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

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.

Study Overview

• Status: Completed
• Conditions: Obesity; Weight Loss; Diet
• Intervention / Treatment: Other: Meal replacement diet using Modifast; Other: Normal diet combined with Modifast diet

• Study Type: Interventional
• Enrollment (Actual): 58
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Limburg
    • Maastricht, Limburg, Netherlands, 6200 MD
      • Maastricht University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Very Low Calorie Diet	Other: Meal replacement diet using Modifast; modifast intensive diet replacing all regular meals (500 kcal/d) for 5 weeks
Active Comparator: Low Calorie Diet; 1250 kcal diet in which Modifast is given in combination with a normal diet	Other: Normal diet combined with Modifast diet; Combination of modifast and regular diet (1250 kcal/d) for 3 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in weight following weight loss	VLCD diet group	at 9 weeks and at 46 weeks
change in weight following weight loss	LCD diet group	at 16 weeks and at 53 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in adipokine profile due to dietary intervention (VLCD-group)	In VLCD-group. Parameters of adipokine profile, including: leptin, acylation stimulating protein (ASP/C3adesarg), adiponectin, resistin, IL-6, RBP4, PAI-1, ACE, FGF-21, Vaspin, Apelin, Nesfatin-1 and TNFa	at baseline and after 5 weeks of VLCD diet
change in adipokine during weight stable-period (VLCD-group)	In VLCD-group. Parameters of adipokine profile, including: leptin, acylation stimulating protein (ASP/C3adesarg), adiponectin, resistin, IL-6, RBP4, PAI-1, ACE, FGF-21, Vaspin, Apelin, Nesfatin-1 and TNFa	after 5 weeks of VLCD diet and after 9 weeks
change in adipokine profile during follow-up (VLCD-group)	In VLCD-group. Parameters of adipokine profile, including: leptin, acylation stimulating protein (ASP/C3adesarg), adiponectin, resistin, IL-6, RBP4, PAI-1, ACE, FGF-21, Vaspin, Apelin, Nesfatin-1 and TNFa	at 9 weeks and after follow-up at 46 weeks
change in adipokine profile due to dietary intervention (LCD-group)	In LCD-group. Parameters of adipokine profile, including: leptin, acylation stimulating protein (ASP/C3adesarg), adiponectin, resistin, IL-6, RBP4, PAI-1, ACE, FGF-21, Vaspin, Apelin, Nesfatin-1 and TNFa	at baseline and after 12 weeks of LCD diet
change in adipokine profile during weight-stable period (LCD-group)	In LCD-group. Parameters of adipokine profile, including: leptin, acylation stimulating protein (ASP/C3adesarg), adiponectin, resistin, IL-6, RBP4, PAI-1, ACE, FGF-21, Vaspin, Apelin, Nesfatin-1 and TNFa	after 12 weeks of LCD diet and at 16 weeks
change in adipokine profile during follow-up (LCD-group)	In LCD-group. Parameters of adipokine profile, including: leptin, acylation stimulating protein (ASP/C3adesarg), adiponectin, resistin, IL-6, RBP4, PAI-1, ACE, FGF-21, Vaspin, Apelin, Nesfatin-1 and TNFa	at 16 weeks and after follow-up at 53 weeks
Changes in adipokine profile in the LCD-group compared to the VLCD-group	In LCD-group. Parameters of adipokine profile, including: leptin, acylation stimulating protein (ASP/C3adesarg), adiponectin, resistin, IL-6, RBP4, PAI-1, ACE, FGF-21, Vaspin, Apelin, Nesfatin-1 and TNFa	at baseline, at 5, 9, 12, 16, 46 and 53 weeks
change in adipokine profile in relation to weight regain during follow-up	In LCD-group and VLCD-group Parameters of adipokine profile, including: leptin, acylation stimulating protein (ASP/C3adesarg), adiponectin, resistin, IL-6, RBP4, PAI-1, ACE, FGF-21, Vaspin, Apelin, Nesfatin-1 and TNFa	at baseline, at 5, 9, 12, 16, 46 and 53 weeks
