Alterations of lipid homeostasis in serum and white adipose tissue in morbid obese patients are partly reversed by the bariatric surgery

Gastric Bypass surgery (GBS) represents a well-established approach to counteract human morbid obesity and its related comorbidities in modern countries. Beside its beneficial effect on weight loss and glucose homeostasis, emerging evidence suggests that GBS impacts on the circulating levels of phospho- and sphingolipids. However, long-term effects of GBS on lipid metabolism have not been explored. Thereby, we aimed to unveil to what extent GBS improves lipid homeostasis in serum and tissues from morbid obese individuals. To investigate alterations in lipidomic signatures associated with massive weight loss following GBS in morbid obese patients, we employed direct infusion tandem mass spectrometry (MS) allowing to quantify a wide range of lipid metabolites in serum and subcutaneous adipose tissue (SAT) samples. Systematic lipidomic analyses were conducted in samples collected in a longitudinal cohort of patients (cohort 1, n = 11) prior to GBS, and one year following the surgery. These novel data were cross compared with our recent lipidomic analyses conducted by the same approach in an independent cohort of morbid obese patients and lean controls, where serum and visceral adipose tissue (VAT) lipids were analysed (cohort 2, n = 39). Over 400 phospholipid and sphingolipid species have been quantified in serum and SAT (cohort 1), allowing to establish detailed lipidomic signatures associated with morbid obesity in a tissue-specific manner. Concomitant with weight loss and improvement of metabolic parameters, a massive rearrangement of lipid metabolites was observed one year following GBS. Strikingly, a substantial reduction of ceramide levels and increased amount of hexosylceramides were detected in both serum and SAT. The comparison of these new lipidomic profiles with the serum and VAT lipidomes established from lean and morbid obese subjects (cohort 2) revealed that GBS partly restored the lipid alterations associated with morbid obesity. Our study provides the first systematic analysis of the long-term lipid homeostasis modifications upon GBS in humans SAT and serum and demonstrates that lipid metabolism alterations associated with morbid obesity might be partly reversed by GBS. The research protocol was registered with the Protocol Registration and Results System at ClinicalTrial.gov [NCT03029572].