Early life Western diet-induced memory impairments and gut microbiome changes in female rats are long-lasting despite healthy dietary intervention

Tsan, Linda; Sun, Shan; Hayes, Anna; Bridi, Lana; Chirala, Lekha S.; Noble, Emily E.; Fodor, Anthony A.; Kanoski, Scott E.

doi:10.1080/1028415x.2021.1980697

Cited by 15 publications

(25 citation statements)

References 79 publications

(99 reference statements)

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“…Some experiments were conducted with a single LCS, ACE-K, as the representative sweetener, given that this LCS is commonly consumed in human populations ( 40 ). Early-life exposure to natural sugars yields sex-specific differences later in life ( 10 , 11 , 41 ); thus it prompted a direct comparison between male and female rats in our initial study. These differences are highlighted below only where overall significant effects or interactions involving sex were detected (results are otherwise plotted by sex in the Supplemental data ).…”

Section: Resultsmentioning

confidence: 99%

Early-life low-calorie sweetener consumption disrupts glucose regulation, sugar-motivated behavior, and memory function in rats

Tsan¹,

Chometton²,

Hayes³

et al. 2022

JCI Insight

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Low-calorie sweetener (LCS) consumption in children has increased dramatically due to 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 post-oral 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 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 sequencing 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.

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Section: Resultsmentioning

confidence: 99%

Early-life low-calorie sweetener consumption disrupts glucose regulation, sugar-motivated behavior, and memory function in rats

Tsan¹,

Chometton²,

Hayes³

et al. 2022

JCI Insight

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“…Rats were habituated to oral gavage, food-restricted 22 h prior to the GTT as previously described [38], and water restricted at the start of the dark cycle (15 h prior to the GTT). Five minutes prior to oral gavage with dextrose, baseline blood glucose readings were obtained from the tail tip and recorded by a blood glucose meter (One-touch Ultra2, LifeScan Inc., Milpitas, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

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

Hayes

Tsan

Kao

et al. 2022

Preprint

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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.

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“…Five days of exposure to a non-standardized cafeteria diet (CAFD) composed of cakes, biscuits, and a protein source, plus a high-sucrose (HSu) solution, compromised hippocampal-dependent place recognition memory in adult rats, although other memory tasks remained unaffected [ 49 ]; comparable deficits were also reported for the CAFD without the HSu solution and the HSu solution without the CAFD. In young rat females, 5 weeks of CAFD or high-fructose solution (HFru) intake induced similar memory impairments, and intervention with a healthier diet was only able to revert HFru-mediated, but not CAFD-mediated deficits [ 44 ]. In adult mouse males, 14 weeks of combined HFD and HFru (HFD-HFru) intake resulted in a poorer cognitive performance than with an HFD alone [ 69 ].…”

Section: Western Dietmentioning

confidence: 99%

“…Other mechanisms are also compromised in WD-induced cognitive damage: insulin (INS) signaling in the brain [ 60 , 68 ], blood-brain barrier (BBB) permeability [ 41 , 57 , 62 ], HPC inflammation [ 45 , 46 , 49 , 54 , 60 , 68 ], microglia activation [ 54 , 57 , 65 , 68 , 72 ], endoplasmic reticulum (ER) and oxidative stress [ 43 , 51 , 58 , 60 , 61 , 71 ], gut microbiome composition [ 44 , 46 , 54 , 56 , 58 ], and neurogenesis [ 59 ]. Therapeutic strategies based on modulating these mechanisms have demonstrated unequal effects on memory loss.…”

Section: Western Dietmentioning

confidence: 99%

“…Furthermore, pre-exposure to a probiotic called VSL#3 prevented WD-induced memory deficits for an HPC-dependent task, but caused deficits for a perirhinal-dependent task, irrespective of diet and dose [ 50 ], suggesting that this probiotic may be detrimental for healthy subjects. In one study, treatment with the antibiotic minocycline, which alters microbiome composition, prevented or reverted CAFD-induced spatial memory impairment [ 46 ]; however, another study showed that dietary intervention restored CAFD-dependent memory loss, but not gut microbiota alterations [ 44 ]. Finally, vitamin E administration normalized the effect of the CAFD on HPC oxidative stress markers and prevented diet-mediated memory decline [ 51 ].…”

Section: Western Dietmentioning

confidence: 99%

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Feeding the Brain: Effect of Nutrients on Cognition, Synaptic Function, and AMPA Receptors

et al. 2022

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In recent decades, traditional eating habits have been replaced by a more globalized diet, rich in saturated fatty acids and simple sugars. Extensive evidence shows that these dietary factors contribute to cognitive health impairment as well as increase the incidence of metabolic diseases such as obesity and diabetes. However, how these nutrients modulate synaptic function and neuroplasticity is poorly understood. We review the Western, ketogenic, and paleolithic diets for their effects on cognition and correlations with synaptic changes, focusing mainly (but not exclusively) on animal model studies aimed at tracing molecular alterations that may contribute to impaired human cognition. We observe that memory and learning deficits mediated by high-fat/high-sugar diets, even over short exposure times, are associated with reduced arborization, widened synaptic cleft, narrowed post-synaptic zone, and decreased activity-dependent synaptic plasticity in the hippocampus, and also observe that these alterations correlate with deregulation of the AMPA-type glutamate ionotropic receptors (AMPARs) that are crucial to neuroplasticity. Furthermore, we explored which diet-mediated mechanisms modulate synaptic AMPARs and whether certain supplements or nutritional interventions could reverse deleterious effects, contributing to improved learning and memory in older people and patients with Alzheimer’s disease.

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Early life Western diet-induced memory impairments and gut microbiome changes in female rats are long-lasting despite healthy dietary intervention

Abstract: 2021): Early life Western diet-induced memory impairments and gut microbiome changes in female rats are long-lasting despite healthy dietary intervention, Nutritional Neuroscience,

Cited by 15 publications

References 79 publications

Early-life low-calorie sweetener consumption disrupts glucose regulation, sugar-motivated behavior, and memory function in rats

Early-life low-calorie sweetener consumption disrupts glucose regulation, sugar-motivated behavior, and memory function in rats

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

Feeding the Brain: Effect of Nutrients on Cognition, Synaptic Function, and AMPA Receptors

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