TY - JOUR
T1 - Differential effects of bariatric surgery and caloric restriction on hepatic one-carbon and fatty acid metabolism
AU - Haran, Arnon
AU - Bergel, Michael
AU - Kleiman, Doron
AU - Hefetz, Liron
AU - Israeli, Hadar
AU - Weksler-Zangen, Sarah
AU - Agranovich, Bella
AU - Abramovich, Ifat
AU - Ben-Haroush Schyr, Rachel
AU - Gottlieb, Eyal
AU - Ben-Zvi, Danny
N1 - Funding Information: This project was financially supported by the Israel Science Foundation (967/19) and the European Research Council (StG 803526) and by a grant from the KAMLA Research Fund of the Hebrew University of Jerusalem and Hadassah Medical Center. We would like to thank and acknowledge the contributions of Dr. Idit Shiff and Dr. Abed Nassereddin of the Genomic Applications Laboratory in the Core Research Facility of the Faculty of Medicine, and of Dr. Yuval Nevo and Inbar Plaschkes of the I-CORE Bioinformatics Unit, of the Hebrew University of Jerusalem and Hadassah Medical Center, for their assistance in RNA sequencing experiments and analysis, respectively. We would also like to thank Dr. Gilad Haran for critical discussions and reading of the manuscript. The graphical abstract was created with the use of BioRender.com. A.H. M.B. R.B.H.S. and S.W.Z. designed the experiments. E.G. assisted in experimental design. A.H. M.B. D.K. S.W.Z. R.B.H.S. and D.B.Z. carried out the animal studies. A.H. M.B. D.K. L.H. H.I. S.W.Z. R.B.H.S. and D.B.Z. participated in sample collection and analysis. BA, IA, and EG conducted the metabolomic analysis. A.H. and D.B.Z. contributed to the final manuscript. The authors declare no competing interests. We support inclusive, diverse, and equitable conduct of research. Funding Information: This project was financially supported by the Israel Science Foundation ( 967/19 ) and the European Research Council ( StG 803526 ) and by a grant from the KAMLA Research Fund of the Hebrew University of Jerusalem and Hadassah Medical Center . We would like to thank and acknowledge the contributions of Dr. Idit Shiff and Dr. Abed Nassereddin of the Genomic Applications Laboratory in the Core Research Facility of the Faculty of Medicine, and of Dr. Yuval Nevo and Inbar Plaschkes of the I-CORE Bioinformatics Unit, of the Hebrew University of Jerusalem and Hadassah Medical Center, for their assistance in RNA sequencing experiments and analysis, respectively. We would also like to thank Dr. Gilad Haran for critical discussions and reading of the manuscript. The graphical abstract was created with the use of BioRender.com . Publisher Copyright: © 2023 The Author(s)
PY - 2023/7/21
Y1 - 2023/7/21
N2 - Weight loss interventions, including dietary changes, pharmacotherapy, or bariatric surgery, prevent many of the adverse consequences of obesity, and may also confer intervention-specific benefits beyond those seen with decreased weight alone. We compared the molecular effects of different interventions on liver metabolism to understand the mechanisms underlying these benefits. Male rats on a high-fat, high-sucrose diet underwent sleeve gastrectomy (SG) or intermittent fasting with caloric restriction (IF-CR), achieving equivalent weight loss. The interventions were compared to ad-libitum (AL)-fed controls. Analysis of liver and blood metabolome and transcriptome revealed distinct and sometimes contrasting metabolic effects between the two interventions. SG primarily influenced one-carbon metabolic pathways, whereas IF-CR increased de novo lipogenesis and glycogen storage. These findings suggest that the unique metabolic pathways affected by SG and IF-CR contribute to their distinct clinical benefits, with bariatric surgery potentially influencing long-lasting changes through its effect on one-carbon metabolism.
AB - Weight loss interventions, including dietary changes, pharmacotherapy, or bariatric surgery, prevent many of the adverse consequences of obesity, and may also confer intervention-specific benefits beyond those seen with decreased weight alone. We compared the molecular effects of different interventions on liver metabolism to understand the mechanisms underlying these benefits. Male rats on a high-fat, high-sucrose diet underwent sleeve gastrectomy (SG) or intermittent fasting with caloric restriction (IF-CR), achieving equivalent weight loss. The interventions were compared to ad-libitum (AL)-fed controls. Analysis of liver and blood metabolome and transcriptome revealed distinct and sometimes contrasting metabolic effects between the two interventions. SG primarily influenced one-carbon metabolic pathways, whereas IF-CR increased de novo lipogenesis and glycogen storage. These findings suggest that the unique metabolic pathways affected by SG and IF-CR contribute to their distinct clinical benefits, with bariatric surgery potentially influencing long-lasting changes through its effect on one-carbon metabolism.
KW - Omics
KW - Surgery
UR - http://www.scopus.com/inward/record.url?scp=85162172294&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.isci.2023.107046
DO - https://doi.org/10.1016/j.isci.2023.107046
M3 - Article
C2 - 37389181
SN - 2589-0042
VL - 26
SP - 107046
JO - iScience
JF - iScience
IS - 7
M1 - 107046
ER -
