bims-mimbat Biomed News
on Mitochondrial metabolism in brown adipose tissue
Issue of 2024‒03‒17
three papers selected by
José Carlos de Lima-Júnior, Washington University

  1. Elife. 2024 Mar 12. pii: RP93151. [Epub ahead of print]13
      Perirenal adipose tissue (PRAT) is a unique visceral depot that contains a mixture of brown and white adipocytes. The origin and plasticity of such cellular heterogeneity remains unknown. Here, we combine single-nucleus RNA sequencing with genetic lineage tracing to reveal the existence of a distinct subpopulation of Ucp1-&Cidea+ adipocytes that arises from brown-to-white conversion during postnatal life in the periureter region of mouse PRAT. Cold exposure restores Ucp1 expression and a thermogenic phenotype in this subpopulation. These cells have a transcriptome that is distinct from subcutaneous beige adipocytes and may represent a unique type of cold-recruitable adipocytes. These results pave the way for studies of PRAT physiology and mechanisms controlling the plasticity of brown/white adipocyte phenotypes.
    Keywords:  beige adipocyte; browning; cell biology; cold-inducible; developmental biology; mouse; perirenal adipose tissue; snRNA-seq; whitening
  2. Am J Physiol Endocrinol Metab. 2024 Mar 13.
      In rodents, loss of estradiol (E2) reduces brown adipose tissue (BAT) metabolic activity. Whether E2 impacts BAT activity in women is not known. BAT oxidative metabolism was measured in premenopausal (N=27, 35±9 years, body mass index (BMI) = 26.0±5.3 kg/m2) and postmenopausal (N=25, 51±8 years, BMI = 28.0±5.0 kg/m2) women at room temperature (RT) and during acute cold exposure using [11C]-acetate with positron emission tomography coupled with computed tomography (PET/CT). BAT glucose uptake was also measured during acute cold exposure using 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG). To isolate the effects of ovarian hormones from biological aging, measurements were repeated in a subset of premenopausal women (N=8, 40±4 years, BMI = 28.0±7.2 kg/m2) after 6 months of gonadotropin-releasing hormone agonist (GnRHAG) therapy to suppress ovarian hormones. At RT, there was no difference in BAT oxidative metabolism between premenopausal (0.56±0.31.min-1) and postmenopausal women (0.63±0.28.min-1). During cold exposure, BAT oxidative metabolism (1.28±0.85 vs. 0.91±0.63.min-1, P=0.03) and net BAT glucose uptake (84.4±82.5 vs. 29.7±31.4 nmol.g-1.min-1, P<0.01) were higher in premenopausal than postmenopausal women. In premenopausal women who underwent GnRHAG, cold-stimulated BAT oxidative metabolism was reduced to a similar level (from 1.36±0.66.min-1 to 0.91±0.41.min-1) to that observed in postmenopausal women (0.91±0.63.min-1). These results provide the first evidence in humans that reproductive hormones are associated with BAT oxidative metabolism and suggest that BAT may be a target to attenuate age-related reduction in energy expenditure and maintain metabolic health in postmenopausal women.
    Keywords:  Cold-induced thermogenesis; energy metabolism; estradiol; human; positron emission tomography
  3. Proc Natl Acad Sci U S A. 2024 Mar 19. 121(12): e2319473121
      Hydrogen sulfide exposure in moderate doses can induce profound but reversible hypometabolism in mammals. At a cellular level, H2S inhibits the electron transport chain (ETC), augments aerobic glycolysis, and glutamine-dependent carbon utilization via reductive carboxylation; however, the durability of these changes is unknown. We report that despite its volatility, H2S preconditioning increases P50(O2), the O2 pressure for half-maximal cellular respiration, and has pleiotropic effects on oxidative metabolism that persist up to 24 to 48 h later. Notably, cyanide, another complex IV inhibitor, does not induce this type of metabolic memory. Sulfide-mediated prolonged fractional inhibition of complex IV by H2S is modulated by sulfide quinone oxidoreductase, which commits sulfide to oxidative catabolism. Since induced hypometabolism can be beneficial in disease settings that involve insufficient or interrupted blood flow, our study has important implications for attenuating reperfusion-induced ischemic injury and/or prolonging the shelf life of biologics like platelets.
    Keywords:  bioenergetics; electron transport chain; hydrogen sulfide; oxygen metabolism