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

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

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

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

Unraveling stress resilience: Insights from adaptations to extreme environments by Astyanax mexicanus cavefish.

Extreme environmental conditions have profound impacts on shaping the evolutionary trajectory of organisms. Exposure to these conditions elicits stress responses, that can trigger phenotypic changes in novel directions. The Mexican Tetra, Astyanax mexicanus, is an excellent model for understanding evolutionary mechanisms in response to extreme or new environments. This fish species consists of two morphs; the classical surface-dwelling fish and the blind cave-dwellers that inhabit dark and biodiversity-reduced ecosystems. In this review, we explore the specific stressors present in cave environments and examine the diverse adaptive strategies employed by cave populations to not only survive but thrive as successful colonizers. By analyzing the evolutionary responses of A. mexicanus, we gain valuable insights into the genetic, physiological, and behavioral adaptations that enable organisms to flourish under challenging environmental conditions.

Maintaining robust size across environmental conditions through plastic brain growth dynamics.

Organ growth is tightly regulated across environmental conditions to generate an appropriate final size. While the size of some organs is free to vary, others need to maintain constant size to function properly. This poses a unique problem: how is robust final size achieved when environmental conditions alter key processes that regulate organ size throughout the body, such as growth rate and growth duration? While we know that brain growth is 'spared' from the effects of the environment from humans to fruit flies, we do not understand how this process alters growth dynamics across brain compartments. Here, we explore how this robustness in brain size is achieved by examining differences in growth patterns between the larval body, the brain and a brain compartment-the mushroom bodies-in Drosophila melanogaster across both thermal and nutritional conditions. We identify key differences in patterns of growth between the whole brain and mushroom bodies that are likely to underlie robustness of final organ shape. Further, we show that these differences produce distinct brain shapes across environments.

Disruption of mitochondrial dynamics affects behaviour and lifespan in Caenorhabditis elegans.

Mitochondria are essential components of eukaryotic cells, carrying out critical physiological processes that include energy production and calcium buffering. Consequently, mitochondrial dysfunction is associated with a range of human diseases. Fundamental to their function is the ability to transition through fission and fusion states, which is regulated by several GTPases. Here, we have developed new methods for the non-subjective quantification of mitochondrial morphology in muscle and neuronal cells of Caenorhabditis elegans. Using these techniques, we uncover surprising tissue-specific differences in mitochondrial morphology when fusion or fission proteins are absent. From ultrastructural analysis, we reveal a novel role for the fusion protein FZO-1/mitofusin 2 in regulating the structure of the inner mitochondrial membrane. Moreover, we have determined the influence of the individual mitochondrial fission (DRP-1/DRP1) and fusion (FZO-1/mitofusin 1,2; EAT-3/OPA1) proteins on animal behaviour and lifespan. We show that loss of these mitochondrial fusion or fission regulators induced age-dependent and progressive deficits in animal movement, as well as in muscle and neuronal function. Our results reveal that disruption of fusion induces more profound defects than lack of fission on animal behaviour and tissue function, and imply that while fusion is required throughout life, fission is more important later in life likely to combat ageing-associated stressors. Furthermore, our data demonstrate that mitochondrial function is not strictly dependent on morphology, with no correlation found between morphological changes and behavioural defects. Surprisingly, we find that disruption of either mitochondrial fission or fusion significantly reduces median lifespan, but maximal lifespan is unchanged, demonstrating that mitochondrial dynamics play an important role in limiting variance in longevity across isogenic populations. Overall, our study provides important new insights into the central role of mitochondrial dynamics in maintaining organismal health.

Building sustainable neuroscience capacity in Africa: the role of non-profit organisations.

While advances in neuroscience are helping to improve many aspects of human life, inequalities exist in this field between Africa and more scientifically-advanced continents. Many African countries lack the infrastructure and appropriately-trained scientists for neuroscience education and research. Addressing these challenges would require the development of innovative approaches to help improve scientific competence for neuroscience across the continent. In recent years, science-based non-profit organisations (NPOs) have been supporting the African neuroscience community to build state-of-the-art scientific capacity for sustainable education and research. Some of these contributions have included: the establishment of training courses and workshops to introduce African scientists to powerful-yet-cost-effective experimental model systems; research infrastructural support and assistance to establish research institutes. Other contributions have come in the form of the promotion of scientific networking, public engagement and advocacy for improved neuroscience funding. Here, we discuss the contributions of NPOs to the development of neuroscience in Africa.