🧵15/ Questions? Comments? Let's chat more about the weird world of naked mole-rats! 🐀🧣

🧵14/ Thanks to all co-authors/collaborators & supporting institutions! We hope our updated model sparks further discussion about how evolution shapes physiology to fit ecological niches. For more, check out the full paper: www.biorxiv.org/content/10.1... #OpenScience

🧵13/ Take-home: NMRs defy classic labels (homeotherm/poikilotherm etc.). Their thermal biology is unique—they are endotherms that can make heat, but can’t keep it without insulation. This nuance helps resolve the debate. #Zoology

🧵12/ Evolutionarily, fur loss in NMRs may be an adaptation to warm, crowded tunnels, facilitating heat exchange and avoiding parasite load—reminding us of convergent evolution with humans, who use social/behavioral insulation (clothes/shelter)! #EvoDevo

🧵11/ So, NMRs can generate heat like other mammals, but their "nakedness" is their Achilles' heel for retaining it—explaining their infamous sensitivity to cold (vs. their usual toasty, communal burrows). #NakedMoleRat #Thermoregulation

🧵10/ For context: when we shaved mice, they lost more heat & had to work harder metabolically—mirroring the NMRs’ natural state. Insulation is critical for small mammals. #ComparativePhysiology

🧵9/ Most strikingly: providing artificial insulation (like a fleece shelter) partially restored NMRs’ thermoregulation. Insulated NMRs maintained higher body temperatures, needed less food/fat to do so, and displayed more “homeothermic” curves. Fur matters! #Adaptation

🧵8/ We tested if "fuel" was limiting by supplementing lipids. This helped NMRs keep body temp higher during cold—suggesting substrate availability is important, but not the whole story. #lipolysis

🧵7/ The culprit: excessive heat loss. NMRs have hairless, highly conductive skin—heat leaks out faster than it can be generated, especially when alone and outside the warm, humid safety of their burrows or colony. #Evolution

🧵6/ When we gave NMRs a β3-adrenergic agonist (mimicking cold responses), they cranked up their metabolism and increased core temp—sometimes even more so than mice. The machinery works. So why don’t NMRs defend stable body temperatures? #Metabolism

🧵5/ We compared them to mice. First surprise: NMRs have fully functional UCP1 (the protein at the heart of mammalian brown fat thermogenesis). Both in vitro and in vivo, their UCP1 acts like the mouse version—activatable and inhibitable, fueling heat production in response to cold! 🔥

🧵4/ Key question: Do NMRs lack the molecular machinery for non-shivering thermogenesis or is something else at play? The genome of NMR shows a unique change to their Uncoupling Protein 1 (UCP1). This variant might explain parts of the strange relationship of these mammals to thermal regulation.

🧵3/ Mice, like most mammals, defend their body temperature, but naked mole-rats do not. At any temperature, mice did an excellent job of maintaining euthermia. NMR were not so hot at keeping themselves warm.
#ComparativePhysiology

🧵2/ The NMR challenges mammalian rules of body temperature maintenance. NMRs are sometimes called a poikilotherm, homeotherm, mesotherm, or heterotherm. We sought to resolve this long-standing controversy by systematically probing their heat-generation and retention abilities.

🧵1/15 Delighted to share our study on the naked mole-rat (NMR): a mammal with bizarre thermal biology, notorious longevity, and cancer resistance. But how do NMRs maintain (or fail to maintain) their body temperature? Our latest work digs deep! #ThermalBiology #Thermogenesis

@bankslab.bsky.social just presented an amazing talk at an IMPC workshop, outlining the long-overdue standardization of metabolic & activity data. At long last, the end of the poisoning of data by poor measurement techniques, equipment & analyses is in sight. Congratulations, Alex & colleagues! 🧪

🧪#metabosky #calorimetry
The world of indirect calorimetry just got better. Our team is nearly ready to launch a new version of CalR. A beta version of CalR2 is available at CalRapp.org. New features include improved visualizations, quality control analysis, statistical power calcs and more. ✔️it out

In-person today at 3pm: First ever joint BIDMC and Joslin Diabetes Center event for #WorldDiabetesDay2023

Me too!