Maternal high-fat diet during lactation reprograms the dopaminergic circuitry in mice
R.N. Lippert, S. Hess, P. Klemm, L.M. Burgeno, T. Jahans-Price, M.E. Walton, P. Kloppenburg, J.C. Brüning
R.N. Lippert, S. Hess, P. Klemm, L.M. Burgeno, T. Jahans-Price, M.E. Walton, P. Kloppenburg, J.C. Brüning
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Research Article Development Neuroscience

Maternal high-fat diet during lactation reprograms the dopaminergic circuitry in mice

Abstract

The maternal perinatal environment modulates brain formation, and altered maternal nutrition has been linked to the development of metabolic and psychiatric disorders in the offspring. Here, we showed that maternal high-fat diet (HFD) feeding during lactation in mice elicits long-lasting changes in gene expression in the offspring’s dopaminergic circuitry. This translated into silencing of dopaminergic midbrain neurons, reduced connectivity to their downstream targets, and reduced stimulus-evoked dopamine (DA) release in the striatum. Despite the attenuated activity of DA midbrain neurons, offspring from mothers exposed to HFD feeding exhibited a sexually dimorphic expression of DA-related phenotypes, i.e., hyperlocomotion in males and increased intake of palatable food and sucrose in females. These phenotypes arose from concomitantly increased spontaneous activity of D1 medium spiny neurons (MSNs) and profoundly decreased D2 MSN projections. Overall, we have unraveled a fundamental restructuring of dopaminergic circuitries upon time-restricted altered maternal nutrition to induce persistent behavioral changes in the offspring.

Authors

R.N. Lippert, S. Hess, P. Klemm, L.M. Burgeno, T. Jahans-Price, M.E. Walton, P. Kloppenburg, J.C. Brüning

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Figure 6

CH female offspring, and not males, exhibit increased consumption and body weight in response to palatable substances.

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CH female offspring, and not males, exhibit increased consumption and bo...
Baseline water intake in CC and CH (A) males (n = 11 vs. 16) and (C) females (n = 13 vs. 25) shows no difference between genotypes. Change in fluid intake in the presence of 4% sucrose and water in CC and CH (E) males and (G) females. Total fluid intake of water and 4% sucrose solution combined in CC and CH (B) males and (D) females as compared with water baseline. Contribution of water intake and 4% sucrose intake in CC and CH (F) males and (H) females. Breakdown of preference for 4% sucrose into high (>80%), low (>80%), and no preference for sucrose groups in CC and CH (I) males and (K) females. Sucrose preference in CC and CH (J) males and (L) females in the high preferring group. Body weight gain on HFD or control diet in CC and CH (M) males (n = 7–34 per time point/diet) and (O) females (n = 7–32 per time point/diet). Body fat percentage on HFD in CC and CH (N) males (n = 7 vs. 9) and (P) females (n = 8 vs. 7). *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001, 2-sided Student’s t test (A–E, G, J, L, and N–P), 2-way ANOVA with Bonferroni’s post hoc analysis (F and H), or mixed effects analysis (M and O).