Obesity-associated deterioration of the hippocampus is partially restored after weight loss

Liśkiewicz, Arkadiusz; Liśkiewicz, Daniela; Marczak, Łukasz; Przybyła, Marta; Grabowska, Konstancja; Student, Sebastian; Dębiec, Magdalena; Sługocka, Anna; Lewin–Kowalik, Joanna

doi:10.1016/j.bbi.2021.05.030

Cited by 7 publications

(4 citation statements)

References 71 publications

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“…In contrast, we did not find any effects of exercise (+BCAA) on neurogenesis, as the amount of doublecortin-positive cells in the hippocampus was similar between groups. In the future, analysis of mature neurons (e.g., NeuN) may provide additional insight into potential treatment effects of exercise and BCAA against obesity-induced neuronal loss [ 118 ]. The effects of BCAA supplementation on cognition are largely unknown.…”

Section: Discussionmentioning

confidence: 99%

The Preventive Effect of Exercise and Oral Branched-Chain Amino Acid Supplementation on Obesity-Induced Brain Changes in Ldlr−/−.Leiden Mice

et al. 2023

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Exercise and dietary interventions are promising approaches to tackle obesity and its obesogenic effects on the brain. We investigated the impact of exercise and possible synergistic effects of exercise and branched-chain amino acids (BCAA) supplementation on the brain and behavior in high-fat-diet (HFD)-induced obese Ldlr−/−.Leiden mice. Baseline measurements were performed in chow-fed Ldlr−/−.Leiden mice to assess metabolic risk factors, cognition, and brain structure using magnetic resonance imaging. Thereafter, a subgroup was sacrificed, serving as a healthy reference. The remaining mice were fed an HFD and divided into three groups: (i) no exercise, (ii) exercise, or (iii) exercise and dietary BCAA. Mice were followed for 6 months and aforementioned tests were repeated. We found that exercise alone changed cerebral blood flow, attenuated white matter loss, and reduced neuroinflammation compared to non-exercising HFD-fed mice. Contrarily, no favorable effects of exercise on the brain were found in combination with BCAA, and neuroinflammation was increased. However, cognition was slightly improved in exercising mice on BCAA. Moreover, BCAA and exercise increased the percentage of epididymal white adipose tissue and muscle weight, decreased body weight and fasting insulin levels, improved the circadian rhythm, and transiently improved grip strength. In conclusion, BCAA should be supplemented with caution, although beneficial effects on metabolism, behavior, and cognition were observed.

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Section: Discussionmentioning

confidence: 99%

The Preventive Effect of Exercise and Oral Branched-Chain Amino Acid Supplementation on Obesity-Induced Brain Changes in Ldlr−/−.Leiden Mice

et al. 2023

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“…Additionally, an intronic variant in the human RYR3 gene has been associated with hippocampal volume ( Alliey-Rodriguez et al, 2019 ). Studies on rats have shown that obesity is associated with abnormal neuronal differentiation in the hippocampus ( Liśkiewicz et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Uncovering structural variants associated with body weight and obesity risk in labrador retrievers: a genome-wide study

Antkowiak,

Szydlowski

2023

Front. Genet.

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Although obesity in the domestic dog (Canis lupus familiaris) is known to decrease well-being and shorten lifespan, the genetic risk variants associated with canine obesity remain largely unknown. In our study, which focused on the obesity-prone Labrador Retriever breed, we conducted a genome-wide analysis to identify structural variants linked to body weight and obesity. Obesity status was based on a 5-point body condition score (BCS) and the obese dog group included all dogs with a BCS of 5, along with dogs with the highest body weight within the BCS 4 group. Data from whole-gene sequencing of fifty dogs, including 28 obese dogs, were bioinformatically analyzed to identify potential structural variants that varied in frequency between obese and healthy dogs. The seven most promising variants were further analyzed by droplet digital PCR in a group of 110 dogs, including 63 obese. Our statistical evidence suggests that common structural mutations in or near six genes, specifically ALPL, KCTD8, SGSM1, SLC12A6, RYR3, and VPS26C, may contribute to the variability observed in body weight and body condition scores among Labrador Retriever dogs. These findings emphasize the need for additional research to validate the associations and explore the specific functions of these genes in relation to canine obesity.

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“…We have previously shown that obesity-induced impairment in cognitive performance was ameliorated after weight loss achieved by either calorie restriction or KD. However, rats fed with a calorie-restricted KD performed better in MWM than those fed with a calorie-restricted standard diet ( 84 ). Finally, Fukushima et al ( 55 ) concluded that the improvement in Y-maze performance may result from KD-induced increased hippocampal expression of the AMPA receptor subunit, GluR1 of naive adult rats.…”

Section: Behavioral Effects Of Kd Treatmentmentioning

confidence: 99%

Ketogenic diet and behavior: insights from experimental studies

Grabowska,

Grabowski,

Przybyła

et al. 2024

Front. Nutr.

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As a journal page for full details. The ketogenic diet (KD) has been established as a treatment for epilepsy, but more recently it has been explored as an alternative or add-on therapy for many other diseases ranging from weight loss to neurological disorders. Animal models are widely used in studies investigating the therapeutic effects of the KD as well as underlying mechanisms. Especially in the context of neurological, psychiatric, and neurodevelopmental disorders essential endpoints are assessed by behavioral and motor tests. Here we summarized research evaluating the influence of the KD on cognition, depressive and anxiety-related behaviors, and social and nutritional behaviors of laboratory rodents. Each section contains a brief description of commonly used behavioral tests highlighting their limitations. Ninety original research articles, written in English, performed on mice or rats, providing measurement of blood beta-hydroxybutyrate (BHB) levels and behavioral evaluation were selected for the review. The majority of research performed in various disease models shows that the KD positively impacts cognition. Almost an equal number of studies report a reduction or no effect of the KD on depressive-related behaviors. For anxiety-related behaviors, the majority of studies show no effect. Despite the increasing use of the KD in weight loss and its appetite-reducing properties the behavioral evaluation of appetite regulation has not been addressed in preclinical studies. This review provides an overview of the behavioral effects of nutritional ketosis addressed to a broad audience of scientists interested in the KD field but not necessarily specializing in behavioral tests.

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Obesity-associated deterioration of the hippocampus is partially restored after weight loss

Cited by 7 publications

References 71 publications

The Preventive Effect of Exercise and Oral Branched-Chain Amino Acid Supplementation on Obesity-Induced Brain Changes in Ldlr−/−.Leiden Mice

The Preventive Effect of Exercise and Oral Branched-Chain Amino Acid Supplementation on Obesity-Induced Brain Changes in Ldlr−/−.Leiden Mice

Uncovering structural variants associated with body weight and obesity risk in labrador retrievers: a genome-wide study

Ketogenic diet and behavior: insights from experimental studies

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