Genome-wide and candidate gene association studies have identified several variants that predispose indi- viduals to developing nonalcoholic fatty liver disease （NAFLD）. However, the gene that has been consis- tentl...Genome-wide and candidate gene association studies have identified several variants that predispose indi- viduals to developing nonalcoholic fatty liver disease （NAFLD）. However, the gene that has been consis- tently involved in the genetic susceptibility of NAFLD in humans is patatin-like phospholipase domain contain- ing 3 （PNPLA3, also known as adiponutrin）. A nonsyn- onymous single nucleotide polymorphism in PNPLA3 （rs738409 C/G, a coding variant that encodes an amino acid substitution I148M） is significantly associated with fatty liver and histological disease severity, not only in adults but also in children. Nevertheless, how PNPLA3 influences the biology of fatty liver disease is still an open question. A recent article describes new aspects about PNPLA3 gene/protein function and suggests that the I148M variant promotes hepatic lipid synthesis due to a gain of function. We revise here the published data about the role of the I148M variant in lipogen- esis/lipolysis, and suggest putative areas of future research. For instance we explored in silico whether the rs738409 C or G alleles have the ability to modify miRNA binding sites and miRNA gene regulation, and we found that prediction of PNPLA3 target miRNAs shows two miRNAs potentially interacting in the 3＇ UTR region （hsa-miR-769-3p and hsa-miR-516a-3p）. In addition, interesting unanswered questions remain to be explored. For example, PNPLA3 lies between two CCCTC-binding factor-bound sites that could be tested for insulator activity, and an intronic histone 3 lysine 4 trimethylation peak predicts an enhancer element, cor- roborated by the DNase I hypersensitivity site peak. Finally, an interaction between PNPLA3 and glycerol- 3-phosphate acyltransferase 2 is suggested by data miming.展开更多
The present work summarizes recent investigations carried out about the usage of natural antioxidants in lipid-rich food during processing. Synthetic antioxidants have been used as food additives to retard lipid oxida...The present work summarizes recent investigations carried out about the usage of natural antioxidants in lipid-rich food during processing. Synthetic antioxidants have been used as food additives to retard lipid oxidation and development of off-flavor for over 50 years. However, the literature has expressed safety concerns and health risks （toxic and carcinogenic effects） associated with the use of synthetic antioxidants recently. Natural antioxidative substances from the polyphenols of edible plants are believed to be safer and may provide with additional health benefits and more effective compared to synthetic antioxidants. Due to the fact that natural antioxidants are additives that people mixed with food and consumed for centuries, they are known to be safe by the consumer. Therefore, it is an area worth to investigate due to consumer concerns about health. In the literature, there are many studies showing that the natural antioxidants have important antioxidant effect. Plants （oil seeds, cereals, vegetables, fruits, herb and spices）, compounds from animal source （peptides and amino acids）, enzymes and some microorganisms are important natural antioxidants. Plant extracts have been widely used to retard lipid oxidation in foods during frying and accelerated storage processes. They were found as strong antioxidant sources due to their high contents of phenolic compounds. There are countless studies about natural antioxidants. However, they have not been investigated completely by means of toxicology.展开更多
基金Supported by Grants PICT 2008-1521 and PICT 2010 0441,from National Agency for Science and TechnologyUBACYT CM04,from Universidad de Buenos AiresSookoian S and Pirola CJ belong to National Council of Scientific and Technical Research
文摘Genome-wide and candidate gene association studies have identified several variants that predispose indi- viduals to developing nonalcoholic fatty liver disease （NAFLD）. However, the gene that has been consis- tently involved in the genetic susceptibility of NAFLD in humans is patatin-like phospholipase domain contain- ing 3 （PNPLA3, also known as adiponutrin）. A nonsyn- onymous single nucleotide polymorphism in PNPLA3 （rs738409 C/G, a coding variant that encodes an amino acid substitution I148M） is significantly associated with fatty liver and histological disease severity, not only in adults but also in children. Nevertheless, how PNPLA3 influences the biology of fatty liver disease is still an open question. A recent article describes new aspects about PNPLA3 gene/protein function and suggests that the I148M variant promotes hepatic lipid synthesis due to a gain of function. We revise here the published data about the role of the I148M variant in lipogen- esis/lipolysis, and suggest putative areas of future research. For instance we explored in silico whether the rs738409 C or G alleles have the ability to modify miRNA binding sites and miRNA gene regulation, and we found that prediction of PNPLA3 target miRNAs shows two miRNAs potentially interacting in the 3＇ UTR region （hsa-miR-769-3p and hsa-miR-516a-3p）. In addition, interesting unanswered questions remain to be explored. For example, PNPLA3 lies between two CCCTC-binding factor-bound sites that could be tested for insulator activity, and an intronic histone 3 lysine 4 trimethylation peak predicts an enhancer element, cor- roborated by the DNase I hypersensitivity site peak. Finally, an interaction between PNPLA3 and glycerol- 3-phosphate acyltransferase 2 is suggested by data miming.
文摘The present work summarizes recent investigations carried out about the usage of natural antioxidants in lipid-rich food during processing. Synthetic antioxidants have been used as food additives to retard lipid oxidation and development of off-flavor for over 50 years. However, the literature has expressed safety concerns and health risks （toxic and carcinogenic effects） associated with the use of synthetic antioxidants recently. Natural antioxidative substances from the polyphenols of edible plants are believed to be safer and may provide with additional health benefits and more effective compared to synthetic antioxidants. Due to the fact that natural antioxidants are additives that people mixed with food and consumed for centuries, they are known to be safe by the consumer. Therefore, it is an area worth to investigate due to consumer concerns about health. In the literature, there are many studies showing that the natural antioxidants have important antioxidant effect. Plants （oil seeds, cereals, vegetables, fruits, herb and spices）, compounds from animal source （peptides and amino acids）, enzymes and some microorganisms are important natural antioxidants. Plant extracts have been widely used to retard lipid oxidation in foods during frying and accelerated storage processes. They were found as strong antioxidant sources due to their high contents of phenolic compounds. There are countless studies about natural antioxidants. However, they have not been investigated completely by means of toxicology.
