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Brown Fat Induced by Lactate and Ketone Bodies

The presence of brown adipose tissue (BAT) in human adults opens attractive perspectives to treat metabolic disorders. This is because BAT dissipates energy as heat via the uncoupling protein-1 (UCP1). So instead of storing energy (calories from our diet), it's burned off as heat. In fact, this is the basis behind being "warm-blooded" and non-shivering thermogenesis (heat production without the use of shivering).

BAT are located in specific deposits or can emerge among white fat through the so-called browning process. I discussed this briefly last year, in THIS POST. Although numerous inducers have been shown to drive this process, no study has investigated whether it could be controlled by specific metabolites. This newly published study on mice, it showed that lactate (lactic acid), an important metabolic intermediate, induces browning of white adipose cells by expression of a functional UCP1 protein. This happens through redox (reduction-oxidation) signalling, which tells the cell how "reduced" or "oxidized" it currently is.

Lactate-induced browning also occurs in cultured human cells and in vivo.  Further, the ketone body β-hydroxybutyrate, another metabolite that impacts redox state, is also a strong browning inducer. Since this redox-dependent increase in UCP1 expression promotes an oxidative phenotype (by uncoupling the mitochondria), browning appears as an adaptive mechanism to alleviate redox pressure. These findings open new perspectives for the control of adipose tissue browning and its physiological relevance.

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Source: Browning of White Adipose Cells by Intermediate Metabolites:An Adaptive Mechanism to Alleviate Redox Pressure.

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