Alex Banks

A consensus guide to preclinical indirect calorimetry experiments - Nature Metabolism The authors highlight inconsistencies and divergencies in the literature reporting data on indirect calorimetry for studies on whole-body energy homeostasis, and propose harmonization of standards to facilitate data comparison and interpretation across different datasets.

REVIEW | A consensus guide to preclinical indirect calorimetry experiments 🧪

@bankslab.bsky.social et al

Researchers establish consensus standards for indirect calorimetry experiments

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

Comparative analysis of naked mole-rat thermogenesis and its potential to maintain euthermia in response to cold The naked mole-rat (NMR) is a subterranean rodent known for its unique thermal biology, exceptional longevity and resistance to cancer and hypoxia. However, its thermal biology remains controversial, ...

🧵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

Thermal image of a NMR in a folded-over fleece bed. The nose and teeth appear cold (green), the face and head are hot (red), and heat appears to be trapped inside of the bed and radiating only a cool blue/green aura.

🧵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

Thermogenesis required fuel to burn. Supplementing NMR with additional fuel allows them to maintain a higher body temperature. Shown are line plots of NMR in the cold with and without supplemental olive oil.

🧵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

Left: Bar plots of the body temperature and energy expenditure of mice and NMR before and after beta-adrenergic receptor activation. Right: Thermal image of mice and NMR before and after activation of the beta-adrenergic receptor system to produce heat from brown fat. The color scale is a gradient from purple (cold) through green (warm) and red (hot). Unstimulated mice show a blue/green mild heat signature. After receptor activation mice turn warm (dark green). Unstimulated NMR go from a pale yellow to a red hot color.

🧵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

Comparison of the Oxygen Consumption Rate (OCR) from cells expressing either the mouse or NMR uncoupling protein 1. Similar levels of activation are seen with the proteins from the two species in vitro.

🧵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

Top: Graph depicting the effect of different ambient housing temperatures (6-30 degrees C) on the core body temperature of mice. Mice maintain a normal euthermic body temperature within a few degrees of 37C at all temperatures tested. Bottom: ambient housing temperatures of naked mole-rats from 16-37 degrees C shows that body temperature hovers just a few degrees above ambient temperature.

🧵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.

Picture of a naked mole-rat in a fleece bed

🧵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! 🧪

The plot shows four time series plots. On top is a visualization from the original CalR, with one data point every 60 minutes. Next down is a plot with data every 3 minutes. Next data every 3 minutes but with a rolling mean smoothing fuction. These data look much cleaner. Finally data smoothed every 60 minutes.

🧪#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!