Study identifies metabotypes that benefit from bariatric surgery

Individuals experienced a greater improvement of insulin resistance and cardiovascular factors after bariatric surgery had lower levels of gluconeogenic precursors, metabolites of the urea metabolism associated with nitric-oxide (NO) mechanisms, and changes in the microcomponents of lipoproteins, according to researchers from the University of Barcelona, Barcelona, the CIBER Fragilidad y Envejecimiento Saludable [CIBERfes], Instituto de Salud Carlos III [ISCIII], Madrid, and the Biomedical Research Institute [IBIMA], Service of Endocrinology and Nutrition, Malaga Hospital Complex [Virgen de la Victoria], Málaga, Spain

In the paper, ‘Metabotypes of response to bariatric surgery independent of the magnitude of weight loss’, published in PlosOne, investigators sought to determine biosignatures of response to bariatric surgery and elucidate short-term metabolic adaptations.

The researchers used a LC- and FIA-ESI-MS/MS approach to quantify acylcarnitines, (lyso)phosphatidylcholines, sphingomyelins, amino acids, biogenic amines and hexoses in serum samples of subjects with morbid obesity (n=39) before and one, three and six months after bariatric surgery. The employed K-means cluster analysis to distinguish metabotypes of response to bariatric surgery. Twenty-six patients underwent Roux-en-Y gastric bypass (RYGB) and 13 patients sleeve gastrectomy (SG), and included 27 females all with more than ten-year history of obesity.

All subjects were stratified according to their degree of metabolic syndrome, as defined by the Adult Treatment Panel III criteria: metabolically healthy (MH) subjects with ≤2 criteria (n=21) and metabolically unhealthy (MU) subjects with ≥ 3 criteria (n=18).

Outcomes

The results showed global metabolic changes following bariatric surgery independent of the baseline health status of the subjects. The researchers found two metabolic phenotypes (metabotypes) at the interval six months-baseline after surgery, which presented differences in the levels of compounds of urea metabolism, gluconeogenic precursors and (lyso)phospholipid particles. Clinically, metabotypes were different in terms of the degree of improvement in insulin resistance, cholesterol, low-density lipoproteins and uric acid independent of the magnitude of weight loss.

“Our results highlight shared and exclusive profiles of the response to surgery among the subjects throughout six months of follow-up, regardless of the baseline metabolic state, gender and age of the subjects and the surgical procedure received,” the authors note.

The also found that the morbidly obese traits almost ‘vanished’ six months after surgery and the metabolic status of the subjects improved. Importantly, changes in metabolites at the increment T6–T0 indicated two potentially different metabolic phenotypes (metabotypes) of short-term adaptation to bariatric surgery, metabotype 1 (cluster 1) and metabotype 2 (cluster 2). Although they researchers found that the clusters were clinically similar at baseline, they noted ‘remarkable’ differences in the post-surgery progression.

Indeed, metabotype 2 presented a greater degree of improvement in fasting insulin, HOMA-IR index, total cholesterol, LDL and uric acid six months after surgery, whereas metabotype 1 showed lower levels of urea, suggesting over- and down-expression of specific metabolic pathways in each phenotype.

“Our data allowed the identification of metabotypes that are more likely to benefit from bariatric surgery, independently of the baseline status of the patients,” the authors conclude. “The complexity of the metabolome requires complementary analytical methodologies in order to expand its coverage for a better understanding of the biological processes. Moreover, other factors such as global lifestyle or even a genetic component might be able to explain these metabotypes. Finally, to go beyond the analysis of individual mechanisms to the study of systems biology from an integral view, further investigation is needed.”