Metabolic shift toward ketosis in asocial cavefish increases social-like affinity.

BACKGROUND: Social affinity and collective behavior are nearly ubiquitous in the animal kingdom, but many lineages feature evolutionarily asocial species. These solitary species may have evolved to conserve energy in food-sparse environments. However, the mechanism by which metabolic shifts regulate social affinity is not well investigated. RESULTS: In this study, we used the Mexican tetra (Astyanax mexicanus), which features riverine sighted surface (surface fish) and cave-dwelling populations (cavefish), to address the impact of metabolic shifts on asociality and other cave-associated behaviors in cavefish, including repetitive turning, sleeplessness, swimming longer distances, and enhanced foraging behavior. After 1 month of ketosis-inducing ketogenic diet feeding, asocial cavefish exhibited significantly higher social affinity, whereas social affinity regressed in cavefish fed the standard diet. The ketogenic diet also reduced repetitive turning and swimming in cavefish. No major behavioral shifts were found regarding sleeplessness and foraging behavior, suggesting that other evolved behaviors are not largely regulated by ketosis. We further examined the effects of the ketogenic diet via supplementation with exogenous ketone bodies, revealing that ketone bodies are pivotal molecules positively associated with social affinity. CONCLUSIONS: Our study indicated that fish that evolved to be asocial remain capable of exhibiting social affinity under ketosis, possibly linking the seasonal food availability and sociality.

Metabolic Framework for the Improvement of Autism Spectrum Disorders by a Modified Ketogenic Diet: A Pilot Study.

The ketogenic diet (KD) can improve the core features of autism spectrum disorders (ASD) in some children, but the effects on the overall metabolism remain unclear. This pilot study investigated the behavioral parameters in relation to blood metabolites and trace elements in a cohort of 10 typically developed controls (TC) and 17 children with ASD at baseline and following 3 months of treatment with a modified KD regimen. A nontargeted, multiplatform metabolomic approach was employed, including gas chromatography-mass spectrometry, 1H nuclear magnetic resonance spectroscopy, and inductively coupled plasma-mass spectrometry. The associations among plasma metabolites, trace elements, and behavior scores were investigated. Employing a combination of metabolomic platforms, 118 named metabolites and 73 trace elements were assessed. Relative to TC, a combination of glutamate, galactonate, and glycerol discriminated ASD with 88% accuracy. ASD had higher concentrations of galactose intermediates, gut microbe-derived trimethylamine N-oxide and N-acetylserotonin, and lower concentrations of 3-hydroxybutyrate and selenium at baseline. Following 3 months of KD intervention, the levels of circulating ketones and acetylcarnitine were increased. KD restored lower selenium levels in ASD to that of controls, and correlation analysis identified a novel negative correlation between the changes in selenium and behavior scores. Based on the different behavior responses to KD, we found that high responders had greater concentrations of 3-hydroxybutyrate and ornithine, with lower galactose. These findings enhance our current understanding of the metabolic derangements present in ASD and may be of utility in predicting favorable responses to KD intervention.

Treatment of Prurigo Pigmentosa with Diet Modification: A Medical Case Study.

Prurigo pigmentosa is a rare inflammatory dermatitis first described in 1971. While the etiology of Prurigo pigmentosa is yet unknown, conditions associated with ketosis often accompany this rash. Prurigo pigmentosa is successfully treated with antibiotics and by resolution of ketosis. However, there is no dietary treatment option to successfully treat the rash without sacrificing ketosis. We report two cases successfully treated with increase of dietary carbohydrate intake. The second case suggests that cessation of ketosis may not be necessary to resolve Prurigo pigmentosa.