The Impact of Phytochemicals in Obesity-Related Metabolic Diseases: Focus on Ceramide Metabolism

Abstract

The prevalence of obesity and related metabolic diseases has increased dramatically worldwide. As obesity progresses, various lipid species accumulate in ectopic tissues. Amongst them, ceramides-a deleterious sphingolipid species-accumulate and cause lipotoxicity and metabolic disturbances. Dysregulated ceramide metabolism appears to be a key feature in the pathogenesis of obesity-related metabolic diseases. Notably, dietary modification might have an impact on modulating ceramide metabolism. Phytochemicals are plant-derived compounds with various physiological properties, which have been shown to protect against obesity-related metabolic diseases. In this review, we aim to examine the impact of a myriad of phytochemicals and their dietary sources in altering ceramide deposition and ceramide-related metabolism from in vitro, in vivo, and human clinical/epidemiological studies. This review discusses how numerous phytochemicals are able to alleviate ceramide-induced metabolic defects and reduce the risk of obesity-related metabolic diseases via diverse mechanisms.

Keywords: ceramide; metabolic disease; obesity; phytochemical; sphingolipid.

Figure 1

Schematic representation of sphingolipid metabolic pathways that alter ceramide levels. Ceramide can be generated through (1) the de novo synthesis pathway; or (2) sphingomyelin hydrolysis pathway. Complex sphingolipids can also be degraded back to ceramide, which is called (3) the salvage pathway. Abbreviations: SPT, serine palmitoyltransferase; KSR, 3-ketosphinganine reductase; CERS, ceramide synthase; DES, dihydroceramide desaturase; CDase, ceramidase; SMS, sphingomyelin synthase, SMase, sphingomyelinase.

Figure 2

The impact of phytochemicals on ceramide metabolism and physiological results.