Lipodystrophy can be uncoupled from detrimental metabolic consequences

SUMMARY Adipose tissue has at least two major functions: storing metabolic energy as triacylglycerols (TG) and coordinating metabolism by secreting hormones, such as leptin. In lipodystrophies, defects of storing TG are typically accompanied by metabolic abnormalities, such as hepatic steatosis, and endocrine perturbations. Thus, the concept emerged that the endocrine function of adipose tissue is coordinated with, and requires, TG stores. To test this notion, we selectively depleted adipose TG stores by deleting the TG synthesis enzymes, DGAT1 and DGAT2, in murine adipose tissue (ADGAT DKO mice). Despite markedly reduced TG storage, ADGAT DKO mice maintained ample adipose tissue endocrine function and surprisingly did not develop metabolic perturbations, even when fed a high-fat diet, owing to increased energy expenditure and beiging of white adipose tissue. These findings, thus, reveal that adipose tissue performs TG storage and endocrine functions largely independently from each other.