Arieh Moussaieff

B. Elena-Herrmann, E. Montellier, A. Fages, R. Bruck-Haimson, and A. Moussaieff. 2020. “Multi-platform NMR Study of Pluripotent Stem Cells Unveils Complementary Metabolic Signatures towards Differentiation.” Scientific Reports, 10, 1. Publisher's Version Abstract
Stem cells, poised to revolutionize current medicine, stand as major workhorses for monitoring changes in cell fate. Characterizing metabolic phenotypes is key to monitor in differentiating cells transcriptional and epigenetic shifts at a functional level and provides a non-genetic means to control cell specification. Expanding the arsenal of analytical tools for metabolic profiling of cell differentiation is therefore of importance. Here, we describe the metabolome of whole pluripotent stem cells (PSCs) using high‐resolution magic angle spinning (HR-MAS), a non-destructive approach for Nuclear Magnetic Resonance (NMR) analysis. The integrated 1H NMR analysis results in detection of metabolites of various groups, including energy metabolites, amino acids, choline derivatives and short chain fatty acids. It unveils new metabolites that discriminate PSCs from differentiated counterparts and directly measures substrates and co-factors of histone modifying enzymes, suggesting that NMR stands as a strategic technique for deciphering metabolic regulations of histone post-translational modifications. HR-MAS NMR analysis of whole PSCs complements the much used solution NMR of cell extracts. Altogether, our multi-platform NMR investigation provides a consolidated picture of PSC metabolic signatures and of metabolic pathways involved in differentiation. © 2020, The Author(s).
A. Zacharia, D. Saidemberg, C.T. Mannully, N.M. Kogan, A. Shehadeh, R. Sinai, A. Zucker, R. Bruck-Haimson, N. Goldstein, Y. Haim, C. Dani, A. Rudich, and A. Moussaieff. 2020. “Distinct infrastructure of lipid networks in visceral and subcutaneous adipose tissues in overweight humans.” American Journal of Clinical Nutrition, 112, 4, Pp. 979-990. Publisher's Version Abstract
Background: Adipose tissue plays important roles in health and disease. Given the unique association of visceral adipose tissue with obesity-related metabolic diseases, the distribution of lipids between the major fat depots located in subcutaneous and visceral regions may shed new light on adipose tissue-specific roles in systemic metabolic perturbations. Objective: We sought to characterize the lipid networks and unveil differences in the metabolic infrastructure of the 2 adipose tissues that may have functional and nutritional implications. Methods: Paired visceral and subcutaneous adipose tissue samples were obtained from 17 overweight patients undergoing elective abdominal surgery. Ultra-performance LC-MS was used to measure 18,640 adipose-derived features; 520 were putatively identified. A stem cell model for adipogenesis was used to study the functional implications of the differences found. Results: Our analyses resulted in detailed lipid metabolic maps of the 2 major adipose tissues. They point to a higher accumulation of phosphatidylcholines, triacylglycerols, and diacylglycerols, although lower ceramide concentrations, in subcutaneous tissue. The degree of unsaturation was lower in visceral adipose tissue (VAT) phospholipids, indicating lower unsaturated fatty acid incorporation into adipose tissue. The differential abundance of phosphatidylcholines we found can be attributed at least partially to higher expression of phosphatidylethanolamine methyl transferase (PEMT). PEMT-deficient embryonic stem cells showed a dramatic decrease in adipogenesis, and the resulting adipocytes exhibited lower accumulation of lipid droplets, in line with the lower concentrations of glycerolipids in VAT. Ceramides may inhibit the expression of PEMT by increased insulin resistance, thus potentially suggesting a functional pathway that integrates ceramide, PEMT, and glycerolipid biosynthetic pathways. Conclusions: Our work unveils differential infrastructure of the lipid networks in visceral and subcutaneous adipose tissues and suggests an integrative pathway, with a discriminative flux between adipose tissues. Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.
A. Shehadeh, R. Bruck-Haimson, D. Saidemberg, A. Zacharia, S. Herzberg, A. Ben-Meir, and A. Moussaieff. 2019. “A shift in follicular fluid from triacylglycerols to membrane lipids is associated with positive pregnancy outcome.” FASEB Journal, 33, 9, Pp. 10291-10299. Publisher's Version Abstract
Follicular fluid (FF) is a liquid that surrounds the ovum. Its metabolite and, specifically, its lipid content have been associated with oocyte development. To characterize possible association between the lipid composition of FF and the outcome of pregnancy, we carried out a lipidomics study and compared the abundance of lipids from FF of patients with positive and negative outcomes. We found a differential lipid network wiring in positive-outcome FF, with a significant decrease (∼2 fold; P < 0.001) in triacylglycerol levels and higher accumulation (10–50%; P < 0.001) of membrane lipids groups (phospholipids and sphingolipids). In addition to this major metabolic alteration, other lipid groups such as cholesteryl esters showed lower levels in positive-outcome patients, whereas derivatives of vitamin D were highly accumulated in positive-outcome FF, supporting previous studies that associate vitamin D levels in FF to pregnancy outcome. Our data also point to specific lipid species with a differential accumulation pattern in positive-outcome FF that predicted pregnancy in a receiver operating characteristic analysis. Altogether, our results suggest that FF lipid network is associated with the oocyte development, with possible implications in diagnostics and treatment.—Shehadeh, A., Bruck-Haimson, R., Saidemberg, D., Zacharia. A., Herzberg, S., Ben-Meir, A., Moussaieff, A. A shift in follicular fluid from triacylglycerols to membrane lipids is associated with positive pregnancy outcome. FASEB J. 33, 10291–10299 (2019). www.fasebj.org. © FASEB