scholarly journals Orexin system is expressed in avian liver and regulates hepatic lipogenesis via ERK1/2 activation

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
E. S. Greene ◽  
M. Zampiga ◽  
F. Sirri ◽  
T. Ohkubo ◽  
Sami Dridi
Keyword(s):  
Fatty Acid Synthase ◽  
Culture Media ◽  
Mammalian Species ◽  
Brefeldin A ◽  
Chicken Liver ◽  
Hepatic Lipogenesis ◽  
Atp Citrate Lyase ◽  
Protein Levels ◽  
Lipogenic Genes ◽  
Lmh Cells

Abstract Orexins are originally characterized as orexigenic hypothalamic neuropeptides in mammals. Subsequent studies found orexin to be expressed and perform pleiotropic functions in multiple tissues in mammals. In avian (non-mammalian) species, however, orexin seemed to not affect feeding behavior and its physiological roles are poorly understood. Here, we provide evidence that orexin and its related receptors are expressed in chicken hepatocytes. Double immunofluorescence staining showed that orexin is localized in the ER, Golgi, and in the lysosomes in LMH cells. Brefeldin A treatment reduced orexin levels in the culture media, but increased it in the cell lysates. Administration of recombinant orexins upregulated the expression of orexin system in the liver of 9-day old chicks, but did not affect feed intake. Recombinant orexins increased fatty acid synthase (FASN) protein levels in chicken liver, activated acetyl-CoA carboxylase (ACCα), and increased FASN, ATP citrate lyase(ACLY), and malic enzyme (ME) protein expression in LMH cells. Blockade ERK1/2 activation by PD98059 attenuated these stimulating effects of orexin on lipogenic factors. Overexpression of ERK1/2 increased the expression of lipogenic genes, and orexin treatment induced the phosphorylated levels of ERK1/2Thr202/Tyr204, but not that of p38 Thr180/Tyr182 or JNK1/2 Thr183/Tyr185 in chicken liver and LMH cells. Taken together, this is the first report evidencing that orexin is expressed and secreted from chicken hepatocytes, and that orexin induced hepatic lipogenesis via activation of ERK1/2 signaling pathway.

scholarly journals Caffeoylquinic Acid-Rich Extract ofAster glehniF. Schmidt Ameliorates Nonalcoholic Fatty Liver through the Regulation of PPARδand Adiponectin in ApoE KO Mice

PPAR Research ◽  
2017 ◽  
Vol 2017 ◽  
pp. 1-19 ◽  
Author(s):  
Yong-Jik Lee ◽  
Yoo-Na Jang ◽  
Yoon-Mi Han ◽  
Hyun-Min Kim ◽  
Jong-Min Jeong ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fatty Liver ◽  
Fatty Acid Synthase ◽  
Serum Triglyceride ◽  
Adenosine Monophosphate ◽  
Serum Triglyceride Level ◽  
Peroxisome Proliferator ◽  
Atp Citrate Lyase ◽  
Nonalcoholic Fatty Liver ◽  
Protein Levels

Aster glehniis well known for its therapeutic properties. This study was performed to investigate the effects ofA. glehnion nonalcoholic fatty liver disease (NAFLD) in atherosclerotic condition, by determining the levels of biomarkers related to lipid metabolism and inflammation in serum, liver, and adipose tissue. Body and abdominal adipose tissue weights and serum triglyceride level decreased in all groups treated withA. glehni. Serum adiponectin concentration and protein levels of peroxisome proliferator-activated receptorδ, 5′ adenosine monophosphate-activated protein kinase, acetyl-CoA carboxylase, superoxide dismutase, and PPARγcoactivator 1-alpha in liver tissues increased in the groups treated withA. glehni. Conversely, protein levels of ATP citrate lyase, fatty acid synthase, tumor necrosis factorα, and 3-hydroxy-3-methylglutaryl-CoA reductase and the concentrations of interleukin 6 and reactive oxygen species decreased uponA. glehni. Triglyceride concentration in the liver was lower in mice treated withA. glehnithan in control mice. Lipid accumulation in HepG2 and 3T3-L1 cells decreased uponA. glehnitreatment; this effect was suppressed in the presence of the PPARδantagonist, GSK0660. Our findings suggest thatA. glehniextracts may ameliorate NAFLD through regulation of PPARδ, adiponectin, and the related subgenes.

