scholarly journals Cytoprotection by a naturally occurring variant of ATP5G1 in Arctic ground squirrels

2020 ◽  
Author(s):  
Neel S. Singhal ◽  
Meirong Bai ◽  
Evan M. Lee ◽  
Shuo Luo ◽  
Kayleigh R. Cook ◽  
...  
Keyword(s):  
Anaerobic Bacteria ◽  
Ectopic Expression ◽  
Metabolic Stress ◽  
Ground Squirrels ◽  
The Arctic ◽  
Cellular Mechanisms ◽  
Base Editing ◽  
Naturally Occurring ◽  
Mitochondrial Atp Synthase ◽  
Arctic Ground Squirrels

AbstractMany organisms, from anaerobic bacteria to hibernating ground squirrels, have evolved mechanisms to tolerate severe hypoxia or ischemia. In particular, the arctic ground squirrel (AGS) has been shown to be highly resilient to ischemic and reperfusion injuries, demonstrating an ability to withstand metabolic stress under hibernation conditions. Although physiological adaptations are critical to ischemic tolerance in AGS, little is known about cellular mechanisms underlying intrinsic AGS cell tolerance to metabolic stressors. Through cell survival-based cDNA expression screens and comparative genomics, we have discovered that in AGS, a cytoprotective variant of ATP5G1 helps confer improved mitochondrial metabolism and cell resilience to metabolic stress. ATP5G1 encodes a proton-transporting subunit of the mitochondrial ATP synthase complex. Ectopic expression in mouse cells and CRISPR/Cas9 base editing of the endogenous AGS locus revealed causal roles of one AGS-specific amino acid substitution (leucine-32) in mediating the cytoprotective effects of AGS ATP5G1. We provide evidence that AGS ATP5G1 promotes cell resilience to stress by modulating mitochondrial morphological change and metabolic functions. Thus, our results identify a naturally occurring variant of ATP5G1 from a mammalian hibernator that causally contributes to intrinsic cytoprotection against metabolic stresses.

scholarly journals Cytoprotection by a naturally occurring variant of ATP5G1 in Arctic ground squirrel neural progenitor cells

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Neel S Singhal ◽  
Meirong Bai ◽  
Evan M Lee ◽  
Shuo Luo ◽  
Kayleigh R Cook ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Ground Squirrel ◽  
Neural Progenitor Cells ◽  
Ectopic Expression ◽  
Metabolic Stress ◽  
Neural Progenitor ◽  
Arctic Ground Squirrel ◽  
Cellular Mechanisms ◽  
Naturally Occurring ◽  
Mitochondrial Atp Synthase

Many organisms in nature have evolved mechanisms to tolerate severe hypoxia or ischemia, including the hibernation-capable Arctic ground squirrel (AGS). Although hypoxic or ischemia tolerance in AGS involves physiological adaptations, little is known about the critical cellular mechanisms underlying intrinsic AGS cell resilience to metabolic stress. Through cell survival-based cDNA expression screens in neural progenitor cells, we identify a genetic variant of AGS Atp5g1 that confers cell resilience to metabolic stress. Atp5g1 encodes a subunit of the mitochondrial ATP synthase. Ectopic expression in mouse cells and CRISPR/Cas9 base editing of endogenous AGS loci revealed causal roles of one AGS-specific amino acid substitution in mediating cytoprotection by AGS ATP5G1. AGS ATP5G1 promotes metabolic stress resilience by modulating mitochondrial morphological change and metabolic functions. Our results identify a naturally occurring variant of ATP5G1 from a mammalian hibernator that critically contributes to intrinsic cytoprotection against metabolic stress.

scholarly journals Ascorbate dynamics and oxygen consumption during arousal from hibernation in Arctic ground squirrels

2001 ◽  
Vol 281 (2) ◽  
pp. R572-R583 ◽  
Author(s):  
Ø. Tøien ◽  
K. L. Drew ◽  
M. L. Chao ◽  
M. E. Rice
Keyword(s):  
Peak Plasma ◽  
Plasma Concentrations ◽  
Metabolic Stress ◽  
Ground Squirrels ◽  
Electromyographic Activity ◽  
Spermophilus Parryii ◽  
Plasma Ascorbate ◽  
Leukocyte Counts ◽  
Plasma Urate ◽  
Arctic Ground Squirrels

