https://www.journal-of-hepatology.eu/article/S0168-8278(10)01066-4/pdf

Drug-induced toxicity on mitochondria and lipid metabolism: Mechanistic diversity and deleterious consequences for the liver

Non-alcoholic fatty liver disease - the most common chronic liver disease - encompasses a histological spectrum ranging from simple steatosis to non-alcoholic steatohepatitis (NASH). Over the next decade, NASH is projected to be the most common indication for liver transplantation. The absence of an effective pharmacological therapy for NASH is a major incentive for research into novel therapeutic approaches for this condition. The current focus areas for research include the modulation of nuclear transcription factors; agents that target lipotoxicity and oxidative stress; and the modulation of cellular energy homeostasis, metabolism and the inflammatory response. Strategies to enhance resolution of inflammation and fibrosis also show promise to reverse the advanced stages of liver disease.

Non-alcoholic steatohepatitis: emerging molecular targets and therapeutic strategies

https://aasldpubs.onlinelibrary.wiley.com/doi/epdf/10.1002/hep.24685

Low doses of bisphenol A induce gene expression related to lipid synthesis and trigger triglyceride accumulation in adult mouse liver.

Many types of cancer cells require a supply of fatty acids (FA) for growth and survival, and interrupting de novo FA synthesis in model systems causes potent anticancer effects. We hypothesized that, in addition to synthesis, cancer cells may obtain pre-formed, diet-derived fatty acids by uptake from the bloodstream. This would require hydrolytic release of FA from triglyceride in circulating lipoprotein particles by the secreted enzyme lipoprotein lipase (LPL), and the expression of CD36, the channel for cellular FA uptake. We find that selected breast cancer and sarcoma cells express and secrete active LPL, and all express CD36. We further demonstrate that LPL, in the presence of triglyceride-rich lipoproteins, accelerates the growth of these cells. Providing LPL to prostate cancer cells, which express low levels of the enzyme, did not augment growth, but did prevent the cytotoxic effect of FA synthesis inhibition. Moreover, LPL knockdown inhibited HeLa cell growth. In contrast to the cell lines, immunohistochemical analysis confirmed the presence of LPL and CD36 in the majority of breast, liposarcoma, and prostate tumor tissues examined (n = 181). These findings suggest that, in addition to de novo lipogenesis, cancer cells can use LPL and CD36 to acquire FA from the circulation by lipolysis, and this can fuel their growth. Interfering with dietary fat intake, lipolysis, and/or fatty acid uptake will be necessary to target the requirement of cancer cells for FA.

https://mct.aacrjournals.org/content/molcanther/10/3/427.full.pdf

Lipoprotein lipase links dietary fat to solid tumor cell proliferation

Obesity with associated comorbidities is currently a worldwide epidemic and among the most challenging health conditions in the 21st century. A major metabolic consequence of obesity is insulin resistance which underlies the pathogenesis of the metabolic syndrome. Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of obesity and metabolic syndrome. It comprises a disease spectrum ranging from simple steatosis (fatty liver), through nonalcoholic steatohepatitis (NASH) to fibrosis, and ultimately liver cirrhosis. Abnormality in lipid and lipoprotein metabolism accompanied by chronic inflammation is the central pathway for the development of metabolic syndrome-related diseases, such as atherosclerosis, cardiovascular disease (CVD), and NAFLD. This paper focuses on pathogenic aspect of lipid and lipoprotein metabolism in NAFLD and the relevant mouse models of this complex multifactorial disease.

/pdf/nonalcoholic-fatty-liver-disease-focus-on-lipoprotein-and-32ciii6avg.pdf

Nonalcoholic Fatty Liver Disease: Focus on Lipoprotein and Lipid Deregulation

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep.22907

Valérie Albalea

Papers

A novel pregnane X receptor and S14-mediated lipogenic pathway in human hepatocyte.