No abstract available.
Inflammation ; Lipogenesis

Cancer cells rewire their metabolism to satisfy the demands of growth and survival, and this metabolic reprogramming has been recognized as an emerging hallmark of cancer. Lipid metabolism is pivotal in cellular process that converts nutrients into energy, building blocks for membrane biogenesis and the generation of signaling molecules. Accumulating evidence suggests that cancer cells show alterations in different aspects of lipid metabolism. The changes in lipid metabolism of cancer cells can affect numerous cellular processes, including cell growth, proliferation, differentiation, and survival. The potential dependence of cancer cells on the deregulated lipid metabolism suggests that enzymes and regulating factors involved in this process are promising targets for cancer treatment. In this review, we focus on the features associated with the lipid metabolic pathways in cancer, and highlight recent advances on the therapeutic targets of specific lipid metabolic enzymes or regulating factors and target-directed small molecules that can be potentially used as anticancer drugs.
Lipid Metabolism ; Lipogenesis ; Membranes ; Metabolic Networks and Pathways ; Metabolism

Fatty acid synthase (FASN, EC 2.3.1.85), is a multi-enzyme dimer complex that plays a critical role in lipogenesis. This lipogenic enzyme has gained importance beyond its physiological role due to its implications in several clinical conditions-cancers, obesity, and diabetes. This has made FASN an attractive pharmacological target. Here, we have attempted to predict the theoretical models for the human enoyl reductase (ER) and beta-ketoacyl reductase (KR) domains based on the porcine FASN crystal structure, which was the structurally closest template available at the time of this study. Comparative modeling methods were used for studying the structure-function relationships. Different validation studies revealed the predicted structures to be highly plausible. The respective substrates of ER and KR domains-namely, trans-butenoyl and beta-ketobutyryl-were computationally docked into active sites using Glide in order to understand the probable binding mode. The molecular dynamics simulations of the apo and holo states of ER and KR showed stable backbone root mean square deviation trajectories with minimal deviation. Ramachandran plot analysis showed 96.0% of residues in the most favorable region for ER and 90.3% for the KR domain, respectively. Thus, the predicted models yielded significant insights into the substrate binding modes of the ER and KR catalytic domains and will aid in identifying novel chemical inhibitors of human FASN that target these domains.
Catalytic Domain* ; Humans ; Lipogenesis ; Models, Theoretical ; Molecular Dynamics Simulation* ; Obesity ; Oxidoreductases*

Liver plays a central role in the biogenesis of major metabolites including glucose, fatty acids, and cholesterol. Increased incidence of obesity in the modern society promotes insulin resistance in the peripheral tissues in humans, and could cause severe metabolic disorders by inducing accumulation of lipid in the liver, resulting in the progression of non-alcoholic fatty liver disease (NAFLD). NAFLD, which is characterized by increased fat depots in the liver, could precede more severe diseases such as non-alcoholic steatohepatitis (NASH), cirrhosis, and in some cases hepatocellular carcinoma. Accumulation of lipid in the liver can be traced by increased uptake of free fatty acids into the liver, impaired fatty acid beta oxidation, or the increased incidence of de novo lipogenesis. In this review, I would like to focus on the roles of individual pathways that contribute to the hepatic steatosis as a precursor for the NAFLD.
Acetyl Coenzyme A/metabolism ; Fatty Acids/metabolism ; Fatty Liver/*metabolism/pathology ; Humans ; Lipogenesis ; Mitochondria/metabolism ; Triglycerides/metabolism

Cell Line ; Cholesterol ; biosynthesis ; Hepatocytes ; drug effects ; metabolism ; Humans ; Hydroxymethylglutaryl-CoA Synthase ; metabolism ; Lipogenesis ; Quercetin ; pharmacology

The aim of this study was to clone the goat RPL29 gene and analyze its effect on lipogenesis in intramuscular adipocytes. Using Jianzhou big-eared goats as the object, the goat RPL29 gene was cloned by reverse transcription-polymerase chain reaction (RT-PCR), the gene structure and expressed protein sequence were analyzed by bioinformatics, and the mRNA expression levels of RPL29 in various tissues and different differentiation stages of intramuscular adipocytes of goats were detected by quantitative real-time PCR (qRT-PCR). The RPL29 overexpression vector pEGFP-N1-RPL29 constructed by gene recombination was used to transfect into goat intramuscular preadipocytes and induce differentiation. Subsequently, the effect of overexpression of RPL29 on fat droplet accumulation was revealed morphologically by oil red O and Bodipy staining, and changes in the expression levels of genes related to lipid metabolism were detected by qRT-PCR. The results showed that the length of the goat RPL29 was 507 bp, including a coding sequence (CDS) region of 471 bp which encodes 156 amino acid residues. It is a positively charged and stable hydrophilic protein mainly distributed in the nucleus of cells. Tissue expression profiling showed that the expression level of this gene was much higher in subcutaneous adipose tissue and inter-abdominal adipose tissue of goats than in other tissues (P < 0.05). The temporal expression profile showed that the gene was expressed at the highest level at 84 h of differentiation in goat intramuscular adipocytes, which was highly significantly higher than that in the undifferentiated period (P < 0.01). Overexpression of RPL29 promoted lipid accumulation in intramuscular adipocytes, and the optical density values of oil red O staining were significantly increased (P < 0.05). In addition, overexpression of RPL29 was followed by a highly significant increase in ATGL and ACC gene expression (P < 0.01) and a significant increase in FASN gene expression (P < 0.05). In conclusion, the goat RPL29 may promote intra-muscular adipocyte deposition in goats by up-regulating FASN, ACC and ATGL.
Animals ; Lipogenesis/genetics* ; Adipogenesis/genetics* ; Goats/genetics* ; Adipocytes ; Cell Differentiation/genetics* ; Sequence Analysis ; Cloning, Molecular

