An Adipocyte-Driven Mechanism For Weight Regain After Weight Loss: The Yo-Yo Effect

An Adipocyte-Driven Mechanism For Weight Regain After Weight Loss: The Yo-Yo Effect

Almost half of the Dutch population is currently characterized by overweight and obesity. Losing weight is not the problem in obesity treatment, it is the seemingly obligatory weight regain after weight loss: the yoyo-effect. The primary objective of this study is to investigate the association between the weight-loss-induced cellular stress response and the rate of weight regain. The secondary objective is to investigate the differences in cellular stress response and weight regain after rapid and slow weight loss. To investigate this, subjects will receive meal replacements replacing either all or part of the daily meals during the intervention period. THe first group will consume 500 kcal/d diet for 5 weeks while the second group consumes a 1250 kcal/d diet for 3 months, both followed by 1 week normalization and a 2 week strict weight maintenance diet. During the 9-month follow-up period subjects will receive dietary advice according to the Dutch recommendations for healthy eating. The association between the amount of weight regain after the weight loss period and changes in adipokines, parameters of adipocyte metabolism, in vivo adipose tissue metabolism, adipocyte extracellular matrix gene expression profiles, adipocyte stress protein expression and gene polymorphisms in selected genes.

Inclusion Criteria:

• Age (years): 20-65
• Body Mass Index (kg/m2): 28-35
• Non-smokers

Exclusion Criteria:

• Subjects using prescription medication, or suffering from diseases or conditions that might influence the outcome of the study: this concerns diseases/medication that influence body weight regulation (malabsorption, untreated hypo/hyperthyroidism, eating disorders, systemic use of steroids, etc.) and obesity-related cardiovascular risk factors (heart disease, systolic and diastolic blood pressures > 160/100 mmHg, blood glucose > 6.1 mmol L-1, blood cholesterol > 7 mmol L-1, blood triglycerides > 3 mmol L-1)
• marked alcohol consumption > 21 alcoholic units week-1 (male), or >14 alcoholic units week-1 (female)
• planned major changes in physical activity during the study to an extent that might interfere with the study outcome as judged by the investigator;
• blood donation within the past 2 months prior to the study
• weight change of >3 kg within 2 months prior to the study
• psychiatric disease (based on medical history only)
• pregnant or lactating women, or women planning to become pregnant within the next 12 months
• surgically treated obesity
• participation in other clinical studies within the last 3 months
• drug abuse (based on clinical judgment)
• unable to give informed consent
• unable to engage in a low-calorie diet
• unable to lose more then 8% of body weight after weight-loss period
• following a special diet (vegetarian, Atkins or other).