change in parameters of adipocyte fat metabolism due to dietary intervention (VLCD-group)	In VLCD-group. Parameters of adipocyte fat metabolism: ALDOC, phospho-annexin2, FABP4, PLIN-B, HADH, phosphorylated HSL and non-phosphorylated HSL - immunohistochemical staining of GLUT-4; Micro-array analysis of gene expression profile	at baseline and after 5 weeks of VLCD diet
change in parameters of adipocyte fat metabolism during weight-stable period (VLCD-group)	In VLCD-group. Parameters of adipocyte fat metabolism: ALDOC, phospho-annexin2, FABP4, PLIN-B, HADH, phosphorylated HSL and non-phosphorylated HSL - immunohistochemical staining of GLUT-4; Micro-array analysis of gene expression profile	after 5 weeks of VLCD diet and at 9 weeks
change in parameters of adipocyte fat metabolism during follow-up period (VLCD-group)	In VLCD-group. Parameters of adipocyte fat metabolism: ALDOC, phospho-annexin2, FABP4, PLIN-B, HADH, phosphorylated HSL and non-phosphorylated HSL - immunohistochemical staining of GLUT-4; Micro-array analysis of gene expression profile	at 9 weeks and after follow-up at 46 weeks
change in parameters of adipocyte fat metabolism due to dietary intervention (LCD-group)	In LCD-group. Parameters of adipocyte fat metabolism: ALDOC, phospho-annexin2, FABP4, PLIN-B, HADH, phosphorylated HSL and non-phosphorylated HSL - immunohistochemical staining of GLUT-4; Micro-array analysis of gene expression profile	at baseline and after 12 weeks of LCD diet
change in parameters of adipocyte fat metabolism during weight-stable period (LCD-group)	In LCD-group. Parameters of adipocyte fat metabolism: ALDOC, phospho-annexin2, FABP4, PLIN-B, HADH, phosphorylated HSL and non-phosphorylated HSL - immunohistochemical staining of GLUT-4; Micro-array analysis of gene expression profile	after 12 weeks of LCD diet and at 16 weeks
change in parameters of adipocyte fat metabolism during follow-up (LCD-group)	In LCD-group. Parameters of adipocyte fat metabolism: ALDOC, phospho-annexin2, FABP4, PLIN-B, HADH, phosphorylated HSL and non-phosphorylated HSL - immunohistochemical staining of GLUT-4; Micro-array analysis of gene expression profile	at 16 weeks and after follow-up at 53 weeks
Changes in parameters of adipocyte fat metabolism in the LCD-group compared to the VLCD-group	Parameters of adipocyte fat metabolism: ALDOC, phospho-annexin2, FABP4, PLIN-B, HADH, phosphorylated HSL and non-phosphorylated HSL - immunohistochemical staining of GLUT-4; Micro-array analysis of gene expression profile	at baseline, at 5, 9, 12, 16, 46 and 53 weeks
change in parameters of adipocyte fat metabolism in relation to weight regain during follow-up	In LCD-group and VLCD-group. Parameters of adipocyte fat metabolism: ALDOC, phospho-annexin2, FABP4, PLIN-B, HADH, phosphorylated HSL and non-phosphorylated HSL - immunohistochemical staining of GLUT-4; Micro-array analysis of gene expression profile	at baseline, at 5, 9, 12, 16, 46 and 53 weeks
change in in-vivo adipose tissue metabolism due to dietary intervention (VLCD-group)	In VLCD-group. In-vivo adipose tissue metabolism assessed in fasting and postprandial conditions: adipose tissue blood flow; adipose tissue PO2; adipose tissue oxygen consumption; adipose tissue capacity for fat uptake from chylomicron-triglycerides	at baseline and after 5 weeks of VLCD diet
change in in-vivo adipose tissue metabolism during weight-stable period (VLCD-group)	In VLCD-group. In-vivo adipose tissue metabolism assessed in fasting and postprandial conditions: adipose tissue blood flow; adipose tissue PO2; adipose tissue oxygen consumption; adipose tissue capacity for fat uptake from chylomicron-triglycerides	after 5 weeks of VLCD diet and at 9 weeks
change in in-vivo adipose tissue metabolism during follow-up period (VLCD-group)	In VLCD-group. In-vivo adipose tissue metabolism assessed in fasting and postprandial conditions: adipose tissue blood flow; adipose tissue PO2; adipose tissue oxygen consumption; adipose tissue capacity for fat uptake from chylomicron-triglycerides	at 9 weeks and after follow-up period at 46 weeks
