Lysosomal Acid Lipase Hydrolyzes Retinyl Ester and Affects Retinoid Turnover

Lysosomal acid lipase (LAL) is essential for the clearance of endocytosed cholesteryl ester and triglyceride-rich chylomicron remnants. Humans and mice with defective or absent LAL activity accumulate large amounts of cholesteryl esters and triglycerides in multiple tissues. Although chylomicrons also contain retinyl esters (REs), a role of LAL in the clearance of endocytosed REs has not been reported. In this study, we found that murine LAL exhibits RE hydrolase activity. Pharmacological inhibition of LAL in the human hepatocyte cell line HepG2, incubated with chylomicrons, led to increased accumulation of REs in endosomal/lysosomal fractions. Furthermore, pharmacological inhibition or genetic ablation of LAL in murine liver largely reduced in vitro acid RE hydrolase activity. Interestingly, LAL-deficient mice exhibited increased RE content in the duodenum and jejunum but decreased RE content in the liver. Furthermore, LAL-deficient mice challenged with RE gavage exhibited largely reduced post-prandial circulating RE content, indicating that LAL is required for efficient nutritional vitamin A availability. In summary, our results indicate that LAL is the major acid RE hydrolase and required for functional retinoid homeostasis

The Development of High-Quality Multispecies Probiotic Formulations: From Bench to Market

Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. To date, there is an increasing number of commercially available products containing probiotics on the market. Probiotics have been recommended by health care professionals for reasons ranging from their long-term immunomodulatory effects to proven benefits in the management of different health conditions. For probiotic products, there are several important aspects that determine the success rate of the development from bench to market. The aim of this review is to explore how the current knowledge on microbe–microbe and host–microbe interactions can be used to develop high-quality, evidence-based probiotic formulations, specifically probiotic dietary supplements, with a focus on the selection of safe strains with relevant functional properties. In addition, we will highlight aspects of the probiotic manufacturing process that need to be considered during the product development and the subsequent manufacturing process to guarantee consistent efficacy of a probiotic product. For each high-quality probiotic formulation, it is important to screen multiple strains, and select only those strains that show relevant functional properties and that can be considered safe for human consumption. In addition, it is imperative that attention is paid to the product development and manufacturing process, and that safety and quality properties are monitored. Importantly, the beneficial effects of probiotics should be evaluated in product efficacy studies and post-marketing surveys in order to demonstrate their clinical efficacy. All these aspects need to be evaluated and validated during the development of a successful high-quality and ready-to-market probiotic

Hepatic Retinyl Ester Hydrolases and the Mobilization of Retinyl Ester Stores

For mammals, vitamin A (retinol and metabolites) is an essential micronutrient that is required for the maintenance of life. Mammals cannot synthesize vitamin A but have to obtain it from their diet. Resorbed dietary vitamin A is stored in large quantities in the form of retinyl esters (REs) in cytosolic lipid droplets of cells to ensure a constant supply of the body. The largest quantities of REs are stored in the liver, comprising around 80% of the body’s total vitamin A content. These hepatic vitamin A stores are known to be mobilized under times of insufficient dietary vitamin A intake but also under pathological conditions such as chronic alcohol consumption and different forms of liver diseases. The mobilization of REs requires the activity of RE hydrolases. It is astounding that despite their physiological significance little is known about their identities as well as about factors or stimuli which lead to their activation and consequently to the mobilization of hepatic RE stores. In this review, we focus on the recent advances for the understanding of hepatic RE hydrolases and discuss pathological conditions which lead to the mobilization of hepatic RE stores

Hepatic Retinyl Ester Hydrolases and the Mobilization of Retinyl Ester Stores

For mammals, vitamin A (retinol and metabolites) is an essential micronutrient that is required for the maintenance of life. Mammals cannot synthesize vitamin A but have to obtain it from their diet. Resorbed dietary vitamin A is stored in large quantities in the form of retinyl esters (REs) in cytosolic lipid droplets of cells to ensure a constant supply of the body. The largest quantities of REs are stored in the liver, comprising around 80% of the body’s total vitamin A content. These hepatic vitamin A stores are known to be mobilized under times of insufficient dietary vitamin A intake but also under pathological conditions such as chronic alcohol consumption and different forms of liver diseases. The mobilization of REs requires the activity of RE hydrolases. It is astounding that despite their physiological significance little is known about their identities as well as about factors or stimuli which lead to their activation and consequently to the mobilization of hepatic RE stores. In this review, we focus on the recent advances for the understanding of hepatic RE hydrolases and discuss pathological conditions which lead to the mobilization of hepatic RE stores