Maternal obesity interrupts the coordination of the unfolded protein response and heat shock response in the postnatal developing hypothalamus of male offspring in mice

Maternal obesity malprograms offspring obesity and associated metabolic disorder. As a common phenomenon in obesity, endoplasmic reticulum (ER) stress also presents early prior to the development. Here, we investigate metabolic effect of early activated hypothalamic ER stress in offspring exposed to maternal obesogenic environment and the underlying mechanism in ICR mice model. We found higher body weight, hyperphagia and defective hypothalamic feeding-circuit in the offspring born to obese dams, with hypothalamic ER stress, and even more comprehensive cell proteotoxic stress were induced during the early postnatal period. However, neonatal inhibition of hypothalamic ER stress worsened the metabolic end. We believe that the uncoordinated interaction between the unfolded protein response and the heat shock response, regulated by heat shock protein 70, might be responsible for the malformed hypothalamic feeding circuit of the offspring exposure to maternal obesogenic conditions and were linked with deleterious metabolism in adulthood, especially when exposure to high-energy conditions.

Automated summary

Maternal obesity can lead to offspring obesity and metabolic disorders, especially with increased endoplasmic reticulum stress during pregnancy. Offspring exposed to an obesogenic environment may exhibit higher body weight, overeating, and hypothalamic feeding circuit defects, possibly related to early postnatal induction of ER stress and proteotoxic stress. Neonatal inhibition of hypothalamic ER stress may exacerbate metabolic outcomes in the long run.