Obesity Abstracts

Obesity is a global crisis associated with other metabolic diseases such as cardiovascular disease and Type 2 Diabetes (T2D). Current pharmacological therapies, including metformin, are prescribed for T2D to control blood glucose levels, however, treatment may be accompanied by undesirable side effects. Compound 14 (Cpd14) is a recently developed compound shown to promote weight loss and improve glucose metabolism in high-fat diet (HFD)-fed mice, treated intraperitoneally for 7 days. This study aimed to determine the effects of Cpd14 on adipose tissue from chow-fed and HFD-fed mice, treated orally for 10 days, as a potential therapeutic agent for diabetes and obesity in humans. Cpd14-treated HFD-fed mice exhibited a reduction in body weight and a decrease in blood glucose levels, without alteration in caloric intake and had significantly smaller adipocytes compared to vehicle-treated HFD-fed mice (P<0.05 and P=0.0001) in gonadal (gWAT) and inguinal white adipose tissue (iWAT), respectively. In vivo, Cpd14-treated HFD-fed mice had significantly reduced gene expression levels of the satiety hormone leptin (P<0.05) and significantly reduced FABP4 gene expression levels (P<0.001) of pre-adipocytes cultured ex vivo from the stromal vascular fraction (SVF) of gWAT in HFD-fed mice. In addition, Cpd14 significantly increased uncoupling protein 1 (UCP1) mRNA levels of chow-fed mice in iWAT (P=0.0001), with a collection of cells morphologically resembling brown-like adipocytes dispersed amongst iWAT. These acquired brown-like cells are known to resemble the traits of classical brown cells, in which UCP1 is highly expressed, thus promoting thermogenesis. Collectively, these results indicate that Cpd14, as well as improving glucose tolerance, may impact on adiposity and body weight through increased energy expenditure and adipocyte lipolysis. In addition, data collected from the SVF of gWAT suggests that as Cpd14 reduced gene expression levels of the pro-adipogenic marker FABP4, this compound may inhibit obesogenic adipogenesis. Furthermore, although the underlying mechanisms are still unknown, further research will focus on elucidating the mechanistic effects of Cpd14 and its potential to act as a therapeutic compound for obese and diabetic individuals.