Maternal high-fat diet and obesity impact palatable food intake and dopamine signaling in nonhuman primate offspring

Abstract

Objective To utilize a nonhuman primate model to examine the impact of maternal high-fat diet (HFD) consumption and pre-pregnancy obesity on offspring intake of palatable food. We will also examine whether maternal HFD consumption impaired development of the dopamine system, critical for the regulation of hedonic feeding. Methods The impact of exposure to maternal HFD and obesity on offspring consumption of diets of varying composition was assessed after weaning. We also examined the influence of maternal HFD consumption on the development of the prefrontal cortex-dopamine system at 13 months of age. Results During a preference test, offspring exposed to maternal obesity and HFD consumption displayed increased intake of food high in fat and sugar content relative to offspring from lean control mothers. Maternal HFD consumption suppressed offspring dopamine signaling (as assessed by immunohistochemistry) relative to control offspring. Specifically, there was decreased abundance of dopamine fibers and of dopamine receptor 1 and 2 protein. Conclusion Our findings reveal that offspring exposed to both maternal HFD consumption and maternal obesity during early development are at increased risk for obesity due to overconsumption of palatable energy-dense food, a behavior that may be related to reduced central dopamine signaling.

Circadian peak dopaminergic activity response at the biological clock pacemaker (suprachiasmatic nucleus) area mediates the metabolic responsiveness to a high‐fat diet

“…and (ii) how does HFD feeding reduce the concurrent circadian peaks in SuMN‐SCN tyrosine hydroxylase activity and dopamine release, as well as SCN responsiveness to peri‐SCN dopamine stimulation? However, the finding of reduced dopaminergic activity is generally consistent with a multitude of studies indicating a reduction of dopamine and/or dopamine receptor levels in other brain areas, particularly the striatal‐mesolimbic system, following chronic HFD feeding, although no specific investigation of such feeding on circadian aspects of dopaminergic activity at these brain sites has been investigated . Interestingly, striatal reduction of dopamine levels may partly be the result of reduced gut synthesis of the diet‐derived satiety factor, oleoylethanolamine, following HFD feeding, the gastric presentation of which is known to inhibit dopamine efflux in the striatum via vagal inputs .…”

Persistent effects of obesity: a neuroplasticity hypothesis

“…Finally, persistent effects seen in offspring exposed to a HFD in utero or in those born to mothers with obesity also support a lasting role for these-at times transient-conditions. Experiments in nonhuman primates showed Japanese macaques exposed to a HFD in utero had lower D1R and D2R protein levels and a decrease in TH positive terminal fibers in the prefrontal cortex, as measured by immunohistochemistry, 203 and that maternal obesity (but not maternal HFD) resulted in increased offspring body weight 7 months after weaning. 203 Rats exposed to a HFD in utero exhibited impaired adaptive dopamine signals in the NAc in response to repeated pinch stress 204 and decreased levels of NAc dopamine in response to a palatable food reward compared with rats born to lean mothers.…”

“…Experiments in nonhuman primates showed Japanese macaques exposed to a HFD in utero had lower D1R and D2R protein levels and a decrease in TH positive terminal fibers in the prefrontal cortex, as measured by immunohistochemistry, 203 and that maternal obesity (but not maternal HFD) resulted in increased offspring body weight 7 months after weaning. 203 Rats exposed to a HFD in utero exhibited impaired adaptive dopamine signals in the NAc in response to repeated pinch stress 204 and decreased levels of NAc dopamine in response to a palatable food reward compared with rats born to lean mothers. 205 Rats exposed to a high-fat, high-sugar diet in utero exhibited increased lever presses to achieve a palatable reward relative to those born to chow-controlled mothers, 206 Together, these studies suggest that exposure to a HFD during development can alter dopamine transmission later in life, which may increase the vulnerability of the offspring to obesity.…”

Maternal High‐Fat Diet Effects on Adaptations to Metabolic Challenges in Male and Female Juvenile Nonhuman Primates

“…The nonhuman primate demonstrates gestational development similar to that of humans but retains the advantage of allowing for separation of preand postnatal diet consumption. Our group has spent many years characterizing the effect of maternal high-fat diet (HFD) exposure on nonhuman primates through 1 year of life (16)(17)(18)(19)(20). These studies have all been carried out in basal metabolic conditions to assess differences in growth curves in the unchallenged state.…”