Weight loss maintenance following an intervention

Obesity is a major risk factor for cardiovascular disease, stroke, and many other adverse health conditions. Weight loss has significant health benefits for individuals with obesity, but long-term weight loss is a considerable challenge for most people, and substantial weight regain is typical within a year of completing a structured weight-loss program. An improved understanding of the drivers of weight loss maintenance is critical to maximize the long-term health benefits. While sustained behavioral change is an important component of weight loss maintenance, the gut microbiome may counteract or exacerbate the effects of returning to pre- dieting lifestyle habits. For instance, gut microbiota characteristics may influence hunger cues and energy expenditure. The goal of this application is to lay the foundation for a comprehensive study of the mechanistic relationships among behaviors, omic profiles, and weight loss maintenance following behavioral interventions. In this project, we collaborate with an ongoing one-year dietary weight loss intervention (R01DK132372; PI: Thomas) comparing the standard-of-care dietary weight loss approach, daily caloric restriction (DCR), to two alternatives, early- or late-day time restricted eating (TRE). We propose to extend the trial by adding a data collection six months after the intervention ends. Our first Aim will compare post-intervention adherence and clinical outcomes (weight, body composition, and markers of cardiometabolic health) between the intervention arms. We hypothesize that TRE will have enhanced adherence that facilitates improved outcomes. Aim 2 will generate pilot gut microbiota data to identify microbial predictors of post-intervention outcomes. We hypothesize that individuals with increases in the abundance of microbial taxa and functions involved in regulating host energy expenditure will have enhanced post-intervention clinical measures, and that these increases counteract the effects of returning to pre-intervention behaviors. This work builds on my ongoing K01 research (K01HL157658), which examines gut microbiota, metabolomic, and genetic pathways during another dietary intervention trial of intermittent fasting versus DCR. My K01 data motivates the hypotheses for this proposed study and will be incorporated into the analyses to enhance the power. This project will provide preliminary insight on how to maximize the long-term health benefits of weight loss strategies and will motivate independent research award applications that combine data from numerous behavioral intervention trials. This work will further my long-term goal of designing more effective clinical interventions that enable both weight loss and weight loss maintenance through innovative, targeted approaches (e.g., offering additional support for individuals predicted to be less responsive, pre-treatment with a microbiome-targeted supplement, or incorporating personalized nutrition therapy). This innovative line of research will complement my ongoing work and advance my career goal to transform obesity prevention and treatment through evidence-based, personalized approaches. Project Number: 1R03HL178754-01 | Fiscal Year: 2025 | NIH Institute/Center: National Heart Lung and Blood Institute (NHLBI) | Principal Investigator: Maggie Stanislawski | Institution: UNIVERSITY OF COLORADO DENVER, Aurora, CO | Award Amount: $234,000 | Activity Code: R03 | Study Section: Special Emphasis Panel[ZHL1 CSR-Q (J1)] View on NIH RePORTER: https://reporter.nih.gov/project-details/1R03HL17875401