Ceramides are early responders in metabolic syndrome development in rhesus monkeys

Abstract

Metabolic syndrome increases risk of complicating co-morbidities. Current clinical indicators reflect established metabolic impairment, preventing earlier intervention strategies. Here we show that circulating sphingolipids are altered in the very early stages of insulin resistance development. The study involved 16 paired overweight but healthy monkeys, one-half of which spontaneously developed metabolic syndrome over the course of 2 years. Importantly, animals did not differ in adiposity and were euglycemic throughout the study period. Using mass spectrometry, circulating sphingolipids, including ceramides and sphingomyelins, were detected and quantified for healthy and impaired animals at both time points. At time of diagnosis, several ceramides were significantly different between healthy and impaired animals. Correlation analysis revealed differences in the interactions among ceramides in impaired animals at diagnosis and pre-diagnosis when animals were clinically indistinguishable from controls. Furthermore, correlations between ceramides and early-stage markers of insulin resistance, diacylglycerols and non-esterified fatty acids, were distinct for healthy and impaired states. Regression analysis identifies coordinated changes in lipid handling across lipid classes as animals progress from healthy to insulin resistant. Correlations between ceramides and the adipose-derived adipokine adiponectin were apparent in healthy animals but not in the metabolically impaired animals, even in advance of loss in insulin sensitivity. These data suggest that circulating ceramides are clinically relevant in identifying disease risk independent of differences in adiposity, and may be important in devising preventative strategies.

Ceramides and metabolic profiles of patients with acute coronary disease: a cross-sectional study

“…Regarding the clinical research area, a recent study involving overweight but healthy monkeys showed a strong correlation between ceramides and the onset of early-stage metabolic syndrome symptoms, highlighting the relevance of circulating ceramides in identifying risk between healthy and impaired study groups. This highlights the potential of ceramides as a simple and minimally invasive diagnostic tool for metabolic syndrome ( Smith et al, 2022 ).…”

Progress in experimental models to investigate the in vivo and in vitro antidiabetic activity of drugs

“…Over several years, it proceeds to necrosis of beta cells, a sharp drop in insulin levels, and hyperglycemia. 59,123,124 The Zebrafish model is an attractive model system for the study of metabolic abnormalities. Zebrafish have preserved energy balance and cholesterol metabolism.…”

“…If kept on an ad libitum laboratory diet, especially fructose, it develops obesity, hyperinsulinemia, and insulin resistance. Over several years, it proceeds to necrosis of beta cells, a sharp drop in insulin levels, and hyperglycemia 59,123,124 …”

“…Over several years, it proceeds to necrosis of beta cells, a sharp drop in insulin levels, and hyperglycemia. 59 , 123 , 124 …”

Ultra‐high performance liquid chromatography‐quadrupole/time‐of‐flight mass spectrometry‐based lipidomics reveals key lipid molecules as potential therapeutic targets of Polygonum cuspidatum against hyperlipidemia in a hamster model

“…Additionally, the four SMs were negative, while the above Cers were positively correlated with TC, TG, LDL-C, ALT, and AST. An abundance of evidence has demonstrated the contribution of Cers and SMs to metabolic disorders and cardiovascular diseases [47,48]. What's more, the chain lengths, number of double bonds, and number of hydroxyls on the sphingoid base and fatty acid residue impact the biological activities of Cers and SMs [49,50].…”