content, are reflected in the transcript levels of genes involved in FA and cis-9, trans-11 CLA biosynthesis. The animals were fed with two diets (A, B) in different days of milk (DIM) due to the different milk yield, body weight etc, in order to have the same food intake and to avoid dietary effects. Diet A was fed to the animals on a group basis as it is traditionally used in practice, while diet B was chosen to avoid individual feed intake variation which is usually observed in group feeding. The results showed that there are significantly lower mRNA levels of acetyl-CoA carboxylase (ACC) in sheep mammary gland compared with those of goats, independently from the diet fed. The same trend was observed with the mRNA level of FA synthase (FAS), but the results were significant only for diet A. The mRNA level of lipoprotein lipase (LPL) in the mammary gland did not differ between sheep and goats fed with diet A. In addition, the concentration of cis-9 trans-11 CLA content was significantly higher in sheep milk fat compared with those of goats. This is in accordance with the significant higher levels on mRNA of stearoyl-CoA desaturase (SCD) which were observed in their mammary adipocytes of sheep compared with those of goats, independently of the fed diet (A or B). In conclusion, these findings demonstrate that the differences between sheep and goats, concerning cis-9, trans-11 CLA and FA milk fat content, under the same dietary treatments could be explained in part by the differences in mRNA of SCD and lipogenic genes in their mammary gland.

Retinoic Acid Treatment Increases Lipid Oxidation Capacity in Skeletal Muscle of Mice

All-trans retinoic acid (ATRA), a carboxylic form of vitamin A, favors in mice a mobilization of body fat reserves that correlates with an increment of oxidative and thermogenic capacity in adipose tissues. The objective of this study has been to investigate the effect of ATRA treatment on skeletal muscle capacity for fatty-acid catabolism. Tissue composition and gene expression related to lipid and oxidative metabolism were analyzed in skeletal muscle of mice acutely treated with ATRA or vehicle (olive oil). ATRA treatment triggered a dose-dependent increase in the muscle mRNA expression levels of selected enzymes, transporters and transcription factors involved in fatty-acid oxidation, respiration, and thermogenesis namely: muscle-type carnitine palmitoyltransferase 1, acyl CoA oxidase 1, subunit II of cytochrome oxidase, uncoupling protein 3, peroxisome proliferator-activated receptor-gamma co-activator -1alpha and peroxisome proliferator-activated receptor-delta (PPARdelta). The treatment also resulted in the upregulation of the mRNA levels of acetyl-CoA carboxylase 2 (ACC2), a key regulatory enzyme for mitochondrial fatty-acid oxidation in muscle. Skeletal muscle protein levels of PPARdelta and retinoid X receptor gamma, a partner for many nuclear receptors involved in lipid metabolism, were increased after ATRA treatment. Muscle lipid content was decreased. These results indicate that ATRA treatment increases the capacity of skeletal muscle for fatty-acid oxidation. Knowledge of nutrients or nutrient-derivatives capable of enhancing oxidative metabolism in muscle and other tissues can contribute to new avenues of prevention and treatment of obesity and related disorders.

Antidiabetic effects of sub-chronic administration of the cannabinoid receptor (CB 1) antagonist, AM251, in obese diabetic ( ob/ob) mice

Recent research suggests that cannabinoid CB 1 receptor antagonism reduces appetite and body weight gain. The present study was designed to assess the sub-chronic effects of the selective cannabinoid CB 1 receptor antagonist, AM251 ( N-(Piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1 H-pyrazole-3-carboxamide), in young ob/ob mice. Pair-fed animals were used as additional controls. Daily injection of AM251 (6 mg/kg body weight) for 18 days significantly ( P < 0.05) decreased daily and 18-day cumulative food intake. The corresponding body weight change did not achieve significance and values were not different from pair-fed mice. Non-fasting plasma glucose was decreased ( P < 0.05) from day 10 onwards by AM251 treatment. The glycaemic response to intraperitoneal glucose was correspondingly improved ( P < 0.05) in AM251 treated mice. In keeping with this, insulin sensitivity was enhanced ( P < 0.05) compared to controls. Furthermore, adipose mRNA levels of acetyl-CoA carboxylase 1 were significantly ( P < 0.05) reduced by 18 days AM251 treatment. There were no differences in either non-fasting or glucose-stimulated insulin release. Pair-feeding had broadly similar metabolic effects to AM251 treatment apart from increased ( P < 0.01) locomotor activity which was only observed in AM251 treated ob/ob mice. These data indicate that sub-chronic antagonism of the cannabinoid CB 1 receptor by daily treatment with AM251 counters aspects of the hyperphagia-related impairment of ob/ob mouse metabolism. Such effects seem predominantly mediated by restriction of energy intake.