change in in-vivo adipose tissue metabolism due to dietary intervention (LCD-group)	In LCD-group. In-vivo adipose tissue metabolism assessed in fasting and postprandial conditions: adipose tissue blood flow; adipose tissue PO2; adipose tissue oxygen consumption; adipose tissue capacity for fat uptake from chylomicron-triglycerides	at baseline and after 12 weeks of LCD diet
change in in-vivo adipose tissue metabolism during weight-stable period (LCD-group)	In LCD-group. In-vivo adipose tissue metabolism assessed in fasting and postprandial conditions: adipose tissue blood flow; adipose tissue PO2; adipose tissue oxygen consumption; adipose tissue capacity for fat uptake from chylomicron-triglycerides	after 12 weeks of LCD diet and at 16 weeks
change in in-vivo adipose tissue metabolism during follow-up period (LCD-group)	In LCD-group. In-vivo adipose tissue metabolism assessed in fasting and postprandial conditions: adipose tissue blood flow; adipose tissue PO2; adipose tissue oxygen consumption; adipose tissue capacity for fat uptake from chylomicron-triglycerides	at 16 weeks and after follow-up period at 53 weeks
change in in-vivo adipose tissue metabolism in the LCD-group compared to the VLCD-group	In-vivo adipose tissue metabolism assessed in fasting and postprandial conditions: adipose tissue blood flow; adipose tissue PO2; adipose tissue oxygen consumption; adipose tissue capacity for fat uptake from chylomicron-triglycerides	at baseline, at 5, 9, 12, 16, 46 and 53 weeks
change in in-vivo adipose tissue metabolism in relation to weight regain during follow-up	In LCD-group and VLCD-group In-vivo adipose tissue metabolism assessed in fasting and postprandial conditions: adipose tissue blood flow; adipose tissue PO2; adipose tissue oxygen consumption; adipose tissue capacity for fat uptake from chylomicron-triglycerides	at baseline, at 5, 9, 12, 16, 46 and 53 weeks
change in the adipocyte extracellular matrix gene and protein expression profile due to dietary intervention (VLCD-group)	VLCD diet group Adipocyte extracellular matrix gene expression profile assessed: micro-arrays on RNA expression; protein expression; Genetic polymorphisms: focus on polymorphisms in genes (a) that are preferentially expressed in white adipose tissue like TIMP4, (b) that have a proposed anchoring role of the cells to the basal lamina like the non-fibrillar type collagens IV and VI, (c) that are essential for adipose tissue development like MMP14, and (d) for which association has been found with obesity or adiposity like TIMP1, MMP2 and MMP9	at baseline and after 5 weeks of VLCD diet
change in the adipocyte extracellular matrix gene and protein expression profile during weight-stable period (VLCD-group)	VLCD diet group Adipocyte extracellular matrix gene expression profile assessed: micro-arrays on RNA expression; protein expression; Genetic polymorphisms: focus on polymorphisms in genes (a) that are preferentially expressed in white adipose tissue like TIMP4, (b) that have a proposed anchoring role of the cells to the basal lamina like the non-fibrillar type collagens IV and VI, (c) that are essential for adipose tissue development like MMP14, and (d) for which association has been found with obesity or adiposity like TIMP1, MMP2 and MMP9	after 5 weeks of VLCD diet and at 9 weeks
change in the adipocyte extracellular matrix gene and protein expression profile during follow-up period (VLCD-group)	VLCD diet group Adipocyte extracellular matrix gene expression profile assessed: micro-arrays on RNA expression; protein expression; Genetic polymorphisms: focus on polymorphisms in genes (a) that are preferentially expressed in white adipose tissue like TIMP4, (b) that have a proposed anchoring role of the cells to the basal lamina like the non-fibrillar type collagens IV and VI, (c) that are essential for adipose tissue development like MMP14, and (d) for which association has been found with obesity or adiposity like TIMP1, MMP2 and MMP9	at 9 weeks and after follow-up period at 46 weeks
