The role of ceramides in metabolic disorders: when size and localization matters

Turpin-Nolan, Sarah M.; Brüning, Jens C.

doi:10.1038/s41574-020-0320-5

Cited by 128 publications

(128 citation statements)

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“…Ceramides are bioactive lipids that play important roles in many central processes of human cells, such as apoptosis and inflammation [for additional information see e.g., the following reviews ( 1 – 5 )]. During the past decade many investigations have revealed a strong association between ceramides and cardiometabolic conditions.…”

Section: Introductionmentioning

confidence: 99%

Ceramides and Ceramide Scores: Clinical Applications for Cardiometabolic Risk Stratification

et al. 2020

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Ceramides are bioactive lipids that have an important role in many cellular functions such as apoptosis and inflammation. During the past decade emerging clinical data have shown that ceramides are not only of great biochemical interest but may also have diagnostic utility. Ceramides have shown independent predictive value for negative cardiovascular outcomes as well as for the onset of type 2 diabetes. Based on abundant published data, risk score using the concentrations of circulating ceramides have been developed and adapted for routine clinical practice. Currently serum ceramides are used clinically as efficient risk stratifiers for primary and secondary prevention of atherosclerotic cardiovascular disease (CVD). A direct cause-effect relationship between CVD and ceramide has not been established to date. As ceramide-specific medications are being developed, conventional strategies such as lipid lowering agents and lifestyle interventions can be used to reduce overall risk. Ceramides can identify a very high-risk coronary heart disease category of patients in need for more intense medical attention, specifically those patients at higher risk as highlighted in the 2019 European Society of Cardiology guidelines for stable chronic coronary syndrome patients. In addition, the ceramide risk score may be used as a decision-making tool in primary prevention patients with moderate CVD risk. Finally, the ceramide risk score may have a unique utility as a motivational tool to increase patient's adherence to medical therapy and lifestyle changes.

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Section: Introductionmentioning

confidence: 99%

Ceramides and Ceramide Scores: Clinical Applications for Cardiometabolic Risk Stratification

et al. 2020

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“…Metabolism ceramide-induced deterioration of metabolic function. 13 In line, ceramide 16 and 24 and certain sphingomyelin species were increased in methionine-choline-deficient mice, indicating upregulation of sphingolipid metabolism in NASH. 14 Recently, Chaurasia et al 15 reported elegant mouse experiments targeting dihydroceramide desaturase-1 (DES-1), a rate-limiting enzyme for de novo ceramide synthesis.…”

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confidence: 89%

Role of ceramide-to-dihydroceramide ratios for insulin resistance and non-alcoholic fatty liver disease in humans

Apostolopoulou

Gordillo

Gancheva

et al. 2020

BMJ Open Diab Res Care

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IntroductionSphingolipid accumulation has been linked to obesity, type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). A recent study showed that depletion of dihydroceramide desaturase-1 (DES-1) in adipose and/or liver tissue decreases ceramide-to-dihydroceramide ratios (ceramide/dihydroceramide) in several tissues and improves the metabolic profile in mice. We tested the hypothesis that ceramide/dihydroceramide would also be elevated and relate positively to liver fat content and insulin resistance in humans.Research design and methodsThus, we assessed total and specific ceramide/dihydroceramide in various biosamples of 7 lean and 21 obese volunteers without or with different NAFLD stages, who were eligible for abdominal or bariatric surgery, respectively. Biosamples were obtained from serum, liver, rectus abdominis muscle as well as subcutaneous abdominal and visceral adipose tissue during surgery.ResultsSurprisingly, certain serum and liver ceramide/dihydroceramide ratios were reduced in both obesity and non-alcoholic steatohepatitis (NASH) and related inversely to liver fat content. Specifically, hepatic ceramide/dihydroceramide (species 16:0) related negatively to hepatic mitochondrial capacity and lipid peroxidation. In visceral adipose tissue, ceramide/dihydroceramide (species 16:0) associated positively with markers of inflammation.ConclusionThese results failed to confirm the relationships of ceramide/dihydroceramide in humans with different degree of insulin resistance. However, the low hepatic ceramide/dihydroceramide favor a role for dihydroceramide accumulation in NASH, while a specific ceramide/dihydroceramide ratio in visceral adipose tissue suggests a role of ceramides in obesity-associated low-grade inflammation.

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“…In recent decades, researchers have emphasized a connection between increased ceramides abundance in muscle, liver and adipose tissue, and impaired response to insulin. Coincidently, the accumulation of ceramides in key metabolic tissues, mostly due to excessive dietary fat and calorie intake, has been recognized as a potential target for novel preventive and/or therapeutic strategies in obesity and related disorders [ 5 ]. Ceramides are central molecules of sphingolipid metabolism, which can act at different cellular compartments (e.g., plasma membrane, endoplasmic reticulum, and mitochondria), with detrimental effects on insulin signaling and glucose homeostasis [ 5 ].…”

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confidence: 99%

“…Coincidently, the accumulation of ceramides in key metabolic tissues, mostly due to excessive dietary fat and calorie intake, has been recognized as a potential target for novel preventive and/or therapeutic strategies in obesity and related disorders [ 5 ]. Ceramides are central molecules of sphingolipid metabolism, which can act at different cellular compartments (e.g., plasma membrane, endoplasmic reticulum, and mitochondria), with detrimental effects on insulin signaling and glucose homeostasis [ 5 ]. Teng and colleagues demonstrated that sulforaphane, a naturally occurring isothiocyanate compound in cruciferous vegetables such as broccoli and cabbage, can dose-dependently recover insulin signaling in in vitro models of hepatic IR by exerting inhibitory activities on the expression of SPTLC3 , the gene encoding the third subunit of the rate-limiting enzyme of ceramide biosynthesis (serine palmytoiltransferase, SPT) [ 6 ].…”

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confidence: 99%

“…As extensively detailed, the subcellular abundance of diacilglycerol (DAG) and/or ceramides, both causing a direct loss of insulin signaling in mechanistic studies, inversely correlates with insulin sensitivity in target organs [ 24 ]. Moreover, the differential impact of specific acyl chain length ceramides on insulin homeostasis and functions represents an emerging concept in the nutritional regulation of glucose metabolism [ 5 ]. However, not all dietary fats have detrimental effects on insulin sensitivity.…”

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The Role of Diet on Insulin Sensitivity

2020

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The role of ceramides in metabolic disorders: when size and localization matters

Cited by 128 publications

References 102 publications

Ceramides and Ceramide Scores: Clinical Applications for Cardiometabolic Risk Stratification

Ceramides and Ceramide Scores: Clinical Applications for Cardiometabolic Risk Stratification

Role of ceramide-to-dihydroceramide ratios for insulin resistance and non-alcoholic fatty liver disease in humans

The Role of Diet on Insulin Sensitivity

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