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Published on: June 27, 2014
Maternal High-Fat Diet Multigenerationally Programs HPA Function and Behaviors in Male Rat Offspring
ChengCheng Lin1, Qiang Lei2, MengNa Yu2
1Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
Insights
Maternal high-fat diet exposure programs the hypothalamic-pituitary-adrenal (HPA) axis and behaviors across generations in male offspring. This multigenerational effect involves calcitonin gene-related peptide (CGRP) signaling.
Area of Science:
- Neuroendocrinology
- Developmental Programming
- Epigenetics
Background:
- Maternal environmental factors significantly impact offspring health.
- Early life stress and diet can alter the hypothalamic-pituitary-adrenal (HPA) axis.
- Previous studies linked maternal high-fat diet (HFD) to HPA axis programming in first-generation (F1) male offspring.
Purpose of the Study:
- To investigate the multigenerational inheritance of HPA axis remodeling in second-generation (F2) male offspring following maternal HFD exposure.
- To assess the impact of maternal HFD on F2 offspring's stress responses and behavior.
- To explore the role of central calcitonin gene-related peptide (CGRP) signaling in this transgenerational programming.
Main Methods:
- Comparison of basal and stress-induced HPA axis activity in F1 and F2 male offspring from HFD-exposed mothers.
- Behavioral testing (depression-like behavior) in F2 offspring subjected to chronic unpredictable mild stress.
- Pharmacological intervention using a CGRP receptor antagonist (αCGRP8-37) in F2 offspring.
Main Results:
- Second-generation male offspring (F2HFD/C) exhibited enhanced basal HPA axis activity and exacerbated stress responses (restraint, lipopolysaccharide).
- Maternal HFD aggravated depression-like behaviors in F2 offspring under chronic stress.
- Central CGRP receptor antagonism attenuated depression-like behaviors and normalized HPA axis hyperresponsiveness to restraint stress in F2HFD/C rats.
Conclusions:
- Maternal high-fat diet consumption induces multigenerational programming of the HPA axis and associated behaviors in male descendants.
- Central CGRP signaling plays a crucial role in mediating these transgenerational effects.
- Findings highlight the long-term health consequences of maternal diet across generations.
Abstract:
Maternal environmental factors have been demonstrated to exert significant influences on the health of offspring. The hypothalamic-pituitary-adrenal (HPA) axis is an important neuroendocrine stress system that can be influenced by early life challenges. Our previous research has revealed that the consumption of a high-fat diet (HFD) by pregnant and lactating rats leads to the programming of HPA axis activity in male offspring of the first generation (referred to as F1HFD/C). The present study aimed to investigate whether the observed remodeling of the HPA axis could be inherited by second-generation male offspring (referred to as F2HFD/C), following maternal HFD exposure. The results showed that F2HFD/C rats exhibited enhanced basal HPA axis activity, similar to their F1HFD/C ancestors. Moreover, F2HFD/C rats displayed exacerbated corticosterone responses to restraint and lipopolysaccharide-induced stress, but not to insulin-induced hypoglycemia stress. Furthermore, maternal HFD exposure significantly aggravated depression-like behavior in the F2 generation subjected to chronic unpredictable mild stress. To investigate the role of central calcitonin gene-related peptide (CGRP) signaling in maternal diet-induced programming of the HPA axis across generations, we conducted central infusion of αCGRP8-37, a CGRP receptor antagonist, in F2HFD/C rats. The results demonstrated that αCGRP8-37 attenuated depression-like behaviors and reduced the hyperresponsiveness of the HPA axis to restraint stress in these rats. Therefore, central CGRP signaling may contribute to maternal diet-induced programming of HPA axis across generations. In conclusion, our study provides evidence that maternal HFD consumption can lead to multigenerational programming of the HPA axis and behaviors in adult male descendants.
