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

Lippert, Rachel N.; Heß, Simon; Klemm, Paul; Burgeno, Lauren M.; Jahans-Price, Thomas; Walton, Mark E.; Kloppenburg, Peter

doi:10.1172/jci134412

Cited by 43 publications

(39 citation statements)

References 74 publications

(75 reference statements)

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“…Although we observed no evidence of direct communication between ARC AgRP →VTA Dat neurons, we report that both physiological and artificial hunger potentiate DA signaling to food 17 . The HFD-induced devaluation of SD observed in the DA system described here aligns with prior work exhibiting changes in basal midbrain DA activity, projections, and release following palatable diet exposure 19 , 25 , 46 , 47 . Going forward, it will be important to determine whether DA accumbal signaling loses reinforcement properties independent of food discovery after HFD exposure.…”

Section: Discussionsupporting

confidence: 88%

High-fat food biases hypothalamic and mesolimbic expression of consummatory drives

et al. 2020

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Summary Maintaining healthy body weight is increasingly difficult in our obesogenic environment. Dieting efforts are often overpowered by the internal drive to consume energy-dense foods. While the selection of calorically-rich substrates over healthier options is identifiable across species, the mechanisms behind this choice remain poorly understood. Using a passive devaluation paradigm, we found that exposure to high-fat diet (HFD) suppresses the intake of nutritionally-balanced standard chow diet (SD) irrespective of age, sex, body mass accrual and functional leptin or melanocortin-4 receptor signaling. Longitudinal recordings revealed this SD devaluation and subsequent shift toward HFD consumption is encoded at the level of hypothalamic Agouti-related peptide (AgRP) neurons and mesolimbic dopamine signaling. Prior HFD consumption vastly diminished the capacity of SD to alleviate the negative valence associated with hunger and the rewarding properties of food discovery even after periods of HFD abstinence. These data reveal a neural basis behind the hardships of dieting.

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Section: Discussionsupporting

confidence: 88%

High-fat food biases hypothalamic and mesolimbic expression of consummatory drives

et al. 2020

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“…Moreover, the sexual dimorphism observed in the blood lipidome of our male and female pups nursed by WD-fed dams could be associated to the differences we observed between males and females in metabolic parameters and feeding behavior [ 30 ] at weaning. Additionally, this WD-derived lipidome of weaned pups may also be consistent with the reprogrammation of the dopaminergic circuitry very recently reported in offspring suckled by mice fed WD only during lactation and the sexually dimorphic expression of dopamine-related phenotypes, i.e., hyperlocomotion in males and increased intake of palatable food and sucrose in females, but at 6 months of age [ 47 ].…”

Section: Discussionsupporting

confidence: 87%

Moderate High Caloric Maternal Diet Impacts Dam Breast Milk Metabotype and Offspring Lipidome in a Sex-Specific Manner

Alexandre-Gouabau

David-Sochard

Royer

et al. 2020

IJMS

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Lactation is a critical period during which maternal sub- or over-nutrition affect milk composition and offspring development that can have lasting health effects. The consequences of moderate high-fat, high-simple carbohydrate diet (WD) consumption by rat dams, during gestation and lactation, on milk composition and offspring blood lipidome and its growth, at weaning, were investigated by using a comprehensive lipidomic study on mass-spectrometric platform combined to targeted fatty- and free amino-acids analysis. This holistic approach allowed clear-cut differences in mature milk-lipidomic signature according to maternal diet with a similar content of protein, lactose and leptin. The lower WD-milk content in total fat and triglycerides (TGs), particularly in TGs-with saturated medium-chain, and higher levels in both sphingolipid (SL) and TG species with unsaturated long-chain were associated to a specific offspring blood-lipidome with decreased levels in TGs-containing saturated fatty acid (FA). The sexual-dimorphism in the FA-distribution in TG (higher TGs-rich in oleic and linoleic acids, specifically in males) and SL species (increased levels in very long-chain ceramides, specifically in females) could be associated with some differences that we observed between males and females like a higher total body weight gain in females and an increased preference for fatty taste in males upon weaning.

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“…In the VTA and NAc, DRD1, DRD2 and DAT expression was decreased at embryonic day 2 and postnatal day 10 in rat female offspring. Similarly, dopaminergic neuronal circuits in mouse offspring were altered by maternal high fat diet consumption during lactation, resulting in hyperlocomotion in male offspring and increased palatable food and sucrose intake in female offspring [ 87 ]. Intriguingly, the timing of maternal overnutrition and maternal dietary pattern with respect to pregnancy can also influence neural circuitries in offspring.…”

Section: Underlying Mechanisms By Which Maternal Obesity Programs mentioning

confidence: 99%

Mechanisms Underlying the Cognitive and Behavioural Effects of Maternal Obesity

2021

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The widespread consumption of ‘western’-style diets along with sedentary lifestyles has led to a global epidemic of obesity. Epidemiological, clinical and preclinical evidence suggests that maternal obesity, overnutrition and unhealthy dietary patterns programs have lasting adverse effects on the physical and mental health of offspring. We review currently available preclinical and clinical evidence and summarise possible underlying neurobiological mechanisms by which maternal overnutrition may perturb offspring cognitive function, affective state and psychosocial behaviour, with a focus on (1) neuroinflammation; (2) disrupted neuronal circuities and connectivity; and (3) dysregulated brain hormones. We briefly summarise research implicating the gut microbiota in maternal obesity-induced changes to offspring behaviour. In animal models, maternal obesogenic diet consumption disrupts CNS homeostasis in offspring, which is critical for healthy neurodevelopment, by altering hypothalamic and hippocampal development and recruitment of glial cells, which subsequently dysregulates dopaminergic and serotonergic systems. The adverse effects of maternal obesogenic diets are also conferred through changes to hormones including leptin, insulin and oxytocin which interact with these brain regions and neuronal circuits. Furthermore, accumulating evidence suggests that the gut microbiome may directly and indirectly contribute to these maternal diet effects in both human and animal studies. As the specific pathways shaping abnormal behaviour in offspring in the context of maternal obesogenic diet exposure remain unknown, further investigations are needed to address this knowledge gap. Use of animal models permits investigation of changes in neuroinflammation, neurotransmitter activity and hormones across global brain network and sex differences, which could be directly and indirectly modulated by the gut microbiome.

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

Cited by 43 publications

References 74 publications

High-fat food biases hypothalamic and mesolimbic expression of consummatory drives

High-fat food biases hypothalamic and mesolimbic expression of consummatory drives

Moderate High Caloric Maternal Diet Impacts Dam Breast Milk Metabotype and Offspring Lipidome in a Sex-Specific Manner

Mechanisms Underlying the Cognitive and Behavioural Effects of Maternal Obesity

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