Maternal cafeteria diet consumption and the programming of food preferences in the offspring: the role of the mu-opioid receptor.

Abstract

Numerous studies in rodent models have shown that the offspring of dams fed a high-fat high-sugar (cafeteria) diet throughout pregnancy and lactation develop a specific preference for the same kinds of foods in adulthood. Furthermore, studies into potential mechanisms have revealed that the offspring of cafeteria diet fed dams also have altered expression of key components of the mesolimbic reward pathway including the mu-opioid receptor. The current work used a rodent model to look specifically at the role of the mu-opioid receptor in the programming of food preferences and investigated when during development exposure to a maternal cafeteria-style diet could be most harmful. The first aim of this thesis was to isolate whether exposure to a cafeteria diet before birth or in the pre-weaning period had a greater effect on the adult food preferences of the offspring. Using a cross-fostering method, we demonstrated that the male offspring of control or cafeteria diet fed (JF) dams that were cross-fostered at birth onto JF dams exhibited higher fat intake when challenged with a cafeteria diet at 7 weeks of age than offspring exposed to the cafeteria diet only before birth or not at all. Building on this work, we then investigated the effect of maternal cafeteria diet exposure on the postnatal development of the mu-opioid receptor. Using an in situ hybridisation method, we showed that female offspring of JF dams had reduced expression of the mu-opioid receptor in the ventral tegmental area in late postnatal development (week 3,4) relative to controls but not at the earlier timepoints explored (birth, week 1). The outcomes of the first two chapters of this thesis highlight the importance of the postnatal period in the establishment of offspring food preferences. The final experiment, which forms the final two chapters of the thesis, used an opioid receptor antagonist to examine in greater detail the potential of the mu-opioid receptor as a mechanism for the programming of food preferences. We demonstrated that whilst the administration of the opioid receptor antagonist naloxone in the fourth week of life significantly reduced fat intake in control offspring given access to a cafeteria diet immediately postweaning, it failed to do so in male JF offspring and was less effective at reducing fat intake in JF females. This outcome provides evidence that changes in mu-opioid receptor expression induced by early life exposure to a cafeteria diet may indeed have functional consequences for the regulation of palatable food by the offspring. We also hypothesised that opioid receptor blockade during the fourth week of life would have long term effects on the food preferences of offspring; this however was not observed in the present study. Nevertheless, this thesis provides considerable evidence to suggest that alterations in the development of the mu-opioid receptor plays an important role in the programming of food preference in offspring exposed to cafeteria diet in early life. In addition, it also identifies the postnatal period as potentially being ‘critical window’ during which exposure to cafeteria diet is most harmful to the offspring.