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

doi:10.1016/j.isci.2023.107046

Differential effects of bariatric surgery and caloric restriction on hepatic one-carbon and fatty acid metabolism

iScience. 2023 Jun 7;26(7):107046. doi: 10.1016/j.isci.2023.107046. eCollection 2023 Jul 21.

Affiliations

¹ Department of Hematology, Haddasah Medical Center, Jerusalem, Israel.
² Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, The Hebrew University of Jerusalem-Hadassah Medical School, Jerusalem, Israel.
³ The Hadassah Diabetes Center, Haddasah Medical Center, Jerusalem, Israel.
⁴ Department of Cell Biology and Cancer Science, Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel.

Abstract

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.

Keywords: Omics; Surgery.