obese

obese：Leptin - Leptin Receptor - JAK +p> STAT >o> related gene products。

obese

• mechanism
  • Cause
    • energy stored = energy consumed - energy expended
    • The major cause in reality is that some people consume huge amount of energy.
  • Subtopic
    • Effector cells
      • arcuate nucleus in hypothalamus
    • Short-term signals
      • During a meal
      • Gastrointestinal Appetite-suppressing signals
        • Cholecystokinin
          • CCK
            • secretor
              • specialized cells of the small intestin.
            • effector
              • brain
        • Glucogon-like peptide 1
          • GLP-1
            • secretor
              • L cells in the intestin
            • effector
              • brain
              • pancrease
                • Increased insulin secretion
                • Increased insulin biosynthesis
                • Increased beta-cell proliferation
                • Increased beta-cell survival
        • Glucagon-like peptide 2
        • Amylin
        • Somatostatin
        • Bombesin
        • Enterostatin
        • Apolipoprotein A-IV
        • Gastric inhibitory peptide
      • Gastrointestinal Appetite enhancing peptides
        • Ghrelin
    • Long-term signals
      • Over all status
      • Leptin
        • secreted by adipocytes
          • the secretion of Leptin increases exponentially when adpocytes mass increase.
          • prolonged fasting significantly decreases plasma lectin.
          • overfeeding increases it.
        • reports on the status of triacylglycerol stores.
        • genetics
          • encoded by ob gene
            • influences
              • food intake
              • energy expenditure
              • body weight
              • neuroendocrine function
            • on chromosome 6
            • 4.5 kb mRNA
            • 167aa ORF
              • pretty well conserved
                • 84% identical with mouse genome
          • obese generation mutations
            • Mutation 1
              • no leptin mRNA
            • Mutation 2
              • over-expresses a truncated mRNA with a premature stop codon, the translated truncated leptin protein is rapidly degraded in adipocytes.
            • Mutation 3
              • muation on OB-Receptor gene
                • produce same symptom as ob knock out, but not respond to exogenous leptin.
          • ob gene knock out mices are obese due to overeat, and they will lose weigt if given exogenous leptin.
        • Leptin Receptor
          • On the surface of POMC neurons in hypothalamus.
            • POMC neurons will secretes POMC proteins to transduce the signal to the real neurons suppressing appitide
              • POMC proteins bind to MC4-R receptors
                • So both POMC proteins and MC4-R mutations are found in human obese
          • Bioinformatics
            • OB-Receptor gene produces 6 protein isoforms, but only one of them is fully functional.
            • all of them have extracellular ligand binding domains, but only the functional one contains the full length intracellular domain.
          • Intracellar signaling
            • Leptin - Leptin Receptor - JAK +p> STAT >o> related gene products
              • SOC3 is actually a family of genes that can suppress JAK2
        • processing
          • 21 aa signal peptide is cleaved before release of leptin into the circulation.
        • detailed hormone signaling downstream of Leptin
      • Insulin
        • secreted by pancreatic β cells
        • reports on the status of carbohydrate availability.
• Symptoms