Cell Biology: Obesity

Cell Biology: Obesity

1. Adipose tissue (Fat)

   • Categorised as
     • White adipose tissue (WAT)
       • Stores energy in the form of lipids
     • Brown adipose tissue (BAT)
       • Generates body heat
   • Or
     • Visceral fat
       • Causes diseases
         • Atherosclerosis
           • Deposition of fatty material on inner lining of arteries
           • Which leads to
             • Cardiovascular disease
               • Reduced blood flow to the heart, can also be caused by thrombosis (blood clot)
         • Diabetes Type II
           • Mechanism still unclear
         • Cancer
       • Can't be grabbed
       • Estrogen prevents build-up of visceral fat and instead promotes subcutaneous fat
       • Metabolically more active
         • More innervated
         • Greater capacity to break down and release lipids
         • More sensitive to adrenergic stimulation
       • Contains larger number of inflammatory and immune cells and produce proinflammatory cytokines
         • eg. IL6 and TNF-α
     • Subcutaneous fat
       • Can be grabbed

2. Lipids inhibit Skeletal Muscle glucose uptake

   • How then?
   • Randle hypothesis
     • Beta-oxidation of fatty acids produce acetyl-CoA as well, feeding Krebs cycle and producing more citrate, transport of citrate into cytoplasm deregulates Phosphofructose kinase activity in glycolysis
       • PROVED FALSE as lipids inhibit glucose uptake not phosphofructokinase activity
   • Lipids inhibit IRS-1 tyrosine phosphorylation and induce IRS-1 serine phosphorylation
     • Measuring protein phosphorylation
       • Radioactively-labelled ATP
         • Using purified protein kinase and substrate, cannot be in vivo otherwise continuous band
         • Immunofluorescence also used to detect protein concentration
       • Mobility decrease (band shift)
         • Reduction in distance of IRS-1 as phosphorylation causes it to bind to SDS gel
       • Immunoprecipitation
         • Phospho-tyrosine, phospho-serine or phospho-threonine antibody
     • mediated by S6K1
   • Conclusion
     • Lipids and inflammatory cytokines inhibit insulin signalling by inducing IRS-1 serine phosphorylation via the activation of different protein kinases

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