change in the adipocyte extracellular matrix gene and protein expression profile due to dietary intervention (LCD-group)	LCD diet group Adipocyte extracellular matrix gene expression profile assessed: micro-arrays on RNA expression; protein expression; Genetic polymorphisms: focus on polymorphisms in genes (a) that are preferentially expressed in white adipose tissue like TIMP4, (b) that have a proposed anchoring role of the cells to the basal lamina like the non-fibrillar type collagens IV and VI, (c) that are essential for adipose tissue development like MMP14, and (d) for which association has been found with obesity or adiposity like TIMP1, MMP2 and MMP9	at baseline and after 12 weeks of LCD diet
change in the adipocyte extracellular matrix gene and protein expression profile during weight-stable period (LCD-group)	LCD diet group Adipocyte extracellular matrix gene expression profile assessed: micro-arrays on RNA expression; protein expression; Genetic polymorphisms: focus on polymorphisms in genes (a) that are preferentially expressed in white adipose tissue like TIMP4, (b) that have a proposed anchoring role of the cells to the basal lamina like the non-fibrillar type collagens IV and VI, (c) that are essential for adipose tissue development like MMP14, and (d) for which association has been found with obesity or adiposity like TIMP1, MMP2 and MMP9	after 12 weeks of LCD diet and at 16 weeks
change in the adipocyte extracellular matrix gene and protein expression profile during follow-up period (LCD-group)	LCD diet group Adipocyte extracellular matrix gene expression profile assessed: micro-arrays on RNA expression; protein expression; Genetic polymorphisms: focus on polymorphisms in genes (a) that are preferentially expressed in white adipose tissue like TIMP4, (b) that have a proposed anchoring role of the cells to the basal lamina like the non-fibrillar type collagens IV and VI, (c) that are essential for adipose tissue development like MMP14, and (d) for which association has been found with obesity or adiposity like TIMP1, MMP2 and MMP9	at 16 weeks and after follow-up period
change in the adipocyte extracellular matrix gene and protein expression profile in the LCD-group compared to the VLCD-group	Adipocyte extracellular matrix gene expression profile assessed: micro-arrays on RNA expression; protein expression; Genetic polymorphisms: focus on polymorphisms in genes (a) that are preferentially expressed in white adipose tissue like TIMP4, (b) that have a proposed anchoring role of the cells to the basal lamina like the non-fibrillar type collagens IV and VI, (c) that are essential for adipose tissue development like MMP14, and (d) for which association has been found with obesity or adiposity like TIMP1, MMP2 and MMP9	at baseline, at 5, 9, 12, 16, 46 and 53 weeks
change in the adipocyte extracellular matrix gene and protein expression profile in relation to weight regain during follow-up	In LCD-group and VLCD-group Adipocyte extracellular matrix gene expression profile assessed: micro-arrays on RNA expression; protein expression; Genetic polymorphisms: focus on polymorphisms in genes (a) that are preferentially expressed in white adipose tissue like TIMP4, (b) that have a proposed anchoring role of the cells to the basal lamina like the non-fibrillar type collagens IV and VI, (c) that are essential for adipose tissue development like MMP14, and (d) for which association has been found with obesity or adiposity like TIMP1, MMP2 and MMP9	at baseline, at 5, 9, 12, 16, 46 and 53 weeks
