Biology subjects

Schier, L. A.

Publications and source records attributed to Schier, L. A..

6 recordsLinked to original sources

bioRxiv2026

Early ingestive experience with a high-fat diet tunes satiation and nutrient-specific appetitive behaviors

Overconsumption of foods rich in fats, sugars, and calories is a major contributing factor to increased risk for cardiometabolic disease. Ingestive experience with these foods can begin early in children, yet there is limited understanding of the impact of early life nutrition on the development of vagal afferent neurons necessary for coordinating appetitive and satiating behaviors. To address this gap, mice reared on a chow diet (control) were compared to those reared on a high-fat diet (HFDEARLY). We demonstrate that the vagally-mediated satiation response to cholecystokinin (CCK) does not mature until adolescence in chow-reared mice. However, HFDEARLY exposure triggers a precocious maturation of this response, accompanied by transcriptomic changes in the nodose ganglion. Durable changes in appetitive behaviors were also evident in adult HFDEARLY mice, which consumed more lipid than control mice. Behavioral analyses point to alterations in orosensory processing and enhanced appetition in adult HFDEARLY mice. Furthermore, female HFDEARLY mice showed a selective increase in consumption of a calorie-dense liquid diet in adulthood, accompanied by changes in body composition, suggesting a lasting, sex-specific vulnerability to overconsumption of palatable, energy-dense foods. Together, these results establish nutrient exposure as a significant contributor to vagal circuit maturation and function.

animal behavior and cognition↗

bioRxiv2026

Consumption of processed foods impairs memory function through dietary advanced glycation end-products

Consumption of processed foods is associated with dementia, obesity, and other negative health outcomes. Sustained heat treatment, a common food processing approach to enhance flavor, induces the chemical Maillard reaction that promotes the formation of dietary advanced glycation end-products (AGEs). The neurocognitive impacts of consuming dietary AGEs are poorly understood. Here we modeled an AGE-rich diet through heat treatment fed to rats during adolescence, a critical period of neural development, to mechanistically evaluate the long-term impact of early life dietary AGEs on behavioral and neural processes. Consuming the AGE-rich diet impaired hippocampal-dependent memory function and altered the gut microbiome without inducing obesity or nonspecific behavioral deficits. AGE-induced memory deficits were coupled with impaired hippocampal glutamatergic synaptic neurotransmission and altered expression in the synapse-pruning complement system. Hippocampal synaptic deficits likely result from direct AGE-complement interactions, as our extended studies reveal competitive antagonist action of AGEs on complement receptors. Memory impairments were prevented by administration of the AGE-inhibitor, alagebrium, and by supplementation with an AGE-inhibiting bacterial taxon, Lactococcus lactis, which was depleted in the heat-treated diet. These findings reveal a functional connection between early life dietary AGEs, the microbiome, and memory impairments, thus illuminating mechanisms through which food processing negatively impacts neurocognition.

neuroscience↗

bioRxiv2025

The vagus nerve promotes memory via septo-hippocampal acetylcholine: Implications for obesity-induced cognitive dysfunction

The vagus nerve relays critical metabolic information between the gastrointestinal (GI) tract and the brain. Recent findings highlight a role for vagus nerve-mediated gut-brain signaling in regulating higher-order cognitive processes, although the underlying mechanisms remain poorly understood. Here we demonstrate that nutrient consumption promotes hippocampal-dependent memory function via vagus nerve-mediated acetylcholine (ACh) release in the dorsal hippocampus (HPCd) from medial septum (MS) neurons. In vivo analyses reveal that HPCd ACh release is engaged during nutrient consumption, and that this response is abolished in animals that received MS cholinergic neuron ablation, subdiaphragmatic vagotomy (SDV), or early-life Western Diet (WD) maintenance. MS cholinergic neuron ablation, SDV, and early-life WD also impaired memory for meal location, suggesting that this gut-brain pathway functions to encode memories for eating events. Collectively, results identify a neurobiological mechanism whereby nutrient consumption promotes memory function, and reveal that disruption of this vagal-brain signaling system mediates WD-associated memory impairments.

neuroscience↗

bioRxiv2022

Hypothalamic melanin-concentrating hormone neurons integrate food-motivated appetitive and consummatory processes

The lateral hypothalamic area (LHA) integrates homeostatic processes and reward-motivated behaviors. Here we show that LHA neurons that produce melanin-concentrating hormone (MCH) are dynamically responsive to both food-directed appetitive and consummatory processes. Specifically, our results reveal that MCH neuron Ca+2 activity increases in response to both discrete and contextual food-predictive cues and is correlated with food-motivated responses. MCH neuron activity also increases during eating and this response is highly predictive of caloric consumption and declines throughout a meal, thus supporting a role for MCH neurons in the positive feedback consummatory process known as appetition. These physiological MCH neural responses are functionally-relevant as chemogenetic MCH neuron activation promotes appetitive behavioral responses to food-predictive cues and increases meal size. Finally, MCH neuron activation enhances preference for a noncaloric flavor paired with intragastric glucose. Collectively, these data identify a hypothalamic neural population that orchestrates both food-motivated appetitive and intake-promoting consummatory processes.

neuroscience↗

bioRxiv2022

Early life low-calorie sweetener consumption impacts energy balance during adulthood

Children frequently consume beverages sweetened with either sugars (sugar-sweetened beverages; SSB) or low-calorie sweeteners (LCS). Here we evaluated the effects of habitual early life consumption of either SSB or LCS on energy balance later during adulthood. Male and female rats were provided with chow, water, and a solution containing either SSB (sucrose), LCS [acesulfame potassium (ACE-K) or stevia], or control (no solution) during the juvenile and adolescent periods (postnatal days 26-70). SSB or LCS consumption was voluntary and restricted within federal recommended daily limits. When subsequently maintained on a cafeteria-style junk food diet (CAF; various high-fat, high-sugar foods) during adulthood, ACE-K-exposed rats demonstrated reduced caloric consumption vs. controls, which contributed to lower body weights in female but not male ACE-K rats. These discrepant intake and body weight effects in male ACE-K rats are likely based on reduced gene expression of thermogenic indicators (UCP1, BMP8B) in brown adipose tissue. Female stevia-exposed rats did not differ from controls in caloric intake or body weight, yet they consumed more SSB during adult CAF exposure. No SSB-exposed rats, neither male nor female, differed from controls in adult total caloric consumption or body weight measures. Collective results reveal that early life LCS consumption alters sugar preference, body weight, and gene expression for markers of thermogenesis during adulthood, with both sex- and sweetener-dependent effects.

physiology↗

bioRxiv2021

Lasting effects of low-calorie sweeteners on glucose regulation, sugar intake, and memory

Low-calorie sweetener (LCS) consumption in children has increased due to widespread LCS presence in the food environment and efforts to mitigate obesity through sugar replacement. However, mechanistic studies on the impact of early-life LCS consumption are lacking. Therefore, we developed a rodent model to evaluate the effects of daily LCS consumption (acesulfame potassium, saccharin, or stevia) during adolescence on adult metabolic, gut microbiome, neural, and behavioral outcomes. Results reveal that habitual early-life LCS consumption disrupts post-oral glucose tolerance and impairs hippocampal-dependent memory in the absence of weight gain. Furthermore, LCS consumption reduces lingual sweet taste receptor expression and alters sugar-motivated appetitive and consummatory responses. RNA sequencing analyses reveal that LCS also impacts collagen- and synaptic signaling-related gene pathways in the hippocampus and nucleus accumbens, respectively, in a sex-dependent manner. Collectively, these results suggest that regular early-life LCS consumption yields long-lasting impairments in metabolism, sugar-motivated behavior, and hippocampal-dependent memory.

neuroscience↗