Metabolic and Immune System Responses to a Mixed Meal
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.

      Knowledge of the role of adipose tissue itself has changed dramatically and it has emerged
      that in addition to storing energy as fats; adipose tissue secretes and responds to various
      chemical messengers in the body that are related to metabolism and inflammation. After a meal
      has been consumed, changes in metabolic (and some inflammatory) markers are seen in the
      blood, which may be influenced by metabolic and inflammatory changes occuring in the adipose
      tissue itself.

      The investigators therefore plan to investigate these changes in adipose tissue before and
      after a meal and compare them to changes occurring in the blood. They also plan to
      investigate whether these responses are different in people who are overweight compared to
      'normal' weight.

      Participants will include males aged between 35-55 years who fit the criteria for inclusion.
      After taking some preliminary measurements and monitoring of normal daily activities,
      participants will attend one day of Laboratory testing in the Physiology Laboratories at the
      University of Bath.

      By investigating differences in metabolism and inflammation in adipose tissue and the
      circulation it is hoped that more will be learnt about the development of diseases associated
      with being overweight and ultimately help to develop more effective methods for prevention
      and treatment.
    

Detailed description: 
      The aim of this research is to investigate differences in metabolism and inflammation in
      adipose tissue and the circulation in response to a meal with increasing adiposity. It is
      hypothesised that participants with increased fat mass, will have a more pronounced
      inflammatory response to a meal compared to participants with a 'healthy' weight. The
      inflammatory response will be assessed by measuring changes in gene expression and protein
      secretion in the adipose tissue and by measuring markers of metabolism, insulin resistance,
      cardiovascular disease and inflammation in the blood.

      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 to be taken, 9 days of physical activity monitoring and the trial
      date (1 full day in the laboratory only).

      Preliminary measurements:

      Preliminary testing will include anthropometric measurements of height, weight, waist and hip
      circumferences, sagittal waist height and blood pressure. These measurements will take place
      at the University of Bath Physiology Laboratories.

      Physical activity monitoring:

      For 9 days, 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 should not make any conscious changes to their normal lifestyle
      habits/routines during this period. The first 2 days of activity monitoring will be excluded
      from analysis to account for reactivity.

      Main trial day:

      In the 3 days prior to the main trial day, participants will be asked to record their food
      and drink intake and 48 hours before they 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 Sports Training Village, University of Bath in the morning
      following a 10 hour fast where they will have their body composition precisely assessed using
      a dual-energy Xray absorptiometer (DEXA). They will then be taken to the Physiology Resting
      Laboratory where baseline expired gases will be collected for assessment of resting metabolic
      rate (RMR). 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 breakfast type meal that is high in
      carbohydrate and fat contents consisting of brioche, jam, butter, and milkshake which has
      been adapted from a meal used by Rijkelijkhuizen J. et al, 2008, which induced stronger beta
      cell responses (i.e. of insulin) compared to a glucose load and showed differences with
      insulin sensitivity, so this meal type should identify differences in metabolism based on
      adiposity.

      Furthermore, there is some evidence that high starch/low fibre foods may induce greater
      inflammation (Manning, Sutherland et al. 2008). The meal composition for all individuals will
      be identical but the energy content from carbohydrate will be calculated as a portion of the
      individuals' resting metabolic rate. This allows standardisation of energy intake for
      differences body weight/composition and will reflect energy requirements of the individual
      whilst at rest.

      The meal should be consumed within 15 minutes and blood samples will be taken from the
      cannula at 15, 30, 60, and 90 minutes and then at every hour for 6 hours after consumption of
      the meal to monitor changes in metabolic and inflammatory markers. Additional blood samples
      will be obtained at 2 and 6 hours post meal by venepuncture for analysis of inflammatory
      markers as there is evidence that the cannula can stimulate local inflammation which
      interferes with the true result.

      Expired gas samples for RMR will also be taken hourly and indirect calorimetry will be used
      to estimate relative fat and carbohydrate metabolism in response to the meal.

      A second fat sample will be taken at 6 hours to examine inflammatory and metabolic responses
      to the meal within adipose tissue. A second blood sample for T cell isolation will also be
      obtained at this time point to examine corresponding metabolic/inflammatory responses in T
      cells.

      Analysis:

      On the day of the trial whole blood will be analysed for white blood cell count, glucose and
      lactate. Plasma and serum samples will be extracted from the whole blood via centrifugation
      and stored at -80. Monocytes and T lymphocytes (populations of white blood cells) will also
      be isolated from whole blood for later assessment of insulin sensitivity and culture
      experiments.

      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. mRNA expression will also be examined in adipose
      tissue and isolated adipocytes. The remaining cells from the adipose tissue (SVF) will also
      be stored for later analysis of cell populations using flow cytometry, and
      expression/secretion analysis.
    

Intervention name(s): Consumption of a mixed meal
Intervention type(s): Other
Intervention description(s): Participants will consume a mixed meal and postprandial responses in blood and adipose tissue will be investigated over 6 hours and compared to baseline.
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Adipose tissue; metabolism; inflammation; post-prandial; human