Metabolomics-Guided Insights on Bariatric Surgery Versus Behavioral Interventions for Weight Loss

Objective: To review the metabolomic studies carried out so far to identify metabolic markers associated with surgical and dietary treatments for weight loss in subjects with obesity. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Results: Thirty-two studies successfully met the eligibility criteria. The metabolic adaptations shared by surgical and dietary interventions mirrored a state of starvation ketoacidosis (increase of circulating ketone bodies), an increase of acylcarnitines and fatty acid beta-oxidation, a decrease of specific amino acids including branched-chain amino acids (BCAA) and (lyso)glycerophospholipids previously associated with obesity, and adipose tissue expansion. The metabolic footprint of bariatric procedures was specifically characterized by an increase of bile acid circulating pools and a decrease of ceramide levels, a greater perioperative decline in BCAA, and the rise of circulating serine and glycine, mirroring glycemic control and inflammation improvement. In one study, 3-hydroxybutyrate was particularly identified as an early metabolic marker of long-term prognosis after surgery and proposed to increase current prognostic modalities and contribute to personalized treatment. Conclusions: Metabolomics helped in deciphering the metabolic response to weight loss treatments. Moving from association to causation is the next challenge to move to a further level of clinical application.