Metabolic impacts of weight loss intervention on morbid obesity

Abstract

Morbid obesity can result in life-altering health issues, such as type 2 diabetes. Roux-en-Y gastric bypass (RYGB) surgery has been demonstrated to be one of the most effective treatments for morbid obesity and its co-morbidities in long-term. This aim of this thesis is to investigate the metabolic impact of weight loss intervention (RYGB, caloric restriction, and gut hormone treatment) on urine, plasma, and faecal profiles from morbidly obese patients, and to answer two hypotheses: 1) RYGB-induced metabolic changes are partially attributed to caloric restriction and increased gut hormones; 2) RYGB alters metabolic profile of faecal bacterial pellets separated using a newly developed method. Samples at pre-intervention time point were compared with post-intervention time point, and multivariate and univariate analysis were applied based on different types of datasets using different software to avoid missing potential biomarkers. Samples at post-intervention time point were compared across the intervention groups using the same strategy as above. At 1-month-post-intervention, RYGB-induced metabolic changes could be attributed by caloric restriction via increased metabolisms of ketone bodies, lactic acid, and tricarboxylic acid, and decreased concentrations of total apolipoprotein A1, high-density lipoprotein (HDL) subfraction 3&4, and very-low-density-lipoprotein (VLDL) subfraction 5. RYGB-induced distinct metabolic changes included metabolisms of amino acids, short chain fatty acids, creatine, increased concentration of low-density lipoprotein fraction of triglycerides, and decreased concentration of HDL subfraction 2 of phospholipids. Gut hormone treatment exerted limited metabolic effects on urine and plasma samples. A separation method was developed for faecal bacterial pellets profiling and applied on RYGB and caloric restriction cohorts. Propionate and butyrate productions via dicarboxylic acid pathway were increased significantly 2-5 years after RYGB and 3 months after caloric restriction, respectively. My study showed RYGB-induced metabolic changes could not be fully explained by caloric restriction nor increased gut hormone levels; Gut hormone treatment induced limited metabolic changes and could be an alternate therapy for morbid obesity followed by clinical trial with increased sample size and follow-up study in long term.