change in adipocyte stress proteins expression due to dietary intervention (VLCD-group)	VLCD diet group Adipocyte stress proteins expression: components of stress fibers and focal adhesions, like integrins; 43 'stress proteins' with focus on 9 stress proteins: actin betaactin, gamma 1, Rho GDP dissociation inhibitor (GDI), alphacofilin 1 (non-muscle), keratin 8, stathmin 1/oncoprotein 18, tropomyosin 3, vimentin, tubulin beta	at baseline and after 5 weeks of VLCD diet
change in adipocyte stress proteins expression during weight-stable period (VLCD-group)	VLCD diet group Adipocyte stress proteins expression: components of stress fibers and focal adhesions, like integrins; 43 'stress proteins' with focus on 9 stress proteins: actin betaactin, gamma 1, Rho GDP dissociation inhibitor (GDI), alphacofilin 1 (non-muscle), keratin 8, stathmin 1/oncoprotein 18, tropomyosin 3, vimentin, tubulin beta	after 5 weeks of VLCD diet and at 9 weeks
change in adipocyte stress proteins expression during follow-up period (VLCD-group)	VLCD diet group Adipocyte stress proteins expression: components of stress fibers and focal adhesions, like integrins; 43 'stress proteins' with focus on 9 stress proteins: actin betaactin, gamma 1, Rho GDP dissociation inhibitor (GDI), alphacofilin 1 (non-muscle), keratin 8, stathmin 1/oncoprotein 18, tropomyosin 3, vimentin, tubulin beta	at 9 weeks and after follow-up period at week 46
change in adipocyte stress proteins expression due to dietary intervention (LCD-group)	LCD diet group Adipocyte stress proteins expression: components of stress fibers and focal adhesions, like integrins; 43 'stress proteins' with focus on 9 stress proteins: actin betaactin, gamma 1, Rho GDP dissociation inhibitor (GDI), alphacofilin 1 (non-muscle), keratin 8, stathmin 1/oncoprotein 18, tropomyosin 3, vimentin, tubulin beta	at baseline and after 12 weeks of LCD diet
change in adipocyte stress proteins expression during weight-stable period (LCD-group)	LCD diet group Adipocyte stress proteins expression: components of stress fibers and focal adhesions, like integrins; 43 'stress proteins' with focus on 9 stress proteins: actin betaactin, gamma 1, Rho GDP dissociation inhibitor (GDI), alphacofilin 1 (non-muscle), keratin 8, stathmin 1/oncoprotein 18, tropomyosin 3, vimentin, tubulin beta	after 12 weeks of LCD diet and at week 16
change in adipocyte stress proteins expression during follow-up period (LCD-group)	LCD diet group Adipocyte stress proteins expression: components of stress fibers and focal adhesions, like integrins; 43 'stress proteins' with focus on 9 stress proteins: actin betaactin, gamma 1, Rho GDP dissociation inhibitor (GDI), alphacofilin 1 (non-muscle), keratin 8, stathmin 1/oncoprotein 18, tropomyosin 3, vimentin, tubulin beta	at week 16 and after follow-up period at 53 weeks
change in adipocyte stress proteins expression in the LCD-group compared to the VLCD-group	Adipocyte stress proteins expression: components of stress fibers and focal adhesions, like integrins; 43 'stress proteins' with focus on 9 stress proteins: actin betaactin, gamma 1, Rho GDP dissociation inhibitor (GDI), alphacofilin 1 (non-muscle), keratin 8, stathmin 1/oncoprotein 18, tropomyosin 3, vimentin, tubulin beta	at baseline, at 5, 9, 12, 16, 46 and 53 weeks
change in adipocyte stress proteins expression in relation to weight regain during follow-up	In LCD-group and VLCD-group Adipocyte stress proteins expression: components of stress fibers and focal adhesions, like integrins; 43 'stress proteins' with focus on 9 stress proteins: actin betaactin, gamma 1, Rho GDP dissociation inhibitor (GDI), alphacofilin 1 (non-muscle), keratin 8, stathmin 1/oncoprotein 18, tropomyosin 3, vimentin, tubulin beta	at baseline, at 5, 9, 12, 16, 46 and 53 weeks
