PMID- 34684414 OWN - NLM STAT- MEDLINE DCOM- 20211129 LR - 20211129 IS - 2072-6643 (Electronic) IS - 2072-6643 (Linking) VI - 13 IP - 10 DP - 2021 Sep 28 TI - Antioxidants Supplementation Reduces Ceramide Synthesis Improving the Cardiac Insulin Transduction Pathway in a Rodent Model of Obesity. LID - 10.3390/nu13103413 [doi] LID - 3413 AB - Obesity-related disruption in lipid metabolism contributes to cardiovascular dysfunction. Despite numerous studies on lipid metabolism in the left ventricle, there is no data describing the influence of n-acetylcysteine (NAC) and alpha-lipoic acid (ALA), as glutathione precursors, on sphingolipid metabolism, and insulin resistance (IR) occurrence. The aim of our experiment was to evaluate the influence of chronic antioxidants administration on myocardial sphingolipid state and intracellular insulin signaling as a potential therapeutic strategy for obesity-related cardiovascular IR. The experiment was conducted on male Wistar rats fed a standard rodent chow or a high-fat diet with intragastric administration of NAC or ALA for eight weeks. Cardiac and plasma sphingolipid species were assessed by high-performance liquid chromatography (HPLC). The proteins expressed from sphingolipid and insulin signaling pathways were determined by Western blot. Antioxidant supplementation markedly reduced ceramide accumulation by lowering the expression of selected proteins from the sphingolipid pathway and simultaneously increased the myocardial sphingosine-1-phosphate level. Moreover, NAC and ALA augmented the expression of GLUT4 and the phosphorylation state of Akt (Ser473) and GSK3beta (Ser9), which improved the intracellular insulin transduction pathway. Based on our results, we may postulate that NAC and ALA have a beneficial influence on the cardiac ceramidose under IR conditions. FAU - Hodun, Katarzyna AU - Hodun K AUID- ORCID: 0000-0002-2102-7638 AD - Department of Physiology, Medical University of Bialystok, 15-089 Bialystok, Poland. FAU - Sztolsztener, Klaudia AU - Sztolsztener K AUID- ORCID: 0000-0003-1354-7585 AD - Department of Physiology, Medical University of Bialystok, 15-089 Bialystok, Poland. FAU - Chabowski, Adrian AU - Chabowski A AUID- ORCID: 0000-0002-7407-8156 AD - Department of Physiology, Medical University of Bialystok, 15-089 Bialystok, Poland. LA - eng GR - SUB/1/DN/20/004/1118/Uniwersytet Medyczny w Bialymstoku/ PT - Journal Article DEP - 20210928 PL - Switzerland TA - Nutrients JT - Nutrients JID - 101521595 RN - 0 (Antioxidants) RN - 0 (Biomarkers) RN - 0 (Ceramides) RN - 0 (Insulin) RN - 0 (Sphingolipids) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Animal Feed MH - Animals MH - Antioxidants/*pharmacology MH - Biomarkers/blood/metabolism MH - Body Weight MH - Ceramides/*biosynthesis MH - Diet, High-Fat MH - *Dietary Supplements MH - Glucose/metabolism MH - Insulin/*metabolism MH - Insulin Resistance MH - Male MH - Metabolic Networks and Pathways MH - Models, Animal MH - Myocardium/*metabolism MH - Obesity/etiology/*metabolism MH - Phosphorylation MH - Rats MH - Rodentia MH - Signal Transduction/*drug effects MH - Sphingolipids/metabolism PMC - PMC8541644 OTO - NOTNLM OT - cardiovascular diseases OT - ceramide OT - insulin resistance OT - left ventricle OT - n-acetylcysteine OT - sphingolipid OT - alpha-lipoic acid COIS- The authors declare no conflict of interest. EDAT- 2021/10/24 06:00 MHDA- 2021/11/30 06:00 PMCR- 2021/09/28 CRDT- 2021/10/23 01:18 PHST- 2021/08/27 00:00 [received] PHST- 2021/09/24 00:00 [revised] PHST- 2021/09/24 00:00 [accepted] PHST- 2021/10/23 01:18 [entrez] PHST- 2021/10/24 06:00 [pubmed] PHST- 2021/11/30 06:00 [medline] PHST- 2021/09/28 00:00 [pmc-release] AID - nu13103413 [pii] AID - nutrients-13-03413 [pii] AID - 10.3390/nu13103413 [doi] PST - epublish SO - Nutrients. 2021 Sep 28;13(10):3413. doi: 10.3390/nu13103413.