Altered hepatic sphingolipid metabolism in insulin resistant mice: Role of advanced glycation endproducts
نویسندگان
چکیده
High plasma levels of the sphingolipid intermediates ceramide (Cer) and sphingosine-1-phosphate (S1P) are suggested to be involved in development insulin resistance (IR). Recent evidence indicates that advanced glycation endproducts (AGEs) can alter sphingolipids metabolism equilibrium. Since enzymes responsible for rheostat maintenance highly expressed liver, we thus investigated whether AGEs accumulation affect hepatic resistant mice. Two different models IR were examined: genetically diabetic LeptrDb-/- (DbDb) diet-induced C57Bl/6J mice fed a 60% trans-fat diet (HFD). In addition, group HFD was supplemented with anti-AGEs compound pyridoxamine. evaluated liver by western blotting. Cer S1P measured UHPLC-MS/MS. The expression RAGE assessed RT-PCR HepG2 cells used study effect major AGE Nε-(carboxymethyl)lysine (CML)-albumin on role receptor (RAGE). detected both DbDb comparison controls. altered models, accompanied increased S1P. Specifically, synthase 5 sphingosine kinase 1 increased, while neutral ceramidase reduced. Pyridoxamine supplementation diminished prevented alterations IR. CML administration evoked similar those observed vivo, part mediated binding RAGE. present shows direct involvement associated modulation through prevention pyridoxamine may reduce
منابع مشابه
Novel inhibitors of advanced glycation endproducts.
Enhanced formation and accumulation of advanced glycation endproducts (AGE's) have been proposed to play a major role in the pathogenesis of diabetic complications, aging, atherosclerosis, and Alzheimer disease leading to progressive and irreversible intermolecular protein crosslinkings. This process is accelerated in diabetes and has been postulated to contribute to the development of a range ...
متن کاملAdvanced glycation endproducts and the kidney.
Advanced glycation end products (AGEs) are a heterogeneous group of protein and lipids to which sugar residues are covalently bound. AGE formation is increased in situations with hyperglycemia (e.g., diabetes mellitus) and is also stimulated by oxidative stress, for example in uremia. It appears that activation of the renin-angiotensin system may contribute to AGE formation through various mech...
متن کاملMethylglyoxal-Derived Advanced Glycation Endproducts in Multiple Sclerosis
Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS). The activation of inflammatory cells is crucial for the development of MS and is shown to induce intracellular glycolytic metabolism in pro-inflammatory microglia and macrophages, as well as CNS-resident astrocytes. Advanced glycation endproducts (AGEs) are stable endproducts formed by a reaction of the dica...
متن کاملCorrection: Advanced Glycation Endproducts and Bone Material Properties in Type 1 Diabetic Mice
[This corrects the article DOI: 10.1371/journal.pone.0154700.].
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
ژورنال
عنوان ژورنال: Free Radical Biology and Medicine
سال: 2021
ISSN: ['1873-4596', '0891-5849']
DOI: https://doi.org/10.1016/j.freeradbiomed.2021.04.028