1. SERCA2b Cycles Its Way to UCP1-Independent Thermogenesis in Beige Fat
Emilio P. Mottillo, Vanesa D. Ramseyer, James G. Granneman 
Cell Metabolism 
Volume 27, Issue 1, Pages 7-9 (January 2018)
DOI: /j.cmet
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2. Figure 1 UCP1-Independent Thermogenic Mechanisms
(A) Previously identified UCP1-independent futile cycling pathways in beige adipocytes. Adrenergic activation promotes an ATP-consuming cycle whereby free fatty acid (FFA) synthesis from glucose and subsequent incorporation in triglyceride (TG) is coupled to hydrolysis, oxidations, and re-esterification (Ramseyer and Granneman, 2016; Anunciado-Koza et al., 2008). Glucose is also used to fuel the tricarboxylic acid (TCA) cycle to replenish reducing equivalents used for fatty acid synthesis. High-energy phosphates can also be consumed in the creatine phosphate shuttle by creatine kinase (CK) in a futile cycle that involves creatine phosphorylation/dephosphorylation (Kazak et al., 2015).
(B) Newly identified UCP1-independent thermogenic mechanism in beige adipocytes by Ikeda et al. (2017). Adrenergic activation promotes calcium cycling whereby Ca2+ released from the sarco(endo)plasmic reticulum (SER) by the ryanodine receptor (RyR2) is taken back up by the SER Ca2+-ATPase 2b (SERCA2b) pump in an ATP-dependent manner. This cycle is dependent on glucose utilization required for ATP synthesis. Not shown, additional mechanisms in skeletal muscle involving SERCA/Sarcolipin uncouple ATP hydrolysis from SERCA Ca2+ transport, resulting in a futile cycle (Pant et al., 2016). All of the above-mentioned futile cycles would dissipate energy as heat, resulting in a wasteful process that could have important implications in regulating whole-body energy homeostasis. G3P, glycerol-3-phosphate; Acyl-CoA, acyl-Coenzyme A; NE, norepinephrine; β3-AR, β3-adrenergic receptor, α1-AR, α1-adrenergic receptor.
Cell Metabolism  , 7-9DOI: ( /j.cmet )
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