Harnessing NAD+ Metabolism as Therapy for Cardiometabolic Diseases

Abstract

Purpose of the review: This review summarizes current understanding on the roles of nicotinamide adenine dinucleotide (NAD⁺) metabolism in the pathogeneses and treatment development of metabolic and cardiac diseases.

Recent findings: NAD⁺ was identified as a redox cofactor in metabolism and a co-substrate for a wide range of NAD⁺-dependent enzymes. NAD⁺ redox imbalance and depletion are associated with many pathologies where metabolism plays a key role, for example cardiometabolic diseases. This review is to delineate the current knowledge about harnessing NAD⁺ metabolism as potential therapy for cardiometabolic diseases. The review has summarized how NAD⁺ redox imbalance and depletion contribute to the pathogeneses of cardiometabolic diseases. Therapeutic evidence involving activation of NAD⁺ synthesis in pre-clinical and clinical studies was discussed. While activation of NAD⁺ synthesis shows great promise for therapy, the field of NAD⁺ metabolism is rapidly evolving. Therefore, it is expected that new mechanisms will be discovered as therapeutic targets for cardiometabolic diseases.

Keywords: Cardiometabolic diseases; Heart failure; NAD+ metabolism; Redox balance.