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Whitehead 2021 Nat Commun

From Bioblast
Publications in the MiPMap
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.

Β» PMID: 33772024 Open Access

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 Ξ²-hydroxyisobutyric acid as small molecule metabokines synthesized in browning adipocytes and secreted via monocarboxylate transporters. 3-methyl-2-oxovaleric acid, 5-oxoproline and Ξ²-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 Ξ²-hydroxyisobutyric acid via mTOR. In humans, plasma and adipose tissue 3-methyl-2-oxovaleric acid, 5-oxoproline and Ξ²-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.

β€’ Bioblast editor: Plangger M β€’ O2k-Network Lab: UK Leeds Peers C, UK Cambridge Murray AJ


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 

2021-07