Grant: Project Grant

Obesity results from an imbalance between energy intake and expenditure. Finding novel means to increase the burning of excess calories is an important area of research for the development of innovative therapeutic solutions against obesity and type 2 diabetes. We have obtained preliminary results suggesting that the protein IGFBP-2 increases energy expenditure by promoting the activity of brown adipose tissue, a specialized organ that uses high amounts of energy to produce heat upon activation for non-shivering thermogenesis. The stimulation of brown adipose tissue has previously been shown to metabolize energy substrates and increase energy expenditure. We will test whether IGFBP-2 increases brown adipose tissue activity using mice that have increased or decreased IGFBP-2 levels. We will also search for the physiological pathways that trigger the increase in IGFBP-2 upon cold exposure or overfeeding. The molecular mechanisms of action of IGFBP-2 will be further assessed by pharmacologic and genetic treatments using mice, cells in culture, and molecular techniques. We expect this research to generate important novel health-related knowledge and to result in innovative and translatable discoveries.