Endocrine Abstracts

JOINT2207

Background: The rise in obesity prevalence is influenced by multiple factors, including the transgenerational hypothesis linking maternal obesity to increased offspring obesity risk. Another significant contributor is the stressogenic environment prevalent in Western societies. We have already shown that it is not merely exposure to stressful events that heightens the risk of developing obesity and its comorbidities, but also the subjective response to these stressogenic events (1). Using a specially bred mouse model with distinct stress response traits - vulnerability (Submissive mice, Sub) and resilience (Dominant mice, Dom) - we demonstrated that stress vulnerability exacerbates metabolic disruptions in mice fed a high-fat diet (HFD).

Research Goal: This study aimed to characterize the interactions between maternal diet, offspring diet, and stress vulnerability traits, and to investigate the impact of these factors on offspring metabolic health. A secondary aim was to elucidate the effects of HFD on maternal and offspring behavior.

Methods: Sub and Dom female mice were divided into groups fed either a high-fat diet (HFD) or a standard diet (STD) from four weeks before breeding until three weeks postpartum. Maternal behaviors were assessed through nesting scores during pregnancy and pup retrieval tests postnatally. Offspring were weaned onto STD until six weeks old, then split into STD and HFD groups. Glucose and insulin tolerance tests were conducted at 12 and 13 weeks of age, respectively. Mice were sacrificed for plasma insulin and leptin measurements, along with histological analyses of liver, pancreas, and adipose tissues.

Results: Maternal obesity had differential effects on pre- and post-natal behaviors in Sub and Dom mice, influencing nesting and pup retrieval differently. HFD improved maternal behavior in Sub mice but disrupted it in Dom mice. Maternal obesity adversely affected metabolic health in Sub offspring, resulting in glucose intolerance, insulin resistance, and hyperleptinemia following HFD feeding. Conversely, Dom offspring were largely unaffected by maternal HFD, showing minimal impairment in leptin sensitivity and glucose tolerance, with no impact on insulin tolerance. Adipose tissue weight increased in Dom mice, while liver weight rose significantly in Sub mice after two generations of HFD exposure.

Conclusion: These findings underscore how inherited stress response traits shape metabolic and behavioral outcomes across generations. They highlight the complex interplay between maternal diet, offspring diet, and stress vulnerability in determining obesity-related health outcomes.

Reference: 1. Inherited stress resiliency prevents the development of metabolic alterations in diet-induced obese mice. Obesity 2023.