New Factor involved in Lipid Disorders
BACKGROUND: Fat cells, or adipocytes, are a specialized cell type that synthesize and store fat (triglycerides) in periods of nutritional abundance, and hydrolyze these fats when needed to meet demand for energy. The size and distribution of adipose tissue stores in humans and animals clearly influences metabolism and development of diseases including obesity and diabetes. Most of the development of mature adipocytes from precursor cells, a process known as differentiation, occurs shortly before or after birth, but further differentiation can occur at any time during life in response to various hormonal or nutritional signals.DESCRIPTION: UC scientists have identified a protein, lipin, that is required for normal development of adipocytes. Based on an analysis of the structure of lipin, UC researchers believe that it represents a new player in the regulatory cascade controlling adipocyte differentiation. Mice exhibiting a mutation in the production of lipin protein exhibit an 80% reduction in fat mass and abnormal, undeveloped fat cells. Fat precursor cells isolated from these mice fail to accumulate fat or respond to insulin normally. As a consequence, mutant mice develop severe insulin resistance, a predisposing condition to diabetes. These mice suffer detrimental side-effects that include impaired fertility, reduced lifespan, and impaired nerve function, the latter of which results in a tremor and difficulty in walking. They also develop atherosclerosis at an accelerated rate. Thus, lipin is a critical factor in development and function of adipose tissue, and mutations affecting the function of this protein could contribute to disorders including diabetes, atherosclerosis, obesity and lipodystrophy.
APPLICATIONS: Mutations or polymorphisms in the human lipin gene may be associated with metabolic disturbances in adipose tissue metabolism including diabetes, obesity, lipodystrophy, and atherosclerosis. Drugs currently used in clinical practice for the treatment of non-insulin dependent diabetes fail to normalize glucose levels in most diabetic patients when taken alone, and many patients do not respond well even when used in combination with insulin. Furthermore, toxicity of these drugs has been a problem in a subset of patients, Much room exists for improvement, such as the identification of novel therapeutic targets within the differentiation pathway. Lipin could be such a novel target for the development of therapeutic drugs in disorders such as diabetes and obesity. Potential mechanisms for modulation of lipin activity are suggested by initial structural studies of the protein and include phosphorylation/ dephosphorylation. Diagnostically, the lipin gene sequences will also potentially be an important tool to screen patients at risk for these conditions.
REFERENCE: 2000-072
Patents:
US 6,869,766 [MORE INFO]
Type of Offer: Licensing
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