The role of protein kinase D (PKD) in obesity: Lessons from the heart and other tissues

• Published in: Biochimica et biophysica acta. Molecular cell research Vol. 1871; no. 7; p. 119814
• Main Authors: Renton, Mark C., McGee, Sean L., Howlett, Kirsten F.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-10-2024
• Subjects: Cardiac dysfunction; Cell signalling; Cell specificity; Obesity; Obesity cardiomyopathy; Protein kinase D; Cell signalling; Obesity; Cell specificity; Protein kinase D; Obesity cardiomyopathy; Cardiac dysfunction
• ISSN: 0167-4889; 1879-2596; 1879-2596
• DOI: 10.1016/j.bbamcr.2024.119814

Obesity causes a range of tissue dysfunctions that increases the risk for morbidity and mortality. Protein kinase D (PKD) represents a family of stress-activated intracellular signalling proteins that regulate essential processes such as cell proliferation and differentiation, cell survival, and exocytosis. Evidence suggests that PKD regulates the cellular adaptations to the obese environment in metabolically important tissues and drives the development of a variety of diseases. This review explores the role that PKD plays in tissue dysfunction in obesity, with special consideration of the development of obesity-mediated cardiomyopathy, a distinct cardiovascular disease that occurs in the absence of common comorbidities and leads to eventual heart failure and death. The downstream mechanisms mediated by PKD that could contribute to dysfunctions observed in the heart and other metabolically important tissues in obesity, and the predicted cell types involved are discussed to suggest potential targets for the development of therapeutics against obesity-related disease.
•Protein kinase D (PKD) senses and modulates tissue-specific adaptations to obesity.•PKD promotes cardiac dysfunction in obesity, but the exact mechanisms are unclear.•Research required to elucidate the role of PKD in non-myocyte cells in the heart.•PKD pathways are attractive treatment targets for tissue dysfunction in obesity.