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

Obesity Clinical Trial

— ADIPOSTRESS  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01559415
• Other study ID #: 38099
• Status: Completed
• Phase: N/A
• First received: March 12, 2012
• Last updated: December 22, 2014
• Start date: March 2012
• Est. completion date: November 2014

Study information

• Verified date: December 2014
• Source: Maastricht University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 58
• Est. completion date: November 2014
• Est. primary completion date: November 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 65 Years

Eligibility

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 Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Body Weight
• Diet
• Obesity
• Weight Loss

Intervention

Other:
• Meal replacement diet using Modifast
modifast intensive diet replacing all regular meals (500 kcal/d) for 5 weeks
• Normal diet combined with Modifast diet
Combination of modifast and regular diet (1250 kcal/d) for 3 months

Locations

Country	Name	City	State
Netherlands	Maastricht University	Maastricht	Limburg

Sponsors (2)

Lead Sponsor	Collaborator
Maastricht University Medical Center	ZonMw: The Netherlands Organisation for Health Research and Development

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	change in weight following weight loss	VLCD diet group	at 9 weeks and at 46 weeks	No
Primary	change in weight following weight loss	LCD diet group	at 16 weeks and at 53 weeks	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	change in fat cell size and fat cell number due to dietary intervention (LCD-group)		at baseline and after 12 weeks of LCD diet	No
Secondary	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	No
Secondary	change in fat cell size and fat cell number during follow-up (LCD-group)		at 16 weeks and after follow-up at 53 weeks	No
Secondary	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	No
Secondary	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	No
Secondary	change in breath volatile organic compounds due to the dietary intervention (VLCD-group)		at baseline and after 5 weeks of VLCD diet	No
Secondary	change in breath volatile organic compounds during weight-stable period (VLCD-group)		after 5 weeks of VLCD diet and at 9 weeks	No
Secondary	change in breath volatile organic compounds during follow-up period (VLCD-group)		at 9 weeks and after follow-up at 46 weeks	No
Secondary	change in breath volatile organic compounds due to dietary intervention (LCD-group)		at baseline and after 12 weeks of LCD diet	No
Secondary	change in breath volatile organic compounds during weight-stable period (LCD-group)		after 12 weeks of LCD diet and at 16 weeks	No
Secondary	change in breath volatile organic compounds during follow-up (LCD-group)		at 16 weeks and after follow-up at 53 weeks	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No