<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03024359</url>
  </required_header>
  <id_info>
    <org_study_id>CAAE: 60698716.1.0000.5404</org_study_id>
    <nct_id>NCT03024359</nct_id>
  </id_info>
  <brief_title>Monounsaturated Fatty Acids and Brown/Beige Adipose Tissue in Humans</brief_title>
  <official_title>Effect of Monounsaturated Fatty Acids Consumption in Brown/Beige Adipose Tissue Activity in Human Adults</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Campinas, Brazil</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Sao Paulo</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Campinas, Brazil</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Considering the high prevalence of obesity its comorbidities in Brazil and in the world,&#xD;
      different therapeutic measures have been suggested. It is currently known that brown/beige&#xD;
      adipose tissue plays an important role in body weight control and there is strong evidence&#xD;
      that its activity is inversely associated with obesity and metabolic diseases. Recent studies&#xD;
      have shown an important role foods and nutrients in the activation of brown/beige adipose&#xD;
      tissue, almost exclusively in animal models. The benefits of monounsaturated fatty acids to&#xD;
      metabolism have been described in several studies, however, the effects of consuming large&#xD;
      amounts of olive oil in the activity of brown/beige adipose tissue in humans have not been&#xD;
      explored. The aim of the study is to evaluate the impact of the consumption of large amounts&#xD;
      of extra virgin olive oil in the activity of brown/beige adipose tissue in lean and obese&#xD;
      humans. This will be a clinical trial with a total duration of 4 weeks. Obese and controls&#xD;
      (normal weight) participants will undergo a dietary intervention for 4 weeks with extra&#xD;
      virgin olive oil. Before and after the intervention period several data will be collected:&#xD;
      dietary intake and physical activity data, evaluation of brown/beige adipose tissue (with&#xD;
      18F-fluorodeoxyglucose positron emission tomography and magnetic resonance imaging -&#xD;
      PET/RMI), assessment of body composition (DXA), lipid profile and inflammatory markers as&#xD;
      well as hypothalamic inflammation (functional magnetic resonance imaging) and brown adipose&#xD;
      tissue biopsies in a subsample of 20 participants. The data will be expressed as mean and&#xD;
      standard deviation and the variables compared by the Student t test or ANOVA for repeated&#xD;
      measures.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      1. HYPOTHESIS The effects of fatty acids consumption on brown / beige adipose tissue have&#xD;
           not yet been explored in humans. However, studies that evaluated the effects of&#xD;
           saturated fatty acid replacement by monounsaturated fatty acids (MUFAs) or&#xD;
           polyunsaturated fatty acids (PUFAs) on animal and human models have observed an&#xD;
           improvement in cardiovascular risk factors, such as reduction of subclinical&#xD;
           inflammation, improvement of lipid profile and increase in insulin sensitivity. The&#xD;
           mechanisms by which these fatty acids act in the improvement of risk factors have not&#xD;
           been completely clarified and it is possible that there is an association between the&#xD;
           reduction of cardiovascular risk factors and the activation of brown / beige adipose&#xD;
           tissue.&#xD;
&#xD;
           Our hypothesis is that consuming extra virgin olive oil in high amounts for one month&#xD;
           will promote increased brown adipose tissue (BAT) activity of the participants and&#xD;
           improve the cardiovascular risk profile, as assessed by inflammatory markers. It is&#xD;
           possible that the response of lean and obese subjects to dietary intervention is&#xD;
           different and that the behavior of BAT is not equal in both groups.&#xD;
&#xD;
        2. OBJECTIVE To evaluate the impact of the consumption of large amounts of extra virgin&#xD;
           olive oil (source of monounsaturated fatty acids) on the activity of brown / beige&#xD;
           adipose tissue in lean and obese humans.&#xD;
&#xD;
           2.1 Specific objectives • To investigate the activity of brown and beige adipose tissue&#xD;
           by FDG PET / RMI, before and after four weeks of intervention with high amount of extra&#xD;
           virgin olive oil; • To evaluate the expression of BAT activity markers: uncoupling&#xD;
           protein 1 (UCP-1), PR domain containing 16 (PRDM16), Peroxisome proliferator-activated&#xD;
           receptor gamma coactivator 1-alpha (PGC-1α), iodothyronine deiodinase 2 (Dio2) in&#xD;
           mononuclear cells in the whole sample;&#xD;
&#xD;
             -  To evaluate levels of fatty acids in the blood by gas chromatography, before and&#xD;
                after the intervention to evaluate changes in fatty acid intake;&#xD;
