Clinical trial NCT01559415: An Adipocyte-Driven Mechanism For Weight Regain After Weight Loss: The Yo-Yo Effect
Official title: An Adipocyte-Driven Mechanism For Weight Regain After Weight Loss: The Yo-Yo Effect
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Obesity
Weight Loss
Diet
Keywords: Adipocytes
Lead sponsor: Maastricht University Medical Center
Sponsor class: OTHER
Collaborators: name: ZonMw: The Netherlands Organisation for Health Research and Development
First posted: 2012-03-21
Enrollment: 58
Sex: ALL
Minimum age (years): 20
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.


Eligibility criteria: 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).

Primary outcomes:
measure: change in weight following weight loss
timeFrame: at 9 weeks and at 46 weeks
measure: change in weight following weight loss
timeFrame: at 16 weeks and at 53 weeks
Secondary outcomes:
measure: change in adipokine profile due to dietary intervention (VLCD-group)
timeFrame: at baseline and after 5 weeks of VLCD diet
measure: change in adipokine during weight stable-period (VLCD-group)
timeFrame: after 5 weeks of VLCD diet and after 9 weeks
measure: change in adipokine profile during follow-up (VLCD-group)
timeFrame: at 9 weeks and after follow-up at 46 weeks
measure: change in adipokine profile due to dietary intervention (LCD-group)
timeFrame: at baseline and after 12 weeks of LCD diet
measure: change in adipokine profile during weight-stable period (LCD-group)
timeFrame: after 12 weeks of LCD diet and at 16 weeks
measure: change in adipokine profile during follow-up (LCD-group)
timeFrame: at 16 weeks and after follow-up at 53 weeks
measure: Changes in adipokine profile in the LCD-group compared to the VLCD-group
timeFrame: at baseline, at 5, 9, 12, 16, 46 and 53 weeks
measure: change in adipokine profile in relation to weight regain during follow-up
timeFrame: at baseline, at 5, 9, 12, 16, 46 and 53 weeks
measure: change in parameters of adipocyte fat metabolism due to dietary intervention (VLCD-group)
timeFrame: at baseline and after 5 weeks of VLCD diet
measure: change in parameters of adipocyte fat metabolism during weight-stable period (VLCD-group)
timeFrame: after 5 weeks of VLCD diet and at 9 weeks
measure: change in parameters of adipocyte fat metabolism during follow-up period (VLCD-group)
timeFrame: at 9 weeks and after follow-up at 46 weeks
measure: change in parameters of adipocyte fat metabolism due to dietary intervention (LCD-group)
timeFrame: at baseline and after 12 weeks of LCD diet
measure: change in parameters of adipocyte fat metabolism during weight-stable period (LCD-group)
timeFrame: after 12 weeks of LCD diet and at 16 weeks
measure: change in parameters of adipocyte fat metabolism during follow-up (LCD-group)
timeFrame: at 16 weeks and after follow-up at 53 weeks
measure: Changes in parameters of adipocyte fat metabolism in the LCD-group compared to the VLCD-group
timeFrame: at baseline, at 5, 9, 12, 16, 46 and 53 weeks
measure: change in parameters of adipocyte fat metabolism in relation to weight regain during follow-up
timeFrame: at baseline, at 5, 9, 12, 16, 46 and 53 weeks
measure: change in in-vivo adipose tissue metabolism due to dietary intervention (VLCD-group)
timeFrame: at baseline and after 5 weeks of VLCD diet
measure: change in in-vivo adipose tissue metabolism during weight-stable period (VLCD-group)
timeFrame: after 5 weeks of VLCD diet and at 9 weeks
measure: change in in-vivo adipose tissue metabolism during follow-up period (VLCD-group)
timeFrame: at 9 weeks and after follow-up period at 46 weeks
measure: change in in-vivo adipose tissue metabolism due to dietary intervention (LCD-group)
timeFrame: at baseline and after 12 weeks of LCD diet
measure: change in in-vivo adipose tissue metabolism during weight-stable period (LCD-group)
timeFrame: after 12 weeks of LCD diet and at 16 weeks
measure: change in in-vivo adipose tissue metabolism during follow-up period (LCD-group)
timeFrame: at 16 weeks and after follow-up period at 53 weeks