During hibernation in Arctic ground squirrels ( Spermophilus parryii), O2 consumption and plasma leukocyte counts decrease by >90%, whereas plasma concentrations of the antioxidant ascorbate increase fourfold. During rewarming, O2 consumption increases profoundly and plasma ascorbate and leukocyte counts return to normal. Here we investigated the dynamic interrelationships among these changes. Plasma ascorbate and uric acid (urate) concentrations were determined by HPLC from blood samples collected at ∼15-min intervals via arterial catheter; leukocyte count and hematocrit were also determined. Body temperature, O2 consumption, and electromyographic activity were recorded continuously. Ascorbate, urate, and glutathione contents in body and brain samples were determined during hibernation and after arousal. During rewarming, the maximum rate of plasma ascorbate decrease occurred at the time of peak O2 consumption and peak plasma urate production. The ascorbate decrease did not correlate with mouth or abdominal temperature; uptake into leukocytes could account for only a small percentage. By contrast, liver and spleen ascorbate levels increased significantly after arousal, which could more than account for ascorbate clearance from plasma. Brain ascorbate levels remained constant. These data suggest that elevated concentrations of ascorbate {[Asc]} in plasma {[Asc]p} provide an antioxidant source that is redistributed to tissues during the metabolic stress that accompanies arousal.

Gluconeogenesis in arctic ground squirrels between periods of hibernation

1975 ◽  
Vol 228 (1) ◽  
pp. 325-330 ◽  
Author(s):  
W Galster ◽  
PR Morrison
Keyword(s):  
Energy Source ◽  
Fatty Acid ◽  
Protein Metabolism ◽  
Ground Squirrel ◽  
Ammonia Nitrogen ◽  
Ground Squirrels ◽  
The Arctic ◽  
Major Energy Source ◽  
Arctic Ground Squirrels ◽  
Gluconeogenic Substrate

The hibernation season in the arctic ground squirrel (Citellus undulatus) is broken into 8- to 18- day cycles by short homeothermal periods during which the carboydrate reserves depleted during hibernation are replenished. This study follows a number of metabolities in tissues and body fluids to assess the sources for reconstitution of the glucose reserves: lactate, urea, ammonia, free fatty acid, glycerol, triglyceride, and glucose in plasma; glycogen in liver and muscle; and urea and ammonia nitrogen in urine. Fat is the major energy source during both homeothermal and heterothermal periods, the contribution from glucose being limited to glycolysis. Reconstitution of glycogen is accomplished prior to reentry through maximal use of substrates from all sources including glycolysis, fat, and protein metabolism. Of the new gluconeogenic substrate, one-fourth is supplied from protein and three-fourths from fat.

scholarly journals Daily body temperature rhythms persist under the midnight sun but are absent during hibernation in free-living arctic ground squirrels

2011 ◽  
Vol 8 (1) ◽  
pp. 31-34 ◽  
Author(s):  
Cory T. Williams ◽  
Brian M. Barnes ◽  
C. Loren Buck
Keyword(s):  
Body Temperature ◽  
Circadian Rhythms ◽  
Ground Squirrels ◽  
The Arctic ◽  
Constant Light ◽  
Polar Regions ◽  
Free Living ◽  
Active Season ◽  
Temperature Rhythms ◽  
Arctic Ground Squirrels

In indigenous arctic reindeer and ptarmigan, circadian rhythms are not expressed during the constant light of summer or constant dark of winter, and it has been hypothesized that a seasonal absence of circadian rhythms is common to all vertebrate residents of polar regions. Here, we show that, while free-living arctic ground squirrels do not express circadian rhythms during the heterothermic and pre-emergent euthermic intervals of hibernation, they display entrained daily rhythms of body temperature ( T b ) throughout their active season, which includes six weeks of constant sun. In winter, ground squirrels are arrhythmic and regulate core body temperatures to within ±0.2°C for up to 18 days during steady-state torpor. In spring, after the use of torpor ends, male but not female ground squirrels, resume euthermic levels of T b in their dark burrows but remain arrhythmic for up to 27 days. However, once activity on the surface begins, both sexes exhibit robust 24 h cycles of body temperature. We suggest that persistence of nycthemeral rhythms through the polar summer enables ground squirrels to minimize thermoregulatory costs. However, the environmental cues (zeitgebers) used to entrain rhythms during the constant light of the arctic summer in these semi-fossorial rodents are unknown.

