Discovery of Novel Genes Mediating Glucose and Lipid Metabolisms.

Glucose and lipid are the major energy sources, and pivotal components of organic metabolism in mammals. Inappropriate diet directly influences the metabolic rate, and can alter the body's homeostasis. The underlying changes in energy storage and utilization would manifest as metabolic syndrome including obesity and high blood pressure, and high blood glucose, which are predisposing factors that significantly increase the risk for cardiovascular diseases and Type 2 Diabetes (T2D). Thus, it is essential to identify the genes that are involved in the process of glucose and lipid metabolism. Utilizing current advanced scientific methodology and technology, as well as computational resources has led to discovery of many novel genes with major roles in energy metabolism. In addition, many studies have focused on the functional analysis of the novel genes. Nowadays, uncovering the genes that are involved in glucose and lipid storage and utilization, as well as underlying pathways that regulate expression of those genes is an area of ongoing research. Here, we summarize the current research related to the novel genes regulating glucose and lipid metabolisms, which enable us to develop more efficient means of prevention and management of metabolic diseases such as T2D, obesity, high blood glucose, and hypertension.

Maintenance of Gastrointestinal Glucose Homeostasis by the Gut-Brain Axis.

Gastrointestinal homeostasis is a dynamic balance under the interaction between the host, GI tract, nutrition and energy metabolism. Glucose is the main energy source in living cells. Thus, glucose metabolic disorders can impair normal cellular function and endanger organisms' health. Diseases that are associated with glucose metabolic disorders such as obesity, diabetes, hypertension, and other metabolic syndromes are in fact life threatening. Digestive system is responsible for food digestion and nutrient absorption. It is also involved in neuronal, immune, and endocrine pathways. In addition, the gut microbiota plays an essential role in initiating signal transduction, and communication between the enteric and central nervous system. Gut-brain axis is composed of enteric neural system, central neural system, and all the efferent and afferent neurons that are involved in signal transduction between the brain and gut-brain. Gut-brain axis is influenced by the gut-microbiota as well as numerous neurotransmitters. Properly regulated gut-brain axis ensures normal digestion, absorption, energy production, and subsequently maintenance of glucose homeostasis. Understanding the underlying regulatory mechanisms of gut-brain axis involved in gluose homeostasis would enable us develop more efficient means of prevention and management of metabolic disease such as diabetic, obesity, and hypertension.

Metabolites of Dietary Protein and Peptides by Intestinal Microbes and their Impacts on Gut.

Dietary protein is a vital nutrient for humans and animals, which is primarily digested into peptides and free amino acids (FAAs) in the upper gastrointestine with the help of proteases. The products are absorbed by the enterocytes and are metabolized in different organs of body. Dietary protein, peptides and FAAs that escape digestion and absorption of the small intestine will enter the large intestine for further fermentation by the vast gut microbiota. Particularly, amino acid (AAs) metabolism by bacteria occurs via either deamination or decarboxylation reactions and generates short chain fatty acids (SCFAs) or amines, respectively. These metabolites elicit a wide range of biological functions via different receptors and mechanisms. This review discusses the interaction between protein metabolites and gastrointestine, illustrates regulation of intestinal motility and immune response by SCFAs and their receptors, and focuses on modulation of intestinal inflammation and signal transduction by biogenic amines (BAs) involving polyamines and monoamine neurotransmitters.

An ontology for microbial phenotypes.

BACKGROUND: Phenotypic data are routinely used to elucidate gene function in organisms amenable to genetic manipulation. However, previous to this work, there was no generalizable system in place for the structured storage and retrieval of phenotypic information for bacteria. RESULTS: The Ontology of Microbial Phenotypes (OMP) has been created to standardize the capture of such phenotypic information from microbes. OMP has been built on the foundations of the Basic Formal Ontology and the Phenotype and Trait Ontology. Terms have logical definitions that can facilitate computational searching of phenotypes and their associated genes. OMP can be accessed via a wiki page as well as downloaded from SourceForge. Initial annotations with OMP are being made for Escherichia coli using a wiki-based annotation capture system. New OMP terms are being concurrently developed as annotation proceeds. CONCLUSIONS: We anticipate that diverse groups studying microbial genetics and associated phenotypes will employ OMP for standardizing microbial phenotype annotation, much as the Gene Ontology has standardized gene product annotation. The resulting OMP resource and associated annotations will facilitate prediction of phenotypes for unknown genes and result in new experimental characterization of phenotypes and functions.

Systematic analysis of cell cycle effects of common drugs leads to the discovery of a suppressive interaction between gemfibrozil and fluoxetine.

Screening chemical libraries to identify compounds that affect overall cell proliferation is common. However, in most cases, it is not known whether the compounds tested alter the timing of particular cell cycle transitions. Here, we evaluated an FDA-approved drug library to identify pharmaceuticals that alter cell cycle progression in yeast, using DNA content measurements by flow cytometry. This approach revealed strong cell cycle effects of several commonly used pharmaceuticals. We show that the antilipemic gemfibrozil delays initiation of DNA replication, while cells treated with the antidepressant fluoxetine severely delay progression through mitosis. Based on their effects on cell cycle progression, we also examined cell proliferation in the presence of both compounds. We discovered a strong suppressive interaction between gemfibrozil and fluoxetine. Combinations of interest among diverse pharmaceuticals are difficult to identify, due to the daunting number of possible combinations that must be evaluated. The novel interaction between gemfibrozil and fluoxetine suggests that identifying and combining drugs that show cell cycle effects might streamline identification of drug combinations with a pronounced impact on cell proliferation.