Ceramides are fuel gauges on the drive to cardiometabolic disease.
Joseph L WilkersonSean M TatumWilliam L HollandScott A SummersPublished in: Physiological reviews (2024)
Ceramides are signals of fatty acid excess that accumulate when a cell's energetic needs have been met and its nutrient storage has reached capacity. As these sphingolipids accrue, they alter the metabolism and survival of cells throughout the body including in the heart, liver, blood vessels, skeletal muscle, brain, and kidney. These ceramide actions elicit the tissue dysfunction that underlies cardiometabolic diseases such as diabetes, coronary artery disease, metabolic-associated steatohepatitis, and heart failure. Here, we review the biosynthesis and degradation pathways that maintain ceramide levels in normal physiology and discuss how the loss of ceramide homeostasis drives cardiometabolic pathologies. We highlight signaling nodes that sense small changes in ceramides and in turn reprogram cellular metabolism and stimulate apoptosis. Finally, we evaluate the emerging therapeutic utility of these unique lipids as biomarkers that forecast disease risk and as targets of ceramide-lowering interventions that ameliorate disease.
Keyphrases
- heart failure
- coronary artery disease
- skeletal muscle
- fatty acid
- cell cycle arrest
- oxidative stress
- type diabetes
- cardiovascular disease
- squamous cell carcinoma
- cell death
- physical activity
- atrial fibrillation
- endoplasmic reticulum stress
- coronary artery bypass grafting
- stem cells
- early stage
- radiation therapy
- percutaneous coronary intervention
- glycemic control
- bone marrow
- acute coronary syndrome
- pi k akt
- acute heart failure
- aortic valve
- blood brain barrier
- sensitive detection
- sentinel lymph node
- weight loss
- neoadjuvant chemotherapy
- free survival
- aortic stenosis