change in physiological parameters due to dietary intervention (VLCD-group)	Physiological parameters: Blood pressure, waist-, and hip-circumference, weight, BMI, age, body fat	at baseline and after 5 weeks of VLCD diet
change in physiological parameters during weight-stable period (VLCD-group)	Physiological parameters: Blood pressure, waist-, and hip-circumference, weight, BMI, age, body fat	after 5 weeks of VLCD diet and at 9 weeks
change in physiological parameters during follow-up period (VLCD-group)	Physiological parameters: Blood pressure, waist-, and hip-circumference, weight, BMI, age, body fat	at 9 weeks and after follow-up at 46 weeks
change in physiological parameters due to dietary intervention (LCD-group)	Physiological parameters: Blood pressure, waist-, and hip-circumference, weight, BMI, age, body fat	at baseline and after 12 weeks of LCD diet
change in physiological parameters during weight-stable period (LCD-group)	Physiological parameters: Blood pressure, waist-, and hip-circumference, weight, BMI, age, body fat	after 12 weeks of LCD diet and at 16 weeks
change in physiological parameters during follow-up (LCD-group)	Physiological parameters: Blood pressure, waist-, and hip-circumference, weight, BMI, age, body fat	at 16 weeks and after follow-up at 53 weeks
Changes in physiological parameters in the LCD-group compared to the VLCD-group	Physiological parameters: Blood pressure, waist-, and hip-circumference, weight, BMI, age, body fat	at baseline, at 5, 9, 12, 16, 46 and 53 weeks
Changes in physiological parameters in relation to weight regain during follow-up	Physiological parameters: Blood pressure, waist-, and hip-circumference, weight, BMI, age, body fat	at baseline, at 5, 9, 12, 16, 46 and 53 weeks
change in plasma metabolic parameters due to dietary intervention (VLCD-group)	Plasma metabolic parameters are measured in fasting and postprandial conditions, focused on: Glucose, insulin, free fatty acid, glycerol and triglycerides	at baseline and after 5 weeks of VLCD diet
change in plasma metabolic parameters during weight-stable period (VLCD-group)	Plasma metabolic parameters are measured in fasting and postprandial conditions, focused on: Glucose, insulin, free fatty acid, glycerol and triglycerides	after 5 weeks of VLCD diet and at 9 weeks
change in plasma metabolic parameters during follow-up period (VLCD-group)	Plasma metabolic parameters are measured in fasting and postprandial conditions, focused on: Glucose, insulin, free fatty acid, glycerol and triglycerides	at 9 weeks and after follow-up at 46 weeks
change in plasma metabolic parameters due to dietary intervention (LCD-group)	Plasma metabolic parameters are measured in fasting and postprandial conditions, focused on: Glucose, insulin, free fatty acid, glycerol and triglycerides	at baseline and after 12 weeks of LCD diet
change in plasma metabolic parameters during weight-stable period (LCD-group)	Plasma metabolic parameters are measured in fasting and postprandial conditions, focused on: Glucose, insulin, free fatty acid, glycerol and triglycerides	after 12 weeks of LCD diet and at 16 weeks
change in plasma metabolic parameters during follow-up (LCD-group)	Plasma metabolic parameters are measured in fasting and postprandial conditions, focused on: Glucose, insulin, free fatty acid, glycerol and triglycerides	at 16 weeks and after follow-up at 53 weeks
Changes in plasma metabolic parameters in the LCD-group compared to the VLCD-group	Plasma metabolic parameters are measured in fasting and postprandial conditions, focused on: Glucose, insulin, free fatty acid, glycerol and triglycerides	at baseline, at 5, 9, 12, 16, 46 and 53 weeks
Changes in plasma metabolic parameters in relation to weight regain during follow-up	In LCD-group and VLCD-group Plasma metabolic parameters are measured in fasting and postprandial conditions, focused on: Glucose, insulin, free fatty acid, glycerol and triglycerides	at baseline, at 5, 9, 12, 16, 46 and 53 weeks
