Research

Research Interests

My research focuses primarily on neuropeptides (small proteins which act as brain signaling molecules), and more specifically on the relative importance of the neuropeptide orexin (hypocretin). The two forms of orexin peptide (orexin A and B, or hypocretin 1 and 2) have previously been shown important in regulating various aspects of sleep-wake behavior, food intake, and energy expenditure [1,2]. Studies in humans and animals suggest that a key factor allowing individuals to resist obesity is the propensity for increased physical activity, and data from animal models strongly support a role for orexin in maintaining increased physical activity levels [1,3]. Because orexins are involved in regulation of a number of physiological processes aside from energy intake and expenditure, I strongly feel that a global approach (in which signaling is altered systemically) is not optimal for understanding the effects of orexin in discrete behaviors. Instead, my research uses discrete application of orexin, receptor agonists and antagonists, or other test substances into specific parts of the brain, with study endpoints focused on the resulting behavioral, physiological, or gene expression-level changes in the organism. Currently planned and funded studies utilize a combination of in vitro and in vivo approaches, using hypothalamic neuronal cell line models, "ex vivo" organotypic hypothalamic explants, and rodent models to evaluate hypotheses.

In my research I draw on over a decade of personal experience working with rodent models of activity and energy expenditure, as well as the expertise of colleagues and collaborators at the Minneapolis VA Health Care System, the Minnesota Obesity Center, and the University of Minnesota Departments of Food Science and Nutrition, Neuroscience, and Medicine. I have a broad background in circadian biology, with training in ecology, evolutionary and behavioral biology. As such I bring a unique perspective to my work, and strive to correlate the relevance of findings to the evolutionary history of the model, to better understand how systems that may have been adaptive in early human history may have become maladaptive in our current obesogenic environment.

    References
  1. Nixon JP, Kotz CM, Novak CM, Billington CJ, Teske JA. Neuropeptides controlling energy balance: orexins and neuromedins. Handb Exp Pharmacol. 2012(209):77-109. Epub 2012/01/18. doi: 10.1007/978-3-642-24716-3_4.
  2. Nixon JP, Mavanji V, Butterick TA, Billington CJ, Kotz CM, and JA Teske, 2014. Sleep disorders, obesity, and aging: The role of orexin. Ageing Res Rev, in press. doi: 10.1016/j.arr.2014.11.001.
  3. Kotz CM, Nixon JP, Butterick TA, Perez-Leighton CE, Teske JA, Billington CJ. Brain orexin promotes obesity resistance. Ann N Y Acad Sci. 2012;1264(1):72-86. Epub 2012/07/19. doi: 10.1111/j.1749-6632.2012.06585.x.
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