Ceramide in Type 2 Diabetes and Obesity: Modulation by Nutrients and Dietary Patterns and Opportunities to Prevent and/or Manage Metabolic-Related Conditions

Ceramides, sphingolipids produced from fatty acids linked to sphingosine and an amide, are structural elements of cellular membranes and lipoproteins. These molecules also retain biological effects in key cellular pathways such as oxidative stress and inflammation, apoptosis, and fibrosis, with a role in the onset and development of many pathophysiological conditions, including obesity, diabetes, and insulin resistance. Increasing evidence suggests that different nutrients and dietary patterns may affect ceramide levels, both negatively (e.g., fructose and the Western diet), whereas others improve the ceramide profile (e.g., ω-3 PUFAs, resveratrol, vitamin D, and the Mediterranean and the Nordic diets). Thus, ceramide nutritional modulation could represent a simple, additive, and reliable tool to improve metabolic health. This review focused on the role of ceramides in the pathophysiology of diabetes and obesity, as well as their pathogenetic mechanisms of action. Ceramides are increasingly recognized as "dynamic metabolic interfaces" linking nutrition and disease. This review aims to address a critical gap by synthesizing recent evidence on how dietary interventions, in addition to pharmacological approaches, can specifically target the enzymatic pathways involved in ceramide synthesis to enhance metabolic health. Thus, this review offers a concentrated analysis of the response of specific ceramide species, such as Cer16:0 and Cer18:0, to distinct dietary factors. Additionally, it incorporates emerging evidence on the role of gut microbiota in the biotransformation of sphingolipids, thereby adding a contemporary dimension to the established nutritional perspective.