Zinc Transporter ZnT1 mRNA Expression Is Negatively Associated with Leptin Serum Concentrations but Is not Associated with Insulin Resistance or Inflammatory Markers in Visceral Adipose Tissue.

The aim of this study was to evaluate the relationship between biomarkers of chronic inflammation, insulin resistance, and zinc transporter ZnT1 expression in human visceral adipose tissue. Visceral adipose tissue obtained from 47 adults undergoing laparoscopic surgery for cholecystectomy was used to analyze ZnT1 mRNA expression by RT-qPCR. ZnT1 mRNA levels were compared between subjects with normal weight, overweight, and obesity. A significantly lower ZnT1 expression was observed in overweight and obesity compared with normal-weight subjects (p = 0.0016). Moreover, subjects with normal weight had significantly higher serum zinc concentration (97.7 ± 13.1 mg/L) than subjects with overweight (87.0 ± 12.8 mg/L) and obesity (83.1 ± 6.6 mg/L) (p = 0.002). Pearson test showed a positive correlation between serum zinc concentrations and ZnT1 mRNA expression in visceral adipose tissue (r = 0.323; p = 0.031) and a negative correlation with body mass index (r = - 0.358; p = 0.013). A linear regression model was used to analyze the associations between ZnT1 mRNA expression and serum zinc levels, insulin resistance (HOMA2-IR), serum adipokines (leptin and adiponectin), and serum inflammation biomarkers (tumor necrosis factor alpha, interleukin-6, and C-reactive protein). Interestingly, leptin concentrations were negatively associated with ZnT1 mRNA expression (p = 0.012); however, no significant associations were found for the rest of the analyzed variables. Future research is needed to analyze the causality of negative association between ZntT1 expression in visceral adipose tissue and leptin.

Fructose promotes more than glucose the adipocytic differentiation of pig mesenchymal stem cells.

The goal of this study was to evaluate how glucose and fructose affected the adipose differentiation of pig newborn mesenchymal stem cells (MSCs). Cells were grown with or without inosine in 7.5 mM glucose (substituted with 1.5 or 6 mM fructose). MSCs displayed adipose morphology after 70 days of differentiation. Fructose stimulated the highest levels of PPARγ and C/EBPß. Fructose at 6 mM, but not glucose at 7.5 mM or fructose at 1.5 mM, promotes differentiation of MSCs into adipocytes and increases 11-hydroxysteroid dehydrogenase (11ß-HSD1) and NADPH oxidase 4 (NOX4) mRNA in the absence of hepatic effects (as simulated by the inosine). Fructose and glucose increased xanthine oxide-reductase (XOR) catalytic activity almost 10-fold and elevated their products: intracellular reactive oxygen species (ROS) pool, extracellular H2 O2 pool by 4 orders of magnitude, and uric acid by a factor of 10. Therefore, in our experimental model, differentiation of MSCs into adipocytes occurs exclusively at the blood concentration of fructose detected after ingestion by people on a high fructose diet. PRACTICAL APPLICATIONS: The results of this study provide new evidence for fructose's adipogenic potential in mesenchymal stem cells, a model in which its effects on XOR activity had not been studied. The increased expression of genes such as C/EBPß, PPARγ, and NOX4, as well as the increased XOR activity and high production of ROS during the differentiation process in the presence of fructose, coincides in pointing to this hexose as an important factor in the development of adipogenesis in young animals, which could have a great impact on the development of future obesity.

Low miR-222 expression in human visceral adipose tissue is associated with insulin resistance and PTEN and p53 mRNA levels.

INTRODUCTION: The aim of this is study was to analyse the expression of miR-193b, miR-378, miR-Let7-d, and miR-222 in human visceral adipose tissue (VAT), as well as their association with obesity, insulin resistance (IR), and their role in the regulation of genes controlling adipose tissue homeostasis, including adipocytokines, the phosphatase and tension homologue (PTEN), and tumour protein 53 (p53). MATERIAL AND METHODS: VAT was obtained from normal-weight (NW), overweight, and obese (OW/OB) subjects with and without IR. Stem-loop RT-qPCR was used to evaluate miRNA expression levels. miRTarBase 4.0, miRWalk, and DIANA-TarBase v8 were used for prediction of validated target gene of the miRNA analysed. A qPCR was used to evaluate PTEN, p53, leptin (LEP), and adiponectin (ADIPOQ) mRNA. RESULTS: miR-222 was lower in IR subjects, and miR-222 and miR-378 negatively correlated with HOMA-IR. PTEN and p53 are miR-222 direct targets according to databases. mRNA expression of PTEN and p53 was lower in OW/OB subjects with and without IR, compared to NW group and its levels positively associated with miR-222. Additionally, p53 and PTEN are positively associated with serum leptin levels. On the other hand, miR-193b and miR-378 negatively correlated with serum leptin but not with mRNA levels. Moreover, miR-Let-7d negatively correlated with serum adiponectin but not with adiponectin mRNA levels. CONCLUSIONS: Lower miR-222 levels are associated with IR, and PTEN and p53 expression; the implication of these genes in adipose tissue homeostasis needs more research.