Environmental conditions experienced in early life can profoundly influence long-term metabolic health, but the additive impact of poor nutrition is poorly understood. Here, we tested the hypothesis that early life stress (ELS) induced by limited nesting material (LN) combined with high-fat and high-
sugar diet (HFHS) post-weaning would worsen diet-related metabolic risk. Sprague-Dawley male rats were exposed to LN, postnatal days 2-9, and at weaning (3 weeks), siblings were given unlimited access to chow or HFHS resulting in (Con-Chow, Con-HFHS, LN-Chow, and LN-HFHS, n = 11-15/group).
Glucose and
insulin tolerance were tested and rats were killed at 13 weeks. LN rats weighed less at weaning but were not different to control at 13 weeks; HFHS diet led to similar increases in
body weight. LN-chow rats had improved
glucose and
insulin tolerance relative to Con-Chow, whereas LN-HFHS improved
insulin sensitivity versus Con-HFHS, associated with increased
peroxisome proliferator-activated receptor gamma co-activator-1-alpha (Pgc-1α)
mRNA in muscle. No effect of LN on plasma or liver
triglycerides was observed, and hepatic gluconeogenic regulatory genes were unaltered. In summary, this study demonstrates that ELS induced by LN conferred some metabolic protection against
insulin and/or
glucose intolerance in a diet-dependent manner during adulthood.