TY - JOUR
T1 - Maternal overnutrition is associated with altered synaptic input to lateral hypothalamic area
AU - Shrivastava, Kuldeep
AU - Swaminathan, Thaarini
AU - Barlotta, Alessandro
AU - Athreya, Vikshar
AU - Choudhry, Hassan
AU - Rossi, Mark A.
N1 - Publisher Copyright: © 2023 The Author(s)
PY - 2023/5
Y1 - 2023/5
N2 - 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.
AB - 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.
KW - Bed nucleus of the stria terminalis
KW - Lateral hypothalamus
KW - Maternal obesity
KW - Overnutrition
KW - Perinatal programming
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U2 - 10.1016/j.molmet.2023.101702
DO - 10.1016/j.molmet.2023.101702
M3 - Article
C2 - 36898526
SN - 2212-8778
VL - 71
JO - Molecular Metabolism
JF - Molecular Metabolism
M1 - 101702
ER -