Serum plays an important role in reprogramming the seasonal transcriptional profile of brown bear adipocytes

Saxton, Michael W.; Perry, Blair W.; Hutzenbiler, Brandon D. Evans; Trojahn, Shawn; Gee, Alexia; Brown, Anthony P.; Merrihew, Gennifer E.; Park, Jea; Cornejo, Omar E.; MacCoss, Michael J.; Robbins, Charles T.; Jansen, Heiko T.; Kelley, Joanna L.

doi:10.1016/j.isci.2022.105084

Cited by 6 publications

(2 citation statements)

References 87 publications

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“…Although the refeeding period is not as widely studied as torpor or fasting, it is a critical period of healing and recovery with biomedical significance. Following extended torpor, hibernators must rapidly recover from immobility ( 15 , 68 , 69 ), nutrient deprivation, insulin resistance ( 16 , 70 ), accumulated wastes and toxins ( 71 ), and tauopathy ( 14 ). Moreover, synaptic connections are regenerated, and neuroprotective mechanisms defend against brain damage from reperfusion with suddenly increased blood flow that has similarities to stroke ( 11 ).…”

Section: Discussionmentioning

confidence: 99%

Genomic Convergence in Hibernating Mammals Elucidates the Genetics of Metabolic Regulation in the Hypothalamus

Ferris,

Murcia,

Rodriguez

et al. 2024

Preprint

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Elucidating the genetic basis of mammalian metabolism could help define mechanisms central to health and disease. Here, we define conservedcis-regulatory elements (CREs) and programs for mammalian metabolic control. We delineate gene expression and chromatin responses in the mouse hypothalamus for 7 steps of the Fed-to-Fasted-to-Refed (FFR) response process. Comparative genomics of hibernating versus non-hibernating lineages then illuminatescis-elements showing convergent changes in hibernators. Hibernators accumulated loss-of-function effects for specific CREs regulating hypothalamic FFR responses. Multi-omics approaches pinpoint key CREs, genes, regulatory programs, and cell types in the divergence of hibernating and homeothermic lineages. The refeeding period after extended fasting is revealed as one critical period of chromatin remodeling with convergent genomic changes. This genetic framework is a step toward harnessing hibernator adaptations in medicine.One sentence summaryConvergent signals definecis-regulatory mechanisms behind food scarcity responses and hibernator-homeotherm divergence.

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Section: Discussionmentioning

confidence: 99%

Genomic Convergence in Hibernating Mammals Elucidates the Genetics of Metabolic Regulation in the Hypothalamus

Ferris,

Murcia,

Rodriguez

et al. 2024

Preprint

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“…al. 2017; Saxton et al 2022). Existing research is primarily focused on accessible lab populations of wild animals (Oriel et al 2008; Kelm et al 2011; Riddle et al 2018; Reznick et al 2021; Guo et al 2022) or restricted within the context of metabolic disorders (Chouchani & Kajimura 2019; Bundgaard et al 2019).…”

Section: Introductionmentioning

confidence: 99%

Sugar assimilation underlying dietary evolution of Neotropical bats

Camacho¹,

Bernal-Rivera²,

Robb³

et al. 2023

Preprint

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Specializations in animal diets drive selective demands on morphology, anatomy, and physiology. Studying adaptations linked to diet evolution benefits from examining Neotropical bats, a remarkable group with high taxonomic and trophic diversity. In this study we performed glucose tolerance tests on wild-caught bats, which revealed distinct responses to three sugars present in different foods: trehalose (insects), sucrose and glucose (fruits and nectar). Insect eating bats responded most strongly to trehalose, while bats with nectar and fruit-based diets exhibited heightened response to glucose and sucrose, reaching blood sugar levels over 600 mg/dL. To reveal positive selection in sugar assimilation genes we performed genome analysis of 22 focal bat species and 2 outgroup species. We identified selection in the ancestral vespertilionid branch (insect-eaters) for the digestive enzyme Trehalase, while sucrase-isomaltase exhibited selection in branches leading to omnivorous and nectar diets. Unexpectedly, the insect-eating lineageMyotisexhibited sucrase-isomaltase selection, potentially explaining their heightened sucrose assimilation. Furthermore, the glucose transporters SLC2A3 and SLC2A2 showed selection in lineages associated with nectar and blood diets. By examining cellular features of the small intestine, we discovered that sugar consumption strongly impacted numerous digestive traits, providing valuable insight into the physiological implications of the identified molecular adaptations. To elucidate this further, we used HCR RNA-FISH to perform single molecule ex vivo gene expression analysis of enterocyte response to a glucose meal in three focal species. We observed unusually high activity in the glucose transporter geneSlc2a2during the fasted state of nectar bats that did not change upon feeding. Comparatively, nectar bats exhibited an enhanced capacity for intestinal absorption of dietary sugar primarily throughSlc2a2, while fruit bats relied on increasing levels ofSlc5a1. Overall, this study highlights the intricate interplay between molecular, morphological, and physiological aspects of diet evolution and provides new insights to our understanding of sugar assimilation mechanisms in mammals.

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Circadian gene transcription plays a role in cellular metabolism in hibernating brown bears, Ursus arctos

Vincent,

Perry,

Kelley

et al. 2023

J Comp Physiol B

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Serum plays an important role in reprogramming the seasonal transcriptional profile of brown bear adipocytes

Cited by 6 publications

References 87 publications

Genomic Convergence in Hibernating Mammals Elucidates the Genetics of Metabolic Regulation in the Hypothalamus

Genomic Convergence in Hibernating Mammals Elucidates the Genetics of Metabolic Regulation in the Hypothalamus

Sugar assimilation underlying dietary evolution of Neotropical bats

Circadian gene transcription plays a role in cellular metabolism in hibernating brown bears, Ursus arctos

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