Metabolic Disease Program - Diabetes and Obesity Research Center
The Wood Lab is interested in genotype/phenotype relationships regarding metabolic diseases, especially those involving fatty acid metabolism. This includes rare inherited enzyme deficiencies that affected primarily children, as well as more common diseases or processes that include obesity-related traits. These include insulin resistance, fatty liver disease, metabolic syndrome and type 2 diabetes mellitus. This approach allows us to identify genes (genotype) that help explain the basic cause of disease traits (phenotype). Furthermore, this information often points us toward disease mechanisms and potential new drug targets.
We are interested in understanding what versions (alleles) of genes in individuals that may cause, predispose, or protect them from disease traits during conditions of excess fat. We study these processes using six mouse models with inherited enzyme deficiencies of the mitochondrial fatty acid beta-oxidation (FAO) pathway, also known as fat burning. Our studies can be summarized in two major areas.
Note: SCAD = short-chain acyl-CoA dehydrogenase deficiency; LCAD = long-chain acyl-CoA dehydrogenase deficiency
1. Inherited enzyme deficiencies in the mitochondrial fatty acid oxidation pathway.
These disorders primarily affect children and are characterized by phenotypes that include poor fasting tolerance, sudden infant death, fatty liver, and heart diseases. We are very interested in testing potential new therapies in our mouse models, as well as our evolving “disease in a dish” platform using individual patient cells in culture.
2. Obesity-related disease traits that include fatty liver, insulin resistance, pro-inflammatory state, metabolic syndrome, pancreatic beta-cell loss and development of type 2 diabetes.
This is a problem of having a genotype that predisposes individuals to these problems in the face of obesity. Thus, this is a genetics of predisposition, poor response or intolerance of the extra fat load provided by obesity. There are also those who, despite their obesity, do not develop these secondary disease processes and that would represent having a genetics of resistance to the excess fat of obesity. Both scenarios are of great interest.
We not only take advantage of a series of mouse models that we have developed over the years with specific enzyme deficiencies in the pathway of mitochondrial b-oxidation of fatty acids, but we have now added human patient derived material for investigation.