Effects of a Short Term Caloric Restriction on T Cell Activation in Fat
Condition: Inflammation
MeSH terms: Inflammation
Study type: Interventional

Summary: 
      Overweight and obesity are major problems and their complications such as cardiovascular
      disease and type 2 diabetes mellitus pose great burdens on healthcare systems. There is
      accumulating evidence to support obesity being a chronic inflammatory disorder mediated in
      part by the expansion of adipose (fat) tissue.

      In addition to adipocytes (fat cells), adipose tissue contains a whole range of other cell
      types including some immune (white blood) cells. The relative proportions of immune cell
      subpopulations and interactions between the different cell types within adipose tissue may be
      important in the development of type 2 diabetes.

      Previous research by the investigators has suggested that there may be important differences
      in the activation status of certain immune cells located in adipose tissue with increased
      overweight and the production of leptin - an appetite regulating hormone. Properties of
      adipose tissue and inflammatory cells located within it may therefore be sensitive to changes
      in our nutritional status.

      The purpose of the present study is to investigate changes in T cell activation in adipose
      tissue alongside other immunometabolic properties before and after a short period of dieting
      compared to changes in blood.

      Participants will include males aged between 35-55 years old who meet the criteria for
      inclusion. After taking some preliminary measurements and monitoring of normal daily
      activities, participants will reduce their calorie intake to 50 % of their normal
      intake/requirements for 3 consecutive days and will attend 1 session of Laboratory testing
      before and 1 after this period which will take place in the Physiology Laboratories at the
      University of Bath.

      It is hoped that investigating immunometabolic responses within adipose tissue following an
      acute nutritional challenge will help lead to a better understanding of the development of
      diseases associated with being overweight and ultimately help in the development of more
      effective methods for prevention and treatment.
    

Detailed description: 
      The aim of this research is to investigate whether the immunometabolic properties of adipose
      tissue and the inflammatory cells located within it can be modified by short term changes in
      nutritional status.

      Following advertisement of the study, interested potential participants will be asked to
      contact the Chief Investigator for further information via email/telephone correspondence.
      There will be an initial assessment of eligibility based on inclusion/exclusion criteria and,
      if these requirements are met, the potential participant will be invited to a meeting to
      further discuss the trial. After they have read the participant information sheet and seen
      the flowchart outlining the timeline for the study, if they would like to take part, they
      will be asked to sign a consent form. Dates will then be scheduled for some preliminary
      anthropometric measurements, 1 week of diet and physical activity monitoring and 3 days of
      calorie restriction with trial dates either side.

      Preliminary measurements:

      Preliminary testing will include anthropometric measurements of height, weight, waist and hip
      circumferences, sagittal waist height and blood pressure. Participants will also have their
      body composition precisely assessed using a dual energy X-ray absorptiometer (DEXA). These
      measurements will take place at the University of Bath Physiology Laboratories.

      Monitoring of energy balance:

      For 1 week, participants will be fitted with a physical activity monitor (Actiheart™) and
      asked to record a corresponding diary of their physical activity during this period to aid
      its interpretation and allow a more accurate calculation of average daily activity energy
      expenditure. Participants will also be asked to record their food and drink intake during
      this period so their corresponding energy intake during this period can be analysed and thus
      their 'energy balance' can be estimated. Participants should not make any conscious changes
      to their normal lifestyle habits/routines during this period. This analysis will then be used
      to write a 'diet prescription' for the 3 days to ensure the participant will receive 50 % of
      their 'normal' calorie intake using foods they would normally consume.

      Main trial day 1:

      In the 2 days prior to the first main trial day, participants should refrain from performing
      any strenuous physical activity. In the 24 hours prior, participants should also refrain from
      consuming any alcohol or caffeine. Participants should arrive at the Physiology Resting
      Laboratory in the morning following a 10 hour fast (approximately 8 am) where blood pressure
      will be measured and a saliva sample collected. A cannula will be inserted into a forearm
      vein and baseline blood sample(s) taken for analysis of metabolic/inflammatory markers and
      isolation of T cells. A fat sample will also be obtained using a needle aspiration technique.
      The participant will then be asked to consume a glucose drink consisting of 75 g anhydrous
      glucose (113 mL Polycal and 87 mL of water) and a cannula blood sample taken every 15 minutes
      for the following 2 hours.

      Intervention - 3 day calorie restriction:

      For the following 3 days, participants will be instructed to consume a diet calculated to be
      50% of their 'normal' energy intake by reducing the proportions of the normal diet consumed.
      No strenuous physical activity should be performed by the participant for the last 2 days of
      this 3 day period and on the final day of this intervention, no caffeine or alcohol should be
      consumed.

      Main trial day 2:

      The following day after the 3 days of calorie restriction, participants will arrive at the
      laboratory at the same time as on main trial day 1 (to minimise variation in timing of sample
      collection) and will undergo exactly the same procedures.

      Analysis:

      On the day of the trial whole blood will be analysed for white blood cell count. Plasma and
      serum samples will be extracted from the whole blood via centrifugation and stored at -80
      degrees C. Monocytes and T lymphocytes (populations of white blood cells) will also be
      isolated from whole blood and stored to later assess changes in their proportions and
      activation following the calorie restriction period. In each fat sample, separate portions of
      either adipose tissue or adipocytes (isolated from the other cells within the adipose tissue
      using a digestion method) will be cultured and media collected for later investigations. The
      remaining cells from the adipose tissue (SVF) will also be stored for later analysis of cell
      populations and their activation using flow cytometry, and expression/secretion analysis.
      mRNA expression will also be examined in adipose tissue.
    

Intervention name(s): Calorie restriction; Activity monitoring; Diet monitoring
Intervention type(s): Other; Other; Other
Intervention description(s): Participants will reduce calorie intake by 50 % for a period of 3 consecutive days.; For 1 week, participants will be fitted with an activity monitor (Actiheart) to estimate energy expenditure (during the same week as the diet monitoring). The activity and diet monitoring data will be used together to confirm that participants are in a state of energy balance and an average of these 2 values taken - 50 % of this average value will be the target calorie intake for the 3 day calorie restriction period.; For 1 week, participants will be asked to record all food and fluids consumed to estimate energy intake (during the same week as the activity monitoring). The activity and diet monitoring data will be used together to confirm that participants are in a state of energy balance and an average of these 2 values taken - 50 % of this average value will be the target calorie intake for the 3 day calorie restriction period.
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: T-lymphocyte; Adipose tissue; Inflammation; Calorie restriction