Michella Soares Coelho

GQ-16, a TZD-Derived Partial PPARγ Agonist, Induces the Expression of Thermogenesis-Related Genes in Brown Fat and Visceral White Fat and Decreases Visceral Adiposity in Obese and Hyperglycemic Mice

Background Beige adipocytes comprise a unique thermogenic cell type in the white adipose tissue (WAT) of rodents and humans, and play a critical role in energy homeostasis. In this scenario, recruitment of beige cells has been an important focus of interest for the development of novel therapeutic strategies to treat obesity. PPARγ activation by full agonists (thiazolidinediones, TZDs) drives the appearance of beige cells, a process so-called browning of WAT. However, this does not translate into increased energy expenditure, and TZDs are associated with weight gain. Partial PPARγ agonists, on the other hand, do not induce weight gain, but have not been shown to drive WAT browning. The present study was designed to investigate the effects of GQ-16 on BAT and on browning of WAT in obese mice. Methods Male Swiss mice with obesity and hyperglycemia induced by high fat diet were treated with vehicle, rosiglitazone (4 mg/kg/d) or the TZD-derived partial PPARγ agonist GQ-16 (40 mg/kg/d) for 14 days. Fasting blood glucose, aspartate aminotransferase, alanine aminotransferase and lipid profile were measured. WAT and brown adipose tissue (BAT) depots were excised for determination of adiposity, relative expression of Ucp-1, Cidea, Prdm16, Cd40 and Tmem26 by RT-qPCR, histological analysis, and UCP-1 protein expression analysis by immunohistochemistry. Liver samples were also removed for histological analysis and determination of hepatic triglyceride content. Results GQ-16 treatment reduced high fat diet-induced weight gain in mice despite increasing energy intake. This was accompanied by reduced epididymal fat mass, reduced liver triglyceride content, morphological signs of increased BAT activity, increased expression of thermogenesis-related genes in interscapular BAT and epididymal WAT, and increased UCP-1 protein expression in interscapular BAT and in epididymal and inguinal WAT. Conclusion This study suggests for the first time that a partial PPARγ agonist may increase BAT activity and induce the expression of thermogenesis-related genes in visceral WAT. General Significance These findings suggest that PPARγ activity might be modulated by partial agonists to induce WAT browning and treat obesity.

Rosiglitazone Inhibits Proliferation and Induces Osteopontin Gene Expression in Human Dental Pulp Cells

INTRODUCTION Rosiglitazone (RSG) is a synthetic full agonist of transcription factor peroxisome proliferator activated receptor gamma. Previous studies have suggested an anti-inflammatory effect of RSG on lipopolysaccharide-induced pulp inflammation. However, its role in other cellular events related to pulp repair has not been investigated. Therefore, the aim of the present study was to evaluate the effect of RSG on human dental pulp cell viability, proliferation, migration, and osteoblastic/odontoblastic differentiation. METHODS Cell proliferation was evaluated by [3H]-thymidine assay. Cell viability was assessed by a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay and by measuring the percentage of apoptotic cells by flow cytometry. Cell migration was estimated by scratch wound healing assay. Mineralization and cell differentiation were evaluated by alizarin red S staining and real-time polymerase chain reaction gene expression assay, respectively. RESULTS RSG significantly decreased cell proliferation and did not have effect on cell viability, apoptosis/necrosis, or migration. Alizarin red S showed that RSG accelerated calcified nodule formation. Results of real-time polymerase chain reaction demonstrated that RSG upregulated osteopontin expression, whereas expression of dentin sialophosphoprotein, dentin matrix protein-1, and osteocalcin was not affected. CONCLUSIONS These findings suggest that RSG decreases human dental pulp cell proliferation, while positively regulating osteopontin expression.

Metabolic effects of aspartame in adulthood: A systematic review and meta-analysis of randomized clinical trials

ABSTRACT Data about harms or benefits associated with the consumption of aspartame, a nonnutritive sweetener worldwide consumed, are still controversial. This systematic review and meta-analysis of randomized controlled clinical trials aimed to assess the effect of aspartame consumption on metabolic parameters related to diabetes and obesity. The search was performed on Cochrane, LILACS, PubMed, SCOPUS, Web of Science databases, and on a gray literature using Open Grey, Google Scholar, and ProQuest Dissertations & Theses Global. Searches across all databases were conducted from the earliest available date up to April 13, 2016, without date and language restrictions. Pooled mean differences were calculated using a random or fixed-effects model for heterogeneous and homogenous studies, respectively. Twenty-nine articles were included in qualitative synthesis and twelve, presenting numeric results, were used in meta-analysis. Fasting blood glucose (mmol/L), insulin levels (μU/mL), total cholesterol (mmol/L), triglycerides concentrations (mmol/L), high-density lipoprotein cholesterol (mmol/L), body weight (kg), and energy intake (MJ) were considered as the main outcomes in subjects that consumed aspartame, and results were presented as mean difference; % confidence interval, range. Aspartame consumption was not associated with alterations on blood glucose levels compared to control (−0.03 mmol/L; 95% CI, −0.21 to 0.14) or to sucrose (0.31 mmol/L; 95% CI, −0.05 to 0.67) and on insulin levels compared to control (0.13 μU/mL; 95% CI, −0.69 to 0.95) or to sucrose (2.54 μU/mL; 95% CI, −6.29 to 11.37). Total cholesterol was not affected by aspartame consumption compared to control (−0.02 mmol/L; 95% CI, −0.31 to 0.27) or to sucrose (−0.24 mmol/L; 95% CI, −0.89 to 0.42). Triglycerides concentrations were not affected by aspartame consumption compared to control (0.00 mmol/L; 95% CI, −0.04 to 0.05) or to sucrose (0.00 mmol/L; 95% CI, −0.09 to 0.09). High-density lipoprotein cholesterol serum levels were higher on aspartame compared to control (−0.03 mmol/L; 95% CI, −0.06 to −0.01) and lower on aspartame compared to sucrose (0.05 mmol/L; 95% CI, 0.02 to 0.09). Body weight did not change after aspartame consumption compared to control (5.00 kg; 95% CI, −1.56 to 11.56) or to sucrose (3.78 kg; 95% CI, −2.18 to 9.74). Energy intake was not altered by aspartame consumption compared to control (−0.49 MJ; 95% CI, −1.21 to 0.22) or to sucrose (−0.17 MJ; 95% CI, −2.03 to 1.69). Data concerning effects of aspartame on main metabolic variables associated to diabetes and obesity do not support a beneficial related to its consumption.