Low-calorie sweetener (LCS) consumption in children has increased dramatically due to its widespread presence in the food environment and efforts to mitigate obesity through sugar replacement. However, mechanistic studies on the long-term impact of early-life LCS consumption on cognitive function and physiological processes are lacking. Here, we developed a rodent model to evaluate the effects of daily LCS consumption (acesulfame potassium, saccharin, or stevia) during adolescence on adult metabolic, behavioral, gut microbiome, and brain transcriptomic outcomes. Results reveal that habitual early-life LCS consumption impacts normal postoral glucose handling and impairs hippocampal-dependent memory in the absence of weight gain. Furthermore, adolescent LCS consumption yielded long-term reductions in lingual sweet taste receptor expression and brought about alterations in sugar-motivated appetitive and consummatory responses. While early-life LCS consumption did not produce robust changes in the gut microbiome, brain region–specific RNA-Seq analyses reveal LCS-induced changes in collagen- and synaptic signaling–related gene pathways in the hippocampus and nucleus accumbens, respectively, in a sex-dependent manner. Collectively, these results reveal that habitual early-life LCS consumption has long-lasting implications for glucoregulation, sugar-motivated behavior, and hippocampal-dependent memory in rats, which may be based in part on changes in nutrient transporter, sweet taste receptor, and central gene pathway expression.

Dietary glucose is a robust elicitor of central reward responses and ingestion, but the key peripheral sensors triggering these orexigenic mechanisms are not entirely known. The objective of this study was to determine whether glucokinase, a phosphorylating enzyme with known glucosensory roles, is also expressed in taste bud cells and contributes to the immediate hedonic appeal of glucose-containing substances. Glucokinase (GCK) gene transcripts were localized in murine taste bud cells with RNAScope®, and GCK mRNA was found to be upregulated in the circumvallate taste papillae in response to fasting and after a period of dietary access to added simple sugars in mice, as determined with real time-qPCR. Pharmacological activation of glucokinase with Compound A increased primary taste nerve and licking responses for glucose but did not impact responsivity to fructose in naïve mice. Virogenetic silencing of glucokinase in the major taste fields attenuated glucose-stimulated licking, especially in mice that also lacked sweet receptors, but did not disrupt consummatory behaviors for fructose or the low-calorie sweetener, sucralose in sugar naïve mice. Knockdown of lingual glucokinase weakened the acquired preference for glucose over fructose in sugar-experienced mice in brief access taste tests. Collectively, our data establish that glucokinase contributes to glucose appetition at the very first site of nutrient detection, in the oral cavity. The findings expand our understanding of orosensory inputs underlying nutrition, metabolism, and food reward.

Several recent studies have shown that post-oral sugar sensing rapidly stimulates ingestion. Here, we explored the specificity with which early-phase post-oral sugar sensing influenced ingestive motivation. In experiment 1, rats were trained to associate the consumption of 0.3 M sucrose with injections of LiCl (3.0 meq/kg ip, conditioned taste aversion) or given equivalent exposures to the stimuli, but in an unpaired fashion. Then, all rats were subjected to two brief-access tests to assess appetitive and consummatory responses to the taste properties of sucrose (0.01–1.0 M), 0.12 M NaCl, and dH₂O (in 10-s trials in randomized blocks). Intraduodenal infusions of either 0.3 M sucrose or equiosmolar 0.15 M NaCl (3.0 ml) were administered, beginning just before each test. For unpaired rats, intraduodenal sucrose specifically enhanced licking for 0.03–1.0 M sucrose, with no effect on trial initiation, relative to intraduodenal NaCl. Rats with an aversion to sucrose suppressed licking responses to sucrose in a concentration-dependent manner, as expected, but the intraduodenal sucrose preload did not appear to further influence licking responses; instead, intraduodenal sucrose attenuated trial initiation. Using a serial taste reactivity (TR) paradigm, however, experiment 2 demonstrated that intraduodenal sucrose preloads suppressed ingestive oromotor responses to intraorally delivered sucrose in rats with a sucrose aversion. Finally, experiment 3 showed that intraduodenal sucrose preloads enhanced preferential licking to some representative tastants tested (sucrose, Polycose, and Intralipid), but not others (NaCl, quinine). Together, the results suggest that the early phase-reinforcing efficacy of post-oral sugar is dependent on the sensory and motivational properties of the ingesta.

The capacity to locate, ingest, and efficiently assimilate glucose is key to health and survival for many organisms. In humans, rodents, and most other mammals, this process begins with specialized...

The simple sugars glucose and fructose share a common “sweet” taste quality mediated by the T1R2+T1R3 taste receptor. However, when given the opportunity to consume each sugar, rats learn to affectively discriminate between glucose and fructose on the basis of cephalic chemosensory cues. It has been proposed that glucose has a unique sensory property that becomes more hedonically positive through learning about the relatively more rewarding post-ingestive effects that are associated with glucose as compared to fructose. We tested this theory using intragastric (IG) infusions to manipulate the post-ingestive consequences of glucose and fructose consumption. Food-deprived rats with IG catheters repeatedly consumed multiple concentrations of glucose and fructose in separate sessions. For rats in the “Matched” group, each sugar was accompanied by IG infusion of the same sugar. For the “Mismatched” group, glucose consumption was accompanied by IG fructose, and vice versa. This condition gave rats orosensory experience with each sugar but precluded the differential post-ingestive consequences. Following training, avidity for each sugar was assessed in brief access and licking microstructure tests. The Matched group displayed more positive evaluation of glucose relative to fructose than the Mismatched group. A second experiment used a different concentration range and compared responses of the Matched and Mismatched groups to a control group kept naïve to the orosensory properties of sugar. Consistent with results from the first experiment, the Matched group, but not the Mismatched or Control group, displayed elevated licking responses to glucose. These experiments yield additional evidence that glucose and fructose have discriminable sensory properties and directly demonstrate that their different post-ingestive effects are responsible for the experience-dependent changes in the motivation for glucose versus fructose.

In cleanroom facilities, both disposable and reusable textile garments (coveralls, boots, hoods, and frocks) meet the particulate standards from the most rigorous to the most basic levels. However, the reusables clearly offer two other important benefits, lower annual cost and lower environmental impact. The objectives of this article are to now provide quantitative reusable product benefits on a U.S. national environmental and economic basis. This is the first quantitative, novel multi-user economic evaluation of selecting cleanroom reusables over disposables. For personal protection equipment (PPE), these cost and environmental benefits indicate there is also an improved environmental and economic aspect to the increased national demand for reusables related to coronavirus disease 2019 (COVID-19), while necessary cleaning with approved detergents is easily achieved. The current reusable cleanroom market (14.1 million packages) was estimated to be 60% nonsterile and 40% sterilized. The total market is about 50% reusable and 50% disposable. This research documents that there is an annual cost reduction of about 58% when selecting reusables over disposables, giving an economic savings to the U.S. cleanroom sector from reusables of about $1.2 billion in the next decade. This is also saving the total U.S. about 136 million MJ natural resource energy/year (38 million kWh) and about 8.4 million kg CO_2eq annually (removal of about 1,650 cars/year). A maximum hypothetical case for reusables at 87.5% of the market (12.5% are mandatory Hazmat disposable) would yield a U.S. national savings of nearly $2.1 billion/decade to the cleanroom sector bottom line, as well as 2.4 billion MJ nre savings in energy or removal of about 29,000 cars/decade. These results indicate there are effective, verifiable, and easily obtained environmental and economic benefits by the basic transition by diverse cleanrooms in deciding to select reusable garments.