The broad goal of this project is to determine whether improvements in the daily pattern of food intake can enhance the beneficial effects of bariatric surgery. Bariatric surgery is currently the most effective and durable weight loss treatment for obese individuals, with clear long-term benefit for cardiometabolic health. Though bariatric surgery was original designed to cause mechanical and consequently caloric restriction, this seems not to be the primary mechanism for weight loss. This is because, first, patients who lose a substantial amount of body weight do not experience excessive hunger which normally follows caloric restriction and, second, the amount of weight loss varies widely between individuals and is not correlated with post-surgical gastric pouch size. Indeed, the interindividual difference in post-surgical weight loss is large and approximately 25% of patients can be considered poor weight-loss responders who either do not lose a substantial amount of weight (i.e., BMI loss < 7 kg/m2) or regain the lost weight afterwards. Of interest, altered daily patterns of food intake, such as skipping breakfast and night snacking, is experienced by over half of the bariatric surgery candidates, raising the question whether interindividual differences in meal timing contribute to interindividual differences in weight loss success. Indeed, there is accumulating animal experimental and human evidence that such altered daily patterns of food intake actually contribute to obesity (detailed in the Background). However, none of the published human bariatric surgery studies have tested the causality between meal timing and the beneficial effects of bariatric surgery on measures of energy balance, glucose control, and cardiovascular risk factors. In this proposal, we aim to test the hypotheses that: 1) Early Eaters have a higher BMI loss 1 year after SG as compared to Late Eaters; 2) patients with poor post-surgical weight loss, as compared to those who respond successfully, have higher hunger-related measures late in the day; and 3) experimentally restricting food intake to the daytime in bariatric surgery patients with poor weight loss improves measures of energy balance, glucose tolerance and cardiovascular function. The first hypothesis will be tested in an observational prospective study (baseline plus after 1 year follow up), monitoring ambulatory meal patterns and BMI loss in the field. The second hypothesis will assess 24-h profiles of hunger and appetite-regulatory peptides in the laboratory. The third hypothesis will be tested in a parallel, randomized controlled trial in which patients with poor weight loss response will undergo a 12-week meal timing intervention or a control dietary intervention, and their baseline and post-intervention 24-h physiological outcomes will be measured under the in-laboratory conditions. This research will provide mechanistic insight into the interindividual differences in the effectiveness of bariatric surgery and may help in designing evidence-based dietary interventions incorporating meal timing to optimize post-surgical outcomes.
Although bariatric surgery is currently the most durable and successful treatment for obesity, the magnitudes of post- surgical weight loss vary widely and have been recently associated with timing of food intake. This research will determine whether the beneficial effects of bariatric surgery is?in part? mediated through improvement in the timing of food intake. This research will provide novel mechanistic insights into the large individual differences in post-surgical outcomes and may help in the design of evidence-based dietary interventions to improve the efficacy of bariatric surgery.
| Wefers, Jakob; van Moorsel, Dirk; Hansen, Jan et al. (2018) Circadian misalignment induces fatty acid metabolism gene profiles and compromises insulin sensitivity in human skeletal muscle. Proc Natl Acad Sci U S A 115:7789-7794 |
| Vera, Beatriz; Dashti, Hassan S; Gómez-Abellán, Purificación et al. (2018) Modifiable lifestyle behaviors, but not a genetic risk score, associate with metabolic syndrome in evening chronotypes. Sci Rep 8:945 |
| Collado, María Carmen; Engen, Phillip A; Bandín, Cristina et al. (2018) Timing of food intake impacts daily rhythms of human salivary microbiota: a randomized, crossover study. FASEB J 32:2060-2072 |
