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

Abstract

This study used a high fat and high sucrose diet to generate obese mice. The offspring of these mice showed activation of the unfolding protein response and the heat-shock response in the hypothalamus as early as weaning. This was associated with malformed paraventricular nucleus axonal projections and defective leptin signaling. Intriguingly early inhibition of hypothalamic ER stress in the offspring failed to improve the metabolic outcome but worsened it. A key molecule (called heat shock protein 70 (HSP70)) was altered in the early postnatal developing hypothalamus which might lead to permanent unfolded protein response activation later in life.