Insight Into New Brown Adipose Tissue Activators.
Condition: Adiposity; Metabolic Complication; Metabolic Disturbance; Healthy; Obesity; Diet Habit; Nutritional and Metabolic Diseases
MeSH terms: Metabolic Diseases
Study type: Observational

Summary: 
      The general purpose of the study was to provide new information about the role of
      macronutrients intake, metabolomics, proteomics and microRNA on BAT activation.

      The invesigator evaluated BAT activity and whole body energy consumption under cold
      stimulation in two gruops of healthy males aged 21-43 years old with normal BMI ( 19-25kg/m2)
      and in overweight/obese subjects.
    

Detailed description: 
      In detail, the main objectives of this study was to measure the influence of biological
      molecules of such fields: genomics, transcriptomics metabolomics and protemics and its
      relationship on BAT activation. The investigator also evaluated the role of diet,
      macronutirnets intake and polyunsaturated fatty acids on BAT activity.

      Study design:

      1. SCREENING VISIT:

        -  obtaining written informed consent from all subjects

        -  physical examination

        -  body composition analysis ( DXA + bioindepedance method inbody 720)

      Laboratory analyses:

        -  Oral glucose tolerance test ( OGGT 75g)

        -  Morphology

        -  CRP

        -  Creatinine

        -  Urine analysis

        -  Lipids profile

        -  TSH

        -  ALT,AST

      Dietary analysis All subjects fulfilled a 3-day food diary. Subjects were asked to compare
      the portion sizes with the colour photographs of each portion size, and to weigh food, if
      possible. The daily total energy, macronutrients, monounsaturated fatty acids (MUFA),
      polyunsaturated fatty acids (PUFA), omega-3, and omega-6 fatty acids intake were analysed.

      2) STUDY VISITS: Patients who met the inclusion criteria and passed the screening stage were
      invited for the first visit when PET / MRI after 2h of cold exposure was performed.

      Subjects were studied in the morning, from approximately 8 a.m. to 12 a.m., after an
      overnight fast beginning at 10 p.m. the night before. At the beginning of the day on which
      the PET study was performed, a catheter was inserted in the subject's antecubital vein for a
      bolus injection of 18F-FDG. Another catheter was inserted in the antecubital vein of the
      contralateral arm and was used to obtain samples of venous blood.

      The subjects rested in a supine position under thermoneutral conditions (22°C) for 1 hour and
      then participants were exposed to cooling for 2 hours. The water perfused blankets were used
      in the applied protocol of cooling. Blood samples were taken before as well as in 60th and
      120th min of cooling. Subjects were cooled until shivering and then temperature is set
      slightly (1-2°C) above the temperature that causes the onset of shivering. Shivering were
      confirmed by visual inspection and by asking the subject each 15 min. After 2 hour the tracer
      18F-FDG (4 MBq/kg ) was administered intravenously, and scanning was performed after the
      injection of tracer.

      Skin temperatures were measured continually by means of electrode attached to skin below
      armpit.

      During the cold exposure, whole body resting energy expenditure (REE) was assessed by a
      computed open-circuit indirect calorimetry method- based on the consumption of O2 and the
      production of CO2. The 30 min long measurements of resting oxygen uptake and resting carbon
      dioxide production were performed by a ventilated canopy Vmax Encore 29n System (Viasys
      HealthCare, Yorba Linda, CA, USA) at the baseline ( -30 min to 0 min) and every 30 min until
      120 min of cold exposure.

      During PET-MRI scanning blood samples were taken in 5', 10' 20' 30' 40' to check the activity
      of 18-FDG. After PET/MRI patient's urine was collected and analyzed for activity of tracer.
      Blood samples were taken for analysis before the cold exposure, at 60 min and 120 min during
      the cold exposure to evaluate:

      Glucose, IL-6, Insulin, Free Fatty Acids (FFA), TSH, fT4,fT3, Irisin, Atrial natriuretic
      peptide (ANP), Brain natriuretic peptide (BNP), plasma nonesterified fatty acid (NEFA), DNA,
      Peripheral Blood Mononuclear Cell (PBMC) for microRNA isolation, metabolomics and proteomics
      analysis.

      SUMMARY:

      The goal of our study is to search for new mechanisms that stimulate activation of BAT. It is
      likely that individuals with different content and activity of the brown adipose will have
      different set of serum markers after exposure to cold. This will allow the identification of
      new biomarkers and to understand the molecular mechanisms responsible for the activation of
      the brown adipose tissue. The outcomes will enable to find new potential therapeutic and
      diagnostic applications given to the current obesity pandemic.
    

Intervention name(s): cold expossure
Intervention type(s): Other
Intervention description(s): subjects were exposed for the cold, to activate and diagnose potential brown tissue activity
Observational model: Other
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        The study group comprised of 28 young, healthy, non - smoking Caucasian males, aged 21-42
        years (mean age 26.75 ±5.11 years old), 16 with normal body weight (BMI < 25 kg/m2) and 12
        obese/overweight (BMI > 25 kg/m2). Only participants without any comorbidities (e.g. hypo-
        and hyperthyroidis, asthma, cardiovascular disease, renal and liver failure, etc.) as well
        as without any medications (beta-blockers etc.) that could have impact on results, were
        enrolled to the study. Outside and shift workers have been excluded from the study as well.
      
Biospecimen description: 
      blood
    
Keywords: brown adipose tissue, obesity, diabetes type 2