Scientists have identified a way in which fat is transferred into tissues, finding that altering this mechanism stopped mice from becoming obese while on a high-fat diet. The results hint at a possible means to reduce obesity. In the gut, dietary fat is packaged into little packets called chylomicrons. Chylomicrons are transported to various body parts via the lymphatic system, particularly lymphatic vessels called lacteals. Previous research suggests that blocking the growth of lacteals, by blocking production of a protein called vascular endothelial growth factor A (VEGF-A), can in turn limit the delivery of fat into tissues. To explore this mechanism in greater detail, Feng Zhang et al. studied mice with two VEGF-A receptors, which previous work hinted could be involved in metabolic regulation. They fed mice a high fat diet for eight weeks, finding that mice with the two receptors disabled did not gain weight, while control mice with the receptors functioning doubled in weight. A closer look at what's occurring within the lacteals reveals that, normally, these vessels have button-like gaps along the lining, which allow chylomicrons to slip through into the surrounding tissues. However, with the two receptors (FLT1 and NRP1) blocked, these button-like openings turn into zipper-shaped openings, which chylomicrons cannot slip through as easily. This reduces the amount of fat entering into tissue, the authors report. Donald McDonald provides more context in a related Perspective.