Effects of In Ovo Administration of DHEA on Lipid Metabolism and Hepatic Lipogenetic Genes Expression in Broiler Chickens During Embryonic Development

In order to study the mechanism of DHEA (Dehydroepiandrosterone) in reducing fat in broiler chickens during embryonic development, fertilized eggs were administrated with DHEA before incubation and its effect on lipid metabolism and expression of hepatic lipogenetic genes was investigated. The mRNA levels of acetyl CoA carboxylase (ACC), fatty acid synthase (FAS), malic enzyme (ME), apolipoprotein B100 (apoB100) and sterol regulator element binding protein-1c (SREBP-1c) were determined using real time quantitative PCR. Samples of livers were collected from the chickens on days 9, 14, and 19 of embryonic development as well as at hatching. Blood samples were extracted on days 14, 19 of incubation and at hatching. The results showed that DHEA decreased the concentration of triacyglycerol in the blood and the content in liver, and the mRNA levels of ACC, FAS, ME, SREBP-1c and apoB. This suggested that DHEA decreased the expression of hepatic lipogenetic genes and suppressed triglycerols transport, by which it reduced the deposition of fat in adipose tissue in broiler chickens during embryonic development and hatching.

Leptin decreases lipogenic enzyme gene expression through modification of SREBP-1c gene expression in white adipose tissue of aging rats

Aging is associated with a significant reduction of lipogenic enzyme gene expression and lipogenesis in white adipose tissue (WAT). The age-related increase of lep gene expression could be, in part, responsible for these changes. Considering that sterol regulatory element binding protein 1c (SREBP-1c) plays an important role in regulation of lipogenic enzyme gene expression, it is likely that the age-related decrease of WAT lipogenic potential could be a consequence of the inhibition of SREBP-1c gene expression by leptin. We determined whether the increase of lep gene expression would account for the age-related decrease in SREBP-1c and its direct target, main lipogenic enzymes acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS), by assaying the messenger RNA (mRNA) levels of SREBP-1c, FAS, ACC , and leptin in WAT of 2-month-old (young) and 20-month-old (old) rats. Leptin mRNA level was much higher in the old animals, whereas in contrast, old rats displayed much lower mRNA levels of SREBP-1c and lipogenic enzymes. Moreover, experimentally increased plasma leptin concentration in young rats to the value observed in old rats resulted in the decrease of SREBP-1c, FAS, and ACC mRNA levels in WAT. Thus, the increase of lep gene expression could, in part, account for the reduced SREBP-1c gene expression and, consequently, the diminished lipogenic activity in WAT of old animals.

Effect of starvation on hepatic acyl-CoA synthetase, carnitine palmitoyltransferase-I, and acetyl-CoA carboxylase mRNA levels in rats

Objectives This study investigated the effect of starvation on mRNA levels of hepatic acyl coenzyme A synthetase (ACS), carnitine palmitoyltransferase-I (CPT-I), and acetyl coenzyme A carboxylase (ACC) and on serum concentrations of leptin, insulin, and glucose in male Sprague-Dawley rats. Methods Rats were fed an AIN-76 diet for 5 wk and then assigned to a normal group (NG) and a starvation group (SG). The SG was starved for 48 h and the NG was fasted for 12 h before being killed. Serum and hepatic lipids and serum levels of leptin, insulin, and glucose were determined. Expressions of ACS, CPT-1, and ACC mRNA were assessed in liver. Results Serum concentrations of triacylglycerol and high-density lipoprotein cholesterol in the SG were lower than those in the NG. Serum concentrations of low-density lipoprotein cholesterol in the SG were significantly higher than in the NG. Hepatic concentrations of total lipid in the SG were significantly higher than those in the NG, and triacylglycerol concentrations in the SG were significantly lower than those in the NG. Serum concentrations of leptin and glucose in the SG were significantly lower than those in the NG. The ratio of abdominal fat to total body weight in the SG was lower than that in the NG. Hepatic ACS and CPT-I mRNA levels in the SG were significantly higher than those in the NG, but hepatic ACC mRNA levels were lower in the SG than in the NG. Conclusions We demonstrated that starvation increases hepatic levels of ACS and CPT-I and decreases transcription levels of ACC, implicating increases in fatty acid oxidation. This research demonstrates a coordinated regulation of ACS, CPT-I, and ACC mRNA levels and serves to enhance our understanding of the molecular mechanisms underlying fatty acid metabolism during starvation.

