Method and Compositions for Modulating PPAR activity in ISCs

Diet profoundly impacts our nutritional landscape, public health, and disease susceptibility. In the gut, nutrients directly influence how intestinal stem cells (ISCs) function and maintain homeostasis. Yet, the connection between metabolic processes and transcriptional regulation are poorly defined. As a long-lived population, adult ISCs maintain the intestinal lining through self-renewal and differentiation. Because they are directly exposed to nutrients within the intestinal crypt, ISCs actively adapt their metabolic processes and fate decisions in response to changes in nutrient availability.

 

Researchers at Arizona State University have elucidated how O-GlcNAcylation (OGN) serves as a metabolic signaling mechanism in intestinal stem cells (ISCs), integrating glucose and lipid metabolism to regulate mitochondrial function and stem cell behavior via PPAR signaling pathways. Dietary factors such as a high-fat diet alter OGN levels in ISC mitochondria, influencing proliferation and regenerative capacity and this dynamic regulation impacts ISC transcriptional programs and tissue homeostasis. Further, novel compositions were developed for metabolic control of ISC function.

 

This technology provides novel methods and compositions to regulate ISC metabolic programming through PPAR signaling influenced by dietary nutrients.

 

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