Fatty acids induce an increase in the transcription of mitochondrial 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthase gene, which encodes enzyme that has been proposed as a control site ketogenesis. We studied whether peroxisome proliferator-activated receptor (PPAR) is involved mechanism this transcriptional induction. found cotransfection rat HMG-CoA promoter-chloramphenicol acetyltransferase reporter plasmid and PPAR expression presence proliferator clofibrate led to more than 30-fold...

Nutrient deprivation or starvation frequently correlates with amino acid limitation. Amino initiates a signal transduction cascade starting the activation of kinase GCN2 (general control non-derepressible 2) phosphorylation eIF2 (eukaryotic initiation factor 2), global protein synthesis reduction and increased ATF4 (activating transcription 4). modulates wide spectrum genes involved in adaptation to dietary stress. The hormone FGF21 (fibroblast growth 21) is induced during fasting liver its...

The expression of several genes involved in intra- and extracellular lipid metabolism, notably those peroxisomal mitochondrial β-oxidation, is mediated by ligand-activated receptors, collectively referred to as peroxisome proliferator-activated receptors (PPARs). To gain more insight into the control carnitine palmitoyltransferase (CPT) genes, which are regulated fatty acids, we have examined transcriptional regulation human MCPT I gene. We cloned polymerase chain reaction 5′-flanking region...

HMGCS2 (hydroxymethylglutaryl CoA synthase 2), the gene that regulates ketone body production, is barely expressed in cultured cell lines. In this study, we restored expression and activity HepG2 cells, thus showing wild type enzyme can induce fatty acid β-oxidation (FAO) ketogenesis, whereas a catalytically inactive mutant C166A did not generate either process. Peroxisome proliferator-activated receptor (PPAR) α also induces endogenous expression. Interestingly, PPARα-mediated induction was...

Lipogenic gene expression in liver is repressed mice upon leucine deprivation. The hormone fibroblast growth factor 21 (FGF21), which critical to the adaptive metabolic response starvation, also induced under amino acid Upon deprivation, we found that FGF21 needed repress of lipogenic genes and white adipose tissue, stimulate phosphorylation hormone-sensitive lipase tissue. increased Ucp1 brown tissue these circumstances impaired FGF21-deficient mice. Our results demonstrate important role...

Fatty acid synthase (FASN) is overexpressed and hyperactivated in several human carcinomas, including lung cancer. We characterize compare the anti-cancer effects of FASN inhibitors C75 (-)-epigallocatechin-3-gallate (EGCG) a cancer model.We evaluated vitro EGCG on fatty metabolism (FASN CPT enzymes), cellular proliferation, apoptosis cell signaling (EGFR, ERK1/2, AKT mTOR) A549 carcinoma cells. In vivo, we their anti-tumour activity effect body weight mice model adenocarcinoma xenograft.C75...

PURPOSE: Fatty acid synthase (FASN) is overexpressed in human breast carcinoma. The natural polyphenol (-)-epigallocatechin-3-gallate blocks vitro FASN activity and leads to apoptosis cancer cells without any effects on carnitine palmitoyltransferase-1 (CPT-1) activity, vivo, does not decrease body weight. We synthesized a panel of new polyphenolic compounds tested their models. EXPERIMENTAL DESIGN: evaluated the cell growth (SK-Br3, MCF-7, MDA-MB-231), [as assessed by cleavage...

Fatty acid synthase (FASN) is a lipogenic enzyme that highly expressed in different human cancers. Here we report the development of new series polyphenolic compounds 5-30 have been evaluated for their cytotoxic capacity SK-Br3 cells, breast cancer cell line with high FASN expression. The an IC(50) < 50 μM tested ability to inhibit activity. Among them, derivative 30 blocks 90% activity at low concentration (4 μM), broad panel tumor induces apoptosis, and activation HER2, AKT, ERK pathways....