Role of Hexosamine Biosynthesis in Glucose-mediated Up-regulation of Lipogenic Enzyme mRNA Levels: EFFECTS OF GLUCOSE, GLUTAMINE, AND GLUCOSAMINE ON GLYCEROPHOSPHATE DEHYDROGENASE, FATTY ACID SYNTHASE, AND ACETYL-CoA CARBOXYLASE mRNA LEVELS

Glucose uptake into adipose and liver cells is known to up-regulate mRNA levels for various lipogenic enzymes such as fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC). To determine whether the hexosamine biosynthesis pathway (HBP) mediates glucose regulation of mRNA expression, we treated primary cultured adipocytes for 18 h with insulin (25 ng/ml) and either glucose (20 mm) or glucosamine (2 mm). A ribonuclease protection assay was used to quantitate mRNA levels for FAS, ACC, and glycerol-3-P dehydrogenase (GPDH). Treatment with insulin and various concentrations of d-glucose increased mRNA levels for FAS (280%), ACC (93%), and GPDH (633%) in a dose-dependent manner (ED50 8-16 mm). Mannose similarly elevated mRNA levels, but galactose and fructose were only partially effective. l-glucose had no effect. Omission of glutamine from the culture medium markedly diminished the stimulatory effect of glucose on mRNA expression. Since glutamine is a crucial amide donor in hexosamine biosynthesis, we interpret these data to mean that glucose flux through the HBP is linked to regulation of lipogenesis through control of gene expression. Further evidence for hexosamine regulation was obtained using glucosamine, which is readily transported into adipocytes where it directly enters the HBP. Glucosamine was 15-30 times more potent than glucose in elevating FAS, ACC, and GPDH mRNA levels (ED50 approximately 0.5 mm). In summary: 1) GPDH, FAS, and ACC mRNA levels are upregulated by glucose; 2) glucose-induced up-regulation requires glutamine; and 3) mRNA levels for lipogenic enzymes are up-regulated by glucosamine. Hyperglycemia is the hallmark of diabetes mellitus and leads to insulin resistance, impaired glucose metabolism, and dyslipidemia. We postulate that disease pathophysiology may have a common underlying factor, excessive glucose flux through the HBP.

The effects of a high-fat or high-sucrose diet on serum lipid profiles, hepatic acyl-CoA synthetase, carnitine palmitoyltransferase-I, and the acetyl-CoA carboxylase mRNA levels in rats.

The purpose of this study was to investigate the effects of altering relative intakes of fat and carbohydrates on serum lipid profiles, hepatic acyl-CoA synthetase (ACS), carnitine palmitoyltransferase-I (CPT-I), and the acetyl-CoA carboxlyase (ACC) mRNA level in Sprague-Dawley rats. For four weeks the rats were fed either an AIN-76 diet or one of its modified diets that were supplemented with 20% beef tallow (high-fat diet, HF) and 66.3% sucrose (high-sucrose diet, HS). The HS group had significantly higher serum triglyceride and total cholesterol concentrations when compared with the other groups. Serum LDL-cholesterol concentrations in the HS and HF groups were significantly higher when compared to the normal diet (ND) group. Serum HDL-cholesterol levels of the ND and HS groups were significantly higher than those of the HF group. The hepatic total lipid level of the HF group was significantly higher than those of other groups; triglyceride levels of the HS and HF groups were significantly higher than those of the ND group. Hepatic ACS mRNA levels of the HF group were significantly higher than those of the ND group. Hepatic CPT-I mRNA levels were higher in the HF group than other groups. Also, ACC mRNA levels in the liver increased in the HF group. In conclusion, changes in the composition of dietary fat and carbohydrates could affect the hepatic ACS, CPT-I, and ACC mRNA levels. These results facilitate our understanding of the coordinated regulation of the ACS, CPT-I, and ACC mRNA levels and will serve to enhance our understanding of the molecular mechanisms that underlie the regulation of fatty acid metabolism.