scholarly journals p38 Mitogen-activated Protein Kinase Plays an Inhibitory Role in Hepatic Lipogenesis

2006 ◽  
Vol 282 (7) ◽  
pp. 4975-4982 ◽  
Author(s):  
Yan Xiong ◽  
Qu Fan Collins ◽  
Jie An ◽  
Edgar Lupo ◽  
Hui-Yu Liu ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Fatty Acid Synthase ◽  
Isolated Hepatocytes ◽  
Mitogen Activated Protein Kinase ◽  
Hepatic Lipogenesis ◽  
Induced Expression ◽  
Lipogenic Genes ◽  
Triglyceride Accumulation ◽  
Inhibitory Role ◽  
Mitogen Activated Protein

Hepatic lipogenesis is the principal route to convert excess carbohydrates into fatty acids and is mainly regulated by two opposing hormones, insulin and glucagon. Although insulin stimulates hepatic lipogenesis, glucagon inhibits it. However, the mechanism by which glucagon suppresses lipogenesis remains poorly understood. In this study, we have observed that p38 mitogen-activated protein kinase plays an inhibitory role in hepatic lipogenesis. Levels of plasma triglyceride and triglyceride accumulation in the liver were both elevated when p38 activation was blocked. Expression levels of central lipogenic genes, including sterol regulatory element-binding protein-1 (SREBP-1), fatty acid synthase, hydroxy-3-methylglutaryl coenzyme A reductase, farnesyl pyrophosphate synthase, and cytochrome P-450-51, were decreased in liver by fasting and in primary hepatocytes by glucagon but increased by the inhibition of p38. In addition, we have shown that p38 can inhibit insulin-induced expression of key lipogenic genes in isolated hepatocytes. Our results in hepatoma cells demonstrate that p38 plays an inhibitory role in the activation of the SREBP-1c promoter. Finally, we have shown that transcription of the PGC-1β gene, a key coactivator of SREBP-1c, was reduced in liver by fasting and in isolated hepatocytes by glucagon. This reduction was significantly reversed by the blockade of p38. Insulin-induced expression of the PGC-1β gene was enhanced by the inhibition of p38 but suppressed by the activation of p38. Together, we have identified an inhibitory role for p38 in the transcription of central lipogenic genes, SREBPs, and PGC-1β and hepatic lipogenesis.

scholarly journals Resveratrol Treatment Enhances the Cellular Response to Leptin by Increasing OBRb Content in Palmitate-Induced Steatotic HepG2 Cells

2019 ◽  
Vol 20 (24) ◽  
pp. 6282 ◽  
Author(s):  
Andrea Ardid-Ruiz ◽  
Maria Ibars ◽  
Pedro Mena ◽  
Daniele Del Rio ◽  
Begoña Muguerza ◽  
...  
Keyword(s):  
Hepatic Steatosis ◽  
Hepg2 Cells ◽  
Cellular Response ◽  
Fatty Acid Synthase ◽  
Sirtuin 1 ◽  
Leptin Resistance ◽  
Independent Manner ◽  
Protein Levels ◽  
Lipogenic Genes ◽  
Leptin Sensitivity

The interaction of leptin with its hepatic longest receptor (OBRb) promotes the phosphorylation of signal transducer and activator of transcription-3 (STAT3), protecting the liver from lipid accumulation. However, leptin signalling is disrupted in hepatic steatosis, causing leptin resistance. One promising strategy to combat this problem is the use of bioactive compounds such as polyphenols. Since resveratrol (RSV) is a modulator of lipid homeostasis in the liver, we investigated whether treatment with different doses of RSV restores appropriate leptin action and fat accumulation in palmitate-induced steatotic human hepatoma (HepG2) cells. Both RSV metabolism and the expression of molecules implicated in leptin signalling were analysed. RSV at a 10 μM concentration was entirely metabolized to resveratrol-3-sulfate after 24 and counteracted leptin resistance by increasing the protein levels of OBRb. In addition, RSV downregulated the expression of lipogenic genes including fatty acid synthase (Fas) and stearoyl-CoA desaturase-1 (Scd1) without any significant change in Sirtuin-1 (SIRT1) enzymatic activity. These results demonstrate that RSV restored leptin sensitivity in a cellular model of hepatic steatosis in a SIRT1-independent manner.