&#xD;
             -  To evaluate concentrations of pro and anti-inflammatory cytokines in the blood&#xD;
                before and after 4 weeks of intervention: tumor necrosis factor alpha (TNF-α),&#xD;
                interleukin 1-beta (IL1β), Monocyte Chemoattractant Protein-1 (MCP-1),&#xD;
                interleukin-6 and interleukin-10);&#xD;
&#xD;
             -  To evaluate the effects of interventions on metabolic markers before and after the&#xD;
                intervention: leptin, insulin, glucose, total cholesterol and fractions,&#xD;
                triglycerides;&#xD;
&#xD;
             -  To evaluate the effects of the intervention on anthropometry (weight, abdominal&#xD;
                circumference) and on the body composition evaluated by Dual-energy X-ray&#xD;
                absorptiometry (DXA);&#xD;
&#xD;
             -  To evaluate the effects of dietary interventions on brain activity (by PET/MRi) in&#xD;
                a subsample of 15 individuals.&#xD;
&#xD;
        3. MATERIALS AND METHODS This will be an open clinical trial lasting for four weeks. The&#xD;
           study consists of two data collections before and after a 4-week dietary intervention in&#xD;
           which participants will be required to consume extra-virgin olive oil provided by the&#xD;
           researchers.&#xD;
&#xD;
           The collection of socio demographic, dietary and physical activity data, as well as the&#xD;
           PET / MRI and the blood collections of 50 participants will be carried out at the&#xD;
           Nuclear Medicine Center of the Medical School of the University of São Paulo. Bone&#xD;
           densitometry (DXA) will be performed at the School of Public Health of the University of&#xD;
           São Paulo.&#xD;
&#xD;
           Selection of participants:&#xD;
&#xD;
           The estimated number of individuals with a detectable brown adipose tissue (50) is 50%,&#xD;
           with the proportion of individuals with detectable brown adipose tissue. It will include&#xD;
           15 obese individuals (degree I obesity) and 35 control subjects (normal weight&#xD;
           individuals). Participants will be selected through print and electronic media.&#xD;
&#xD;
           • Inclusion criteria For the group with obesity: Both genders, age between 25 and 40&#xD;
           years, BMI ≥ 30 and &lt;35 kg / m2.&#xD;
&#xD;
           For the normal weight group (control): Both genders, age between 25 and 40 years, BMI&#xD;
           &lt;25 kg / m2.&#xD;
&#xD;
             -  Exclusion Criteria&#xD;
&#xD;
                1) Residing outside of São Paulo / Campinas; 2) pregnant women; 3) patients with&#xD;
                severe or non-stabilized neurological or psychiatric problems; 4) use of&#xD;
                anti-obesity or lipid-lowering medication; 5) use of adrenergic or benzodiazepine&#xD;
                drugs; 6) individuals with neoplasms, transmissible and rheumatic diseases, hepatic&#xD;
                or renal insufficiency, untreated thyroid dysfunction; Diabetes mellitus; 7) change&#xD;
                of more than 5% of body weight in the last six months; 8) to be carrying out some&#xD;
                kind of diet or modification in the usual dietary pattern; 9) have metal&#xD;
                prostheses.&#xD;
&#xD;
             -  Design This is an open clinical trial with a total duration of four weeks. Obese&#xD;
                and controls participants will be enrolled into a dietary intervention for 4 weeks&#xD;
                with extra virgin olive oil (MUFA rich). Extra-virgin olive oil (2 liters) is&#xD;
                provided to participants and the researchers adivice the participants to use the&#xD;
                oil in all preparations during the four weeks.&#xD;
&#xD;
           Before and after each intervention period the following data will be collected:&#xD;
&#xD;
           - Food consumption: 24-hour recall (before and after dietary intervention) and 3-day&#xD;
           food diary;&#xD;
&#xD;
             -  Physical activity data: International Physical Activity Questionnaire (IPAQ);&#xD;
&#xD;
             -  Evaluation of brown / beige adipose tissue volume and activity:&#xD;
&#xD;
           Positron emission tomography with fluoride-18-labeled fluorodeoxyglucose (18F-FDG) in&#xD;
           combination with magnetic resonance (PET / MRi).&#xD;
&#xD;
           For the FDG PET / RMI the participants will be allocated in a room with controlled&#xD;
           temperature (19 degrees), with light clothes and a cooling vest for 2 hours.&#xD;
&#xD;
           - Body composition assessment: Weight (digital scale) and height (fixed stadiometer);;&#xD;
           abdominal circumference; body composition: by Dual-energy X-ray absorptiometry (DXA);&#xD;
&#xD;
           - Biochemical dosages: plasma glucose, triglycerides, total cholesterol and HDL-c will&#xD;
           be determined routinely and inflammatory markers will be determined by enzyme-linked&#xD;
           immunosorbent assay (ELISA);&#xD;
