Ceramide: a contributor to insulin resistance or an innocent bystander?

Boden, Guenther

doi:10.1007/s00125-008-1015-y

Cited by 37 publications

(29 citation statements)

References 12 publications

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“…The metabolism of SL is dysregulated in obesity, in which increased adipose tissue mass affects whole body insulin resistance and cardiovascular disease risk via adipose-tissue derived inflammatory cytokines that induce chronic inflammation, as well as increasing cardiovascular risk while the antagonizing insulin signaling and mitochondrial function, thereby impairing glucose homeostasis (23,149,153). These data suggest that SLs are effective targets for the treatment of diseases associated with chronic inflammation (23,20,24).…”

Section: Sl Pathways In Diabetes Nafld and Nashmentioning

confidence: 99%

“…SLs are also relevant in the pathogenesis of these diseases. Obesity-related inflammatory pathways modulate SL metabolism (20,23,24). Metabolomics profiling, liquid chromatography mass spectrometry, and gene expression analyses showed increased hepatic Cer and a higher levels of SLs in NASH (21,22,28,30,36,38).…”

Section: Sl Pathways In Diabetes Nafld and Nashmentioning

confidence: 99%

“…Cers can affect cellular proliferation, differentiation, cell death, insulin resistance, oxidative stress, inflammation, and apoptosis, all of which are linked to NAFLD (24,132,136). De novo Cer synthesis plays a role in liver metabolism and has been investigated in the context of hepatic insulin resistance, NASH, obesity, dyslipidemia, hypertension, and cardiovascular diseases (25,72,76).…”

Section: Sl Pathways In Diabetes Nafld and Nashmentioning

confidence: 99%

“…Cer, GC, ganglioside GM3, and other SLs are related to insulin resistance, pancreatic ␤-cell failure, and vascular dysfunction (33,75,79). Both Cer and GC are minor components of the lipid milieu in most tissues and they are potential pathogenic lipids in several conditions, including states of excess adiposity (24,25,33,34,75,79). GSLs are structural membrane components located mainly in the plasma membrane, with their sugar moieties exposed at the cell surface (4,5,31).…”

Section: Sl Pathways In Diabetes Nafld and Nashmentioning

confidence: 99%

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Compounds of the sphingomyelin-ceramide-glycosphingolipid pathways as secondary messenger molecules: new targets for novel therapies for fatty liver disease and insulin resistance

Ilan

2016

American Journal of Physiology-Gastrointestinal and Liver Physi

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The compounds of sphingomyelin-ceramide-glycosphingolipid pathways have been studied as potential secondary messenger molecules in various systems, along with liver function and insulin resistance. Secondary messenger molecules act directly or indirectly to affect cell organelles and intercellular interactions. Their potential role in the pathogenesis of steatohepatitis and diabetes has been suggested. Data samples collected from patients with Gaucher's disease, who had high levels of glucocerebroside, support a role for compounds from these pathways as a messenger molecules in the pathogenesis of fatty liver disease and diabetes. The present review summarizes some of the recent data on the role of glycosphingolipid molecules as messenger molecules in various physiological and pathological conditions, more specifically including insulin resistance and fatty liver disease.

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Section: Sl Pathways In Diabetes Nafld and Nashmentioning

confidence: 99%

Section: Sl Pathways In Diabetes Nafld and Nashmentioning

confidence: 99%

Section: Sl Pathways In Diabetes Nafld and Nashmentioning

confidence: 99%

Section: Sl Pathways In Diabetes Nafld and Nashmentioning

confidence: 99%

See 2 more Smart Citations

Compounds of the sphingomyelin-ceramide-glycosphingolipid pathways as secondary messenger molecules: new targets for novel therapies for fatty liver disease and insulin resistance

Ilan

2016

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…158 The potential contribution of ceramide to insulin resistance was recently reviewed. 159 It was suggested that both ceramide and glucosylceramides, although being a relatively minor component of the lipid milieu in most tissues, may be among the most pathogenic lipids in the onset of the sequelae associated with excess adiposity. 158 Circulating factors associated with obesity including saturated fatty acids and inflammatory cytokines, can selectively induce enzymes that promote sphingolipid synthesis thus affecting their role in.…”

Section: Potential Role For Ceramidementioning

confidence: 99%

Glucocerebroside: an evolutionary advantage for patients with Gaucher disease and a new immunomodulatory agent

2009

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Gaucher disease (GD) is caused by the reduced activity of a lysosomal enzyme, glucocerebrosidase, leading to the accumulation of glucocerebroside (GC). The relatively high prevalence of this disease within an ethnic group is believed to reflect a selective advantage. Treatment with enzyme replacement therapy (ERT) is safe and effective in ameliorating the primary symptoms of the disease, yet there have been reports that some patients on ERT have developed type 2 diabetes or metabolic syndrome, malignancies and central nervous system disorders. A series of animal studies suggest that these complications may be related to the reduction of GC levels by the enzyme administered. GC has been shown to have an immunomodulatory effect through the promotion of dendritic cells, natural killer T cells, and regulatory T cells. The break down of GC to ceramide can underline part of these findings. Clinical trials suggested a beneficial effect of GC in type 2 diabetes or nonalcoholic steatohepatitis. This review of the data from animal models and humans proposes that the increased level of GC may provide an evolutionary advantage for patients with GD. Indirectly, these data support treating symptomatic patients with mild/moderate GD with lowdose ERT and re-evaluating the use of ERT in asymptomatic patients.

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Metabolic Diseases: Biological Mechanisms

Arbeeny¹

2008

Wiley Encyclopedia of Chemical Biology

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Obesity, type 2 diabetes (T2D), lipid disorders, and hypertension are chronic and disabling diseases that afflict hundreds of millions of individuals worldwide. In this article, they are collectively referred to as “cardiometabolic diseases,” because they have “common ground:” They increase the risk of cardiovascular disease (CVD) morbidity and mortality. Considerable research has been performed to understand the etiology of cardiometabolic diseases and to translate this research into effective treatment paradigms. However, it has been challenging to understand the initiation and progression of cardiometabolic diseases. This difficulty is attributed to the complexities involved in metabolic regulation, a resultant “snowballing” effect, and a downward spiral as disease progresses. The first line of therapy for treating obesity, T2D, and/or dyslipidemia is lifestyle intervention, which can impact significantly on disease and decrease CV risk, but is usually not effective because of lack of patient compliance. Patients are then given a plethora of drugs to treat the individual risk factors. However, new therapies are critically needed, because most patients require multiple drugs, some drugs may treat one CVD risk factor and exacerbate another, and most patients do not meet treatment goals. A “magic bullet” that treats the underlying causes that contribute to cardiometabolic risk has been a longstanding goal but remains elusive. Ongoing research to uncover novel targets holds promise for future therapeutics that might treat multiple facets of cardiometabolic diseases. This introductory review focuses on the epidemiology and etiology of cardiometabolic diseases, current therapies, and future treatment strategies.

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Ceramide: a contributor to insulin resistance or an innocent bystander?

Cited by 37 publications

References 12 publications

Compounds of the sphingomyelin-ceramide-glycosphingolipid pathways as secondary messenger molecules: new targets for novel therapies for fatty liver disease and insulin resistance

Compounds of the sphingomyelin-ceramide-glycosphingolipid pathways as secondary messenger molecules: new targets for novel therapies for fatty liver disease and insulin resistance

Glucocerebroside: an evolutionary advantage for patients with Gaucher disease and a new immunomodulatory agent

Metabolic Diseases: Biological Mechanisms

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