Early-life stress and the development of obesity and insulin resistance in juvenile bonnet macaques.
Stress is a risk factor for chronic illnesses such as obesity, type 2 diabetes, and hypertension and has been postulated to cause the metabolic syndrome via perturbation of the hypothalamo-pituitary-adrenal (HPA) axis. In our model of early-life stress (variable foraging demand [VFD]), food insecurity is imposed on monkey mothers for 16 weeks beginning when their nursing offspring are 3-5 months of age. Under VFD, food availability is never restricted, and the infant's growth is unaffected. VFD rearing does, however, cause a range of neurobiological abnormalities, including dysregulation of the HPA axis, manifested in abnormal cerebrospinal fluid cortisol and corticotropin-releasing factor levels. We previously reported spontaneous occurrence of metabolic syndrome in 14% of normally reared peripubertal bonnet macaques given ad libitum access to standard monkey chow. Here, we show that compared with normally reared monkeys, peripubertal VFD juveniles exhibit greater weight, BMI, abdominal circumference, and glucagon-like peptide-1 and decreased glucose disposal rates during hyperinsulinemic-euglycemic clamps. Our data suggest that early-life stress during a critical period of neuro development can result in the peripubertal emergence of obesity and insulin resistance.
Kaufman
Daniel
D
Department of Surgery, State University of New York Downstate Medical Center, Brooklyn, NY 11203, USA.
Banerji
Mary Ann
MA
Shorman
Igor
I
Smith
Eric L P
EL
Coplan
Jeremy D
JD
Rosenblum
Leonard A
LA
Kral
John G
JG
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004195:Disease Models, Animal; D005247:Feeding Behavior; D005260:Female; D007333:Insulin Resistance / Q000502:physiology*; D008255:Macaca radiata; D008297:Male; D008425:Maternal Behavior; D008426:Maternal Deprivation; D009765:Obesity / Q000503:physiopathology*; D013315:Stress, Psychological; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D014280:Triglycerides