&#xD;
           - Expression of UCP-1, PGC-1α, PRDM16 and Dio2 will be performed by Real-Time Polymerase&#xD;
           chain reaction (RT-PCR);&#xD;
&#xD;
           - Composition of fatty acids in plasma will be determined by gas chromatography;&#xD;
&#xD;
           - Brain activity: will be performed in a subsample of 15 individuals using 18F-FDG&#xD;
           PET/MRi.&#xD;
&#xD;
           • Statistical analysis Data will be expressed as mean and standard deviation and the&#xD;
           variables compared by Student's t-test or ANOVA for repeated measures.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 2017</start_date>
  <completion_date type="Actual">July 2020</completion_date>
  <primary_completion_date type="Actual">December 2019</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>All subjects receive a dietary intervention with olive oil.</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Brown adipose tissue activity measured by increase in mean standardized disposal value (SUV)</measure>
    <time_frame>Four weeks</time_frame>
    <description>We will investigate whether 4 weeks of olive oil consumption can increase the activity of brown adipose tissue measured by mean standardized disposal value (volume) using magnetic resonance imaging</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Hypothalamic inflammation</measure>
    <time_frame>Four weeks</time_frame>
    <description>To see whether the consumption of 4 weeks of olive oil is able to reduce hypothalamic inflammation in lean and obese individuals as measured by functional resonance imaging</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lipid profile</measure>
    <time_frame>Four weeks</time_frame>
    <description>To see whether the consumption of 4 weeks of olive oil is able to reduce LDL and total cholesterol, as well as triglycerides concentrations</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Inflammatory markers</measure>
    <time_frame>Four weeks</time_frame>
    <description>To see whether the consumption of 4 weeks of olive oil is able to reduce pro-inflammatory markers (TNF-alpha, interleukin-1beta) and increase interleukin-10</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">45</enrollment>
  <condition>Obese</condition>
  <arm_group>
    <arm_group_label>obese individuals</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Individuals with BMI between 30 and 35 kg/m2 will be included in this group and will receive 4 weeks of extra virgin olive oil. Before and after the intervention period data regarding dietary intake and physical activity, brown/beige adipose tissue activity, body composition (DXA), lipid profile and inflammatory markers and brain activity (18F-FDG PET/MRI; in a subsample of 5 obese individuals)will be collected.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>normal weight individuals</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Individuals with BMI between 18.5 and 24.99 kg/m2 will be included in this group and will receive 4 weeks of extra virgin olive oil. Before and after the intervention period data regarding dietary intake and physical activity, brown/beige adipose tissue activity, body composition (DXA), lipid profile and inflammatory markers and and brain activity (18F-FDG PET/MRI; in a subsample of 10 normal weight individuals) will be collected.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Extra virgin olive oil</intervention_name>
    <description>2 liters of extra virgin olive oil will be given to participants to include/use in their daily foods.</description>
    <arm_group_label>normal weight individuals</arm_group_label>
    <arm_group_label>obese individuals</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Gender: Both Age: 25 to 40 years&#xD;
&#xD;
        Body mass index (BMI):&#xD;
&#xD;
        Normal body weight group: BMI lower than 25 kg/m2 Obese group: BMI between 30 and 35 kg/m2&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Living outside of São Paulo;&#xD;
&#xD;
          2. pregnant women;&#xD;
&#xD;
          3. patients with severe or non-stabilized neurological or psychiatric problems;&#xD;
&#xD;
          4. use of anti-obesity or lipid-lowering medication;&#xD;
&#xD;
          5. use of adrenergic or benzodiazepine drugs;&#xD;
&#xD;
          6. individuals with neoplasms, transmissible and rheumatic diseases, hepatic or renal&#xD;
             insufficiency, untreated thyroid dysfunction; Diabetes mellitus;&#xD;
&#xD;
          7. individuals that changed more than 5% of body weight in the last six months; 8) to be&#xD;
             carrying out some kind of diet or modification in the usual dietary pattern; 9) having&#xD;
             metal prostheses.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>25 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Milena Monfort-Pires, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Campinas</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Licio A Velloso, Professor</last_name>
    <role>Study Director</role>
