Whitehead 2021 Nat Commun
|Whitehead A, Krause FN, Moran A, MacCannell ADV, Scragg JL, McNally BD, Boateng E, Murfitt SA, Virtue S, Wright J, Garnham J, Davies GR, Dodgson J, Schneider JE, Murray AJ, Church C, Vidal-Puig A, Witte KK, Griffin JL, Roberts LD (2021) Brown and beige adipose tissue regulate systemic metabolism through a metabolite interorgan signaling axis. Nat Commun 12:1905.|
Whitehead Anna, Krause Fynn N, Moran Amy, MacCannell Amanda D V, Scragg Jason L, McNally Ben D, Boateng Edward, Murfitt Steven A, Virtue Samuel, Wright John, Garnham Jack, Davies Graeme R, Dodgson James, Schneider Jurgen E, Murray Andrew J, Church Christopher, Vidal-Puig Antonio, Witte Klaus K, Griffin Julian L, Roberts Lee D (2021) Nat Commun
Abstract: Brown and beige adipose tissue are emerging as distinct endocrine organs. These tissues are functionally associated with skeletal muscle, adipose tissue metabolism and systemic energy expenditure, suggesting an interorgan signaling network. Using metabolomics, we identify 3-methyl-2-oxovaleric acid, 5-oxoproline, and β-hydroxyisobutyric acid as small molecule metabokines synthesized in browning adipocytes and secreted via monocarboxylate transporters. 3-methyl-2-oxovaleric acid, 5-oxoproline and β-hydroxyisobutyric acid induce a brown adipocyte-specific phenotype in white adipocytes and mitochondrial oxidative energy metabolism in skeletal myocytes both in vitro and in vivo. 3-methyl-2-oxovaleric acid and 5-oxoproline signal through cAMP-PKA-p38 MAPK and β-hydroxyisobutyric acid via mTOR. In humans, plasma and adipose tissue 3-methyl-2-oxovaleric acid, 5-oxoproline and β-hydroxyisobutyric acid concentrations correlate with markers of adipose browning and inversely associate with body mass index. These metabolites reduce adiposity, increase energy expenditure and improve glucose and insulin homeostasis in mouse models of obesity and diabetes. Our findings identify beige adipose-brown adipose-muscle physiological metabokine crosstalk.
Labels: MiParea: Respiration
Organism: Human Tissue;cell: Skeletal muscle Preparation: Permeabilized cells
Coupling state: LEAK, OXPHOS, ET Pathway: F, N, S, NS HRR: Oxygraph-2k