Brown (BAT) and white (WAT) adipose tissues are significant contributors to whole-body energy homeostasis. A disturbance in their metabolic function could result in the development of obesity and subsequent metabolic complications. The energy-sensing enzyme of the cell, AMP-activated protein kinase (AMPK), has been vastly studied in skeletal muscle and liver, but its role in BAT and WAT metabolism is elusive. We generated an inducible, adipocyte-specific knockout mouse model for the two AMPK β subunits (iβ1β2AKO) and found that iβ1β2AKO mice were intolerant to cold, and resistant to β3-adrenergic activation of BAT and browning of WAT. These defects in BAT activity were not due to the AMPK-ACC axis, but instead were due to compromised integrity of mitochondria. Mitochondrial morphology, function, and autophagy were all distorted in iβ1β2AKO mice, measured via transmission electron microscopy (TEM), respiration, and immunoblotting, respectively. These findings provide strong evidence that adipocyte AMPK regulates a fine-tuned program that responds to environmental and pharmacological inputs by maintaining mitochondrial integrity through autophagy and subsequent mitochondrial biogenesis in chronic settings. / Thesis / Master of Science (MSc) / Traditionally, there are two types of adipose tissue that appear and function differently. White adipose tissue (WAT) has evolved to store away energy in an efficient manner for later use. In contrast, brown adipose tissue (BAT) is a unique organ in mammals that has evolved over time to maintain body temperature. In essence, BAT has the ability to burn away calories as heat and is a promising therapeutic target to combat obesity and metabolic diseases such as type 2 diabetes. In our study, we have identified a potential factor that not only promotes BAT activity, but also promotes WAT to function more like BAT. By targeting this factor through drugs, there is potential to increase resting metabolic rate and fight the global epidemic of obesity.
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/19890 |
| Date | January 2016 |
| Creators | Desjardins, Eric |
| Contributors | Steinberg, Gregory, Medicine |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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