    <affiliation>University of Campinas</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Faculdade de Ciências Médicas Unicamp</name>
      <address>
        <city>Campinas</city>
        <state>São Paulo</state>
        <zip>13083-887</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <reference>
    <citation>van Marken Lichtenbelt WD, Vanhommerig JW, Smulders NM, Drossaerts JM, Kemerink GJ, Bouvy ND, Schrauwen P, Teule GJ. Cold-activated brown adipose tissue in healthy men. N Engl J Med. 2009 Apr 9;360(15):1500-8. doi: 10.1056/NEJMoa0808718. Erratum In: N Engl J Med. 2009 Apr 30;360(18):1917.</citation>
    <PMID>19357405</PMID>
  </reference>
  <reference>
    <citation>Vijgen GH, Bouvy ND, Teule GJ, Brans B, Hoeks J, Schrauwen P, van Marken Lichtenbelt WD. Increase in brown adipose tissue activity after weight loss in morbidly obese subjects. J Clin Endocrinol Metab. 2012 Jul;97(7):E1229-33. doi: 10.1210/jc.2012-1289. Epub 2012 Apr 24.</citation>
    <PMID>22535970</PMID>
  </reference>
  <reference>
    <citation>Chondronikola M, Annamalai P, Chao T, Porter C, Saraf MK, Cesani F, Sidossis LS. A percutaneous needle biopsy technique for sampling the supraclavicular brown adipose tissue depot of humans. Int J Obes (Lond). 2015 Oct;39(10):1561-4. doi: 10.1038/ijo.2015.76. Epub 2015 Apr 29.</citation>
    <PMID>25920777</PMID>
  </reference>
  <verification_date>November 2020</verification_date>
  <study_first_submitted>January 11, 2017</study_first_submitted>
  <study_first_submitted_qc>January 13, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 18, 2017</study_first_posted>
  <last_update_submitted>November 3, 2020</last_update_submitted>
  <last_update_submitted_qc>November 3, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">November 4, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Campinas, Brazil</investigator_affiliation>
    <investigator_full_name>Milena Monfort Pires</investigator_full_name>
    <investigator_title>LDN, MSc, PhD</investigator_title>
  </responsible_party>
  <keyword>Obesity</keyword>
  <keyword>Brown adipose tissue</keyword>
  <keyword>Monounsaturated fatty acids</keyword>
  <keyword>Hypothalamic inflammation</keyword>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03024359
org study id: CAAE: 60698716.1.0000.5404
nct id: NCT03024359
lead sponsor: 
collaborator: 
has dmc: Yes
Considering the high prevalence of obesity its comorbidities in Brazil and in the world,
      different therapeutic measures have been suggested. It is currently known that brown/beige
      adipose tissue plays an important role in body weight control and there is strong evidence
      that its activity is inversely associated with obesity and metabolic diseases. Recent studies
      have shown an important role foods and nutrients in the activation of brown/beige adipose
      tissue, almost exclusively in animal models. The benefits of monounsaturated fatty acids to
      metabolism have been described in several studies, however, the effects of consuming large
      amounts of olive oil in the activity of brown/beige adipose tissue in humans have not been
      explored. The aim of the study is to evaluate the impact of the consumption of large amounts
      of extra virgin olive oil in the activity of brown/beige adipose tissue in lean and obese
      humans. This will be a clinical trial with a total duration of 4 weeks. Obese and controls
      (normal weight) participants will undergo a dietary intervention for 4 weeks with extra
      virgin olive oil. Before and after the intervention period several data will be collected:
      dietary intake and physical activity data, evaluation of brown/beige adipose tissue (with
      18F-fluorodeoxyglucose positron emission tomography and magnetic resonance imaging -
      PET/RMI), assessment of body composition (DXA), lipid profile and inflammatory markers as
      well as hypothalamic inflammation (functional magnetic resonance imaging) and brown adipose
      tissue biopsies in a subsample of 20 participants. The data will be expressed as mean and
      standard deviation and the variables compared by the Student t test or ANOVA for repeated
      measures.
1. HYPOTHESIS The effects of fatty acids consumption on brown / beige adipose tissue have
           not yet been explored in humans. However, studies that evaluated the effects of
           saturated fatty acid replacement by monounsaturated fatty acids (MUFAs) or
           polyunsaturated fatty acids (PUFAs) on animal and human models have observed an
           improvement in cardiovascular risk factors, such as reduction of subclinical
           inflammation, improvement of lipid profile and increase in insulin sensitivity. The
           mechanisms by which these fatty acids act in the improvement of risk factors have not
           been completely clarified and it is possible that there is an association between the
           reduction of cardiovascular risk factors and the activation of brown / beige adipose
           tissue.

