Malonyl-CoA is a conserved endogenous ATP-competitive mTORC1 inhibitor.

Cell growth is regulated by the mammalian/mechanistic target of rapamycin complex 1 (mTORC1), which functions both as a nutrient sensor and a master controller of virtually all biosynthetic pathways. This ensures that cells are metabolically active only when conditions are optimal for growth. Notably, although mTORC1 is known to regulate fatty acid biosynthesis, how and whether the cellular lipid biosynthetic capacity signals back to fine-tune mTORC1 activity remains poorly understood.

miR-155 regulates differentiation of brown and beige adipocytes via a bistable circuit.

Brown adipocytes are a primary site of energy expenditure and reside not only in classical brown adipose tissue but can also be found in white adipose tissue. Here we show that microRNA 155 is enriched in brown adipose tissue and is highly expressed in proliferating brown preadipocytes but declines after induction of differentiation. Interestingly, microRNA 155 and its target, the adipogenic transcription factor CCAAT/enhancer-binding protein β, form a bistable feedback loop integrating hormonal signals that regulate proliferation or differentiation.

A VASP-Rac-soluble guanylyl cyclase pathway controls cGMP production in adipocytes.

The ubiquitous second messenger cyclic guanosine monophosphate (cGMP) plays an important role in metabolism and promotes brown adipocyte differentiation. We showed that ablation of the gene encoding vasodilator-stimulated phosphoprotein (VASP), a major downstream component of the cGMP signaling cascade, increased cellular cGMP content in brown and white adipocytes and mouse embryonic fibroblasts. VASP-deficient cells showed increased activation of Rac1, which in turn increased the abundance of the cGMP-producing enzyme soluble guanylyl cyclase (sGC), the main receptor for nitric oxide.