Abstract
This paper reviews our present knowledge on the contribution of ceramide (Cer), sphingomyelin (SM), dihydroceramide (DhCer) and sphingosine-1-phosphate (S1P) in obesity and related co-morbidities. Specifically, in this paper, we address the role of acyl chain composition in bodily fluids for monitoring obesity in males and females, in aging persons and in situations of environmental hypoxia adaptation. After a brief introduction on sphingolipid synthesis and compartmentalization, the node of detection methods has been critically revised as the node of the use of animal models. The latter do not recapitulate the human condition, making it difficult to compare levels of sphingolipids found in animal tissues and human bodily fluids, and thus, to find definitive conclusions. In human subjects, the search for putative biomarkers has to be performed on easily accessible material, such as serum. The serum “sphingolipidome” profile indicates that attention should be focused on specific acyl chains associated with obesity, per se, since total Cer and SM levels coupled with dyslipidemia and vitamin D deficiency can be confounding factors. Furthermore, exposure to hypoxia indicates a relationship between dyslipidemia, obesity, oxygen level and aerobic/anaerobic metabolism, thus, opening new research avenues in the role of sphingolipids.
Highlights
Sphingolipids (SLs) are molecular components of membranes responsible for their homeostasis, changes in lipid composition affect membrane structure, and receptor organization and function
This review will provide a short overview of metabolism, localization, and compartmentalization of SLs in the frame of obesity in human subjects and animal models, highlighting similarities and discrepancies with the aim of defining which can be considered a possible biomarker that can be utilized in the clinical setting for obesity, and obesity-related co-morbidities as cardiovascular disorders (CVD), type 2 diabetes mellitus (T2DM) and osteoarthritis (OA) [5,6,7,8]
Cer has been identified as one of the first sphingolipids acting during ischemia reperfusion (IR) mediated apoptosis
Summary
Sphingolipids (SLs) are molecular components of membranes responsible for their homeostasis, changes in lipid composition affect membrane structure, and receptor organization and function. The increase of non-esterified fatty acids, hormones, cytokines and pro-inflammatory markers is directly linked to insulin resistance, in which elevated plasma fatty acids cause a decreased glucose transport in muscle cells, as well as increased fat breakdown, leading to elevated hepatic glucose production. These events, together with pancreatic β-cell dysfunction, can lead to T2DM [11] in obese subjects, in those unable to counteract insulin resistance [12]. A clear picture of the signaling network generated by lipids in obesity-associated OA is still missing
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