21) Control of energy uptake

• Obesity

  A rising problem associated with perturbation of normal energy uptake and expenditure
• Body Mass Index (BMI)

  An individual's weight (Kg)/ square of their height (in meters)
• BMI scale

  • BMI > 25 = Overweight
  • BMI > 30 = Obese
  • BMI > 40 = Morbid obesity

  
• DEXA scan

  To determine lean and fat mass

  
• Currently: USA - 30% of adults have BMI > 30, 50% with BMI > 20
• Adverse consequences of Obesity for the individual

  • Type 2 Diabetes
  • Cardiovascular/ heart disease
  • Arthritis
  • Certain cancers (e.g. ovarian)
  • Other 'emerging' effects/ diseases ('Time Bomb')
• Rodents kept in captivity do not eat continuously (Rodents are nocturnal animals and eat mostly at night!)

  
• If raised on a 'high-fat' diet, captive rodents do gain weight
• Energy uptake

  Ultimately controlled by the brain (In response to convergence of diverse peripheral signals)

  
• Peripheral signals that converge on the brain to control energy uptake

  • Hormones (e.g. Ghrelin, Leptin)
  • Neurotransmitters
  • Sensory input (Smell, Taste)
  • Plasma glucose concentration

  
• Organs that provide peripheral signals to the brain to control energy uptake

  • Hypothalamus
  • Gut
  • Liver
  • Skeletal muscle
  • Pancreas
  • Adipocytes

  
• Hypothalamus

  • Plays a crucial role in regulating various physiological processes, including appetite and energy homeostasis
• Hypothalamic nuclei involved in regulating appetite and energy homeostasis

  • Arcuate nucleus
  • Paraventricular nucleus (PVN)
  • Lateral hypothalamic Area (LHA)
  • Dorsomedial nucleus (DMN)
• Orexigenic neurons

  Neurons that stimulate appetite and eating
• Anorexigenic neurons

  Neurons that suppress appetite and eating
• Arcuate nucleus contains the 'first order' neurons that are orexigenic or anorexigenic
• First order neurons in the arcuate nucleus release neuropeptide Y (NPY) and pro-opiomelanocortin (POMC)
• Satiety (state of fullness) is controlled by the Nucleus Tractus Solitarius (NTS) in the brain stem
• If the hypothalamic feeding centre is destroyed, mice stop eating altogether
• If areas that control 'Satiety' are destroyed, mice will eat continuously
• Theories regarding how hypothalamic feeding circuits are controlled

  • Glucostatic theory (short term)
  • Lipostatic theory (long term)
• Ghrelin

  A gut-derived hormone that increases before a meal in anticipation of eating
• PYY3-36 and Cholecystokinin

  Gut-derived hormones that increase during and soon after a meal
• Eating slowly allows feedback, preventing overeating
• Leptin

  A hormone produced by fat cells (adipocytes) that is anorexigenic
• Mice that lack the gene for Leptin (termed Ob), are Obese
• Leptin resistance contributes towards overeating/weight gain in humans
• Other 'Adipokines' produced by Adipocytes


  • Adiponectin
  • Resistin
  • Visfatin
  • TNF-α and IL6
• Visceral fat


  Fat that surrounds vital organs and is distributed along the abdomen
• Subcutaneous fat


  Fat that is distributed throughout the body
• Factors that may affect control of energy uptake

  • Genetic (mutations, inheritance of obesity genes)
  • Exposure to particular nutrients during pre and post-natal period
  • Efficiency in extracting nutrients and converting these to heat > fat
  • Composition of Gut bacteria
• High-fat content diet alters gut microbiome, and transfer of gut microbiome from lean mice into obese mice reverses their obesity
• Increased prevalence of obesity may be related to increased use of antibiotics
• Shorter sleep duration (< 4-6 hours per night) is associated with 23%-75% increased risk of obesity compared to 7-9 hour sleepers
• Treatments and prevention of obesity

  • Diet
  • Increased mobility (increased energy expenditure)
  • Gastric banding (Physical reduction in food intake)
  • Bariatric surgery (impacts on amount of gut hormones release)
  • Drugs

  
• Drugs that mimic hormones can lead to negative emotional side effects as the receptors are distributed all over the brain
• The adult mouse hypothalamus contains dividing cells, and this proliferation is enhanced further by injection of CNTF into the 3rd ventricle
• Tanycytes, a radially-arranged population of cells in the floor of the third ventricle, exhibit markers of neural stem cells and can produce new neurons
• Modulating the number of appetite-suppressing or appetite-promoting neurons in the hypothalamus could be a potential approach to alleviate eating disorders