Porter 2018 MiP2018a

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Evidence of functional uncoupling protein 1 in the white adipose tissue of hypermetabolic humans.

Link: MiP2018

Porter C, Herndon DN, Chondronikola M, Chao T, Saraf MK, Bhattarai N, Ogunbileje JO, Malagaris I, Rontoyianni VG, Clayton P, Bohannon FJ, Nunez Lopez O, Capek KD, Radhakrishnan RS, Sidossis LS (2018)

Event: MiP2018

COST Action MitoEAGLE

Whether subcutaneous white adipose tissue (sWAT) can undergo a browning response in humans remains controversial. Our aim was to determine if sWAT develops functional uncoupling protein 1 (UCP1) in a human model of profound hypermetabolism, and to determine the role of chronic adrenergic stress in this response.

We recruited and studied healthy children and adults and severely burned children and adults to determine if human sWAT develops functional UCP1 (i.e. undergoes browning) in response to the chronic adrenergic stress that accompanies a severe burn. sWAT was collected during scheduled surgical procedures. Sub-platysmal and peri-renal brown adipose tissue (BAT) was also collected to serve as a positive control. Whole body metabolic rate and sWAT morphology and UCP1 expression were quantified. sWAT respiratory capacity, coupling control and UCP1 function were determined by high-resolution respirometry.

Patients had severe burns, covering 53±17 of their total body surface area. Patients were hypermetabolic, where resting energy expenditure was ~50% above normal during their acute hospitalization. Patients had altered sWAT morphology and significantly elevated (65±31-fold; P<0.001) UCP1 mRNA levels. Mitochondrial respiratory capacity was greater in sWAT of patients compared to healthy controls (1.06±0.13 vs. 5.88±0.61 pmol/s/mg; P<0.001), a component of which was purine nucleotide (GDP) sensitive, indicating functional UCP1 (0.04±0.02 vs. 0.80±0.18 pmol/s/mg). UCP1 dependent respiration in sWAT was significantly correlated (r=0.77; P<0.001) with whole body metabolic rate. sWAT UCP1 function corresponded to around 3% of that of sub-platysmal BAT (30.5±10.5 vs. 0.8±0.2 pmol/s/mg). Increased sWAT leak respiration was significantly related with time post injury (P<0.01), peaking at approximately 5-6 weeks post injury. To determine the role of adrenergic stress in sWAT browning, we also studied burned patients who were randomized to receive either a placebo or the non-selective β-blocker propranolol (4 mg/kg/day) during their acute hospitalization. Propranolol treatment attenuated burn-induced hypermetabolism and blunted the increases in sWAT respiratory capacity in response to burns.

Collectively, these data demonstrate browning of sWAT in hypermetabolic humans, where sWAT develops functional UCP1. This chronic phenotype is under adrenergic control, and can be attenuated by the β-blocker propranolol.


Bioblast editor: Plangger M, Kandolf G O2k-Network Lab: US TX Galveston Porter C


Labels: MiParea: Respiration, Patients, Pharmacology;toxicology 


Organism: Human  Tissue;cell: Fat 

Enzyme: Uncoupling protein 


HRR: Oxygraph-2k 


Affiliations

  1. Dept Surgery, Univ Texas Medical Branch
  2. Shriners Hospitals Children; Galveston, TX, USA. - cr2porte@utmb.edu