Center for Technology Commercialization

Therapeutic Protection from Diet-Induced Obesity and Insulin Resistance Through Targeting of RP105/MD-1

CHMC Ref. Id: 2007-0803)

Overview:

Obesity is increasing in prevalence in adults and children, and authorities view it as one of the most serious public health problems of the 21st century. It is a primary risk factor for insulin resistance and type 2 diabetes mellitus (T2DM). It has become clear in recent years that inflammation provides a critical link between these two metabolic syndromes. While it has been thought that relevant Toll-like receptor-4 (TLR4) ligands are driving such inflammation, TLR4-/- mice are protected from high fat diet-induced insulin resistance, despite gaining increased weight on such diets, compared with wild type controls.

Researchers at Cincinnati Children's have recently discovered that a novel endogenous inhibitor of TLR4 signaling, RP105 (also referred to as CD180) is a specific TLR4 homolog, whose association with a secreted protein, MD-2, is necessary for cell signaling, and whose association with a secreted protein, MD-1, is necessary for surface expression and function, and that the RP105/MD-1 complex inhibits the ability of the TLR4/MD-2 complex to bind lipopolysaccharide (LPS). The researchers have developed methods for treating and/or preventing diet-induced obesity and/or one or more sequelae thereof, as well as methods of screening candidate compounds which can be used to treat and/or prevent obesity and/or one or more sequelae thereof by administering a therapeutically effective amount of at least one inhibitor of RP105 and/or MD-1 activity and/or expression.

Applications:

Treating and/or preventing diet-induced obesity and/or one or more sequelae thereof

Advantages:

Provides methods for treating and/or preventing diet-induced obesity
Provides a prevention for developing insulin resistance and type 2 diabetes mellitus caused by obesity

Patent Information: