Reporting in Nature, Huang et al. have found that mice born to obese mothers develop fatty liver disease (FLD), even on a control diet, owing to aberrant Kupffer cell (KC) programming during their gestation. Postnatally, their KCs show persistent metabolic changes and promote lipid uptake in neighbouring hepatocytes, which drives FLD.

KCs, the resident macrophages of the liver, were increased in the offspring of obese mothers, and RNA sequencing on sorted KCs from the different experimental groups showed that KCs clustered according to in utero exposure to a lean or obese mother. In the offspring KCs, maternal obesity was associated with upregulation of genes involved in immune responses, including Trem2 and Myd88, as well as upregulation of genes involved in glycolysis and gluconeogenesis. By contrast, genes involved in oxidative phosphorylation, cellular respiration and xenobiotic metabolism were downregulated. Therefore, maternal obesity-induced FLD is associated with a KC switch from oxidative phosphorylation to glycolysis, as well as changes in other immune-related genes.