There is growing evidence that metabolic alterations play an important role in cancer development and progression. The metabolism of cancer cells is reprogrammed in order to support their rapid proliferation. Elevated fatty acid synthesis is one of the most important aberrations of cancer cell metabolism. An enhancement of fatty acids synthesis is required both for carcinogenesis and cancer cell survival, as inhibition of key lipogenic enzymes slows down the growth of tumor cells and impairs their survival. Based on the data that serum fatty acid synthase (FASN), also known as oncoantigen 519, is elevated in patients with certain types of cancer, its serum level was proposed as a marker of neoplasia. This review aims to demonstrate the changes in lipid metabolism and other metabolic processes associated with lipid metabolism in pancreatic ductal adenocarcinoma (PDAC), the most common pancreatic neoplasm, characterized by high mortality. We also addressed the influence of some oncogenic factors and tumor suppressors on pancreatic cancer cell metabolism. Additionally the review discusses the potential role of elevated lipid synthesis in diagnosis and treatment of pancreatic cancer. In particular, FASN is a viable candidate for indicator of pathologic state, marker of neoplasia, as well as, pharmacological treatment target in pancreatic cancer. Recent research showed that, in addition to lipogenesis, certain cancer cells can use fatty acids from circulation, derived from diet (chylomicrons), synthesized in liver, or released from adipose tissue for their growth. Thus, the interactions between de novo lipogenesis and uptake of fatty acids from circulation by PDAC cells require further investigation.

Common molecular changes in cancer cells are high carbon flux through the glycolytic pathway and overexpression of fatty acid synthase, a key lipogenic enzyme. Since glycerol 3-phosphate dehydrogenase creates a link between carbohydrates and the lipid metabolism, we have investigated the activity of glycerol 3-phosphate dehydrogenase and various lipogenic enzymes in human bladder cancer. The data presented in this paper indicate that glycerol 3-phosphate dehydrogenase activity in human bladder cancer is significantly higher compared to adjacent non-neoplastic tissue, serving as normal control bladder tissue. Increased glycerol 3-phosphate dehydrogenase activity is accompanied by increased enzyme activity, either directly (fatty acid synthase) or indirectly (through ATP-citrate lyase, glucose 6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase and citrate synthase) involved in fatty acid synthesis. Coordinated upregulation of glycerol 3-phosphate dehydrogenase and lipogenic enzymes activities in human bladder cancer suggests that glycerol 3-phosphate dehydrogenase supplies glycerol 3-phosphate for lipid biosynthesis.

Clinical studies have indicated that circulating bile acid (BA) concentrations increase following bariatric surgery, especially following malabsorptive procedures such as Roux-en-Y gastric bypasses (RYGB). Moreover, total circulating BA concentrations in patients following RYGB are positively correlated with serum glucagon-like peptide-1 concentrations and inversely correlated with postprandial glucose concentrations. Overall, these data suggest that the increased circulating BA concentrations following bariatric surgery - independently of calorie restriction and body-weight loss - could contribute, at least in part, to improvements in insulin sensitivity, incretin hormone secretion, and postprandial glycemia, leading to the remission of type-2 diabetes (T2DM). In humans, the primary and secondary BA pool size is dependent on the rate of biosynthesis and the enterohepatic circulation of BAs, as well as on the gut microbiota, which play a crucial role in BA biotransformation. Moreover, BAs and gut microbiota are closely integrated and affect each other. Thus, the alterations in bile flow that result from anatomical changes caused by bariatric surgery and changes in gut microbiome may influence circulating BA concentrations and could subsequently contribute to T2DM remission following RYGB. Research data coming largely from animal and cell culture models suggest that BAs can contribute, via nuclear farnezoid X receptor (FXR) and membrane G-protein-receptor (TGR-5), to beneficial effects on glucose metabolism. It is therefore likely that FXR, TGR-5, and BAs play a similar role in glucose metabolism following bariatric surgery in humans. The objective of this review is to discuss in detail the results of published studies that show how bariatric surgery affects glucose metabolism and subsequently T2DM remission.

The importance of coenzyme A (CoA) as a carrier of acyl residues in cell metabolism is well understood. Coenzyme A participates in more than 100 different catabolic and anabolic reactions, including those involved in the metabolism of lipids, carbohydrates, proteins, ethanol, bile acids, and xenobiotics. However, much less is known about the importance of the concentration of this cofactor in various cell compartments and the role of altered CoA concentration in various pathologies. Despite continuous research on these issues, the molecular mechanisms in the regulation of the intracellular level of CoA under pathological conditions are still not well understood. This review summarizes the current knowledge of (a) CoA subcellular concentrations; (b) the roles of CoA synthesis and degradation processes; and (c) protein modification by reversible CoA binding to proteins (CoAlation). Particular attention is paid to (a) the roles of changes in the level of CoA under pathological conditions, such as in neurodegenerative diseases, cancer, myopathies, and infectious diseases; and (b) the beneficial effect of CoA and pantethine (which like CoA is finally converted to Pan and cysteamine), used at pharmacological doses for the treatment of hyperlipidemia.

Increased serum 2PY concentration, along with a deterioration of kidney function and its toxic properties (significant inhibition of PARP-1 by 2PY), suggest that it could be a novel uremic toxin.