change in fat cell size and fat cell number due to the dietary intervention (VLCD-group)		at baseline and after 5 weeks of VLCD diet
change in fat cell size and fat cell number during weight-stable period (VLCD-group)		after 5 weeks of VLCD diet and at 9 weeks
change in fat cell size and fat cell number during follow-up period (VLCD-group)		at 9 weeks and after follow-up at 46 weeks
change in fat cell size and fat cell number due to dietary intervention (LCD-group)		at baseline and after 12 weeks of LCD diet
change in fat cell size and fat cell number during weight-stable period (LCD-group)		after 12 weeks of LCD diet and at 16 weeks
change in fat cell size and fat cell number during follow-up (LCD-group)		at 16 weeks and after follow-up at 53 weeks
Changes in fat cell size and fat cell number in the LCD-group compared to the VLCD-group		at baseline, at 5, 9, 12, 16, 46 and 53 weeks
Changes in fat cell size and fat cell number in relation to weight regain after weight loss	In LCD-group and VLCD-group	at baseline, at 5, 9, 12, 16, 46 and 53 weeks
change in breath volatile organic compounds due to the dietary intervention (VLCD-group)		at baseline and after 5 weeks of VLCD diet
change in breath volatile organic compounds during weight-stable period (VLCD-group)		after 5 weeks of VLCD diet and at 9 weeks
change in breath volatile organic compounds during follow-up period (VLCD-group)		at 9 weeks and after follow-up at 46 weeks
change in breath volatile organic compounds due to dietary intervention (LCD-group)		at baseline and after 12 weeks of LCD diet
change in breath volatile organic compounds during weight-stable period (LCD-group)		after 12 weeks of LCD diet and at 16 weeks
change in breath volatile organic compounds during follow-up (LCD-group)		at 16 weeks and after follow-up at 53 weeks
Changes in breath volatile organic compounds in the LCD-group compared to the VLCD-group		at baseline, at 5, 9, 12, 16, 46 and 53 weeks
Changes in breath volatile organic compounds in relation to weight regain during follow-up	In LCD-group and VLCD-group	at baseline, at 5, 9, 12, 16, 46 and 53 weeks
change in inflammatory parameters due to the dietary intervention (VLCD-group)	In VLCD-group. Inflammatory parameters are analyzed in: Plasma (including: TNF-a, IL-6, IL-8 and MCP-1); Micro-array; PCR: (including: TNF-a, IL-6, IL-8 and MCP-1)	at baseline and after 5 weeks of VLCD diet
change in inflammatory parameters during weight-stable period (VLCD-group)	In VLCD-group. Inflammatory parameters are analyzed in: Plasma (including: TNF-a, IL-6, IL-8 and MCP-1); Micro-array; PCR: (including: TNF-a, IL-6, IL-8 and MCP-1)	after 5 weeks of VLCD diet and at 9 weeks
change in inflammatory parameters during follow-up period (VLCD-group)	In VLCD-group. Inflammatory parameters are analyzed in: Plasma (including: TNF-a, IL-6, IL-8 and MCP-1); Micro-array; PCR: (including: TNF-a, IL-6, IL-8 and MCP-1)	at 9 weeks and after follow-up at 46 weeks
change in inflammatory parameters due to dietary intervention (LCD-group)	In LCD-group. Inflammatory parameters are analyzed in: Plasma (including: TNF-a, IL-6, IL-8 and MCP-1); Micro-array; PCR: (including: TNF-a, IL-6, IL-8 and MCP-1)	at baseline and after 12 weeks of LCD diet
change in inflammatory parameters during weight-stable period (LCD-group)	In LCD-group. Inflammatory parameters are analyzed in: Plasma (including: TNF-a, IL-6, IL-8 and MCP-1); Micro-array; PCR: (including: TNF-a, IL-6, IL-8 and MCP-1)	after 12 weeks of LCD diet and at 16 weeks
change in inflammatory parameters during follow-up (LCD-group)	In LCD-group. Inflammatory parameters are analyzed in: Plasma (including: TNF-a, IL-6, IL-8 and MCP-1); Micro-array; PCR: (including: TNF-a, IL-6, IL-8 and MCP-1)	at 16 weeks and after follow-up at 53 weeks