We report the isolation and characterization of a 1994-base-pair cDNA that encompasses entire transcription unit mitochondrial 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase (EC 4.1.3.5.) gene from rat. Analysis nucleotide sequence reveals encodes polypeptide 508 residues 56,918-Da molecular mass. Identify clone isolated as HMG-CoA was confirmed by following criteria: (i) Amino acid are 65% homologous with hamster cytosolic synthase. (ii) 19-amino probably corresponding to...

HMGCS2, the gene that regulates ketone body production, is expressed in liver and several extrahepatic tissues, such as colon. In CaCo-2 colonic epithelial cells, expression of this increases with cell differentiation. Accordingly, immunohistochemistry specific antibodies shows HMGCS2 mainly differentiated cells human epithelium. Here, we used a chromatin immunoprecipitation assay to study molecular mechanism responsible for pattern. The revealed direct target c-Myc, which represses...

FSP27 [cell death-inducing DFFA-like effector c (CIDEC) in humans] is a protein associated with lipid droplets that downregulates the fatty acid oxidation (FAO) rate when it overexpressed. However, little known about its physiological role liver. Here, we show fasting regulates liver expression of Fsp27 time-dependent manner. Thus, during initial stages fasting, maximal induction 800-fold was achieved, whereas later phase decreased. The early response to can be explained by canonical...

Scope Fibroblast growth factor 21 (FGF21) is considered a promising therapeutic candidate for the treatment of obesity. Since FGF21 production regulated by various nutritional factors, we analyze impact low protein intake on circulating levels this hormone in mice and sub cohort PREDIMED ( Prevención con Dieta Mediterránea ) trial. We also describe role hepatic metabolic adaptation to low‐protein diet (LPD). Methods results fed control liver‐specific Fgf21 knockout (L KO) LPD. This increased...

Maqui (Aristotelia Chilensis) berry features a unique profile of anthocyanidins that includes high amounts delphinidin-3-O-sambubioside-5-O-glucoside and delphinidin-3-O-sambubioside has shown positive effects on fasting glucose insulin levels in humans murine models type 2 diabetes obesity. The molecular mechanisms underlying the impact maqui onset development obese phenotype resistance was investigated fat diet-induced mice supplemented with lyophilized berry. Maqui-dietary animals showed...

Cholesterol 7 alpha-hydroxylase (7 alpha-hydroxylase) is the rate-limiting enzyme in bile acid biosynthesis. It subject to a feedback control, whereby high levels of acids suppress its activity, and cholesterol exerts positive control. has been suggested that posttranscriptional control plays major part regulation. We have studied mechanisms by which regulate expression gene found it be solely at transcriptional level using two different approaches. First, tissue culture system, we localized...

The expression of several genes involved in fatty acid metabolism is regulated by peroxisome proliferator-activated receptors (PPARs). To gain more insight into the control carnitine palmitoyltransferase (CPT) gene expression, we examined transcriptional regulation human CPT II gene. We show that 5′-flanking region this transcriptionally active and binds PPARα vivo a chromatin immunoprecipitation assay. In addition, characterized proliferator-responsive element (PPRE) proximal promoter gene,...

Normal physiological responses to carbohydrate shortages cause the liver increase production of ketone bodies from acetyl-CoA generated fatty acid oxidation. This allows use for energy, thereby preserving limited glucose by brain. adaptative response is switched off insulin rapidly inhibiting expression mitochondrial 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthase (HMGCS2) gene, which a key control site ketogenesis. We decided investigate molecular mechanism this inhibition. In present...

Class I alcohol dehydrogenases (ADH1s) are the rate-limiting enzymes for ethanol and vitamin A (retinol) metabolism in liver. Because previous studies have shown that human ADH1 may participate bile acid metabolism, we investigated whether acid-activated nuclear receptor farnesoid X (FXR) regulates genes. In hepatocytes, both endogenous FXR ligand chenodeoxycholic synthetic FXR-specific agonist GW4064 increased mRNA, protein, activity. Moreover, overexpression of a constitutively active form...