The Use of Transcriptomics to Unveil the Role of Nutrients in Mammalian Liver

Abstract

Liver is the organ primarily responding to diet, and it is crucial in determining plasma carbohydrate, protein, and lipid levels. In addition, it is mainly responsible for transformation of xenobiotics. For these reasons, it has been a target of transcriptomic analyses. In this review, we have covered the works dealing with the response of mammalian liver to different nutritional stimuli such as fasting/feeding, caloric restriction, dietary carbohydrate, cholesterol, fat, protein, bile acid, salt, vitamin, and oligoelement contents. Quality of fats or proteins has been equally addressed, and has the influence of minor dietary components. Other compounds, not purely nutritional as those represented by alcohol and food additives, have been included due to their relevance in processed food. The influence has been studied not only on mRNA but also on miRNA. The wide scope of the technology clearly reflects that any simple intervention has profound changes in many metabolic parameters and that there is a synergy in response when more compounds are included in the intervention. Standardized arrays to systematically test the same genes in all studies and analyzing data to establish patterns of response are required, particularly for RNA sequencing. Moreover, RNA is a valuable, easy-screening ally but always requires further confirmation.

Effect of various diets on the expression of phase-I drug-metabolizing enzymes in livers of mice

“…Nutrition may have a global impact on genes involved in metabolism (Osada, 2013), and lifestyle diseases due to imbalance of nutrition intake are often attempted to be treated by long-term polypharmacotherapy. In addition, drugs are used in people that are on various diets.…”

“…Various amounts, types and lengths of dietary lipids and carbohydrates have been examined to determine their influence on phase-I drug metabolism enzymes and their transcriptional regulators (Osada, 2013). High-fat diet induced PPARα, β, γ1, and γ2, HNF4, LXRα and their target Cyp mRNAs (Anderson et al , 2009), and reduced Cyp3a11, Cyp2b10, Cyp2a4, PXR, and CAR mRNAs (Ghose et al , 2011).…”

“…An atherogenic diet for 3 months decreased Pon1 mRNA and activity (Costa et al , 2005). A western diet induced LXR and PPARα expression in mice (Osada, 2013). A diet rich in polyunsaturated fatty acids (including DHA), activated CYP4a and 4f subfamilies (Comba et al , 2011).…”

Mechanisms of CCl₄-induced liver fibrosis with combined transcriptomic and proteomic analysis

“…In studies of transcriptomics, microarray technology is a widely used approach because of its easy, high-throughput data generation and affordable cost (Osada, 2013). Isobaric tags for relative and absolute quantitation (iTRAQ), a high-throughput detection technology for measuring expression levels of different proteins has been widely used.…”

Effect of nine diets on xenobiotic transporters in livers of mice

“…Energy required for endo- and xenobiotic processing originates from the metabolism of carbohydrates and lipids, therefore, nutrition may have a global impact on genes involved in metabolism (Osada, 2013). Altering the nutrients in diets of laboratory animals is a good method to investigate the effects of various diets, which are important in lifestyle diseases, especially when done at the same time to exclude complex genetic and husbandry variables.…”