           Our hypothesis is that consuming extra virgin olive oil in high amounts for one month
           will promote increased brown adipose tissue (BAT) activity of the participants and
           improve the cardiovascular risk profile, as assessed by inflammatory markers. It is
           possible that the response of lean and obese subjects to dietary intervention is
           different and that the behavior of BAT is not equal in both groups.

        2. OBJECTIVE To evaluate the impact of the consumption of large amounts of extra virgin
           olive oil (source of monounsaturated fatty acids) on the activity of brown / beige
           adipose tissue in lean and obese humans.

           2.1 Specific objectives • To investigate the activity of brown and beige adipose tissue
           by FDG PET / RMI, before and after four weeks of intervention with high amount of extra
           virgin olive oil; • To evaluate the expression of BAT activity markers: uncoupling
           protein 1 (UCP-1), PR domain containing 16 (PRDM16), Peroxisome proliferator-activated
           receptor gamma coactivator 1-alpha (PGC-1α), iodothyronine deiodinase 2 (Dio2) in
           mononuclear cells in the whole sample;

             -  To evaluate levels of fatty acids in the blood by gas chromatography, before and
                after the intervention to evaluate changes in fatty acid intake;

             -  To evaluate concentrations of pro and anti-inflammatory cytokines in the blood
                before and after 4 weeks of intervention: tumor necrosis factor alpha (TNF-α),
                interleukin 1-beta (IL1β), Monocyte Chemoattractant Protein-1 (MCP-1),
                interleukin-6 and interleukin-10);

             -  To evaluate the effects of interventions on metabolic markers before and after the
                intervention: leptin, insulin, glucose, total cholesterol and fractions,
                triglycerides;

             -  To evaluate the effects of the intervention on anthropometry (weight, abdominal
                circumference) and on the body composition evaluated by Dual-energy X-ray
                absorptiometry (DXA);

             -  To evaluate the effects of dietary interventions on brain activity (by PET/MRi) in
                a subsample of 15 individuals.

