Project Grant R01AR086828

The National Institute of Arthritis and Musculoskeletal and Skin Diseases awarded the University of Texas Southwestern Medical Center $578,211 on August 7, 2026, under the Arthritis, Musculoskeletal and Skin Diseases Research program (CFDA 93.846) to fund investigator-initiated research defining how epidermal NADPH depletion and redox imbalance disrupt skin barrier function and drive systemic metabolic effects.

The project addresses the physiological roles of NAD kinase (NADK) and NADPH metabolism in skin homeostasis using an inducible, keratinocyte-specific NADK knockout mouse model. Preliminary findings show that loss of NADK in the skin produces impaired barrier integrity coupled with systemic fat loss and resistance to diet-induced obesity, independent of food intake or thermogenesis, revealing a previously unrecognized skin-initiated metabolic signaling pathway. The funded research will test whether epidermal NADPH depletion causes redox imbalance that disrupts lipid metabolism and drives barrier failure locally while activating a redox-dependent skin-to-fat signaling axis that produces systemic lipolysis. Aim 1 will employ isotope tracing, metabolomics, and lipidomics to define specific metabolic pathways disrupted by redox imbalance, including lipid peroxidation and suppressed de novo lipogenesis.

The award is classified as a Project Grant. Performance occurs in Dallas, Texas. The period of performance runs through July 31, 2031.