LSD1 Promotes Brown Adipose Tissue Thermogenesis Via Repressing Glucocorticoid Activation

[Terma]

There must be 50+ studies on the short and long term metabolic effects of LSD1 (FAD-dependent) on adipocytes from the last 2 or 3 years. But I figured this one is probably the most interesting (you can easily find all the other from the citations and simple pubmed search):

Lysine-specific demethylase 1 promotes brown adipose tissue thermogenesis via repressing glucocorticoid activation

Lysine-specific demethylase 1 promotes brown adipose tissue thermogenesis via repressing glucocorticoid activation
Brown adipocytes display phenotypic plasticity, as they can switch between the active states of fatty acid oxidation and energy dissipation versus a more dormant state. Cold exposure or β-adrenergic stimulation favors the active thermogenic state, whereas sympathetic denervation or glucocorticoid administration promotes more lipid accumulation. Our understanding of the molecular mechanisms underlying these switches is incomplete. Here we found that LSD1 (lysine-specific demethylase 1), a histone demethylase, regulates brown adipocyte metabolism in two ways. On the one hand, LSD1 associates with PRDM16 to repress expression of white fat-selective genes. On the other hand, LSD1 represses HSD11B1 (hydroxysteroid 11-β-dehydrogenase isozyme 1), a key glucocorticoid-activating enzyme, independently from PRDM16. Adipose-specific ablation of LSD1 impaired mitochondrial fatty acid oxidation capacity of the brown adipose tissue, reduced whole-body energy expenditure, and increased fat deposition, which can be significantly alleviated by simultaneously deleting HSD11B1. These findings establish a novel regulatory pathway connecting histone modification and hormone activation with mitochondrial oxidative capacity and whole-body energy homeostasis.

There are actually other studies that suggest that in short term or some circumstances LSD1 will actually lower cell energy expenditure (this makes sense since it promotes adipocyte differentiation), but on the longer term it appears to support beige fat conversion, and the HSD11B1 oppression is neat. My understanding of this is partial due to limited reading time.