Obesity and type 2 diabetes are major contributors to the growing prevalence of non-alcoholic fatty liver disease (NAFLD), a chronic liver condition characterized by accumulation of fat in individuals without a significant amount of alcohol intake. The NAFLD spectrum ranges from simple steatosis (early stages, known as NAFL), to non-alcoholic steatohepatitis (NASH), which can progress to fibrosis and cirrhosis or hepatocellular carcinoma. Obesity, type 2 diabetes, and NAFLD are strongly associated with insulin resistance. In the liver, insulin resistance increases hepatic glucose output, lipogenesis, and VLDL secretion, leading to a combination of hyperglycemia and hypertriglyceridemia. Aberrant gene expression is a hallmark of insulin resistance. Non-coding RNAs (ncRNAs) have emerged as prominent regulators of gene expression that operate at the transcriptional, post-transcriptional, and post-translational levels. In the last couple of decades a wealth of studies have provided evidence that most processes of liver metabolism are orchestrated by ncRNAs. This review focuses on the role of microRNAs, long non-coding RNAs and circular RNAs as coordinators of hepatic function, as well as the current understanding on how their dysregulation contributes to abnormal metabolism and pathophysiology in animal models of insulin resistance and NAFLD. Moreover, ncRNAs are emerging as useful biomarkers that may be able to discriminate between the different stages of NAFLD. The potential of ncRNAs as therapeutic drugs for NAFLD treatment and as biomarkers is discussed.

Abstractis responsible for over 35% of all foodborne illness Salmonella typhimurium related hospitalizations in the United States. This Gram-negative bacterium possesses an inner and an outer membrane (OM), the latter allowing its survival and replication within host tissues. During infection, OM is remodeled by transport of glycerophospholipids across the periplasm and into the OM. Increased levels of cardiolipin in the OM were observed upon PhoPQ activation and led to the discovery of YejM; an inner membrane protein essential for cell growth involved in cardiolipin binding and transport to the OM. Another protein that might be playing a role in cardiolipin transport is YejL, as its gene is localized upstream of on the same operon. Here we report how yejm YejM was engineered to facilitate crystal growth and X-ray diffraction analysis. Furthermore, we present for the first time that YejL is a ligand for YejM. Successful structure determination of YejM and YejL will help us understand how they interact and how YejM facilitates cardiolipin transport to the OM. Ultimately, , being an essential gene, may lead to new drug targets yejm inhibiting the pathogenic properties of . S. typhimuriumSusanne Ressl ( )

Salmonella  typhimurium is responsible for over 35% of all foodborne illness related hospitalizations in the United States. This Gram-negative bacterium possesses an inner and an outer membrane (OM), the latter allowing its survival and replication within host tissues. During infection, OM is remodeled by transport of glycerophospholipids across the periplasm and into the OM. Increased levels of cardiolipin in the OM were observed upon PhoPQ activation and led to the discovery of YejM; an inner membrane protein essential for cell growth involved in cardiolipin binding and transport to the OM. Here we report how YejM was engineered to facilitate crystal growth and X-ray diffraction analysis. Successful structure determination of YejM will help us understand how they interact and how YejM facilitates cardiolipin transport to the OM. Ultimately, yejm, being an essential gene, may lead to new drug targets inhibiting the pathogenic properties of  S. typhimurium.

Background/Objective:  Diabetes mellitus is a disease with increasing incidence worldwide affecting more than 435 million patients, most of whom have Type II diabetes (T2D). Of the many organs affected by T2D, the liver is responsible for much of the dysregulated metabolic pathways in response to insulin signaling. These include, but are not limited to gluconeogenesis, glycogen storage, fatty acid and cholesterol biosynthesis and transport, and fatty acid oxidation. Recent studies show significant differences in miRNA expression profiles between healthy and disease states of T2D. This implicates an important role of miRNAs in T2D pathogenesis and makes miRNAs an attractive therapeutic target and diagnostic marker for T2D patients. The aim of this review is to provide an overview of the hepatic miRNAs relevant to T2D pathogenesis.    Methods:  We compiled and reviewed articles from the PubMed database that were relevant to miRNAs and T2D pathogenesis in the liver.    Results:  We found that hepatic miRNAs affect most if not all dysregulated metabolic pathways in T2D pathogenesis, which we categorized into carbohydrate metabolism, lipid metabolism, and insulin signaling. The miRNAs that are most represented in our literature include miR-122, miR-33a/b, miR-29, and miR-21. These miRNAs target a variety of molecules, including transcription factors that are master regulators of metabolic pathways (FOXO1, HNF4α), lipid transporters (ABCA1, ABCG1), or key insulin signaling molecules (IRS1/2, caveolin-1). In addition, circulating miR-122 is associated with the risk of developing metabolic syndrome and T2D in the general population.    Conclusion and Potential Impact:  Multiple miRNAs are dysregulated in the liver of animal models of T2D. Administration of miRNA mimics or antagomirs to correct aberrant miRNA expression improved the pathophysiology in vivo. miRNAs are also promising tools as markers for disease development. Ultimately, the identification of miRNAs can guide future research to facilitate the diagnosis and improve the treatment of T2D.