Sex-Specific Effects of a Maternal Obesogenic Diet High in Fat and Sugar on Offspring Adiposity, Growth, and Behavior.

With rising rates of human obesity, this study aimed to determine the relationship between maternal diet-induced obesity, offspring morphometrics, and behavior in mice. Pregnant and lactating female mice fed a diet high in fat and sugar (HFHS) commonly consumed by human populations showed decreased food, calorie, and protein intake but increased adiposity at the expense of lean mass. The pre-weaning body weight of the HFHS offspring was reduced for the first postnatal week but not thereafter, with HFHS female offspring having higher body weights by weaning due to continuing higher fractional growth rates. Post-weaning, there were minor differences in offspring food and protein intake. Maternal diet, however, affected fractional growth rate and total body fat content of male but not female HFHS offspring. The maternal diet did not affect the offspring's locomotor activity or social behavior in either sex. Both the male and female HFHS offspring displayed reduced anxiety-related behaviors, with sex differences in particular aspects of the elevated plus maze task. In the novel object recognition task, performance was impaired in the male but not female HFHS offspring. Collectively, the findings demonstrate that maternal obesity alters the growth, adiposity, and behavior of male and female offspring, with sex-specific differences.

Age and an obesogenic diet affect mouse behaviour in a sex-dependent manner.

Obesity is rising globally and is associated with neurodevelopmental and psychiatric disorders among children, adolescents and young adults. Whether obesity is the cause or the consequence of these disorders remains unclear. To examine the behavioural effects of obesity systematically, locomotion, anxiety and social behaviour were assessed in male and female C57Bl/6J mice using the open field, elevated plus maze and social preference task. First, the effects of age and sex were examined in control mice, before investigating post-weaning consumption of a high fat-high sugar diet commonly consumed in human populations with high rates of obesity. In the open field and elevated plus maze, locomotor activity and anxiety-related behaviours reduced with aging in both sexes, but with different sex-specific profiles. The high fat-high sugar diet reduced food and calorie intake and increased body mass and fat deposition in both sexes. In the open field, both male and female mice on the obesogenic diet showed reduced locomotion; whereas, in the elevated plus maze, only females fed with the obesogenic diet displayed reduced anxiety-related behaviours. Both male and female mice on the obesogenic diet had a significantly higher social preference index than the control group. In conclusion, the findings demonstrate that the behavioural effects of age and diet-induced obesity all depend on the sex of the mouse. This emphasises the importance of considering the age of the animal and including both sexes when assessing behavioural phenotypes arising from dietary manipulations.

Diet-induced maternal obesity impacts feto-placental growth and induces sex-specific alterations in placental morphology, mitochondrial bioenergetics, dynamics, lipid metabolism and oxidative stress in mice.

AIM: The current study investigated the impact of maternal obesity on placental phenotype in relation to fetal growth and sex. METHODS: Female C57BL6/J mice were fed either a diet high in fat and sugar or a standard chow diet, for 6 weeks prior to, and during, pregnancy. At day 19 of gestation, placental morphology and mitochondrial respiration and dynamics were assessed using high-resolution respirometry, stereology, and molecular analyses. RESULTS: Diet-induced maternal obesity increased the rate of small for gestational age fetuses in both sexes, and increased blood glucose concentrations in offspring. Placental weight, surface area, and maternal blood spaces were decreased in both sexes, with reductions in placental trophoblast volume, oxygen diffusing capacity, and an increased barrier to transfer in males only. Despite these morphological changes, placental mitochondrial respiration was unaffected by maternal obesity, although the influence of fetal sex on placental respiratory capacity varied between dietary groups. Moreover, in males, but not females, maternal obesity increased mitochondrial complexes (II and ATP synthase) and fission protein DRP1 abundance. It also reduced phosphorylated AMPK and capacity for lipid synthesis, while increasing indices of oxidative stress, specifically in males. In females only, placental mitochondrial biogenesis and capacity for lipid synthesis, were both enhanced. The abundance of uncoupling protein-2 was decreased by maternal obesity in both fetal sexes. CONCLUSION: Maternal obesity exerts sex-dependent changes in placental phenotype in association with alterations in fetal growth and substrate supply. These findings may inform the design of personalized lifestyle interventions or therapies for obese pregnant women.

Mouse maternal protein restriction during preimplantation alone permanently alters brain neuron proportion and adult short-term memory.