Increased hepatic lipogenesis but decreased expression of lipogenic gene in adipose tissue in human obesity

2002 ◽  
Vol 282 (1) ◽  
pp. E46-E51 ◽  
Author(s):  
Frédérique Diraison ◽  
Eric Dusserre ◽  
Hubert Vidal ◽  
Monique Sothier ◽  
Michel Beylot
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid Synthase ◽  
Regulatory Element ◽  
Energy Restriction ◽  
Mrna Levels ◽  
Hepatic Lipogenesis ◽  
Deuterated Water ◽  
Human Obesity ◽  
Fas Mrna ◽  
Obese Subjects

To determine whether increased lipogenesis contributes to human obesity, we measured (postabsorptive state), in lean and obese subjects, lipid synthesis (deuterated water method) and the mRNA concentration (RT-competitive PCR) in subcutaneous adipose tissue of fatty acid synthase (FAS) and sterol regulatory element-binding protein (SREBP)-1c. Before energy restriction, obese subjects had an increased contribution of hepatic lipogenesis to the circulating triglyceride pool (14.5 ± 1.3 vs. 7.5 ± 1.9%, P < 0.01) without enhancement of cholesterol synthesis. This increased hepatic lipogenesis represented an excess of 2–5 g/day of triglycerides, which would represent 0.7–1.8 kg on a yearly basis. The lipogenic capacity of adipose tissue appeared, on the contrary, decreased with lower FAS mRNA levels ( P < 0.01) and a trend for decreased SREBP-1c mRNA ( P = 0.06). Energy restriction in obese patients decreased plama insulin ( P < 0.05) and leptin ( P < 0.05) and normalized hepatic lipogenesis. FAS mRNA levels were unchanged, whereas SREBP-1c increased. In conclusion, subjects with established obesity have an increased hepatic lipogenesis that could contribute to their excessive fat mass but no evidence for an increased lipogenic capacity of adipose tissue.

scholarly journals Hepatic lipogenesis in young rats given proteins of different quality

1984 ◽  
Vol 52 (1) ◽  
pp. 131-137 ◽  
Author(s):  
G. R. Herzberg ◽  
Minda Rogerson
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Protein Quality ◽  
Fatty Acid Synthetase ◽  
Acid Synthesis ◽  
Hepatic Lipogenesis ◽  
Atp Citrate Lyase ◽  
Specific Activities ◽  
Glucose 6 Phosphate Dehydrogenase

1. The effect of feeding casein, lactalbumin, soya-bean protein, gluten or gelatin on hepatic lipogenesis and the levels of hepatic fatty acid synthetase (FAS), glucose-6-phosphate dehydrogenase (EC 1. 1. 1.49; G6PD), malic enzyme (EC 1. 1. 1.40; ME) ATP-citrate lyase (EC 4. 1. 3. 8; CL), acetyl CoA carboxylase (EC 6.4.1.2; ACCx) and glucokinase (EC 2. 7. 1. 2; GK) was examined in young growing rats.2. The total activities of ACCx, FAS, CL, GK, G6PD, GK, ME and fatty acid synthesis in vivo were positively correlated with protein quality.3. The specific activities of ACCx, FAS, CL, G6PD and fatty acid synthesis in vivo were positively correlated with protein quality.4. The specific activities of GK and ME were unrelated to protein quality.5. The results demonstrate a dissociation between ME and hepatic lipogenesis and suggest a role for the NADPH generated by ME which is not related to the needs of fatty acid synthesis.

scholarly journals ATP citrate-lyase and glycogen synthase kinase-3β in 3T3-L1 cells during differentiation into adipocytes

