Weight Loss Maintenance and Compensatory Mechanisms Activated With a Very-low Calorie Diet

Very-low calorie diets are relatively safe and effective in inducing significant weight loss, when used in selective individuals and under clinical supervision. However, weight loss maintenance in the long-term remains the main challenge, with many experiencing a significant weight regain. Several compensatory mechanisms are activated under weight reduction, both at the level of energy intake (such as increased appetite) and energy expenditure (such as reduced energy expenditure), and increase the risk of relapse. The main aim of this study is to compare the effect of two multidisciplinary lifestyle interventions on weight loss maintenance at one year, after initial weight loss during 8 weeks very-low calorie diet. Participants will be allocated (non-randomly) to either an outpatient program in the obesity unit of the local hospital, or to an inpatient program consisting of a "continuous care" intervention, with three intermittent stays (each with three-week duration) in a rehabilitation center over a one year period. Moreover, the investigators aim to assess the impact of weight loss (achieved with a very low calorie diet) and weight loss maintenance on compensatory mechanisms activated during weight reduction.

This study included a sub-study (n=30) to determine the timeline over which compensatory mechanisms (at both the level of energy expenditure and appetite control system) are activated with progressive weight loss. Additional measurements were taken at day-3, 5 and 10 % weight loss, and after 4 weeks weight stabilization (after gradually reintroduction of food).

Multidisciplinary outpatient program including both individual and group-based therapy. During the first visit, there will be offered an individual consultation with the dietician, physiotherapist and psychiatric nurse. Follow-up will be in groups meeting every month for the first four months and every two months afterwards up to one year. The intervention will focus on nutritional education, healthy eating, increased physical activity levels (aiming initially at 10 minutes/day, then increasing to 30 minutes/day) and cognitive therapy.

Inpatient lifestyle program consisting of a "continuous care" weight loss program offered at a rehabilitation center, with three intermittent stays (each with 3-week duration) over a one year period.

assessed through: the Three-Factor Eating Questionnaire (TFEQ) fasting and postprandial release of appetite related hormones in blood samples, for a period of 3h (0, 30, 60, 120, 180 minutes), after a standard breakfast feelings of hunger/fullness by a visual analog scale

assessed through: the Three-Factor Eating Questionnaire (TFEQ) fasting and postprandial release of appetite related hormones in blood samples, for a period of 3h (0, 30, 60, 120, 180 minutes), after a standard breakfast feelings of hunger/fullness by a visual analog scale

Inclusion Criteria: volunteers from Central Norway if female: taking oral contraceptives or post-menopausal body mass index 30-45 kg/m2 stable weight (<2kg variation in the last 3 months) not currently dieting to lose weight Exclusion Criteria: Pregnancy breast feeding drug or alcohol abuse within the last two years current medication known to affect appetite or induce weight loss enrollment in another obesity treatment program history of psychological disorders history of eating disorders history of diabetes type 1 or 2 gastrointestinal disorders (particular cholelithiasis) kidney -, liver -, lung- or cardiovascular disease malignancies

Nymo S, Coutinho SR, Jorgensen J, Rehfeld JF, Truby H, Kulseng B, Martins C. Timeline of changes in appetite during weight loss with a ketogenic diet. Int J Obes (Lond). 2017 Aug;41(8):1224-1231. doi: 10.1038/ijo.2017.96. Epub 2017 Apr 25.

Martins C, Nymo S, Truby H, Rehfeld JF, Hunter GR, Gower BA. Association Between Ketosis and Changes in Appetite Markers with Weight Loss Following a Very Low-Energy Diet. Obesity (Silver Spring). 2020 Dec;28(12):2331-2338. doi: 10.1002/oby.23011.

DeBenedictis JN, Nymo S, Ollestad KH, Boyesen GA, Rehfeld JF, Holst JJ, Truby H, Kulseng B, Martins C. Changes in the Homeostatic Appetite System After Weight Loss Reflect a Normalization Toward a Lower Body Weight. J Clin Endocrinol Metab. 2020 Jul 1;105(7):e2538-46. doi: 10.1210/clinem/dgaa202.

Lyngstad A, Nymo S, Coutinho SR, Rehfeld JF, Truby H, Kulseng B, Martins C. Investigating the effect of sex and ketosis on weight-loss-induced changes in appetite. Am J Clin Nutr. 2019 Jun 1;109(6):1511-1518. doi: 10.1093/ajcn/nqz002.

Nymo S, Coutinho SR, Rehfeld JF, Truby H, Kulseng B, Martins C. Physiological Predictors of Weight Regain at 1-Year Follow-Up in Weight-Reduced Adults with Obesity. Obesity (Silver Spring). 2019 Jun;27(6):925-931. doi: 10.1002/oby.22476. Epub 2019 Apr 20.