Small Parts of a Big Problem – Uncovering the Molecular Basis of Obesity

By Tara Fernandez & Michelle Kwon

Resisting the urge to reach for that donut, or taking the stairs instead of the elevator, we all know that eating healthy and staying active helps in the battle of the bulge. Still, obesity remains an ever-growing global concern, with a whopping 60% of Canadians found to be overweight. Considerably less is known about the molecular mechanisms that orchestrate the physiology of fat tissue, and their relation to the plethora of obesity-related conditions, such as heart disease, stroke and diabetes.

A collaborative project between two young researchers at UBC’s Centre for Blood Research (CBR) and the Diabetes Research Group (DRG) hopes to change that. Together, they are uncovering compelling new facets to the development of obesity and diabetes on a cellular level – with the hopes of revolutionizing preventative and therapeutic strategies against these diseases.

Michelle Kwon, DRG graduate student in Dr. Timothy Kieffer’s laboratory and Tara Fernandez, Postdoctoral Fellow with Dr. Ed Conway’s team at the CBR are working on a collaborative venture to study the intricate interplay between fat tissue and metabolic regulation. Specifically, they are interested in identifying the biological cues that govern fat cell growth and function. By combining their expertise on different experimental models of obesity and methods for analyzing fat’s metabolic potential, Michelle and Tara hope to shed light on how to harness these pathways clinically.

Fat, or adipose, is a complex tissue, mainly functioning as a lipid repository of the body’s energy reserves, but also important in producing various hormones and thermoregulation. ‘White fat’ constitutes 20-25% of human body weight, with obese individuals having markedly elevated white fat levels. On the other hand, the relatively recently discovered ‘brown fat’, is a highly specialized adipose tissue which acts as a furnace, utilizing sugar and lipids as fuel to generate heat energy.

As Michelle explains, “There has been an enormous interest in trying to therapeutically target brown adipose to lower circulating fats.” Indeed, this represents the holy grail of anti-obesity therapeutics, in which those late night pizza indulgences would simply be burnt off as heat, and not through hours of sweating on the treadmill. Fascinatingly, Michelle and her lab have also discovered a role of brown adipose in resisting diabetes. “Our studies highlight that brown adipose metabolism can also be harnessed to lower blood sugar levels in experimental models of diabetes”. Michelle adds, saying she looks forward to exploring whether igniting brown fat activity has a potential in a clinical setting.

Zooming in on the cellular characteristics that distinguish brown and white adipose is Tara’s main research focus. Exciting new discoveries from the Conway lab are revealing that proteins present on the surface of fat cells may hold the key to brown fat’s energy-burning properties. Tara shares some insights into the progression of these novel findings, saying “Initially, we were interested in the role of these proteins in inflammatory conditions. Surprisingly, these molecules also control how fat cells grow and behave.” Using a range of cell-based and molecular biology platforms, clues as to how this molecule fits within network of pathways that govern weight gain and glucose metabolism are slowly being uncovered.

Expanding collaborative networks is one of the most essential means of solving formidable biological problems. Indeed, both Michelle and Tara have experienced this first hand through this joint research venture. “It’s great to bounce ideas off each other,” they said about their team effort, adding that their different perspectives drive the project in ways that would not have been possible if done in isolation. When they are not making waves in the lab, Michelle is putting her laboratory skills to good use in brewing the perfect ale and baking delicious breads, while Tara enjoys playing Ultimate Frisbee and the ukulele.