UCP

links: reference: 11-3-2021

Uncoupling Protein #

Located in the Inner Mitochondrial Membrane. Thermogenin is found in the inner mitochondrial membrance of the cell.

• Promotes heat production by dissociating, “uncoupling” Oxidative Phosphorylation from respiration; by using the H+ that the Electron Transport Chain ejects via UCP enzymes (instead of ATPase) - which produce heat instead of ATP.
  • The enhanced proton flux process reduces the mitochondrial membrane potential, increases mitochondrial respiration, decreases the ATP/ADP ratio, and dissipates chemical energy in the form of heat.
  • This has a higher rate of O2 production and CO2 consumption. Excessive uncoupling will still reduce ATP and cause hyperthermia, so it’s not all good. Excessive uncoupling is how people die from DNP.
    • Acute mitochondrial decoupling reduces mitochondrial ATP production; however, chronic mitochondrial decoupling promotes an increase in the number of mitochondria and an increased level of ATP production
      • A Central Thermogenic-like Mechanism in Feeding Regulation: An Interplay between Arcuate Nucleus T3 and UCP2
        • Deiodinase II is present in the arcuate nucleus, and DII-producing glial cells are in apposition to (association with) neurons coexpressing Neuropeptide Y, AgRP and UCP2.
• Mitochondrial uncoupling proteins in the cns: in support of function and survival (2003)
  • By allowing controlled proton leak back into the mitochondrial matrix, it ==reduces ΔΨ==.
  • They propose local temperature gradients increase neurochemical diffusion through extracellular compartments to postsynaptic neuronal targets, along with the elevated ATP for vesicular transport/exocytosis.
• Turning WAT into BAT: a review on regulators controlling the browning of white adipocytes
• UCP1: Lowers ROS, generates heat
  • Identified in Brown Adipose; mRNA is upregulated from Exercise in subutaneous white Adipose but not visceral. Women perhaps do not see this effect
• UCP2: Reduce Nitric Oxide production.
  • Hypothalamus - especially Arcuate Nucleus, limbic system, cerebellum, etc.
  • Disruption of the uncoupling protein-2 gene in mice reveals a role in immunity and reactive oxygen species production
  • Associated with Mitochondrial Fission, increased density and diminished size.
• UCP3
• UCP4: Can prevent entry of excess calcium into cells, preventing cell death.
• UCP5
  • Cerebral cortex, hippocampus, thalamus, hypothalamus, amygdala, basal ganglia, spinal cord

• Mitochondrial uncoupler BAM15 reverses diet-induced obesity and insulin resistance in mice
  • Standard stuff: increases nutrient oxidation and decreases fat in body and liver and doesn’t alter food intake, lean body mass, body temperature, or markers of liver toxicity, and is antioxidant.
  • BAM15 also downregulates Fatty Acid Synthase and similar genes like SCD1, SREBF1, and PPAR-γ.