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Review
. 2012 Jul;69(13):2135-46.
doi: 10.1007/s00018-012-0917-5.

A role for sphingolipids in the pathophysiology of obesity-induced inflammation

Benjamin T Bikman  1
Affiliations
Review

A role for sphingolipids in the pathophysiology of obesity-induced inflammation

Benjamin T Bikman. Cell Mol Life Sci. 2012 Jul.

Abstract

Following the initial discovery that adipose tissue actively synthesizes and secretes cytokines, obesity-induced inflammation has been implicated in the etiology of a host of disease states related to obesity, including cardiovascular disease and type II diabetes. Interestingly, a growing body of evidence similarly implicates sphingolipids as prime instigators in these same diseases. From the recent discovery that obesity-related inflammatory pathways modulate sphingolipid metabolism comes a novel perspective—sphingolipids may act as the dominant mediators of deleterious events stemming from obesity-induced inflammation. This paradigm may identify sphingolipids as an effective target for future therapeutics aimed at ameliorating diseases associated with chronic inflammation.

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Figures

Fig. 1
Fig. 1
Adipocyte expansion, leading to obesity, is associated with reduced adiponectin levels and elevated TNFα and ceramide
Fig. 2
Fig. 2
The TLR4-induced activation of ceramide biosynthesis represents a common pathway between lipotoxicity- and inflammation-induced insulin resistance. Saturated fatty acids (SFA); lipopolysaccharide (LPS); tumor necrosis factor (TNF) α; inhibitor of κB kinase (IKK) β; sphingomyelinase (SMAase)
Fig. 3
Fig. 3
TNFα induces ceramide biosynthesis and accrual through multiple mechanisms, whereas adiponectin activates ceramide degradation and eventual formation of S1P. Ceramide (Cer); sphingosine 1-phosphoate (S1P)
Fig. 4
Fig. 4
Ceramide has been shown to cause virtually all of the pathological states elicited by obesity-induced inflammation
Fig. 5
Fig. 5
Several sphingolipids elicit metabolically deleterious results, similar to ceramide. However, only ceramide formation (red pathways) has been shown to mediate inflammation-induced disturbances. Inhibition of the indicated enzymes invites the indicated results. Serine palmitoyltransferase (SPT); dihydroceramide desaturase 1 (Des1); sphingomyelinase synthase (SMS); sphingomyelinase (SMase); glucosylceramide synthase (GCS); sphingosine kinase (SK)
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