Reduced brain CRH and GR mRNA expression precedes obesity in juvenile rats bred for diet-induced obesity

Abstract

To assess the role of endogenous peptides involved in stress responsivity in the development of diet-induced obesity (DIO), selectively bred DIO and diet-resistant (DR) male were weaned onto a low fat (4.5%) chow diet at 3 weeks of age and then fed either chow or a 31% fat by energy content (high energy (HE)) diet for 9 days beginning at 4 weeks of age. Regardless of diet, DIO rats gained more weight than DR rats but did not show the selective DIO weight gain trait characteristic of older DIO rats fed HE diet. At this early age, both DR and DIO rats on HE diet ate more and had higher leptin levels but gained less body weight and had lower feed efficiency (body weight gain (g)/food intake (kcal)) than their chow-fed controls. HE diet also prevented the decline in 24h urine corticosterone levels from the third to fifth week observed in chow-fed rats. Terminally, DIO rats had lower hippocampal glucocorticoid receptor (GR) and amygdalar central nucleus corticotrophin-releasing hormone (CRH) mRNA than DR rats, regardless of their diets. Taken together with prior studies in these rats, there appears to be a critical period between 3 and 5 weeks of age when DIO and DR rats are not phenotypically different and hypothalamo-pituitary-adrenal (HPA) function is rapidly changing. The reduced expression of brain GR and CRH expression at the end of this period might contribute to the propensity of DIO rats to become obese selectively on HE diet after 5 weeks of age.