A Proposition for a Cancer Treatment Study Using Radioactive Metal co-Factor Enzymes and Inhibitors of Lipogenic Enzymes as a Potential Therapy against Cancer

Researchers have discovered an enzyme that inhibits the growth of cancer cells by stimulating proteins. In this study, the ability of each human cell to divide into two parts is discussed. For each division, a cell must follow certain steps, most of which are amplified by proteins called cyclins. Keywords: Cancer; Cells; Tissues, Tumors; Prevention, Prognosis; Diagnosis; Imaging; Screening; Treatment; Management

155 Low Insulin Sensitivity Is Associated with Increased Body Fat and Changes in Gene Expression of Lipogenic Enzymes in the Adipose Tissue of Finishing Pigs

Variations in body fat (BF) among pigs can be associated with differences in insulin sensitivity given the insulin anabolic effect in lipid synthesis. The study objectives were to characterize this association and compare the relative mRNA abundance of genes associated with insulin resistance and de novo lipogenesis in the adipose tissue of fat and lean pigs. Thirty 95 kg pigs, catheterized in the jugular vein, received an oral dose of 1.75 g glucose/kg of BW after 18 hours of fasting. Blood samples were collected at -20, -10, 5, 10, 15, 20, 25, 30, 45, 60, 90, 120, 150, 180, 210, 240, 300 and 360 minutes following glucose ingestion. Insulin sensitivity indexes were calculated and analyzed. The BF (%) was estimated by dual X-ray densitometry. The 8 fattest (22 % BF) and the 8 leanest pigs (17.2 % BF) were used to determine the relative mRNA abundance of studied genes using real-time qPCR analyses. Insulin sensitivity was determined using QUICKI and Matsuda indexes, respectively, and their association with body fat was studied with Spearman correlations. Differences in gene expression and insulin sensitivity between fat and lean pigs were studied with a one-way ANOVA. The QUICKI and Matsuda indexes negatively correlated with BF (r = -0.67 and r = -0.59; P < 0.001). Fat pigs had reduced insulin sensitivity and higher relative mRNA abundance of lipogenic enzymes (ACACA, ACLY, FASN; P < 0.05) than lean pigs. The higher expression level of glucose-6-phosphate dehydrogenase (G6PD) combined with the trend (P < 0.10) of lower expression of peroxisome proliferator-activated receptor-gamma (PPAR-γ) in fat pigs may explain part of their reduced insulin sensitivity. These results suggest that an increased BF is associated with reduced insulin sensitivity and greater expression of lipogenic enzymes in pig adipose tissue.

Expanding Roles of De Novo Lipogenesis in Breast Cancer

In recent years, lipid metabolism has gained greater attention in several diseases including cancer. Dysregulation of fatty acid metabolism is a key component in breast cancer malignant transformation. In particular, de novo lipogenesis provides the substrate required by the proliferating tumor cells to maintain their membrane composition and energetic functions during enhanced growth. However, it appears that not all breast cancer subtypes depend on de novo lipogenesis for fatty acid replenishment. Indeed, while breast cancer luminal subtypes rely on de novo lipogenesis, the basal-like receptor-negative subtype overexpresses genes involved in the utilization of exogenous-derived fatty acids, in the synthesis of triacylglycerols and lipid droplets, and fatty acid oxidation. These metabolic differences are specifically associated with genomic and proteomic changes that can perturb lipogenic enzymes and related pathways. This behavior is further supported by the observation that breast cancer patients can be stratified according to their molecular profiles. Moreover, the discovery that extracellular vesicles act as a vehicle of metabolic enzymes and oncometabolites may provide the opportunity to noninvasively define tumor metabolic signature. Here, we focus on de novo lipogenesis and the specific differences exhibited by breast cancer subtypes and examine the functional contribution of lipogenic enzymes and associated transcription factors in the regulation of tumorigenic processes.

Osthol Ameliorates Kidney Damage and Metabolic Syndrome Induced by a High-Fat/High-Sugar Diet

Excessive intake of fructose results in metabolic syndrome (MS) and kidney damage, partly mediated by its metabolism by fructokinase-C or ketohexokinase-C (KHK-C). Osthol has antioxidant properties, is capable of regulating adipogenesis, and inhibits KHK-C activity. Here, we examined the potential protective role of osthol in the development of kidney disease induced by a Western (high-fat/high-sugar) diet. Control rats fed with a high-fat/high-sugar diet were compared with two groups that also received two different doses of osthol (30 mg/kg/d or 40 mg/kg/d body weight BW). A fourth group served as a normal control and received regular chow. At the end of the follow-up, kidney function, metabolic markers, oxidative stress, and lipogenic enzymes were evaluated. The Western diet induced MS (hypertension, hyperglycemia, hypertriglyceridemia, obesity, hyperuricemia), a fall in the glomerular filtration rate, renal tubular damage, and increased oxidative stress in the kidney cortex, with increased expression of lipogenic enzymes and increased kidney KHK expression. Osthol treatment prevented the development of MS and ameliorated kidney damage by inhibiting KHK activity, preventing oxidative stress via nuclear factor erythroid 2-related factor (Nrf2) activation, and reducing renal lipotoxicity. These data suggest that the nutraceutical osthol might be an ancillary therapy to slow the progression of MS and kidney damage induced by a Western diet.

