Mechanisms of Weight Loss After Obesity Surgery

Obesity surgery remains the most effective treatment for obesity and its complications. Weight loss was initially attributed to decreased energy absorption from the gut but has since been linked to reduced appetitive behavior and potentially increased energy expenditure. Implicated mechanisms associating rearrangement of the gastrointestinal tract with these metabolic outcomes include central appetite control, release of gut peptides, change in microbiota, and bile acids. However, the exact combination and timing of signals remain largely unknown. In this review, we survey recent research investigating these mechanisms, and seek to provide insights on unanswered questions over how weight loss is achieved following bariatric surgery which may eventually lead to safer, nonsurgical weight-loss interventions or combinations of medications with surgery. E.A. was supported by a grant from the Rosetrees Trust (M825) and from the British Society for Neuroendocrinology. A.D.M. has been supported from grants from the JP Moulton Charitable Foundation, National Institute of Health Research, Imperial College Healthcare Charity and Novo Nordisk. The Section of Investigative Medicine is funded by grants from the MRC, BBSRC, NIHR, an Integrative Mammalian Biology Capacity Building Award, an FP7-HEALTH-2009-241592 EuroCHIP grant and is supported by the NIHR Biomedical Research Centre Funding Scheme. The views expressed are those of the authors and not necessarily those of the National Health Service, the NIHR, or the Department of Health and Social Care. G.A.R. was supported by a Wellcome Trust Investigator Award (212625/Z/18/Z), MRC program grants (MR/R022259/1, MR/J0003042/1, MR/L020149/1), an Experimental Challenge Grant (DIVA, MR/L02036X/1), a Diabetes UK Project grant (BDA16/0005485). This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking, under grant agreement no. 115881 (RHAPSODY). This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation program and EFPIA. C.lR. is funded by the Irish Research Council (IRCLA/2017/234) and The Health Research Board (USIRL-2016-2).