Contribution of specific ceramides to obesity-associated metabolic diseases

Abstract

Ceramides are a heterogeneous group of bioactive membrane sphingolipids that play specialized regulatory roles in cellular metabolism depending on their characteristic fatty acyl chain lengths and subcellular distribution. As obesity progresses, certain ceramide molecular species accumulate in metabolic tissues and cause cell-type-specific lipotoxic reactions that disrupt metabolic homeostasis and lead to the development of cardiometabolic diseases. Several mechanisms for ceramide action have been inferred from studies in vitro, but only recently have we begun to better understand the acyl chain length specificity of ceramide-mediated signaling in the context of physiology and disease in vivo. New discoveries show that specific ceramides affect various metabolic pathways and that global or tissue-specific reduction in selected ceramide pools in obese rodents is sufficient to improve metabolic health. Here, we review the tissue-specific regulation and functions of ceramides in obesity, thus highlighting the emerging concept of selectively inhibiting production or action of ceramides with specific acyl chain lengths as novel therapeutic strategies to ameliorate obesity-associated diseases.

Effect of circulating ceramides on adiposity and insulin resistance in patients with type 2 diabetes: An observational cross‐sectional study

“…In a separate but related study, circulating LDL‐ceramides led to IR and inflammation in lean mice, and they decreased glucose disposal uptake in cultured myotubes 37 . Ceramides, thus, contribute to the homeostatic control of lipid metabolism by influencing the absorption, storage and oxidation of fatty acids in adipocytes, hepatocytes and myocytes 57,58 …”

“… 37 Ceramides, thus, contribute to the homeostatic control of lipid metabolism by influencing the absorption, storage and oxidation of fatty acids in adipocytes, hepatocytes and myocytes. 57 , 58 …”

“…37 Ceramides, thus, contribute to the homeostatic control of lipid metabolism by influencing the absorption, storage and oxidation of fatty acids in adipocytes, hepatocytes and myocytes. 57,58 Blood pressure, BMI, percent body fat, FPG, HbA1c, total cholesterol, triglycerides and low-density lipoproteins were significantly higher among the case group when compared with the control group. This finding corroborates other studies.…”

The Effect of Broccoli Glucoraphanin Supplementation on Ameliorating High‐Fat‐Diet‐Induced Obesity through the Gut Microbiome and Metabolome Interface

“…Studies have shown that reduced circulating ceremide levels in obese cohort are a biomarker for ameliorated metabolic health. [62,95] Glycerol is a major metabolite in LPC and phosphatidylcholine biosynthesis. Circulating LPC can transport fatty acids, glycerol, and phosphatidylcholine to tissues that induce triglycerides synthesis and lipogenesis associated with obesity.…”

Role of ceramides in diabetic foot ulcers (Review)

“…The third pathway is the salvage pathway, in which sphingolipids degraded to sphingosine (Sph) are reutilized by reacylation to produce ceramides. Lipid phosphate phosphatases or Sph-1-phosphate (S1P) phosphatase are used to obtain Sph ( 22 ). CerSs may acylate Sph to form ceramides.…”