Changes in inflammatory parameters in the LCD-group compared to the VLCD-group	Inflammatory parameters are analyzed in: Plasma (including: TNF-a, IL-6, IL-8 and MCP-1); Micro-array; PCR: (including: TNF-a, IL-6, IL-8 and MCP-1)	at baseline, at 5, 9, 12, 16, 46 and 53 weeks
Changes in inflammatory parameters in relation to weight regain during the follow-up	Inflammatory parameters are analyzed in: Plasma (including: TNF-a, IL-6, IL-8 and MCP-1); Micro-array; PCR: (including: TNF-a, IL-6, IL-8 and MCP-1)	at baseline, at 5, 9, 12, 16, 46 and 53 weeks
Changes in protein concentration of metabolic parameters due to the dietary intervention (VLCD-group)	Protein concentrations of metabolic parameters, including: CD36, FABP4, Vimentin, Vimentin25, HSL, ALDOC, ALDOA, TUBB5, ANXA2, HADH, ACAA2 and ACADS	at baseline and after 5 weeks of VLCD diet
Changes in protein concentration of metabolic parameters during weight-stable period (VLCD-group)	Protein concentrations of metabolic parameters, including: CD36, FABP4, Vimentin, Vimentin25, HSL, ALDOC, ALDOA, TUBB5, ANXA2, HADH, ACAA2 and ACADS	after 5 weeks of VLCD diet and at 9 weeks
change in protein concentration of metabolic parameters during follow-up (VLCD-group)	Protein concentrations of metabolic parameters, including: CD36, FABP4, Vimentin, Vimentin25, HSL, ALDOC, ALDOA, TUBB5, ANXA2, HADH, ACAA2 and ACADS	at 9 weeks and after follow-up at 46 weeks
change in protein concentration of metabolic parameters due to dietary intervention (LCD-group)	Protein concentrations of metabolic parameters, including: CD36, FABP4, Vimentin, Vimentin25, HSL, ALDOC, ALDOA, TUBB5, ANXA2, HADH, ACAA2 and ACADS	at baseline and after 12 weeks of LCD diet
change in protein concentration of metabolic parameters during weight-stable period (LCD-group)	Protein concentrations of metabolic parameters, including: CD36, FABP4, Vimentin, Vimentin25, HSL, ALDOC, ALDOA, TUBB5, ANXA2, HADH, ACAA2 and ACADS	after 12 weeks of LCD diet and at 16 weeks
change in protein concentration of metabolic parameters during follow-up (LCD-group)	Protein concentrations of metabolic parameters, including: CD36, FABP4, Vimentin, Vimentin25, HSL, ALDOC, ALDOA, TUBB5, ANXA2, HADH, ACAA2 and ACADS	at 16 weeks and after follow-up at 53 weeks
change in protein concentration of metabolic parameters in the LCD-group compared to the VLCD-group	Protein concentrations of metabolic parameters, including: CD36, FABP4, Vimentin, Vimentin25, HSL, ALDOC, ALDOA, TUBB5, ANXA2, HADH, ACAA2 and ACADS	at baseline, at 5, 9, 12, 16, 46 and 53 weeks
change in protein concentration of metabolic parameters in relation to weight regain during follow-up	In LCD-group and VLCD-group Protein concentrations of metabolic parameters, including: CD36, FABP4, Vimentin, Vimentin25, HSL, ALDOC, ALDOA, TUBB5, ANXA2, HADH, ACAA2 and ACADS	at baseline, at 5, 9, 12, 16, 46 and 53 weeks

Collaborators and Investigators

• Sponsor: Maastricht University Medical Center
• Collaborators: ZonMw: The Netherlands Organisation for Health Research and Development
• Investigators: Principal Investigator: Marleen van Baak, Professor, Maastricht University

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (Actual): November 1, 2014
• Study Completion (Actual): November 1, 2014

Study Registration Dates

• First Submitted: March 12, 2012
• First Submitted That Met QC Criteria: March 19, 2012
• First Posted (Estimate): March 21, 2012

Study Record Updates

• Last Update Posted (Estimate): December 23, 2014
• Last Update Submitted That Met QC Criteria: December 22, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Keywords: Adipocytes
• Additional Relevant MeSH Terms: Body Weight Changes; Weight Loss; Body Weight
• Other Study ID Numbers: 38099