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A catecholamine-independent pathway controlling adaptive adipocyte lipolysis

ABSTRACT: Several adipose depots, including constitutive bone marrow adipose tissue (cBMAT), resist conventional lipolytic cues. However, under starvation, wasting, or cachexia, the body eventually catabolizes stable adipocytes through unknown mechanisms. Here, we developed a mouse model of brain-evoked depletion of all fat, including stable cBMAT, independent of food intake, to study this phenomenon. Genetic, surgical, and chemical approaches demonstrated that catabolism of stable adipocytes required adipose triglyceride lipase-dependent lipolysis but was independent of local nerves, the sympathetic nervous system, and catecholamines. Instead, concurrent hypoglycemia and hypoinsulinemia activated a potent catabolic state by suppressing lipid storage and increasing catecholamine-independent lipolysis via downregulation of cell-autonomous lipolytic inhibitors including G0s2. This was also sufficient to delipidate classical adipose depots and was recapitulated in tumor-associated cachexic mice. Overall, this defines unique adaptations of stable adipocytes to resist lipolysis in healthy states while isolating a potent catecholamine-independent neurosystemic pathway by which the body can rapidly catabolize all adipose tissues.

ORGANISM(S): Mus musculus

PROVIDER: GSE275147 | GEO | 2025/10/27

REPOSITORIES: GEO

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