About the Speaker

Dr Andrew Butler completed his doctorate at the University of Auckland in 1995.  He then completed post doctoral training with Dr Derek LeRoith at the National Institutes of Health (NIH) in Bethesda, MD, investigating signaling by the Igf1 receptor and its role in growth and tumorigenesis. Realizing that obesity and diabetes are the major health issues facing industrialized countries, Dr Butler undertook a postdoctoral fellowship with Dr Roger Cone in 1998.  Dr Cone’s laboratory published some of the seminal observations linking the melanocortin system to appetite regulation and energy homeostasis.

In 2001, Dr Butler moved to the Pennington Biomedical Research Center in Baton Rouge, LA, and established the Neuropeptides laboratory to investigate the physiology of obesity and insulin resistance. Research by Dr Butler and others have demonstrated that melanocortin receptor, MC4R, regulates energy balance through effecting systems that have been classically associated with the prevention of obesity and insulin resistance. MC4R regulates satiety, diet-induced thermogenesis and fat oxidation, thyroid function, and sympathetic nervous activity.  Dr Butler was involved in the first description of a role for another melanocortin receptor, MC3R, in energy homeostasis. Funded by the NIH, Dr Butler’s lab is investigating a novel function for the MC3R, working on the hypothesis that this receptor functions to regulate circadian rhythms with feeding.  Finally, a developing focus is a novel gene encoding a secreted peptide that may be a new factor associating obesity with insulin resistance.  His lab has named the gene encoding this protein "Energy Homeostasis Associated" (Enho).

Abstract

Energy homeostasis is classically seen from the viewpoint of matching calorie intake with energy expenditure.  Clearly, excess caloric consumption in the absence of increased total energy expenditure causes weight gain and metabolic disorders.  However, this concept fails to take into account that energy metabolism involves heterogeneity in substrate (fatty acids and glucose) utilization.  Organisms can adapt substrate in response to variable macronutrient composition of the diet.  How do organisms match the metabolic activity of a diverse group of cell types with macronutrient consumption?  The nature of the signals involved in coordinating substrate metabolism with macronutrient consumption systemically is only beginning to be defined.  At a cellular level, nuclear receptors have been identified that act as “sensors” of carbohydrate and lipids.  However, it is likely that cell-to-cell communication of energy status involves secreted peptides and the deterioration in the function of these systems contributes to the pathogenesis of obesity.  A classic example is leptin, which is secreted from adipocytes and which regulates fatty acid and carbohydrate metabolism in liver and muscle.
 
Cross-talk between tissues is thus essential for coordinating macronutrient consumption with substrate metabolism to maintain energy homeostasis and insulin sensitivity.  In this presentation, I will describe a newly identified circulating protein, adropin, which functions as a link between macronutrient consumption and energy homeostasis.  In liver, adropin expression is potently stimulated by high fat diets; whereas in brain, adropin expression is positively correlated with total caloric intake. Hepatosteatosis, inflammation in white adipose tissue and the hyperinsulinemia associated with obesity were all attenuated with adropin therapy.  Adropin reduces expression of genes involved in lipogenesis, including Peroxisome Proliferator-Activated Receptor Gamma (Pparg) in adipocytes, and alters whole body energy metabolism by substrate selection, as indicated by a lower respiratory quotient.  These effects on lipid metabolism are associated with protection from diet-induced obesity and insulin resistance. Preliminary data from the analysis of adropin knockout mice suggest increased Pparg in white adipose tissue and an increase in adiposity.  Collectively, these data lead to the hypothesis that adropin is a neuroendocrine factor that coordinates fatty acid metabolism with macronutrient consumption to protect against hepatosteatosis, inflammation and the hyperinsulinemia associated with diet-induced obesity.

All are welcome! Please RSVP to This e-mail address is being protected from spam bots, you need JavaScript enabled to view it by 28 April.