Metabolic and behavioural effects in offspring exposed to maternal sucrose consumption: a systematic review and meta-analysis of data from rodent models.

Consumption of sugar-sweetened beverages (SSBs) during pregnancy has been associated with childhood obesity. Research in which rodent dams have been given high-fat/high-sugar diets has consistently found metabolic alterations in their offspring. However, what remains unclear is the potential impact on the developing fetus of giving sugar in isolation at concentrations similar to SSBs to the mothers. Therefore, we conducted a systematic review and meta-analysis (Protocol No: 127115 on Prospero) to identify potential relationships between maternal sucrose consumption and metabolic outcomes in offspring of rodent (rat or mouse) models. We analysed studies that provided rodent mothers dams with access to sucrose solutions (8-20% w/v) prior to conception, during pregnancy and/or lactation and that reported offspring outcomes of body weight (BW), body composition and glycaemic control. Following a systematic search of four databases (PubMed, EMBASE, Web of Science and Scopus) performed on 15 January 2019, maternal and offspring data from 15 papers were identified for inclusion. Only rat studies were identified. Meta-analyses were performed on standardised mean differences for maternal and offspring BW and fasting glucose levels, with subgroup analyses of strain, sucrose concentration, exposure period and sex of offspring. A bias towards the inclusion of only data from male offspring was identified and this limited interpretation of potential sexually dimorphic outcomes. Maternal sucrose exposure was associated with an increased risk of obesity and poor glucose disposal in adult and aged offspring.

Metabolic and behavioural effects of prenatal exposure to non-nutritive sweeteners: A systematic review and meta-analysis of rodent models.

Little is known about possible effects of maternal non-nutritive sweetener (NNS) consumption on the metabolic health of a child. Animal models of maternal NNS consumption during pregnancy or weaning have yielded widely varying results, and there appears to be no clear consensus on the consequences for offspring body weight, glycaemic control or sweet preference choices. Moreover, heterogeneity in study design has hampered a clear focus for future research relevant to human health. In an effort to bring clarity, we have conducted a systematic review and meta-analysis (protocol no: CRD42018109509) in animal models (rat or mouse) of maternal NNS feeding (compared to water or basal diet) during pre-gestation, pregnancy or lactation. Four databases were searched from inception to 15th September 2018: PubMed, EMBASE, SCOPUS and Web of Science. We present maternal and offspring data from 24 included studies, which have been quantitatively analysed after study quality assessment, to identify relationships between maternal diet and offspring body weight (BW), feeding behaviour and glycaemic control. In 11 data sets, exposure to NNS reduced maternal BW during pregnancy, with no effect on litter outcomes. Meta-analyses on offspring BW during weaning (1123 offspring) and adulthood (646 offspring) identified small decreases in BW for both sexes. Subgroup analyses revealed reductions in BW of rat, but not mouse models. High dosage appears to be a potential factor for reduced palatability that could influence BW results; however, a lack of reported data limited our ability to confirm. Despite this, and the fact many papers were predisposed to bias, the balance of evidence suggests a maternal NNS diet during pregnancy or lactation did not increase the body weight in offspring.

Unaltered instrumental learning and attenuated body-weight gain in rats during non-rotating simulated shiftwork.

Exposure to shiftwork has been associated with multiple health disorders and cognitive impairments in humans. We tested if we could replicate metabolic and cognitive consequences of shiftwork, as reported in humans, in a rat model comparable to 5 wks of non-rotating night shifts. The following hypotheses were addressed: (i) shiftwork enhances body-weight gain, which would indicate metabolic effects; and (ii) shiftwork negatively affects learning of a simple goal-directed behavior, i.e., the association of lever pressing with food reward (instrumental learning), which would indicate cognitive effects. We used a novel method of forced locomotion to model work during the animals' normal resting period. We first show that Wistar rats, indeed, are active throughout a shiftwork protocol. In contrast with previous findings, the shiftwork protocol attenuated the normal weight gain to 76 ± 8 g in 5 wks as compared to 123 ± 15 g in the control group. The discrepancy with previous work may be explained by the concurrent observation that with our shiftwork protocol rats did not adjust their between-work circadian activity pattern. They maintained a normal level of activity during the "off-work" periods. In the control experiment, rats were kept active during the dark period, normally dominated by activity. This demonstrated that forced activity, per se, did not affect body-weight gain (mean ± SEM: 85 ± 11 g over 5 wks as compared to 84 ± 11 g in the control group). Rats were trained on an instrumental learning paradigm during the fifth week of the protocol. All groups showed equivalent increases in lever pressing from the first (3.8 ± .7) to the sixth (21.3 ± 2.4) session, and needed a similar amount of sessions (5.1 ± .3) to reach a learning criterion (≥ 27 out of 30 lever presses). These results suggest that while on prolonged non-rotating shiftwork, not fully reversing the circadian rhythm might actually be beneficial to prevent body-weight gain and cognitive impairments.

Increases in extracellular serotonin and dopamine metabolite levels in the basal forebrain during sleep deprivation.

The basal forebrain (BF) is an important mediator of cortical arousal, which is innervated by all ascending arousal systems. During sleep deprivation (SD) a site-specific accumulation of sleep factors in the BF results in increased sleep pressure (Kalinchuk et al., 2006; Porkka-Heiskanen et al., 1997; Porkka-Heiskanen et al., 2000). However, animals are able to stay awake and even increase their neuronal activity in the BF and cortex during SD, suggesting increased activity of the ascending arousal systems to counteract the effect of sleep pressure. This study used in vivo microdialysis to measure the effect of a 6h SD, by "gentle handling" in freely moving rats, on the extracellular levels of serotonin and dopamine metabolites (5-HIAA, and DOPAC and HVA respectively) in the BF. Additionally, because glucocorticoids can interact with monoaminergic neurotransmission, and SD could be stressful, corticosterone levels were measured. We found an increase in extracellular serotonin and dopamine metabolite levels (n=8, p≤0.05). No interaction between corticosterone and the monoaminergic systems was apparent. Extracellular corticosterone levels showed no increase during the first 3h of SD, and the subsequent increase (n=8, p≤0.05) did not result in values exceeding the normal diurnal maximum, indicating that no substantial stress was induced. The results demonstrate that SD increases extracellular dopamine and serotonin metabolites in the BF, suggesting increased activity of the ascending arousal systems. It remains to be investigated what the specific roles of the dopaminergic and serotonergic ascending arousal systems are in BF-mediated cortical arousal.