Effect of Type of Pregnancy on Transcriptional and Plasma Metabolic Response in Sheep and Its Further Effect on Progeny Lambs

The following study was performed in order to determine the effect of type of pregnancy on the transcriptional expression of genes that are engaged in angiogenesis and cell turnover/lactogenesis in the ewe mammary gland, evaluating its impact on the plasma metabolic response. In addition, an assessment of its further influence on plasma metabolic response, performance, and muscle transcriptional expression of lipogenic enzymes in progeny lambs was made. Thirteen Ile de France sheep (six twin- and seven single-bearing ewes) were allocated to graze ad libitum naturalized pasture from d 45 pre-partum to day 70 post-partum, while keeping their lambs on the same diet until day 60 after weaning. The samples were collected at different times and analyzed by qRT-PCR and plasma metabolic indicators. The data were processed using SPSS package. The results showed that twin-bearing ewes overexpressed VEGFR1 at birth, and BCL2 at birth and day 35 post-partum; however, single-bearing ewes overexpressed CAIV and IGF1 at day 35 post-partum. Similar metabolite concentrations in blood plasma were found between groups of ewes. The plasma metabolic response in lambs was similar between groups and it did not influence their performance, where a similar transcriptional expression of lipogenic enzymes in muscle was observed. Therefore, the type of pregnancy can explain the slight differences in mRNA expression that were found in angiogenesis and cell turnover/lactogenesis in mammary gland, although these differences not only did not affect the plasma metabolic response in ewes, but they also had no influence on plasma metabolic response, performance, and muscle transcriptional expression of their lambs.

Antioxidant-rich Tamarindus indica L. leaf extract reduced high-fat diet-induced obesity in rat through modulation of gene expression

Background Different parts of the medicinal plant Tamarindus indica L. are full of phytochemicals that are able to reduce elevated blood pressure, blood sugar and lipids. These pharmacological effects are due to the presence of antioxidant type compounds in those parts of the plant. This study was aimed to explore the molecular mechanism of anti-obesity effects of ethanolic extract of T. indica L. leaves (TILE) through the evaluation of biochemical parameters and gene expression analysis in high-fat diet (HFD) consuming Wistar rats. Methods Male Wistar rats were supplied with a standard diet (SD), or HFD, or HFD with 100 mg/kg or 200 mg/kg or 400 mg/kg TILE for 8 weeks. The body weight, liver weight, fat weight, plasma lipids, and oxidative stress-related parameters were measured. The transcript levels of different adipogenesis related transcription factors, lipogenic enzymes, and lipolytic enzymes were also evaluated by quantitative real-time PCR. Result Phytochemical analysis demonstrated that TILE is enriched with a substantial level of polyphenols (287.20 ± 9.21 mg GAE/g extract) and flavonoids (107.52 ± 11.12 mg QE/g extract) which might be the reason of significant antioxidant and radical scavenging activities. Feeding of TILE (400 mg/kg/day) to HFD-fed rats increased activity of superoxide dismutase and catalase which is reflected as a significant reduction of oxidative stress markers like nitric oxide and malondialdehyde. TILE (400 mg/kg/day) feeding also down-regulated the mRNA levels of proadipogenic transcription factors including liver X receptor alpha (LXRα), peroxisome proliferator-activated receptor gamma (PPARγ), and sterol regulatory element-binding protein 1c (SREBP1c) in diet-induced obese rats. As a consequence of this, the mRNA level of lipogenic enzymes like acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), diacylglycerol acyltransferase (DGAT), and HMG-CoA reductase was down-regulated with a parallel up-regulation of the transcript level of lipolytic enzyme, hormone-sensitive lipase (HSL). Conclusion Observations from this study indicate that antioxidant-rich TILE can reduce HFD-induced body weight, fat weight and liver weight as well as blood lipids through down-regulating the gene expression of proadipogenic transcription factors and lipogenic enzymes with a concerted diminution of the gene expression of lipolytic enzyme, HSL.