1994 ◽  
Vol 300 (2) ◽  
pp. 477-482 ◽  
Author(s):  
W B Benjamin ◽  
S N Pentyala ◽  
J R Woodgett ◽  
Y Hod ◽  
D Marshak
Keyword(s):  
Glycogen Synthase ◽  
Protein Band ◽  
Glycogen Synthase Kinase ◽  
Fat Cells ◽  
Apparent Mass ◽  
Atp Citrate Lyase ◽  
Protein Levels ◽  
Citrate Lyase ◽  
Sds Page ◽  
Dependent Protein

ATP citrate-lyase (CL), acetyl-CoA carboxylase (ACC) and glycogen synthase kinase-3 beta (GSK-3 beta) levels were measured in cytosol from 3T3-L1 cells during differentiation from fibroblasts into fat-cells. Protein levels were estimated from immunoblots using specific antisera. Cytosol from confluent cells contain significant amounts of GSK-3 beta, which fell during differentiation of these cells into adipocytes. CL from confluent cells was found to be mostly in the form of a single protein band of apparent mass 110 kDa. Levels of CL and ACC increased during cell differentiation into adipocytes. During the first 3 days of differentiation, CL migration changed, and it was expressed as a complex of protein bands of apparent mass 110 kDa, 113 kDa and 115 kDa. At later stages of differentiation, when these cells had assumed the phenotype of fat-cells, they expressed CL mainly as protein bands of 110 and 113 kDa. When samples containing these bands were treated with alkaline phosphatase, the 113 kDa protein band collapsed into the 110 kDa species. This suggests that the slower-migrating species of CL is a higher-order phosphorylation state of the same protein. Furthermore, when purified CL, mostly expressed as the 110 kDa species, was phosphorylated with cyclic AMP-dependent protein kinase alone or together with GSK-3 and resolved by SDS/PAGE, the phosphorylated CL now migrated more slowly as the 113 kDa and 115 kDa forms. CL phosphorylation was hormone-regulated, since, in samples from fat-cells that had the complex two-band pattern, when cultured in medium without serum or hormones, CL migration reverted to a single band of 110 kDa, similar to confluent cells. Treatment of these ‘down-regulated’ cells with insulin rapidly induced substantial amounts of the 113 kDa species, with a concomitant decrease in the 110 kDa species.

scholarly journals UDP-glucuronosyltransferase 2B15 (UGT2B15) and UGT2B17 Enzymes Are Major Determinants of the Androgen Response in Prostate Cancer LNCaP Cells

2007 ◽  
Vol 282 (46) ◽  
pp. 33466-33474 ◽  
Author(s):  
Sarah Chouinard ◽  
Olivier Barbier ◽  
Alain Bélanger
Keyword(s):  
Culture Media ◽  
Cancer Cell Line ◽  
Mrna Levels ◽  
Uridine Diphosphate ◽  
Lncap Cells ◽  
Protein Levels ◽  
Prostate Cells ◽  
Target Probe ◽  
Interfering Rna ◽  
The Impact

Uridine diphosphate-glucuronosyltransferase 2 (UGT2)B15 and B17 enzymes conjugate dihydrotestosterone (DHT) and its metabolites androstane-3α, 17β-diol (3α-DIOL) and androsterone (ADT). The presence of UGT2B15/B17 in the epithelial cells of the human prostate has been clearly demonstrated, and significant 3α-DIOL glucuronide and ADT-glucuronide concentrations have been detected in this tissue. The human androgen-dependent cancer cell line, LNCaP, expresses UGT2B15 and -B17 and is also capable of conjugating androgens. To assess the impact of these two genes in the inactivation of androgens in LNCaP cells, their expression was inhibited using RNA interference. The efficient inhibitory effects of a UGT2B15/B17 small interfering RNA (siRNA) probe was established by the 70% reduction of these UGT mRNA levels, which was further confirmed at the protein levels. The glucuronidation of dihydrotestosterone (DHT), 3α-DIOL, and ADT by LNCaP cell homogenates was reduced by more than 75% in UGT2B15/B17 siRNA-transfected LNCaP cells when compared with cells transfected with a non-target probe. In UGT2B15/B17-deficient LNCaP cells, we observe a stronger response to DHT than in control cells, as determined by cell proliferation and expression of eight known androgen-sensitive genes. As expected, the amounts of DHT in cell culture media from control cells were significantly lower than that from UGT2B15/B17 siRNA-treated cells, which was caused by a higher conversion to its corresponding glucuronide derivative. Taken together these data support the idea that UGT2B15 and -B17 are critical enzymes for the local inactivation of androgens and that glucuronidation is a major determinant of androgen action in prostate cells.

