Highlights TBK1 operates at the intersection of energy expenditure and inflammation TBK1 deficiency attenuates HFD-induced obesity but exaggerates inflammation TBK1 represses energy expenditure by phosphorylating and inhibiting AMPK TBK1 attenuates NF-κB activation and mediates the anti-inflammatory effect of AMPK   Do you ever wonder why fat body burns even fewer calories, or why dieting for weight loss always has bottlenecks? That’s because in both cases, our body tries to defend…