Starvation-resistant cavefish reveal conserved mechanisms of starvation-induced hepatic lipotoxicity

Life Science Alliance, Год журнала: 2024, Номер 7(5), С. e202302458 - e202302458

Опубликована: Март 11, 2024

Starvation causes the accumulation of lipid droplets in liver, a somewhat counterintuitive phenomenon that is nevertheless conserved from flies to humans. Much like fatty liver resulting overfeeding, hepatic (steatosis) during undernourishment can lead lipotoxicity and atrophy liver. Here, we found although surface populations Astyanax mexicanus undergo this evolutionarily response starvation, starvation-resistant cavefish larvae same species do not display an upon starvation. Moreover, are resistant providing unique system explore strategies for protection. Using comparative transcriptomics between zebrafish, fish, cavefish, identified acid transporter slc27a2a/fatp2 be correlated with development Pharmacological inhibition slc27a2a zebrafish rescues steatosis Furthermore, down-regulation FATP2 Drosophila inhibits starvation-induced steatosis, suggesting importance gene regulating nutrition deprivation. Overall, our study identifies conserved, druggable target protect

Язык: Английский

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Elevated DNA Damage without signs of aging in the short-sleeping Mexican Cavefish

Опубликована: Фев. 10, 2025

Dysregulation of sleep has widespread health consequences and represents an enormous burden. Short-sleeping individuals are predisposed to the effects neurodegeneration, suggesting a critical role for in maintenance neuronal health. While on cellular function not completely understood, growing evidence identified association between loss DNA damage, raising possibility that facilitates efficient repair. The Mexican tetra fish, Astyanax mexicanus provides model investigate evolutionary basis changes loss. Multiple cave-adapted populations these fish have evolved substantially less time compared surface same species without identifiable impacts healthspan or longevity. To whether is associated with damage stress, we Damage Response (DDR) oxidative stress levels A. populations. We measured markers chronic discovered elevated marker γH2AX brain, increased gut cavefish, consistent deprivation. Notably, found acute UV-induced elicited increase but cavefish. On transcriptional level, only activated photoreactivation repair pathway following UV damage. These findings suggest reduction DDR cavefish coincides examine pathways at created embryonic fibroblast cell line from two . observed both were diminished cells, corroborating vivo response lost long-term impact changes, transcriptome brain aged Strikingly, many genes differentially expressed young old do transcriptionally vary by age Taken together, developed resilience loss, despite possessing hallmarks

Язык: Английский

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Reproductive Adaptation of Astyanax mexicanus Under Nutrient Limitation

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Фев. 17, 2025

Abstract Reproduction is a fundamental biological process for the survival and continuity of species. Examining changes in reproductive strategies offers valuable insights into how animals have adapted their life histories to different environments. Since reproduction one most energy-intensive processes female animals, nutrient scarcity expected interfere with ability invest gametes. Lately, new model study adaptation limitation has emerged; Mexican tetra Astyanax mexicanus . This fish species exists as two morphs, surface river morph cave-dwelling morph. The dark, biodiversity, nutrient-limited cave environment consequently evolved an impressive starvation resistance. However, limitations this remains poorly understood. Here, we compared breeding activities maternal contributions between laboratory-raised cavefish. We found that cavefish produce clutch sizes eggs larger yolk fish, indicating greater deposition embryos. To systematically characterize compositions, used untargeted proteomics lipidomics approaches analyze protein lipid profiles 2-cell stage embryos increased proportion sphingolipids fish. Additionally, generated transcriptomic ovaries using combination single cell bulk RNA sequencing examine differences contribution. genes essential hormone regulation were upregulated follicular somatic cells evaluate whether these contribute abilities under natural-occurring stress, induced starved Remarkably, maintained breed starvation, whereas largely lost ability. identified insulin-like growth factor 1a receptor ( igf1ra ) potential candidate gene mediating downregulation ovarian development genes, potentially contributing starvation-resistant fertility Taken together, investigated , which will provide adaptations environments extreme deficit.

Язык: Английский

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Genetic Mapping of Orofacial Traits Reveals a Single Genomic Region Associated With Differences in Multiple Parameters of Jaw Size Between Astyanax mexicanus Surface and Cavefish

Evolution & Development, Год журнала: 2025, Номер unknown

Опубликована: Фев. 20, 2025

ABSTRACT The regulation of bone size is a poorly understood and complex developmental process. Evolutionary models can enable insight through interrogation the molecular underpinnings natural variation in shape. Here, we examine Mexican tetra ( Astyanax mexicanus ), species teleost fish comprising an extant river‐dwelling surface obligate cave‐dwelling fish. These divergent morphs have evolved for thousands years drastically different habitats, which led to diverse phenotypic differences. Among many craniofacial aberrations, cavefish harbor wider gape, underbite, larger jaws compared surface‐dwelling morphs. Morphotypes are inter‐fertile, allowing quantitative genetic analyses F 2 pedigrees derived from × crosses. used trait locus (QTL) analysis determine basis jaw size. Strikingly, discovered single genomic region associated with several metrics. Future work identifying lesions that explain differences development will provide new mechanisms driving across vertebrate taxa.

