PHOSPHO1 puts the breaks on thermogenesis in brown adipocytes

Abstract

The nonshivering heat production in mitochondria-rich brown or beige adipocytes allows rodents and humans to adapt to cold stress (1). The best-characterized thermogenic effector is uncoupling protein 1 (UCP1), which dissipates energy as heat by proton transport across the mitochondrial inner membrane. Of note, there are also important UCP1-independent pathways mediating brown adipose tissue (BAT) thermogenesis (2). The discovery of significant brown and beige adipose depots in humans initiated efforts to leverage the thermogenic process as a means to increase the metabolic rate to prevent metabolic disease, such as obesity and diabetes (3). Currently, there are limited browning regimens for increased energy expenditure in humans short of cold exposure (4). In PNAS, Jiang et al. (5) investigated how the enzyme phosphoethanolamine and phosphocholine phosphatase 1 (PHOSPHO1) regulates thermogenesis in BAT, triggering changes in systemic insulin sensitivity and energy balance. PHOSPHO1 catalyzes the hydrolysis of phosphocholine (PC) to choline as well as of phosphoethanolamine (PEA) to ethanolamine and in the process, releases an inorganic phosphate group. PHOSPHO1 is not widely expressed, although it has been well characterized as the PC and PEA phosphatase in bone, where free inorganic phosphate is essential for bone mineralization (6). Additionally, PHOSPHO1 is a key regulator that coordinates the change in PC and phospholipid composition during terminal erythropoiesis (7). It is remarkable that bone and red blood cell progenitors rely on different aspects of PHOSPHO1 enzymatic activity. The authors discovered that PHOSPHO1 is highly enriched in murine BAT and accumulates during in vitro differentiation of primary brown adipocytes. PHOSPHO1 expression also increased during cold exposure in mice. Furthermore, they determined that metabolically active BAT from humans at the fetal stage has high levels of PHOSPHO1 vs. adult fat tissues. There is little known about the role of PHOSPHO1 in adipose tissue. Based on the literature, the … [↵][1]1To whom correspondence may be addressed. Email: philipp.scherer{at}utsouthwestern.edu. [1]: #xref-corresp-1-1