scholarly journals Hibernation strategies and patterns in sympatric arctic species, the Alaska marmot and the arctic ground squirrel

2015 ◽  
Vol 97 (1) ◽  
pp. 135-144 ◽  
Author(s):  
Trixie N. Lee ◽  
Franziska Kohl ◽  
C. Loren Buck ◽  
Brian M. Barnes
Keyword(s):  
Ground Squirrel ◽  
Core Body Temperature ◽  
Ground Squirrels ◽  
The Arctic ◽  
Arctic Ground Squirrel ◽  
Slow Cooling ◽  
Ambient Temperatures ◽  
The Difference ◽  
Arctic Ground Squirrels ◽  
Core Body

Abstract We compared patterns of core body temperature ( Tb ) change, including inter-individual synchrony, in 2 free-living arctic hibernators that differ in size and sociality, the Alaska marmot ( Marmota broweri ) and the arctic ground squirrel ( Urocitellus parryii ). We report overwinter Tb changes from 3 to 4 marmots from the same hibernaculum in each of 3 years and from 7 ground squirrels that hibernated at 2 nearby burrow sites in 1 year. Very close synchrony in the timing of torpor and arousal cycles in Alaska marmots indicates social hibernation and thermoregulation, while lack of synchrony in arctic ground squirrels further confirms solitary hibernation. The mean duration between the first and last marmot measured within the group to initiate an arousal was 3.7±2.5h and to recool to 30°C during torpor entrance was 5.7±3.7h. The minimum Tb recorded in marmots was 0.6°C and in ground squirrels was −2.0°C. Marmots entering torpor displayed an interrupted pattern of Tb change defined by 2 distinct rates of cooling, early and late during entry, that differed by 21-fold. Ground squirrels cooled in a continuous pattern, initially 3-fold slower than marmots during rapid cooling but 4-fold faster during slow cooling. Both species must minimize energy expenditure to survive long arctic winters; our results suggest that Alaska marmots do this through social thermoregulation, while arctic ground squirrels decrease Tb below freezing to minimize the difference between body and ambient temperatures.

Seasonal changes in body composition of the arctic ground squirrel, Citellus undulatus

1976 ◽  
Vol 54 (1) ◽  
pp. 74-78 ◽  
Author(s):  
William Galster ◽  
Peter Morrison
Keyword(s):  
Seasonal Changes ◽  
Ground Squirrel ◽  
Significant Loss ◽  
Ground Squirrels ◽  
The Arctic ◽  
Average Weight ◽  
Active Season ◽  
Loss Of Weight ◽  
Glucose Synthesis ◽  
Arctic Ground Squirrels

The depletion or accumulation of body reserves is followed in terms of the weight and proportion of lipid, protein, water, and minerals in arctic ground squirrels during the entry, deep, and emergent phases of the hibernation season and after the reproductive phase of the active season. Average weight increased slowly through the summer, from a minimum of 346 g, until mid-August when 190 g accumulated in 3 weeks to be used subsequently during the 220-day hibernation season beginning in mid-September. During hibernation, the 325-g loss in weight represents 62% lipid, 26% water, 9% protein, and 2% mineral. Fat in lipid provides most of the energy but insufficient amounts of carbon for glucose synthesis during hibernation. However, protein provides an adequate gluconeogenic reserve. Significant loss of mineral indicates that skeletal reserves of calcium are important during hibernation. After hibernation, continued loss of weight by females indicates further utilization of reserves during gestation and nursing.

scholarly journals Effects of Season and Host Physiological State on the Diversity, Density, and Activity of the Arctic Ground Squirrel Cecal Microbiota

2014 ◽  
Vol 80 (18) ◽  
pp. 5611-5622 ◽  
Author(s):  
Timothy J. Stevenson ◽  
Khrystyne N. Duddleston ◽  
C. Loren Buck
Keyword(s):  
Seasonal Changes ◽  
Ground Squirrel ◽  
Short Chain Fatty Acid ◽  
Chain Fatty Acid ◽  
Ground Squirrels ◽  
Short Chain ◽  
The Arctic ◽  
Content Type ◽  
Cecal Microbiota ◽  
Arctic Ground Squirrels

