TNF and cancer: Under cold conditions, FGF21 derived from BAT serves as a mediator of β3-adrenergic-dependent GDF15 gene transcription and is released in BAT, which suppresses proinflammatory gene expression and decreases TNF and CCL2 secretion in macrophages.140 However, GDF15 appears to exert a proinflammatory effect in cancer cachexia,141 implying that the same factor can have various effects depending on the physiological or pathological context.