Loss of phospholipase PLAAT3 causes a mixed lipodystrophic and neurological syndrome due to impaired PPARγ signaling.

Phospholipase A/acyltransferase 3 (PLAAT3) is a phospholipid-modifying enzyme predominantly expressed in neural and white adipose tissue (WAT). It is a potential drug target for metabolic syndrome, as Plaat3 deficiency in mice protects against diet-induced obesity. We identified seven patients from four unrelated consanguineous families, with homozygous loss-of-function variants in PLAAT3, who presented with a lipodystrophy syndrome with loss of fat varying from partial to generalized and associated with metabolic complications, as well as variable neurological features including demyelinating neuropathy and intellectual disability. Multi-omics analysis of mouse Plaat3-/- and patient-derived WAT showed enrichment of arachidonic acid-containing membrane phospholipids and a strong decrease in the signaling of peroxisome proliferator-activated receptor gamma (PPARγ), the master regulator of adipocyte differentiation. Accordingly, CRISPR-Cas9-mediated PLAAT3 inactivation in human adipose stem cells induced insulin resistance, altered adipocyte differentiation with decreased lipid droplet formation and reduced the expression of adipogenic and mature adipocyte markers, including PPARγ. These findings establish PLAAT3 deficiency as a hereditary lipodystrophy syndrome with neurological manifestations, caused by a PPARγ-dependent defect in WAT differentiation and function.

Pesticide contamination of Tenebrio molitor (Coleoptera: Tenebrionidae) for human consumption.

The use of pesticides contributes to the productivity and the quality of the cultivated crop. A large portion of the agricultural produce is not consumed as it is not an edible part or the quality of the product is too low. This waste of agricultural produce can be valorised as a substrate for the production of certain insects for human consumption. However, pesticides applied on the plants might accumulate during the life cycle of the insects fed on the waste materials and may cause a health risk to humans consuming the insects. Pesticide residues in larvae of the yellow mealworm, Tenebrio molitor, were investigated. We monitored the accumulation of pesticides in the larvae upon consumption of contaminated fresh produce. An increased uptake rate by the insects was found for pesticides with higher Kow-values. Excretion of pesticides by the insect was inversely related to the log(Kow) values of the pesticides.