Offspring of obese mice display enhanced intake and sensitivity for palatable stimuli, with altered expression of taste signaling elements

Abstract

Maternal body mass index and gestational weight gain predict future obesity status of the offspring. In studies of both rodents and non-human primates, maternal obesity also predicts a preference for palatable foods in the offspring. In this study, we used C57BL/6J mice to investigate whether an underlying cause for an increase in palatable food consumption in the offspring of obese mice was a change in taste function. Adult female mice were fed a normal chow (NC) or a high fat diet (HFD) for 5 weeks before mating, then also during the gestation (3 weeks) and lactation (3 weeks) periods, with offspring always maintained on a normal chow diet; thus the only experience offspring had with high fat food was via maternal exposure. Offspring exhibited similar weight, blood glucose levels and baseline water and chow intake in adulthood. Taste response was assessed after reaching maturity, using brief-access taste testing, with female offspring of obese dams showing an enhanced response to sucrose, and both sexes consuming more sucrose, sucralose and high fat diet if from obese mothers. Offspring also exhibited increased taste bud expression of mRNA for sweet receptor subunits T1R (Taste receptor type) 2 and 3, as well as other markers associated with taste signaling. Taste morphology in both groups appeared similar. Results indicate that obesity in the mother may lead to unhealthy feeding behavior in the offspring, correlating with altered expression of taste signaling elements, which likely drive increased avidity for palatable foods.

Figure 1

Schematic of study design. 8 week old females were fed normal chow (NC) or high-fat diet (HFD) for 5 weeks pre-conception and throughout the gestation/ lactation period. All offspring were then weaned onto regular chow and examined as adults, at 8 weeks of age giving them time to reach maturity.

Figure 2

Metabolic parameters in maternal NC (blue) and HFD (red) offspring at 8–9 weeks of age. Values are expressed as mean ± SEM. (A) Mouse body weight. (B) Perigonadal fat pad mass. (C) Water intake over 48 h. (D) Blood glucose (E) Chow intake over 48 h. Data were analyzed by two-way ANOVA and post-hoc Tukey multiple comparisons test.

Figure 3

Behavioral responses of HFD offspring to appetitive stimuli differ from NC controls. Bars/points denote mean ± SEM. (A) Lickometer responses of offspring show a trend towards higher responsiveness to sucrose in maternal HFD offspring (red), compared to controls (blue), with female (B) offspring driving differences compared to males (C). Star represents statistical difference between curves. Preference (two-bottle, or two-diet) for sucrose (D, n = 9 M, 11F per treatment), sucralose (E, n = 9 M, 11F per treatment), and HFD (F, n = 7 HFD offspring, n = 8 controls) show similar patterns for HFD (red) offspring compared to controls (blue). 48 h intake patterns show enhanced consumption of sucrose (G), sucralose (H), and HFD (I) in offspring of HFD-fed dams (sample size as in D–F). Data were analyzed by two-way ANOVA and post-hoc Tukey multiple comparisons. Stars denote significance, where *p < 0.05; **p < 0.01; ***p < 0.001.

Figure 4

mRNA expression of taste bud signaling elements in NC (blue) and HFD (red) offspring. Bars denote mean ± SEM. Genes tested were sweet receptor subunits (A), sweet signaling components (B), umami (C), Fat (D) and bitter (E) taste receptors/detectors. Each biological sample (n = 4 mice per group) was run in triplicate. Data were analyzed by two-way ANOVA, with post-hoc Tukey multiple comparisons test. */**/*** signifies p < 0.05/0.01/0.001 for maternal diet main effect. Sex and interaction effects described in body.

Figure 5

Taste bud morphology is similar in offspring of NC (blue) and HFD (red) fed dams. Bars denote mean ± SEM. (A) Image of anterior tongue of NC offspring stained with methylene blue to visualize fungiform papillae. (B) Anterior tongue of HFD offspring. (C) Fungiform density within 1 mm × 1 mm square in NC (n = 18) and HFD (n = 21) offspring. (D) Image of circumvallate taste buds of NC offspring. (E) HFD offspring. (F) quantification of taste buds/circumvallate papilla. (G) H&E stained CV papilla of NC offspring. (H) H&E image of HFD offspring papilla. (I) Taste bud size between treatment groups. (J) Immunofluorescent image of Type II taste cells in NC offspring. (K) Type II cells in HFD offspring. (L) Quantification of Type II cells. (M) Immunofluorescent image of sweet/bitter sensitive taste cells in NC offspring (green) with taste bud boundary highlighted (red). (N) Sweet/umami cells in HFD offspring. (O) Quantification of sweet/umami taste cells. Counting was performed from every 8 section of immunofluorescent stains, stars denote significance, where *p < 0.05; **p < 0.01; ***p < 0.001.