scholarly journals A high-amylopectin diet caused hepatic steatosis associated with more lipogenic enzymes and increased serum insulin concentration

2011 ◽  
Vol 106 (10) ◽  
pp. 1470-1475 ◽  
Author(s):  
Jun He ◽  
Daiwen Chen ◽  
Keying Zhang ◽  
Bing Yu
Keyword(s):  
Fatty Acid Synthase ◽  
Serum Insulin ◽  
Metabolic Responses ◽  
Maize Starch ◽  
Lipogenic Enzymes ◽  
Weaned Pigs ◽  
Lipogenic Genes ◽  
Metabolic Genes ◽  
Major Energy Source ◽  
Coa Reductase

Starch is the major energy source for monogastric mammals and humans. The present study was conducted to evaluate the liver metabolic responses of weaned pigs fed with different dietary starches. A total of sixteen weaned pigs were fed with two experimental diets containing either cassava starch (CS, 80 % amylopectin and 20 % amylose) or maize starch (70 % amylopectin and 30 % amylose). The present results showed that the growth performance was not affected by different dietary starches (P>0·05). However, ingestion of CS not only increased the lipid content in liver tissues, but also elevated the concentrations of serum cholesterol and insulin (P < 0·05). The metabolic responses induced by CS were associated with more lipogenic enzymes such as fatty acid synthase and 3-hydroxy-3-methyl-glutaryl-CoA reductase in liver (P < 0·05). Real-time PCR quantification for lipid metabolic genes indicated that ingestion of CS not only up-regulated the expression of these lipogenic genes, but also decreased the expression of lipolytic genes. These results suggested that the metabolic responses of weaned pigs fed with different dietary starches may vary widely depending on their composition, and ingestion of starches that are high in amylopectin may produce a stronger insulinaemic response and lead to an up-regulation of lipogenesis in the liver.

scholarly journals ADD1/SREBP-1c Is Required in the Activation of Hepatic Lipogenic Gene Expression by Glucose

1999 ◽  
Vol 19 (5) ◽  
pp. 3760-3768 ◽  
Author(s):  
Marc Foretz ◽  
Corinne Pacot ◽  
Isabelle Dugail ◽  
Patricia Lemarchand ◽  
Colette Guichard ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fatty Acid Synthase ◽  
Primary Cultures ◽  
Rat Hepatocytes ◽  
Dominant Negative ◽  
Temporal Association ◽  
Lipogenic Gene ◽  
Lipogenic Genes ◽  
Lipogenic Gene Expression ◽  
Carbohydrate Feeding

ABSTRACT The transcription of genes encoding proteins involved in the hepatic synthesis of lipids from glucose is strongly stimulated by carbohydrate feeding. It is now well established that in the liver, glucose is the main activator of the expression of this group of genes, with insulin having only a permissive role. While ADD1/SREBP-1 has been implicated in lipogenic gene expression through temporal association with food intake and ectopic gain-of-function experiments, no genetic evidence for a requirement for this factor in glucose-mediated gene expression has been established. We show here that the transcription of ADD1/SREBP-1c in primary cultures of hepatocytes is controlled positively by insulin and negatively by glucagon and cyclic AMP, establishing a link between this transcription factor and carbohydrate availability. Using adenovirus-mediated transfection of a powerful dominant negative form of ADD1/SREBP-1c in rat hepatocytes, we demonstrate that this factor is absolutely necessary for the stimulation by glucose of l-pyruvate kinase, fatty acid synthase, S14, and acetyl coenzyme A carboxylase gene expression. These results demonstrate that ADD1/SREBP-1c plays a crucial role in mediating the expression of lipogenic genes induced by glucose and insulin.

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