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other·preclinical research, biomedical research, endocrinology, neurology, nutrition·PMC10025284

Maternal overnutrition is associated with altered synaptic input to lateral hypothalamic area

Molecular Metabolism · 6 authors, 3 centres

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TL;DR

This mouse study found that maternal overnutrition rewires a key brain circuit (BNST→LHA) in adult offspring, making them highly susceptible to diet-induced obesity when fed palatable food.

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While offspring body weights normalized after weaning onto chow, both male and female offspring from HFD-fed dams became obese and hyperphagic when given highly palatable food as adults. Electrophysiological recordings revealed increased excitatory input onto LHA neurons synaptically connected to the BNST in these offspring. The strength of inhibitory input from the BNST and the overall excitatory drive onto these neurons were predicted by the offspring's early-life growth rate.

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other

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preclinical research

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ORIGINAL PAPER

PMC10025284

Maternal overnutrition is associated with altered synaptic input to lateral hypothalamic area

Molecular Metabolism

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ABSTRACT

Abstract Objective Maternal overnutrition is associated with adverse outcomes in offspring, including increased risk for obesity and diabetes. Here, we aim to test the effects of maternal obesity on lateral hypothalamic feeding circuit function and determine the relationship with body weight regulation. Methods Using a mouse model of maternal obesity, we assessed how perinatal overnutrition affected food intake and body weight regulation in adult offspring. We then used channelrhodopsin-assisted circuit mapping and electrophysiological recordings to assess the synaptic connectivity within an extended amygdala-lateral hypothalamic pathway. Results We show that maternal overnutrition during gestation and throughout lactation produces offspring that are heavier than controls prior to weaning. When weaned onto chow, the body weights of over-nourished offspring normalize to control levels. However, when presented with highly palatable food as adults, both male and female maternally over-nourished offspring are highly susceptible to diet-induced obesity. This is associated with altered synaptic strength in an extended amygdala-lateral hypothalamic pathway, which is predicted by developmental growth rate. Additionally, lateral hypothalamic neurons receiving synaptic input from the bed nucleus of the stria terminalis have enhanced excitatory input following maternal overnutrition which is predicted by early life growth rate. Conclusions Together, these results demonstrate one way in which maternal obesity rewires hypothalamic feeding circuits to predispose offspring to metabolic dysfunction. Keywords: Bed nucleus of the stria terminalis, Lateral hypothalamus, Maternal obesity, Overnutrition, Perinatal programming

CITATION EXPORT

Kuldeep Shrivastava, Thaarini Swaminathan, Alessandro Barlotta et al.. Maternal overnutrition is associated with altered synaptic input to lateral hypothalamic area. Molecular Metabolism. (2023). https://doi.org/10.1016/j.molmet.2023.101702

AUTHORS

6 · 3 CENTRES

Kuldeep Shrivastava, Thaarini Swaminathan, Alessandro Barlotta, Vikshar Athreya, Hassan Choudhry, Mark A Rossi

1Child Health Institute of New Jersey, USA
2Department of Psychiatry, Robert Wood Johnson Medical School, USA
3Brain Health Institute, Rutgers University, New Brunswick, NJ, USA