Identification of Critical Windows of Metabolic Programming of Metabolism and Lung Function in Male Offspring of Obese Dams.

Perinatal nutritional determinants known as metabolic programming could be either detrimental or protective. Maternal obesity in the perinatal period determines susceptibility for diseases, such as obesity, metabolic disorders, and lung disease. Although this adverse metabolic programming is well-recognized, the critical developmental window for susceptibility risk remains elusive. Thus, we aimed to define the vulnerable window for impaired lung function after maternal obesity; and to test if dietary intervention protects. First, we studied the impact of high-fat diet (HFD)-induced maternal obesity during intrauterine (HFDiu ), postnatal (HFDpost ), or perinatal (i.e., intrauterine and postnatal (HFDperi ) phase on body weight, white adipose tissue (WAT), glucose tolerance, and airway resistance. Although HFDiu , HFDpost , and HFDperi induced overweight in the offspring, only HFDperi and HFDiu led to increased WAT in the offspring early in life. This early-onset adiposity was linked to impaired glucose tolerance in HFDperi -offspring. Interestingly, these metabolic findings in HFDperi -offspring, but not in HFDiu -offspring and HFDpost -offspring, were linked to persistent adiposity and increased airway resistance later in life. Second, we tested if the withdrawal of a HFD immediately after conception protects from early-onset metabolic changes by maternal obesity. Indeed, we found a protection from early-onset overweight, but not from impaired glucose tolerance and increased airway resistance. Our study identified critical windows for metabolic programming of susceptibility to impaired lung function, highlighting thereby windows of opportunity for prevention.