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

Study Overview
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Brief Summary
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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.

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

Conditions
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Obesity, Weight Loss, Diet

Intervention / Treatment
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* Other: Meal replacement diet using Modifast
* Other: Normal diet combined with Modifast diet


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Adipocytes