Non-alcoholic fatty liver disease (NAFLD), one of the most common liver diseases, is caused by the disruption of hepatic lipid homeostasis. It is associated with insulin resistance as seen in type 2 diabetes mellitus. Glucagon-like peptide-1 (GLP-1) is an incretin that increases insulin sensitivity and aids glucose metabolism. In recent in vivo and in vitro studies, GLP-1 presents a novel therapeutic approach against NAFLD by increasing fatty acid oxidation, decreasing lipogenesis, and improving hepatic glucose metabolism. In this report, we provide an overview of the role and mechanism of GLP-1 in relieving NAFLD.
Diabetes Mellitus, Type 2 ; Fatty Liver ; Glucagon-Like Peptide 1 ; Glucose ; Homeostasis ; Incretins ; Insulin Resistance ; Lipogenesis ; Liver Diseases ; Receptors, Glucagon

Nonalcoholic fatty liver disease (NAFLD) is strongly associated with insulin resistance, obesity, and dyslipidemia. NAFLD encompasses a wide range of states from the simple accumulation of triglycerides in the hepatocytes to serious states accompanied by inflammation and fibrosis in the liver. De novo lipogenesis has been shown to be a significant factor in the development of hepatic steatosis in insulin-resistant states. Sterol regulatory element binding protein-1c (SREBP-1c) is the main transcription factor that mediates the activation of lipogenesis, and SREBP cleavage activating protein (SCAP) is required for the activation of SREBPs. Here, recent animal studies that suggest SCAP as a therapeutic target for hepatic steatosis and hypertriglyceridemia are discussed.
Animals ; Dyslipidemias ; Fibrosis ; Hepatocytes ; Hypertriglyceridemia ; Inflammation ; Insulin Resistance ; Lipogenesis ; Liver ; Non-alcoholic Fatty Liver Disease ; Obesity ; Transcription Factors ; Triglycerides

PURPOSE: This study aimed to investigate the potential of freeze-dried persimmon powder (Diospyros kaki Thumb.) to protect against dyslipidemia induced by a high-fat/cholesterol diet (HFD) in a rat model. METHODS: Fifty Wistar rats were randomly divided into five groups: normal control (NC), high-fat/cholesterol control (HC), tannin in HFD (HT, 1% of diet), immature persimmon in HFD (HI, 7% of diet), and mature persimmon in HFD (HM, 7% of diet). Tannin was used as a positive control. Biochemical, molecular, and histopathological changes were observed in the blood and liver. RESULTS: We confirmed that a high fat/cholesterol diet successfully induced dyslipidemia, which was characterized by significantly altered lipid profiles in the plasma and liver. However, oxidized low-density lipoprotein levels, histopathological damage in the liver, and hepatic triglyceride levels were significantly reduced in all HT, HI, and HM groups compared to those in the HF group. In contrast, plasma apolipoprotein B level was significantly reduced only in the HT and HM groups, whereas reduction of the LDL-C level was detected only in the HI group. Although HF-induced sterol regulatory element-binding protein (SREBP) gene expression was significantly reduced in all treated groups, downstream gene expression levels varied among the different groups; significant reduction of fatty acid synthase (FAS) and 3-hydroxy-3-methylglutaryl-CoA (HMGCR) gene expression was detected only in the HI group, whereas cholesterol 7α-hydroxylase (CYP7A1) gene expression was significantly elevated only in the HM group. CONCLUSION: Taken together, the data suggest that protection of LDL oxidation and hepatic lipogenesis might be, at least partly, attributed to tannin in persimmons. However, the identified mechanisms varied up to the maturation stage of persimmon. In the case of immature persimmon, modulation of FAS and HMGCR gene expression was prominent, whereas in the case of mature persimmon, modulation of CYP7A1 gene expression was prominent.
Animals ; Apolipoproteins ; Cholesterol ; Diet ; Diospyros* ; Dyslipidemias ; Gene Expression ; Lipogenesis ; Lipoproteins ; Liver ; Models, Animal ; Plasma ; Rats* ; Rats, Wistar ; Triglycerides

Multiple symmetrical lipomatosis (MSL) is a rare disorder characterized by the presence of multiple, symmetric, unencapsulated fat masses in the face, neck, and other areas. Typically, this entity has been related to the presence of three anterior bulges in the neck. MSL is usually described in adults from 30 to 60 years old, with an incidence of about 1 in 25,000 and a male-to-female ratio of 15 : 1 to 30 : 1. More than 90% of the patients have associated alcoholism. The etiology of MSL remains unknown, but an abnormal lipogenesis induced by catecholamines has been observed. The accumulation of fat prevents accurate clinical assessment of the neck and obscures other underlying abnormalities. In the current report, the authors described one case of MSL associated with bilateral vocal cord palsy and reviewed the associated literature.
Adult ; Alcoholism ; Catecholamines ; Humans ; Incidence ; Lipogenesis ; Lipomatosis, Multiple Symmetrical ; Middle Aged ; Neck ; Vocal Cord Paralysis* ; Vocal Cords*