measure: change in in-vivo adipose tissue metabolism in the LCD-group compared to the VLCD-group
timeFrame: at baseline, at 5, 9, 12, 16, 46 and 53 weeks
measure: change in in-vivo adipose tissue metabolism in relation to weight regain during follow-up
timeFrame: at baseline, at 5, 9, 12, 16, 46 and 53 weeks
measure: change in the adipocyte extracellular matrix gene and protein expression profile due to dietary intervention (VLCD-group)
timeFrame: at baseline and after 5 weeks of VLCD diet
measure: change in the adipocyte extracellular matrix gene and protein expression profile during weight-stable period (VLCD-group)
timeFrame: after 5 weeks of VLCD diet and at 9 weeks
measure: change in the adipocyte extracellular matrix gene and protein expression profile during follow-up period (VLCD-group)
timeFrame: at 9 weeks and after follow-up period at 46 weeks
measure: change in the adipocyte extracellular matrix gene and protein expression profile due to dietary intervention (LCD-group)
timeFrame: at baseline and after 12 weeks of LCD diet
measure: change in the adipocyte extracellular matrix gene and protein expression profile during weight-stable period (LCD-group)
timeFrame: after 12 weeks of LCD diet and at 16 weeks
measure: change in the adipocyte extracellular matrix gene and protein expression profile during follow-up period (LCD-group)
timeFrame: at 16 weeks and after follow-up period
measure: change in the adipocyte extracellular matrix gene and protein expression profile in the LCD-group compared to the VLCD-group
timeFrame: at baseline, at 5, 9, 12, 16, 46 and 53 weeks
measure: change in the adipocyte extracellular matrix gene and protein expression profile in relation to weight regain during follow-up
timeFrame: at baseline, at 5, 9, 12, 16, 46 and 53 weeks
measure: change in adipocyte stress proteins expression due to dietary intervention (VLCD-group)
timeFrame: at baseline and after 5 weeks of VLCD diet
measure: change in adipocyte stress proteins expression during weight-stable period (VLCD-group)
timeFrame: after 5 weeks of VLCD diet and at 9 weeks
measure: change in adipocyte stress proteins expression during follow-up period (VLCD-group)
timeFrame: at 9 weeks and after follow-up period at week 46
measure: change in adipocyte stress proteins expression due to dietary intervention (LCD-group)
timeFrame: at baseline and after 12 weeks of LCD diet
measure: change in adipocyte stress proteins expression during weight-stable period (LCD-group)
timeFrame: after 12 weeks of LCD diet and at week 16
measure: change in adipocyte stress proteins expression during follow-up period (LCD-group)
timeFrame: at week 16 and after follow-up period at 53 weeks
measure: change in adipocyte stress proteins expression in the LCD-group compared to the VLCD-group
timeFrame: at baseline, at 5, 9, 12, 16, 46 and 53 weeks
measure: change in adipocyte stress proteins expression in relation to weight regain during follow-up
timeFrame: at baseline, at 5, 9, 12, 16, 46 and 53 weeks
measure: change in physiological parameters due to dietary intervention (VLCD-group)
timeFrame: at baseline and after 5 weeks of VLCD diet
measure: change in physiological parameters during weight-stable period (VLCD-group)
timeFrame: after 5 weeks of VLCD diet and at 9 weeks
measure: change in physiological parameters during follow-up period (VLCD-group)
timeFrame: at 9 weeks and after follow-up at 46 weeks
measure: change in physiological parameters due to dietary intervention (LCD-group)
timeFrame: at baseline and after 12 weeks of LCD diet
measure: change in physiological parameters during weight-stable period (LCD-group)
timeFrame: after 12 weeks of LCD diet and at 16 weeks
measure: change in physiological parameters during follow-up (LCD-group)
timeFrame: at 16 weeks and after follow-up at 53 weeks
measure: Changes in physiological parameters in the LCD-group compared to the VLCD-group
timeFrame: at baseline, at 5, 9, 12, 16, 46 and 53 weeks
