Carboxytherapy-Induced Fat loss is Associated with VEGF-Mediated Vascularization.

BACKGROUND: Carboxytherapy is the transcutaneous administration of CO2 gas for therapeutic purposes. Although this non-surgical procedure has been widely used for reducing localized adiposity, its effectiveness on fat loss in obese patients and its underlying mechanisms remain unclear. METHODS: C57BL/6 mice were fed with a high-fat diet for 8 weeks to generate obese animal models. Obese mice were randomly assigned to two groups: One group was administered air to both inguinal fat pads (air/air), and the other group was treated with air to the left inguinal fat pad and with CO2 to the right inguinal fat pad (air/CO2). Each group was treated every other day for 2 weeks. Morphological changes and expression levels of genes associated with lipogenesis and vascularization in fat were determined by histological and qRT-PCR analyses. RESULTS: Mice treated with air/CO2 showed lower body weights and blood glucose levels compared to air/air-treated mice. Paired comparison analysis revealed that CO2 administration significantly decreased adipose tissue weights and adipocyte sizes compared to air treatment. Additionally, CO2 treatment markedly increased vessel numbers and expressions of Vegfa and Fgf1 genes in adipose tissues. The expressions of Fasn and Fabp4 genes were also modestly reduced in CO2-treated adipose tissue. Moreover, Ucp1 expression, the target gene of VEGF and a key regulator in energy expenditure, was significantly increased in CO2-treated adipose tissue. CONCLUSIONS: Carboxytherapy is effective in the reduction of localized fat in obese patients which is mechanistically associated with alteration of the vasculature involved in VEGF. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Macrophage Lamin A/C Regulates Inflammation and the Development of Obesity-Induced Insulin Resistance.

Obesity-induced chronic low-grade inflammation, in particular in adipose tissue, contributes to the development of insulin resistance and type 2 diabetes. However, the mechanism by which obesity induces adipose tissue inflammation has not been completely elucidated. Recent studies suggest that alteration of the nuclear lamina is associated with age-associated chronic inflammation in humans and fly. These findings led us to investigate whether the nuclear lamina regulates obesity-mediated chronic inflammation. In this study, we show that lamin A/C mediates inflammation in macrophages. The gene and protein expression levels of lamin A/C are significantly increased in epididymal adipose tissues from obese rodent models and omental fat from obese human subjects compared to their lean controls. Flow cytometry and gene expression analyses reveal that the protein and gene expression levels of lamin A/C are increased in adipose tissue macrophages (ATMs) by obesity. We further show that ectopic overexpression of lamin A/C in macrophages spontaneously activates NF-κB, and increases the gene expression levels of proinflammatory genes, such as Il6, Tnf, Ccl2, and Nos2. Conversely, deletion of lamin A/C in macrophages reduces LPS-induced expression of these proinflammatory genes. Importantly, we find that myeloid cell-specific lamin A/C deficiency ameliorates obesity-induced insulin resistance and adipose tissue inflammation. Thus, our data suggest that lamin A/C mediates the activation of ATM inflammation by regulating NF-κB, thereby contributing to the development of obesity-induced insulin resistance.

Anti-neuroinflammatory activity of Kamebakaurin from Isodon japonicus via inhibition of c-Jun NH2-terminal kinase and p38 mitogen-activated protein kinase pathway in activated microglial cells.

Compelling evidence supports the notion that the majority of neurodegenerative diseases are associated with microglia-mediated neuroinflammation. Therefore, quelling of microglial activation may lead to neuronal cell survival. The present study investigated the effects of Kamebakaurin (KMBK), a kaurane diterpene isolated from Isodon japonicus HARA (Labiatae), on the production of pro-inflammatory mediators in lipopolysaccharide (LPS)-stimulated cytotoxicity in rat primary microglial cultures and the BV-2 cell line. KMBK significantly inhibited the LPS-induced production of nitric oxide (NO) in a concentration-dependent fashion in activated microglial cells. The mRNA and protein levels of inducible nitric oxide synthase (iNOS) and cyclooxycenase-2 (COX-2) were also decreased dose-dependently. Furthermore KMBK inhibited the JNK and p38 mitogen-activated protein kinases (MAPKs) in LPS-stimulated BV-2 microglial cells. Considering the results obtained, the present study authenticated the potential benefits of KMBK as a therapeutic target in ameliorating microglia-mediated neuroinflammatory diseases.