A new metabolic role for TGFβ2

Previous work has shown that transplantation of subcutaneous white adipose tissue (scWAT) from exercise-trained mice into sedentary mice improves metabolism, suggesting that exercise-trained scWAT might produce endocrine factors. A new study in Nature Metabolism identifies transforming growth factor-β2 (TGFβ2) as an exercise-induced adipokine that regulates metabolism.

The researchers first performed microarray analysis on scWAT from mice and humans before and after exercise training and identified TGFB2 as an upregulated gene. Furthermore, compared with sedentary participants, exercised-trained humans and mice had significantly higher serum concentrations of TGFβ2.

In vitro experiments using recombinant TGFβ2, TGFβ2 receptor inhibitors and cellular models of WAT, brown adipose tissue (BAT) and muscle suggested that TGFβ2 stimulates cellular uptake of glucose and fatty acids.

These findings were replicated in vivo, as mice that were fed a normal chow diet and infused with TGFβ2 using an osmotic pump had improved glucose uptake in mitochondria-enriched oxidative tissues, including muscle, BAT and heart. Moreover, TGFβ2 infusion improved metabolic parameters and body composition in obese mice that had been fed a high-fat diet (HFD). In addition, TGFβ2 treatment attenuated adipose tissue inflammation in HFD-fed mice.

Finally, microarray data revealed that lactate metabolic pathways were highly correlated with Tgfb2 expression. Injection of a lactate-lowering agent during exercise training could block the beneficial metabolic effects of TGFβ2 in mice.

This study has identified a previously undescribed function for TGFβ2 as an exercise-induced adipokine that regulates glucose and fatty acid metabolism. Moreover, the research has established a new mechanism of lactate–TGFβ2 signalling by which exercise training can modulate systemic metabolism. TGFβ2 might represent a new therapeutic target to treat obesity-induced insulin resistance.