measure: Changes in physiological parameters in relation to weight regain during follow-up
timeFrame: at baseline, at 5, 9, 12, 16, 46 and 53 weeks
measure: change in plasma metabolic parameters due to dietary intervention (VLCD-group)
timeFrame: at baseline and after 5 weeks of VLCD diet
measure: change in plasma metabolic parameters during weight-stable period (VLCD-group)
timeFrame: after 5 weeks of VLCD diet and at 9 weeks
measure: change in plasma metabolic parameters during follow-up period (VLCD-group)
timeFrame: at 9 weeks and after follow-up at 46 weeks
measure: change in plasma metabolic parameters due to dietary intervention (LCD-group)
timeFrame: at baseline and after 12 weeks of LCD diet
measure: change in plasma metabolic parameters during weight-stable period (LCD-group)
timeFrame: after 12 weeks of LCD diet and at 16 weeks
measure: change in plasma metabolic parameters during follow-up (LCD-group)
timeFrame: at 16 weeks and after follow-up at 53 weeks
measure: Changes in plasma metabolic parameters in the LCD-group compared to the VLCD-group
timeFrame: at baseline, at 5, 9, 12, 16, 46 and 53 weeks
measure: Changes in plasma metabolic parameters in relation to weight regain during follow-up
timeFrame: at baseline, at 5, 9, 12, 16, 46 and 53 weeks
measure: change in fat cell size and fat cell number due to the dietary intervention (VLCD-group)
timeFrame: at baseline and after 5 weeks of VLCD diet
measure: change in fat cell size and fat cell number during weight-stable period (VLCD-group)
timeFrame: after 5 weeks of VLCD diet and at 9 weeks
measure: change in fat cell size and fat cell number during follow-up period (VLCD-group)
timeFrame: at 9 weeks and after follow-up at 46 weeks
measure: change in fat cell size and fat cell number due to dietary intervention (LCD-group)
timeFrame: at baseline and after 12 weeks of LCD diet
measure: change in fat cell size and fat cell number during weight-stable period (LCD-group)
timeFrame: after 12 weeks of LCD diet and at 16 weeks
measure: change in fat cell size and fat cell number during follow-up (LCD-group)
timeFrame: at 16 weeks and after follow-up at 53 weeks
measure: Changes in fat cell size and fat cell number in the LCD-group compared to the VLCD-group
timeFrame: at baseline, at 5, 9, 12, 16, 46 and 53 weeks
measure: Changes in fat cell size and fat cell number in relation to weight regain after weight loss
timeFrame: at baseline, at 5, 9, 12, 16, 46 and 53 weeks
measure: change in breath volatile organic compounds due to the dietary intervention (VLCD-group)
timeFrame: at baseline and after 5 weeks of VLCD diet
measure: change in breath volatile organic compounds during weight-stable period (VLCD-group)
timeFrame: after 5 weeks of VLCD diet and at 9 weeks
measure: change in breath volatile organic compounds during follow-up period (VLCD-group)
timeFrame: at 9 weeks and after follow-up at 46 weeks
measure: change in breath volatile organic compounds due to dietary intervention (LCD-group)
timeFrame: at baseline and after 12 weeks of LCD diet
measure: change in breath volatile organic compounds during weight-stable period (LCD-group)
timeFrame: after 12 weeks of LCD diet and at 16 weeks
measure: change in breath volatile organic compounds during follow-up (LCD-group)
timeFrame: at 16 weeks and after follow-up at 53 weeks
measure: Changes in breath volatile organic compounds in the LCD-group compared to the VLCD-group
timeFrame: at baseline, at 5, 9, 12, 16, 46 and 53 weeks
measure: Changes in breath volatile organic compounds in relation to weight regain during follow-up
timeFrame: at baseline, at 5, 9, 12, 16, 46 and 53 weeks
measure: change in inflammatory parameters due to the dietary intervention (VLCD-group)
timeFrame: at baseline and after 5 weeks of VLCD diet
measure: change in inflammatory parameters during weight-stable period (VLCD-group)
timeFrame: after 5 weeks of VLCD diet and at 9 weeks
measure: change in inflammatory parameters during follow-up period (VLCD-group)
timeFrame: at 9 weeks and after follow-up at 46 weeks