ABSTRACTWe examined the seasonal changes of the cecal microbiota of captive arctic ground squirrels (Urocitellus parryii) by measuring microbial diversity and composition, total bacterial density and viability, and short-chain fatty acid concentrations at four sample periods (summer, torpor, interbout arousal, and posthibernation). Abundance ofFirmicuteswas lower, whereas abundances ofBacteroidetes,Verrucomicrobia, andProteobacteriawere higher during torpor and interbout arousal than in summer. Bacterial densities and percentages of live bacteria were significantly higher in summer than during torpor and interbout arousal. Likewise, total short-chain fatty acid concentrations were significantly greater during summer than during torpor and interbout arousal. Concentrations of individual short-chain fatty acids varied across sample periods, with butyrate concentrations higher and acetate concentrations lower during summer than at all other sample periods. Characteristics of the gut community posthibernation were more similar to those during torpor and interbout arousal than to those during summer. However, higher abundances of the generaBacteroidesandAkkermansiaoccurred during posthibernation than during interbout arousal and torpor. Collectively, our results clearly demonstrate that seasonal changes in physiology associated with hibernation and activity affect the gut microbial community in the arctic ground squirrel. Importantly, similarities between the gut microbiota of arctic ground squirrels and thirteen-lined ground squirrels suggest the potential for a core microbiota during hibernation.

Patterns of hibernation in the arctic ground squirrel

1975 ◽  
Vol 53 (9) ◽  
pp. 1345-1355 ◽  
Author(s):  
Peter Morrison ◽  
William Galster
Keyword(s):  
Annual Cycle ◽  
Ground Squirrel ◽  
Ground Squirrels ◽  
The Arctic ◽  
Light Cycle ◽  
Arctic Ground Squirrel ◽  
Active Season ◽  
Cyclic Patterns ◽  
Arctic Ground Squirrels ◽  
Normal Light

Cyclic patterns were defined in subspecies of arctic ground squirrels (Citellus undulatus) from the Brooks and Alaskan Ranges. In the annual cycle a heterothermal (hibernation) season with entry, maintenance, and emergence stages was distinguished from a homeothermal (active) season with reproductive, recovery/growth, maintenance, and fattening stages. The heterothermal season consisted of a series of short hibernation cycles in which heterothermal (hibernation) periods with reentry, refractory, and irritable phases were distinguished from homeothermal (active) periods with arousal, maintenance, and preparation phases. Squirrels in which exposure to darkness at 5 °C was delayed (Nov. vs. Sept.) showed a lesser response but emerged synchronously with the normal group. Entry was attenuated with a normal light cycle at 5 °C (8 vs. 3 weeks). Juveniles showed a 2- to 4-week delay in entry as compared to adults.

Flavonoids in adipose tissue inflammation and atherosclerosis: one arrow, two targets

2020 ◽  
Vol 134 (12) ◽  
pp. 1403-1432 ◽  
Author(s):  
Manal Muin Fardoun ◽  
Dina Maaliki ◽  
Nabil Halabi ◽  
Rabah Iratni ◽  
Alessandra Bitto ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fruits And Vegetables ◽  
Metabolic Diseases ◽  
Therapeutic Agents ◽  
Adipose Tissue Inflammation ◽  
Cellular Mechanisms ◽  
Tissue Inflammation ◽  
Cholesterol Levels ◽  
Naturally Occurring ◽  
Pro Inflammatory Cytokines

Abstract Flavonoids are polyphenolic compounds naturally occurring in fruits and vegetables, in addition to beverages such as tea and coffee. Flavonoids are emerging as potent therapeutic agents for cardiovascular as well as metabolic diseases. Several studies corroborated an inverse relationship between flavonoid consumption and cardiovascular disease (CVD) or adipose tissue inflammation (ATI). Flavonoids exert their anti-atherogenic effects by increasing nitric oxide (NO), reducing reactive oxygen species (ROS), and decreasing pro-inflammatory cytokines. In addition, flavonoids alleviate ATI by decreasing triglyceride and cholesterol levels, as well as by attenuating inflammatory mediators. Furthermore, flavonoids inhibit synthesis of fatty acids and promote their oxidation. In this review, we discuss the effect of the main classes of flavonoids, namely flavones, flavonols, flavanols, flavanones, anthocyanins, and isoflavones, on atherosclerosis and ATI. In addition, we dissect the underlying molecular and cellular mechanisms of action for these flavonoids. We conclude by supporting the potential benefit for flavonoids in the management or treatment of CVD; yet, we call for more robust clinical studies for safety and pharmacokinetic values.

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