Differential effects of bariatric surgery and caloric restriction on hepatic one-carbon and fatty acid metabolism
Arnon Haran,
Michael Bergel,
Doron Kleiman,
Liron Hefetz,
Hadar Israeli,
Sarah Weksler-Zangen,
Bella Agranovich,
Ifat Abramovich,
Rachel Ben-Haroush Schyr,
Eyal Gottlieb,
Danny Ben-Zvi
Affiliations
Arnon Haran
Department of Hematology, Haddasah Medical Center, Jerusalem, Israel; Corresponding author
Michael Bergel
Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, The Hebrew University of Jerusalem-Hadassah Medical School, Jerusalem, Israel
Doron Kleiman
Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, The Hebrew University of Jerusalem-Hadassah Medical School, Jerusalem, Israel
Liron Hefetz
Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, The Hebrew University of Jerusalem-Hadassah Medical School, Jerusalem, Israel
Hadar Israeli
Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, The Hebrew University of Jerusalem-Hadassah Medical School, Jerusalem, Israel
Sarah Weksler-Zangen
The Hadassah Diabetes Center, Haddasah Medical Center, Jerusalem, Israel
Bella Agranovich
Department of Cell Biology and Cancer Science, Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel
Ifat Abramovich
Department of Cell Biology and Cancer Science, Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel
Rachel Ben-Haroush Schyr
Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, The Hebrew University of Jerusalem-Hadassah Medical School, Jerusalem, Israel
Eyal Gottlieb
Department of Cell Biology and Cancer Science, Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel
Danny Ben-Zvi
Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, The Hebrew University of Jerusalem-Hadassah Medical School, Jerusalem, Israel; Corresponding author
Summary: 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.