        3. MATERIALS AND METHODS This will be an open clinical trial lasting for four weeks. The
           study consists of two data collections before and after a 4-week dietary intervention in
           which participants will be required to consume extra-virgin olive oil provided by the
           researchers.

           The collection of socio demographic, dietary and physical activity data, as well as the
           PET / MRI and the blood collections of 50 participants will be carried out at the
           Nuclear Medicine Center of the Medical School of the University of São Paulo. Bone
           densitometry (DXA) will be performed at the School of Public Health of the University of
           São Paulo.

           Selection of participants:

           The estimated number of individuals with a detectable brown adipose tissue (50) is 50%,
           with the proportion of individuals with detectable brown adipose tissue. It will include
           15 obese individuals (degree I obesity) and 35 control subjects (normal weight
           individuals). Participants will be selected through print and electronic media.

           • Inclusion criteria For the group with obesity: Both genders, age between 25 and 40
           years, BMI ≥ 30 and <35 kg / m2.

           For the normal weight group (control): Both genders, age between 25 and 40 years, BMI
           <25 kg / m2.

             -  Exclusion Criteria

                1) Residing outside of São Paulo / Campinas; 2) pregnant women; 3) patients with
                severe or non-stabilized neurological or psychiatric problems; 4) use of
                anti-obesity or lipid-lowering medication; 5) use of adrenergic or benzodiazepine
                drugs; 6) individuals with neoplasms, transmissible and rheumatic diseases, hepatic
                or renal insufficiency, untreated thyroid dysfunction; Diabetes mellitus; 7) change
                of more than 5% of body weight in the last six months; 8) to be carrying out some
                kind of diet or modification in the usual dietary pattern; 9) have metal
                prostheses.

             -  Design This is an open clinical trial with a total duration of four weeks. Obese
                and controls participants will be enrolled into a dietary intervention for 4 weeks
                with extra virgin olive oil (MUFA rich). Extra-virgin olive oil (2 liters) is
                provided to participants and the researchers adivice the participants to use the
                oil in all preparations during the four weeks.

           Before and after each intervention period the following data will be collected:

           - Food consumption: 24-hour recall (before and after dietary intervention) and 3-day
           food diary;

             -  Physical activity data: International Physical Activity Questionnaire (IPAQ);

             -  Evaluation of brown / beige adipose tissue volume and activity:

           Positron emission tomography with fluoride-18-labeled fluorodeoxyglucose (18F-FDG) in
           combination with magnetic resonance (PET / MRi).

           For the FDG PET / RMI the participants will be allocated in a room with controlled
           temperature (19 degrees), with light clothes and a cooling vest for 2 hours.

           - Body composition assessment: Weight (digital scale) and height (fixed stadiometer);;
           abdominal circumference; body composition: by Dual-energy X-ray absorptiometry (DXA);

           - Biochemical dosages: plasma glucose, triglycerides, total cholesterol and HDL-c will
           be determined routinely and inflammatory markers will be determined by enzyme-linked
           immunosorbent assay (ELISA);

           - Expression of UCP-1, PGC-1α, PRDM16 and Dio2 will be performed by Real-Time Polymerase
           chain reaction (RT-PCR);

           - Composition of fatty acids in plasma will be determined by gas chromatography;

           - Brain activity: will be performed in a subsample of 15 individuals using 18F-FDG
           PET/MRi.

