Intranasal nerve growth factor bypasses the blood-brain barrier and affects spinal cord neurons in spinal cord injur y

The purpose of this work was to investigate whether, by intranasal administration, the nerve growth factor bypasses the blood-brain barrier and turns over the spinal cord neurons and if such therapeutic approach could be of value in the treatment of spinal cord injury. Adult Sprague-Dawley rats with intact and injured spinal cord received daily intranasal nerve growth factor administration in both nostrils for 1 day or for 3 consecutive weeks. We found an in-creased content of nerve growth factor and enhanced expression of nerve growth factor receptor in the spinal cord 24 hours after a single intranasal administration of nerve growth factor in healthy rats, while daily treatment for 3 weeks in a model of spinal cord injury improved the deifcits in locomotor behaviour and increased spinal content of both nerve growth factor and nerve growth factor receptors. These outcomes suggest that the intranasal nerve growth factor bypasses blood-brain barrier and affects spinal cord neurons in spinal cord injury. They also suggest exploiting the possible therapeutic role of intranasally delivered nerve growth factor for the neuroprotection of damaged spinal nerve cells.     

Differentiation between free and bound leptin in depressed patients

The relationship between leptin and affective disorders is still unknown. We measured free and bound leptin in 13 drug naïve subjects. Leptin did not significantly differ between patients and controls. As part of future studies, it also appears useful to distinguish between free and bound leptin.     

Central obesity and altered peripheral adipose tissue gene expression characterize the NAFLD patient with insulin resistance: Role of nutrition and insulin challenge

ObjectiveInsulin resistance (IR) and white adipose tissue (WAT) dysfunction frequently are associated with nonalcoholic fatty liver disease (NAFLD); however, the pathogenic mechanisms contributing to their clustering are not well defined. The aim of this study was to define some nutritional, anthropometric, metabolic, and genetic mechanisms contributing to their clustering.MethodsForty-five (20 men, 25 women) patients (age 45.7 ± 11.1 y) with recent diagnosis of NAFLD were grouped according to IR state. Energy balance was assessed using a food questionnaire and indirect calorimetry, and body composition with anthropometry and dual-energy x-ray absorptiometry. Biochemical and hormonal parameters combined with adipose tissue gene expression were determined. Microarray analysis of gene expression was performed in a subset of WAT samples from IR patients (n = 9), in the fasted state, after specific test meals (monounsaturated fatty acid [MUFA], saturated fat [SAT], and carbohydrate-rich) and after being challenged with insulin.ResultsIR patients exhibited higher trunk fat to leg fat ratio (P < 0.05) and had a higher ratio of SAT/MUFA fat intake (P < 0.05) than insulin-sensitive (IS) individuals. Deposition of fat in the trunk but not in the leg was directly related to liver enzyme levels (P < 0.05). IR patients also had lower adiponectin serum levels and leptin (LEP) mRNA expression in WAT compared with IS patients (P < 0.01 and P < 0.05, respectively). Microarray analysis after insulin challenge confirmed that insulin treatment induces the expression of PPARG gene and LEP and decreases GCGR gene (P < 0.05 for all) in WAT. No changes in these genes were observed in the postprandial state induced after the acute effect of specific diets.ConclusionsPatients exhibiting NAFLD and IR had preferential central fat deposition directly related to their serum alanine aminotransferase levels. These patients showed peripheral adipose tissue dysfunction and exhibited inappropriately low LEP biosynthesis that could be partially restored after anabolic conditions induced by insulin signaling.     

2型糖尿病并发高血压者血清瘦素、胰岛素、胰高血糖素的水平变化及关系研究

目的：探讨2型糖尿病并发高血压者血清瘦素（Leptin）、胰岛素（Insulin）、胰高血糖素（Glucagon）水平变化与关系。方法：采用放射免疫分析对30例2型糖尿病并发高血压者和30例不伴高血压者进行血清瘦素、胰岛素及胰高血糖素含量测定,分析两组瘦素水平及其相关性。结果：两组糖尿病患者上述三指标显著高于健康正常人组（30例）,具有统计学意义（P〈0．01）;合并高血压的糖尿病病人与无高血压病人比较,差异也非常显著（P〈0．05）,且与血压的程度呈正相关关系。结论：糖尿病并发高血压者血清瘦素、胰岛素、胰高血糖素的升高,参与了本病的发生与发展过程,作为判断其病情指标有重要临床价值。     

Obesity and Leptin Resistance in the Regulation of the Type I Interferon Early Response and the Increased Risk for Severe COVID-19

Obesity, and obesity-associated conditions such as hypertension, chronic kidney disease, type 2 diabetes, and cardiovascular disease, are important risk factors for severe Coronavirus disease-2019 (COVID-19). The common denominator is metaflammation, a portmanteau of metabolism and inflammation, which is characterized by chronically elevated levels of leptin and pro-inflammatory cytokines. These induce the “Suppressor Of Cytokine Signaling 1 and 3” (SOCS1/3), which deactivates the leptin receptor and also other SOCS1/3 sensitive cytokine receptors in immune cells, impairing the type I and III interferon early responses. By also upregulating SOCS1/3, Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 adds a significant boost to this. The ensuing consequence is a delayed but over-reactive immune response, characterized by high-grade inflammation (e.g., cytokine storm), endothelial damage, and hypercoagulation, thus leading to severe COVID-19. Superimposing an acute disturbance, such as a SARS-CoV-2 infection, on metaflammation severely tests resilience. In the long run, metaflammation causes the “typical western” conditions associated with metabolic syndrome. Severe COVID-19 and other serious infectious diseases can be added to the list of its short-term consequences. Therefore, preventive measures should include not only vaccination and the well-established actions intended to avoid infection, but also dietary and lifestyle interventions aimed at improving body composition and preventing or reversing metaflammation.