week 8

• What is adipose tissue?

  A specialised type of connective tissue in which adipocytes or fat cells predominate
• Adipose tissue % in men

  15 - 20%
• Adipose tissue % in women

  20 - 25%
• Subcutaneous adipose tissue


  Adipose tissue located under the skin

  
  

  Abdominal, femoral
• Intraabdonimal adipose tissue


  Visceral (mesentric and omental)

  Retroperitoneal (prerienal and perigonadic)
• Perivascular distribution


  Around vascular system
• White adipose tissue cell structure


  More common

  Cells contain one large central droplet of whitish-yellow fat in their cytoplasm

  
  

  More white appearance
• Brown adipose tissue cell structure

  Contains cells with multiple lipid droplets, interspersed among abundant mitochondria

  
  

  Darker appearance
• Is brown fat present in adult humans?

  Yes
• Similarities between white and brown AT

  - Rich blood supply
• Major functions of white adipocyte

  Energy storage

  Can secrete hormones (endocrine)

  
  

  It is UCP1 negative
• Major functions of brown adipocyte

  Thermogenesis and can secrete hormones

  
  

  It is UCP1 positive
• UCP1


  Promotes production of heat rather then energy in cellular respiration

  
  

  Brown fat is UCP1 positive (white is negative)
• WAT vs BAT development origin

  Brown and white have different developmental origins.

  
  

  Myf5 is very important and the key difference, it is the precursor cells for brown fat.
• Myf5 positive


  Becomes brown adipocyte
• Myf5 negative


  Becomes beige preadipocyte and white preadipocyte. Depending on what genetic program occurs, they become beige or white adipocytes.

  
  

  White and beige adipocytes can change into one another - transdifferentation
• UCP1 positive


  Brown and beige adipocytes
• Unilocular


  Having one compartment or unit

  
  

  This is in white adipocytes - triglycerides are stored in a single locus
• Cell types in white adipose tissue

  Adipocytes are 30%

  Preadipocytes and fibroblasts

  Matrix of collagen fibres

  Blood vessels (capillaries/endothelial cells)

  Immune cells (macrophages, lymphocytes)
• Coordination of the regulation of fat deposition and fat mobilization


  Under fed states, energy that comes into the gut. The triglycerides are made into fatty acids.

  
  

  During fasting, fat is mobilised and burnt to provide energy.
• Noradrenaline


  From nerve endings stimulates the cyclic AMP system, activating hormones which hydrolyse the stored triglycerides
• What do triglycerides become?

  Free fatty acids and glycerol
• Why is BAT brown?

  It is due to the numerous mitochondria, and the large number of blood capillaries
• Organisation of brown adipocytes

  They are organised into discrete lobules, surrounded by connective tissue

  
  

  Extensive blood vessels and numerous sympathetic nerves are terminating on the adipocytes and blood vessels
• Distribution of brown and beige fat

  In human adults, mainly found in the neck and collarbone area, and some paravertebral. It is more dispersed - more beige.

  
  

  In infants, found in the back - much more localised.
• Metabilosation of BAT fatty acids

  Unlike white fat, the liberated fatty acids are metabolised quickly

  
  

  Heat production is increased in these cells because the mitochondria have in their inner membrane protein UCP1
• What does UCP1 do?

  Permits the backflow of protons without passing through ATP-synthase during oxidative phosphorylation

  
  

  Consequently, energy is not used to synthesize ATP and is dissipated as heat
• Beige adipose tissue


  An inducible cell type, dispersed throughout white adipose tissue

  
  

  Has greater variability in lipid droplet size and a greater proportion of lipid droplets to mitochondria - giving it a light brown appearance
• Induction of brown/beige adiposcytes in adipose depots


  Some of the things that can induce brown fat are not good long term.

  
  

  So brown fat could be an anti-obesity to target, but need to find the right way
• Consequence of excess white adipose tissue

  White adipose tissue appears histologically and physioligcally similar, differences are in gene expression.

  
  

  More visceral (abdomenal) have an increased risk of diabetes and cardiovascular disease.

  
  

  Subcutaneous deposits of white fat do not have the same risks
• Why is visceral more dangerous the subcutaneous?

  The release of visceral fat products directly to the portal circulation and liver may also influence the medical importance
• Medical complications of obesity

  - Pulmonary disease

  - Nonalcoholic fatty liver disease

  - Osteoarthritis

  - Skin

  - Gout

  - Cancer

  - Stroke

  - Coronary heart disease
• Leptin


  Adipoctyes are the sole source of leptin

  
  

  Regulates appetite under normal condition, and regulating the amount of adipose tissue
• IL-6


  Pro-inflammatory factor

  
  

  Important in body regulation, lipid and glucose metabolise
• Factor


  If there is a transfromation of lean adipose tissue to obese adipose tissue.

  
  

  This will result in release of chemokines which recruit macrophages

  
  

  Leads to free fatty acids increase, leptin increase

  
  

  Overall can lead to systemic insulin resistance

  
  

  Some things that are released by adipocytes are bad, but some are beneficial.
• More leptin...


  Can result to a resistant to this hormone

  
  

  So many of the metabolic benefits of leptin is lost

  
  

  Increased appetite
• Functions of bone marrow

  Haemopoiesis

  Phagocytosis of cell debris

  Storage and recycling iron (Hb synthesis)

  Production of antibodies
• What are the two major bone structure types?

  Compact and spongy bone
• Bone marrow in adults consists of...

  - Connective tissue stroma of reticular cells and fibres in a meshwork

  - Islands or cords of haemopoietic cells

  - Fat cells

  - Macrophages

  - Megakaryocytes

  - Sinusoids
• Sinusoids


  blood-filled spaces