Poster abstracts
Poster number 6 submitted by Pablo Vidal Souza
Topical overexpression of Prdm16 as an effective approach to combat obesity
Pablo Vidal (MCDB), Revati S. Dewal (MCDB), Devleena Das, Silvia Duarte-Sanmiguel (Biomedical Engineering), Lisa A. Baer (Physiology and Cell Biology), Daniel Gallego-Perez (Biomedical Engineering), Kristin I. Stanford (Physiology and Cell Biology)
Abstract:
Obesity is increasing rapidly and is associated with co-morbidities including type 2 diabetes and metabolic syndrome. Obesity is characterized by an excessive amount of white adipose tissue (WAT), while other tissues such as brown adipose tissue (BAT) are decreased. WAT functions in energy storage, while BAT is involved in energy expenditure. WAT can undergo beiging, a process where WAT acquires brown-like characteristics including increased UCP1 expression and mitochondrial density. Beiging is controlled by Prdm16, and genetic mouse models show that an adipose-specific overexpression of Prdm16 is protective against obesity. Here, we used Tissue Nanotransfection (TNT) to increase expression of Ucp1 or Prdm16 in obese mice and study its effect in metabolic function. We chose Ucp1 because it is the main marker of beiging, and Prdm16 is the master regulator of beiging. TNT is a nanochannel-based transfection approach that delivers your gene of interest directly in vivo. TNT is a non-viral, non-invasive approach that can be performed in living organisms, with the potential of being highly translatable in humans. Mice were placed on a high-fat diet (HFD) for 6 weeks to induce obesity. Next, they underwent TNT weekly for a total of 8 weeks while maintained on HFD. Mice were divided into 3 groups: 1) Sham, 2) TNT-Ucp1 and 3) TNT-Prdm16. Interestingly, while the Sham and TNT-Ucp1 mice had increased body weight, fat mass, and became glucose intolerant over time, TNT-Prdm16 attenuated the increase in body weight and fat mass caused by HFD and significantly improved whole-body glucose tolerance. Mice were sacrificed and gene expression was measured in WAT, BAT, tibialis anterior and liver. Excitingly, the most pronounced phenotype was found in liver, where TNT-Prdm16 induced an overall upregulation in metabolic processes such as mitochondrial function and fatty acid metabolism. These data indicate that TNT with Prdm16 is an effective approach to combat obesity.
Keywords: Obesity, Diabetes, Glucose Metabolism