Iowa State University
College of Human Sciences and College of Agriculture College of Human Sciences College of Agriculture



The metabolic syndrome in humans reflects a pre-diabetic state that is characterized by visceral obesity, impaired glucose tolerance, and a dyslipidemia which includes an increase in both the circulating triglyceride concentration and the LDL:HDL. Recent discoveries have established a new paradigm for the adipocyte as an active endocrine cell and participant in immune response pathways. Dr. Spurlock's research program addresses this new paradigm, as it relates to obesity and insulin resistance, with emphasis on leptin and adiponectin. These two adipocyte-derived hormones regulate energy metabolism and immunological pathways, locally, and in other cell types.

His laboratory has cloned the porcine adiponectin gene, and shown that this adipocyte-derived hormone regulates the production of pro-inflammatory cytokines in pig macrophages and a monocyte cell line, and that the anti-inflammatory activity of adiponectin also encompasses an induction of the anti-inflammatory cytokine, IL10 in the macrophage. In the adipocyte, Dr. Spurlock's laboratory has shown that gram negative bacterial lipopolysaccharide does indeed stimulate NFkB-mediated gene expression and cytokine production in isolated adipocytes and that adiponectin is a negative regulator of this response to lipopolysaccharide. Furthermore, his laboratory has identified an important differential response in adipocytes vs. macrophages in that cAMP attenuates NFkB signaling in macrophages and stimulates it in adipocytes. This finding has broad potential implications for cell-specific means of regulating IkBα, the cytosolic inhibitor of NFkB signaling. Leptin and adiponectin establish strong integrated linkages among energy metabolism, adiposity, and immune function, and are potentially very important to human health because of their relationship to obesity and its co-morbidities.

Current projects in Dr. Spurlock’s laboratory target the mechanism by which increased adipocyte size (as occurs with obesity) invokes an inflammatory response and causes insulin resistance. He is also collaborating with Dr. Sergei Zolotukhin at the University of Florida to develop a novel gene therapy for obesity that is based on viral expression of adiponectin. Whereas rodent models have been used widely to study the metabolic syndrome, certain physiologic differences between rodents and humans, including the presence of significant brown adipose tissue depots in young and adult rodents, complicate the application of rodent data to humans. The Ossabaw breed of swine is genetically predisposed to the metabolic syndrome, and thus has much potential as a model for the human disease.

Dr. Spurlock is working with members in the Comparative Medicine Program at Purdue University, and with Dr. Michael Sturek, Indiana University School of Medicine, to develop the Ossabaw pig as a model for the metabolic syndrome in humans.

Diet Formulations

Food Science and Human Nutrition