Riordan Article in International Journal of Obesity
An article co-authored by PNDRI Scientist Jesse Riordan, Ph.D., and PNDRI Principal Investigator Joe Nadeau, Ph.D., was recently accepted in International Journal of Obesity, the leading obesity journal and a publication of Nature. The article investigates genetic and dietary contributions to metabolic syndrome.
Metabolic syndrome (MetS), which includes obesity, high cholesterol, type 2 diabetes, and high blood pressure, is among the most common medical disorders in the United States. It is associated with increased risk of developing cardiovascular disease, stroke, and some forms of cancer. Effective methods for predicting a patient’s progression from MetS to life-threatening conditions, or of preventing or reversing the course of the disease, are underexplored due, in part, to insufficient understanding of the factors driving MetS. While it is understood that genetics and environment both play important roles, how they influence and how much they influence metabolic health has not been extensively studied. Understanding those interactions is critical to the development of effective therapies for MetS patients.
Riordan, Nadeau, and team assessed the effect of genetics and diet on MetS using two inbred mouse strains, one of which develops severe diet-induced MetS and the other of which is completely resistant. The team employed a unique genetic resource first developed by Nadeau, called CSS or Chromosome Substitution Strain panel. CSS consists of 22 inbred mouse strains each containing a different chromosome substituted onto the same genetic background. The panel allows scientists to study individual chromosomes independently in a uniform and tightly controlled manner.
The CSS panel identified specific chromosomes associated with MetS disease severity, including chromosomes that conferred nearly complete protection from diet-induced MetS. Other chromosomes provided either resistance to a subset of conditions or minimally impacted the development of the disease. Additional work found strong interactions between individual MetS traits regardless of the strain of mouse and identified specific regions of a single chromosome that were associated with the severity of the disease.
Overall, the results provide insight into how genetic factors promote MetS and identify several genomic regions associated with disease susceptibility and severity. They provide a solid basis for future studies aimed at discovering specific genes and sequence variants that contribute to MetS, and may ultimately lead to identification of methods of prediction and therapies for patients with MetS.