Язык: Английский

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Reproductive Adaptation of Astyanax mexicanus Under Nutrient Limitation

Developmental Biology, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

Язык: Английский

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Elevated DNA Damage without signs of aging in the short-sleeping Mexican Cavefish

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Апрель 21, 2024

Dysregulation of sleep has widespread health consequences and represents an enormous burden. Short-sleeping individuals are predisposed to the effects neurodegeneration, suggesting a critical role for in maintenance neuronal health. While on cellular function not completely understood, growing evidence identified association between loss DNA damage, raising possibility that facilitates efficient repair. The Mexican tetra fish,

Язык: Английский

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Trawling aquatic life for new models in biomedical research and evolutionary developmental biology

Journal of Experimental Zoology Part B Molecular and Developmental Evolution, Год журнала: 2024, Номер 342(3), С. 123 - 125

Опубликована: Апрель 30, 2024

Язык: Английский

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Postprandial sleep in short-sleeping Mexican cavefish

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июль 5, 2024

Abstract Interaction between sleep and feeding behaviors are critical for adaptive fitness. Diverse species suppress when food is scarce to increase the time spent foraging. Post-prandial sleep, an in following a event, has been documented vertebrate invertebrate animals. While interactions appear be highly conserved, evolution of postprandial response changes availability remains poorly understood. Multiple populations Mexican cavefish, Astyanax mexicanus, have independently evolved loss increased consumption compared surface-dwelling fish same species, providing opportunity investigate feeding. Here, we effects on larval adult surface fish, two parallelly cave A. mexicanus. Larval mexicanus immediately meal, first evidence model. The amount was not correlated meal size occurred time. In contrast larvae, detected or that can survive months without food. Together, these findings reveal present multiple short-sleeping suggesting sleep-feeding retained despite loss. These raise possibility energy conservation survival larvae sensitive deprivation.

Язык: Английский

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eLife assessment: Elevated DNA Damage without signs of aging in the short-sleeping Mexican Cavefish

Опубликована: Июль 26, 2024

Dysregulation of sleep has widespread health consequences and represents an enormous burden. Short-sleeping individuals are predisposed to the effects neurodegeneration, suggesting a critical role for in maintenance neuronal health. While on cellular function not completely understood, growing evidence identified association between loss DNA damage, raising possibility that facilitates efficient repair. The Mexican tetra fish, Astyanax mexicanus provides model investigate evolutionary basis changes loss. Multiple cave-adapted populations these fish have evolved substantially less time compared surface same species without identifiable impacts healthspan or longevity. To whether is associated with damage stress, we Damage Response (DDR) oxidative stress levels A. populations. We measured markers chronic discovered elevated marker γH2AX brain, increased gut cavefish, consistent deprivation. Notably, found acute UV-induced elicited increase but cavefish. On transcriptional level, only activated photoreactivation repair pathway following UV damage. These findings suggest reduction DDR cavefish coincides examine pathways at created embryonic fibroblast cell line from two mexicanus. observed both were diminished cells, corroborating vivo response lost long-term impact changes, transcriptome brain aged Strikingly, many genes differentially expressed young old do transcriptionally vary by age Taken together, developed resilience loss, despite possessing hallmarks

Язык: Английский

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Elevated DNA Damage without signs of aging in the short-sleeping Mexican Cavefish

Опубликована: Июль 26, 2024

Dysregulation of sleep has widespread health consequences and represents an enormous burden. Short-sleeping individuals are predisposed to the effects neurodegeneration, suggesting a critical role for in maintenance neuronal health. While on cellular function not completely understood, growing evidence identified association between loss DNA damage, raising possibility that facilitates efficient repair. The Mexican tetra fish, Astyanax mexicanus provides model investigate evolutionary basis changes loss. Multiple cave-adapted populations these fish have evolved substantially less time compared surface same species without identifiable impacts healthspan or longevity. To whether is associated with damage stress, we Damage Response (DDR) oxidative stress levels A. populations. We measured markers chronic discovered elevated marker γH2AX brain, increased gut cavefish, consistent deprivation. Notably, found acute UV-induced elicited increase but cavefish. On transcriptional level, only activated photoreactivation repair pathway following UV damage. These findings suggest reduction DDR cavefish coincides examine pathways at created embryonic fibroblast cell line from two . observed both were diminished cells, corroborating vivo response lost long-term impact changes, transcriptome brain aged Strikingly, many genes differentially expressed young old do transcriptionally vary by age Taken together, developed resilience loss, despite possessing hallmarks

Язык: Английский

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