measure: change in inflammatory parameters due to dietary intervention (LCD-group)
timeFrame: at baseline and after 12 weeks of LCD diet
measure: change in inflammatory parameters during weight-stable period (LCD-group)
timeFrame: after 12 weeks of LCD diet and at 16 weeks
measure: change in inflammatory parameters during follow-up (LCD-group)
timeFrame: at 16 weeks and after follow-up at 53 weeks
measure: Changes in inflammatory parameters in the LCD-group compared to the VLCD-group
timeFrame: at baseline, at 5, 9, 12, 16, 46 and 53 weeks
measure: Changes in inflammatory parameters in relation to weight regain during the follow-up
timeFrame: at baseline, at 5, 9, 12, 16, 46 and 53 weeks
measure: Changes in protein concentration of metabolic parameters due to the dietary intervention (VLCD-group)
timeFrame: at baseline and after 5 weeks of VLCD diet
measure: Changes in protein concentration of metabolic parameters during weight-stable period (VLCD-group)
timeFrame: after 5 weeks of VLCD diet and at 9 weeks
measure: change in protein concentration of metabolic parameters during follow-up (VLCD-group)
timeFrame: at 9 weeks and after follow-up at 46 weeks
measure: change in protein concentration of metabolic parameters due to dietary intervention (LCD-group)
timeFrame: at baseline and after 12 weeks of LCD diet
measure: change in protein concentration of metabolic parameters during weight-stable period (LCD-group)
timeFrame: after 12 weeks of LCD diet and at 16 weeks
measure: change in protein concentration of metabolic parameters during follow-up (LCD-group)
timeFrame: at 16 weeks and after follow-up at 53 weeks
measure: change in protein concentration of metabolic parameters in the LCD-group compared to the VLCD-group
timeFrame: at baseline, at 5, 9, 12, 16, 46 and 53 weeks
measure: change in protein concentration of metabolic parameters in relation to weight regain during follow-up
timeFrame: at baseline, at 5, 9, 12, 16, 46 and 53 weeks
Other outcomes:
Locations:
city: Maastricht
country: Netherlands
facility: Maastricht University
state: Limburg
Study officials:
affiliation: Maastricht University
name: Marleen van Baak, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Qiao Q, Bouwman FG, van Baak MA, Roumans NJT, Vink RG, Mariman ECM. Plasma Levels of Triglycerides and IL-6 Are Associated With Weight Regain and Fat Mass Expansion. J Clin Endocrinol Metab. 2022 Jun 16;107(7):1920-1929. doi: 10.1210/clinem/dgac198.
citation: Tareen SHK, Kutmon M, de Kok TM, Mariman ECM, van Baak MA, Evelo CT, Adriaens ME, Arts ICW. Stratifying cellular metabolism during weight loss: an interplay of metabolism, metabolic flexibility and inflammation. Sci Rep. 2020 Feb 3;10(1):1651. doi: 10.1038/s41598-020-58358-z.
citation: Roumans NJT, Wang P, Vink RG, van Baak MA, Mariman ECM. Combined Analysis of Stress- and ECM-Related Genes in Their Effect on Weight Regain. Obesity (Silver Spring). 2018 Mar;26(3):492-498. doi: 10.1002/oby.22093. Epub 2018 Feb 5.
citation: Vink RG, Roumans NJ, van der Kolk BW, Fazelzadeh P, Boekschoten MV, Mariman EC, van Baak MA. Adipose Tissue Meal-Derived Fatty Acid Uptake Before and After Diet-Induced Weight Loss in Adults with Overweight and Obesity. Obesity (Silver Spring). 2017 Aug;25(8):1391-1399. doi: 10.1002/oby.21903. Epub 2017 Jun 22.
citation: Roumans NJ, Vink RG, Fazelzadeh P, van Baak MA, Mariman EC. A role for leukocyte integrins and extracellular matrix remodeling of adipose tissue in the risk of weight regain after weight loss. Am J Clin Nutr. 2017 May;105(5):1054-1062. doi: 10.3945/ajcn.116.148874. Epub 2017 Mar 15.
citation: Vink RG, Roumans NJ, Cajlakovic M, Cleutjens JPM, Boekschoten MV, Fazelzadeh P, Vogel MAA, Blaak EE, Mariman EC, van Baak MA, Goossens GH. Diet-induced weight loss decreases adipose tissue oxygen tension with parallel changes in adipose tissue phenotype and insulin sensitivity in overweight humans. Int J Obes (Lond). 2017 May;41(5):722-728. doi: 10.1038/ijo.2017.38. Epub 2017 Feb 9.