Volume 4 Issue 4, April 2022

Maria Ermolaeva and Liron Boyman share their scientific journeys in this instalment of Career pathways and highlight the value of mentors and collaborators, and the importance of following your research interests.

Although food-craving episodes during pregnancy are common in humans, the neural, cellular and molecular mechanisms that underlie these eating bouts remain unknown. New work points to dopamine receptor D2-expressing neurons of the reward system as critical mediators of compulsive feeding during pregnancy.

Oncometabolites are pro-tumourigenic metabolites that can determine tumour aggressiveness. This study found that methylmalonic acid is upregulated in breast lung metastasis and metastatic cancer cells. Methylmalonic acid alters the gene expression profile to induce a pro-metastatic phenotype in breast and lung cancer cells.

The clearance of dying cells by macrophages releases mediators that switch off inflammation. Ampomah et al. reveal how an amino acid derived from apoptotic cargo changes the methylation epigenome of macrophages to take the brakes off an ERK-dependent pathway that terminates inflammatory responses.

Perino and Schoonjans summarize the most recent literature on the receptor-mediated role of bile acid signalling in the control of peripheral and central energy homeostasis.

Haddad-Tóvolli et al. show that food craving-like episodes in pregnant mice result from a reorganization of the dopaminergic mesolimbic circuitry, and can have long-lasting negative metabolic and neuropsychological effects on the offspring.

Gomes, Ilter, Low et al. show that alterations in propionate metabolism contribute to cancer aggressiveness through the accumulation of the by-product methylmalonic acid.

Ampomah et al. show that apoptotic cell-derived methionine taken up by macrophages during efferocytosis plays a role in mediating tissue resolution by providing a substrate for DNA methylation and repression of the ERK1/2 phosphatase Dusp4, causing activation of ERK1/2 and expression of pro-resolving mediators

Different gut bacteria have been shown to promote colorectal cancer (CRC) progression. The authors identify formate as an oncometabolite derived from Fusobacterium nucleatum, which promotes CRC formation by increasing cancer stemness.

Obesity-associated AT fibro-inflammation and metabolic disturbances are linked to PEPD activity and PEPD extracellular levels.