The route of autophagy regulation by osteopontin: a review on the linking mechanisms.

Autophagy is a dynamic intracellular process of protein degradation, which is mostly triggered by nutrient deprivation. This process initiates with the formation of autophagosomes, which they capture cytosolic material that is then degraded upon fusion with the lysosome. Several factors have been found to be associated with autophagy modulation, of which extracellular matrix (ECM) components has attracted the attention of recent studies. Osteopontin (OPN) is an important extracellular matrix component that has been detected in a wide range of tumor cells, and is involved in cancer cell invasion and metastasis. Recently, a number of studies have focused on the relationship of OPN with autophagy, by delineating the intracellular signaling pathways that connect OPN to the autophagy process. We will summarize signaling pathways and cell surface receptors, through which OPN regulates the process of autophagy.

The up-regulation of markers of adipose tissue fibrosis by visfatin in pre-adipocytes as well as obese children and adolescents.

Adipocytes are surrounded by a three-dimensional network of extracellular matrix (ECM) proteins. Aberrant ECM accumulation and remodeling leads to adipose tissue fibrosis. Visfatin is one of the adipocytokines that is increased in obesity and is implicated in insulin resistance. The objective of this study was to investigate the effect of visfatin on major components of ECM remodeling. In this study, plasma levels of both endotrophin and visfatin in obese children and adolescents were significantly higher than those in control subjects and they showed a positive correlation with each other. Treatment of 3T3-L1 pre-adipocytes with visfatin caused significant up-regulation of Osteopontin (Opn), Collagen type VI (Col6), matrix metalloproteinases MMP-2 and MMP-9. By using inhibitors of major signaling pathways it was shown that visfatin exerted its effect on Col6a3 gene expression through PI3K, JNK, and NF-кB pathways, while induced Opn gene expression via PI3K, JNK, MAPK/ERK, and NOTCH1. Our conclusion is that, the relationship between visfatin, endotrophin and insulin resistance parameters in obesity as well as increased expression of ECM proteins by visfatin suggests adipose tissue fibrosis as a mechanism for devastating effects of visfatin in obesity.

Adipose triglyceride lipase gene expression in peripheral blood mononuclear cells of subjects with obesity and its association with insulin resistance, inflammation and lipid accumulation in liver.

Introduction: Adipose triglyceride lipase (ATGL) is a crucial enzyme responsible for the release of fatty acids from various tissues. The expression of ATGL is regulated by insulin and this enzyme is linked to Insulin resistance (IR). On the other hand, ATGL-mediated lipolysis is connected to macrophage function and thus, ATGL is involved in inflammation and the pathogenesis of lipid-related disorders. This study aimed to investigate the correlation between ATGL, obesity, Metabolic Syndrome (MetS), and inflammation. Methods: A total of 100 participants, including 50 individuals with obesity and 50 healthy participants, were recruited for this study and underwent comprehensive clinical evaluations. Blood samples were collected to measure plasma lipid profiles, glycemic indices, and liver function tests. Additionally, peripheral blood mononuclear cells (PBMCs) were isolated and used for the assessment of the gene expression of ATGL, using real-time PCR. Furthermore, PBMCs were cultured and exposed to lipopolysaccharides (LPS) with simultaneous ATGL inhibition, and the gene expression of inflammatory cytokines, along with the secretion of prostaglandin E2 (PGE2), were measured. Results: The gene expression of ATGL was significantly elevated in PBMCs obtained from participants with obesity and was particularly higher in those diagnosed with MetS. It exhibited a correlation with insulin levels and Homeostatic Model Assessment for IR (HOMA-IR), and it was associated with lipid accumulation in the liver. Stimulation with LPS increased ATGL expression in PBMCs, while inhibition of ATGL attenuated the inflammatory responses induced by LPS. Conclusions: Obesity and MetS were associated with dysregulation of ATGL. ATGL might play a role in the upregulation of inflammatory cytokines and act as a significant contributor to the development of metabolic abnormalities related to obesity.

MiR-613 Promotes Cell Death in Breast Cancer Cells by Downregulation of Nicotinamide Phosphoribosyltransferase and Reduction of NAD.

NAD is mainly biosynthesized by the enzymatic action of nicotinamide phosphoribosyltransferase (NAMPT) through the salvage pathway. NAD is indispensable for the proper function and metabolism of all living cells, including cancer cells. Our previous researches revealed that inhibition of NAMPT by miRNA (miR) could suppress NAD levels and thereby hinder the growth and promotion of breast cancer (BC). Therefore, the current study was undertaken to investigate the inhibitory effects of miR-613 on NAMPT and BC cells' survival. Bioinformatics analysis and luciferase reporter assay confirmed that NAMPT 3'-untranslated region is a direct target for miR-613. The expression of miR-613 was noticed to be significantly decreased in both clinical tissue samples and BC cells by real-time PCR. Following transfection with miR-613 mimic, the expression of miR-613 was elevated in the BC cells leading to inhibition of NAMPT expression at both mRNA and protein level as measured by real-time PCR and western blotting, respectively. Inhibition of NAMPT led to a remarkable reduction in the concentration of NAD in the BC cells. The transfection also declined cell viability roughly 40% in MD Anderson-Metastatic Breast-231 (MDA-MB-231) cells. Consistently, the apoptosis rate was remarkably increased, around 65% in these cells as assayed by labeling the cells with Annexin V-fluorescein isothiocyanate (FITC) and Propidium Iodide. Targeting the NAMPT-mediated NAD salvage pathway by miR-613 is a novel approach for managing BC, which is worth further investigation.