Effect of Oral Feeding on Gastric Emptying, Gut Blood Flow, and Hormone Responses in Obese and Healthy Weight Subjects
Condition: Obesity
MeSH terms: Obesity
Study type: Observational

Summary: 
      Obesity is a complicated condition that is poorly understood. The aim of this study is to
      increase our knowledge of how the condition may arise, and what makes obese people remain
      obese.

      We will be investigating 12 people who are overweight and comparing them to 12 people who are
      lean, to look at how quickly food empties out of the stomach (gastric emptying) and travels
      through the gut, what the blood flow to the gut is, and also to examine the hormones which
      are involved in determining how full people feel after eating. In order to do this, we will
      be using a magnetic resonance imaging (MRI) scanner, and performing blood tests.

      The rate of gastric emptying may have an impact on satiety (how full one feels) and has been
      implied in the development of obesity. This effect has been shown to impact on subsequent
      meal intake to a greater degree in overweight subjects, and may be due to a difference in
      gastric emptying of food in overweight individuals, or to hormones such as ghrelin,
      glucagon-like peptide 1, and Peptide YY.
    

Detailed description: 
      The World Health Organisation (WHO) has deemed being overweight or obese as the fifth leading
      cause for global deaths, with more than 1.9 billion adults being defined as overweight, and
      600 million defined as being obese. Conditions associated with obesity, such as stroke, type
      2 diabetes, certain cancers, cardiovascular, fatty liver and airway disease can lead to
      premature death. Obesity results from an imbalance in energy intake versus expenditure, and
      fat mass accumulates. Studies have indicated that obese animals have a faster gastric
      emptying time, a weaker contraction of the duodenum, but a stronger contraction and
      relaxation of the ileum, with associated changes in gastrointestinal neurohormonal levels.
      The rate of gastric emptying may have an impact on feelings of satiety and has been implied
      in the pathogenesis of obesity. Moreover, mesenteric blood flow increases 3-fold following a
      meal and in a swine experimental model, a reduction in weight gain was seen when blood flow
      was intentionally limited to the gut using flow-restricting endovascular stenting. The
      authors concluded that this intervention may play a role in the treatment of obesity where
      other interventions have failed or are inappropriate; however the role of blood flow to the
      gut in obese individuals is important to elucidate. We hypothesize that nutrient absorption
      in obese and healthy weight individuals after a standardized meal is determined by
      differences in gastric emptying and mesenteric blood flow which give rise to different
      insulin, glucose and gut hormone responses. These may be contributory mechanisms to the
      evolution or maintenance of obesity.

      The aim of this study is to establish the effects of food ingestion on gastric emptying,
      gallbladder emptying, small bowel water content and splanchnic blood flow as measured by
      serial magnetic resonance imaging (MRI) in the context of changes in plasma gastrointestinal
      hormone secretion in human subjects who are obese or healthy weight. In addition, this pilot
      study will provide the data necessary to power a larger study investigating methods of
      dietary manipulation in the treatment of obesity.

      Method: In order to normalize the pre-study diet, volunteers will have consumed a standard
      diet for the 3 days immediately before the study visit, which will be based on foods in their
      normal diet and will be designed to meet their estimated energy requirements and provide 15%
      of total daily energy intake as protein, 35% as fat and 50% as carbohydrate. Participants
      will report at 0800 hours following a fast from midnight and after having abstained from
      alcohol, nicotine, and caffeine from 1800 hours the day before. On arrival, participants will
      be given a drink of water (200ml). A retrograde cannula will be inserted into a dorsal foot
      vein after prior intradermal infiltration of 1% lidocaine, with the foot placed in a magnetic
      resonance (MR) compatible warming box that we have developed, for arterialized-venous blood
      sampling. Prior to baseline blood sampling, participants will undergo a magnetic resonance
      imaging (MRI) scan to determine baseline values for superior mesenteric artery (SMA) blood
      flow, small bowel water content and gastric fluid and gas volumes. Liver fat, visceral fat
      and subcutaneous fat volumes will also be assessed at this time. Subsequently, a blood sample
      will be drawn for analysis of concentrations of hemoglobin, glucose, insulin, glucagon-like
      peptide 1 (GLP-1), glucagon-like peptide 2 (GLP-2), ghrelin and peptide YY (PYY). Serum
      osmolality will also be measured and subjective appetite assessed using visual analogue
      scales. The participants will then be given the test meal (in an upright, seated position)
      and asked to consume it within 15 minutes. The test meal will be comprised of pasta, cheese
      and tomato sauce, and provides 13% of total energy (E) from protein, 39%E fat, and 48%E
      carbohydrate.

      Following the test meal (time = 0 minutes), subjective appetite will be measured as before,
      then participants will be scanned at 30 minute intervals for 4 hours to assess gastric
      emptying, gastric accommodation, gastric motility and small bowel water content, as well as
      SMA blood flow. Blood samples will be drawn at 15 minutes, then every half hour until 240
      minutes after the test meal, with a final blood sample taken at 300 minutes. Subjective
      appetite will be assessed every hour over the 300 minute study.
    

Observational model: Cohort
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        Recruitment will be from the male population residing within 20 miles of the research site.
        This will include those from Nottinghamshire, Leicestershire and Derbyshire, UK
      
Keywords: satiety; gut blood flow; gastric emptying; obesity; incretin hormones