Maternal protein malnutrition throughout pregnancy and lactation compromises brain development in late gestation and after birth, affecting structural, biochemical, and pathway dynamics with lasting consequences for motor and cognitive function. However, the importance of nutrition during the preimplantation period for brain development is unknown. We have previously shown that maternal low-protein diet (LPD) confined to the preimplantation period (Emb-LPD) in mice, with normal nutrition thereafter, is sufficient to induce cardiometabolic and locomotory behavioral abnormalities in adult offspring. Here, using a range of in vivo and in vitro techniques, we report that Emb-LPD and sustained LPD reduce neural stem cell (NSC) and progenitor cell numbers at E12.5, E14.5, and E17.5 through suppressed proliferation rates in both ganglionic eminences and cortex of the fetal brain. Moreover, Emb-LPD causes remaining NSCs to up-regulate the neuronal differentiation rate beyond control levels, whereas in LPD, apoptosis increases to possibly temper neuron formation. Furthermore, Emb-LPD adult offspring maintain the increase in neuron proportion in the cortex, display increased cortex thickness, and exhibit short-term memory deficit analyzed by the novel-object recognition assay. Last, we identify altered expression of fragile X family genes as a potential molecular mechanism for adverse programming of brain development. Collectively, these data demonstrate that poor maternal nutrition from conception is sufficient to cause abnormal brain development and adult memory loss.

Accuracy of the use of triaxial accelerometry for measuring daily activity as a predictor of daily maintenance energy requirement in healthy adult Labrador Retrievers.

OBJECTIVE: To determine accuracy of the use of triaxial accelerometry for measuring daily activity as a predictor of maintenance energy requirement (MER) in healthy adult Labrador Retrievers. ANIMALS: 10 healthy adult Labrador Retrievers. PROCEDURES: Dogs wore an accelerometer for two 2-week periods, with data on daily activity successfully collected for 24 to 26 days. These data, along with body weight, were used as independent variables in a multiple linear regression model to predict the dependent variable of daily MER. The predictive accuracy of the model was compared with that of a model that excluded activity. Dietary energy intake at a stated amount of body weight stability was used as an equivalent measure of MER in these analyses. RESULTS: The multiple linear regression model that included body weight and daily activity as independent variables could be used to predict observed MER with a mean absolute error of 63.5 kcal and an SE of estimation of 94.3 kcal. Removing activity from the model reduced the predictive accuracy to a mean absolute error of 129.8 kcal and an SE of estimation of 165.4 kcal. CONCLUSIONS AND CLINICAL RELEVANCE: Use of triaxial accelerometers to provide an independent variable of daily activity yielded a marked improvement in predictive accuracy of the regression model, compared with that for a model that used only body weight. Improved accuracy in estimations of MER could be made for each dog if an accelerometer was used to record its daily activity.

Comparison of flow-mediated vasodilation in femoral and brachial arteries in healthy dogs.

OBJECTIVE: To compare flow-mediated vasodilation (FMD) measurements in brachial and femoral arteries of healthy dogs habituated to the assessment method, evaluate repeatability of these measurements, and investigate effects of blood pressure cuff inflation time on femoral artery FMD measurements. ANIMALS: 11 healthy adult Miniature Schnauzers. PROCEDURES: Arterial luminal diameter and blood flow velocity integral (FVI) were measured before and after cuff inflation of 5 minutes' (brachial and femoral arteries) or 3 minutes' duration (femoral artery) in separate experiments. A blood pressure cuff was inflated to > 200 mm Hg distal to each imaging site to increase local blood flow to induce reactive hyperemia. Changes in FVI after cuff deflation, FMD, and between-dog and within-dog coefficients of variation (CVs) were determined. RESULTS: After cuff inflation of 5 minutes' duration, greater changes were detected in median change in FVI and FMD of brachial arteries (174.0% and 8.0%, respectively), compared with values determined for femoral arteries (32.0% and 2.1%, respectively). Between-dog CV for brachial artery FMD was 34.0%, compared with 89.6% for femoral arteries, and within-dog CV was 32.5% for brachial arteries versus 51.6% for femoral arteries after cuff inflation of 5 minutes' duration. CONCLUSIONS AND CLINICAL RELEVANCE: In healthy Miniature Schnauzers, FMD was greater and more repeatable in brachial arteries than in femoral arteries. Reactive hyperemia was inconsistently induced in femoral arteries following 3- or 5-minute cuff inflation times. Brachial, but not femoral, artery FMD measurement is a potentially useful research technique for measurement of endothelial function in dogs.