           • Statistical analysis Data will be expressed as mean and standard deviation and the
           variables compared by Student's t-test or ANOVA for repeated measures.
allocation: Non-Randomized
intervention model: Single Group Assignment
intervention model description: All subjects receive a dietary intervention with olive oil.
primary purpose: Prevention
masking: None (Open Label)
measure: Brown adipose tissue activity measured by increase in mean standardized disposal value (SUV)
time frame: Four weeks
description: We will investigate whether 4 weeks of olive oil consumption can increase the activity of brown adipose tissue measured by mean standardized disposal value (volume) using magnetic resonance imaging
measure: Hypothalamic inflammation
time frame: Four weeks
description: To see whether the consumption of 4 weeks of olive oil is able to reduce hypothalamic inflammation in lean and obese individuals as measured by functional resonance imaging
measure: Lipid profile
time frame: Four weeks
description: To see whether the consumption of 4 weeks of olive oil is able to reduce LDL and total cholesterol, as well as triglycerides concentrations
measure: Inflammatory markers
time frame: Four weeks
description: To see whether the consumption of 4 weeks of olive oil is able to reduce pro-inflammatory markers (TNF-alpha, interleukin-1beta) and increase interleukin-10
arm group label: obese individuals
arm group type: Active Comparator
description: Individuals with BMI between 30 and 35 kg/m2 will be included in this group and will receive 4 weeks of extra virgin olive oil. Before and after the intervention period data regarding dietary intake and physical activity, brown/beige adipose tissue activity, body composition (DXA), lipid profile and inflammatory markers and brain activity (18F-FDG PET/MRI; in a subsample of 5 obese individuals)will be collected.
arm group label: normal weight individuals
arm group type: Active Comparator
description: Individuals with BMI between 18.5 and 24.99 kg/m2 will be included in this group and will receive 4 weeks of extra virgin olive oil. Before and after the intervention period data regarding dietary intake and physical activity, brown/beige adipose tissue activity, body composition (DXA), lipid profile and inflammatory markers and and brain activity (18F-FDG PET/MRI; in a subsample of 10 normal weight individuals) will be collected.
intervention type: Dietary Supplement
intervention name: Extra virgin olive oil
description: 2 liters of extra virgin olive oil will be given to participants to include/use in their daily foods.
arm group label: normal weight individuals
arm group label: obese individuals
criteria: 
gender: All
minimum age: 25 Years
maximum age: 40 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Milena Monfort-Pires, PhD
role: Principal Investigator
affiliation: University of Campinas
last name: Licio A Velloso, Professor
role: Study Director
affiliation: University of Campinas
facility: 
country: Brazil
citation: van Marken Lichtenbelt WD, Vanhommerig JW, Smulders NM, Drossaerts JM, Kemerink GJ, Bouvy ND, Schrauwen P, Teule GJ. Cold-activated brown adipose tissue in healthy men. N Engl J Med. 2009 Apr 9;360(15):1500-8. doi: 10.1056/NEJMoa0808718. Erratum In: N Engl J Med. 2009 Apr 30;360(18):1917.
PMID: 19357405
citation: Vijgen GH, Bouvy ND, Teule GJ, Brans B, Hoeks J, Schrauwen P, van Marken Lichtenbelt WD. Increase in brown adipose tissue activity after weight loss in morbidly obese subjects. J Clin Endocrinol Metab. 2012 Jul;97(7):E1229-33. doi: 10.1210/jc.2012-1289. Epub 2012 Apr 24.
PMID: 22535970
citation: Chondronikola M, Annamalai P, Chao T, Porter C, Saraf MK, Cesani F, Sidossis LS. A percutaneous needle biopsy technique for sampling the supraclavicular brown adipose tissue depot of humans. Int J Obes (Lond). 2015 Oct;39(10):1561-4. doi: 10.1038/ijo.2015.76. Epub 2015 Apr 29.
PMID: 25920777
responsible party type: Principal Investigator
investigator affiliation: University of Campinas, Brazil
investigator full name: Milena Monfort Pires
investigator title: LDN, MSc, PhD
sharing ipd: No