Browsing by Subject "Energy Metabolism"
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Item Open Access Body Mass and Tail Girth Predict Hibernation Expression in Captive Dwarf Lemurs.(Physiological and biochemical zoology : PBZ, 2022-03) Blanco, Marina B; Greene, Lydia K; Klopfer, Peter H; Lynch, Danielle; Browning, Jenna; Ehmke, Erin E; Yoder, Anne DAbstractHibernation, a metabolic strategy, allows individuals to reduce energetic demands in times of energetic deficits. Hibernation is pervasive in nature, occurring in all major mammalian lineages and geographical regions; however, its expression is variable across species, populations, and individuals, suggesting that trade-offs are at play. Whereas hibernation reduces energy expenditure, energetically expensive arousals may impose physiological burdens. The torpor optimization hypothesis posits that hibernation should be expressed according to energy availability. The greater the energy surplus, the lower the hibernation output. The thrifty female hypothesis, a variation of the torpor optimization hypothesis, states that females should conserve more energy because of their more substantial reproductive costs. Contrarily, if hibernation's benefits offset its costs, hibernation may be maximized rather than optimized (e.g., hibernators with greater fat reserves could afford to hibernate longer). We assessed torpor expression in captive dwarf lemurs, primates that are obligate, seasonal, and tropical hibernators. Across 4.5 mo in winter, we subjected eight individuals at the Duke Lemur Center to conditions conducive to hibernation, recorded estimates of skin temperature hourly (a proxy for torpor), and determined body mass and tail fat reserves bimonthly. Across and between consecutive weigh-ins, heavier dwarf lemurs spent less time in torpor and lost more body mass. At equivalent body mass, females spent more time torpid and better conserved energy than did males. Although preliminary, our results support the torpor optimization and thrifty female hypotheses, suggesting that individuals optimize rather than maximize torpor according to body mass. These patterns are consistent with hibernation phenology in Madagascar, where dwarf lemurs hibernate longer in more seasonal habitats.Item Open Access Constraint and trade-offs regulate energy expenditure during childhood.(Science advances, 2019-12-18) Urlacher, Samuel S; Snodgrass, J Josh; Dugas, Lara R; Sugiyama, Lawrence S; Liebert, Melissa A; Joyce, Cara J; Pontzer, HermanChildren's metabolic energy expenditure is central to evolutionary and epidemiological frameworks for understanding variation in human phenotype and health. Nonetheless, the impact of a physically active lifestyle and heavy burden of infectious disease on child metabolism remains unclear. Using energetic, activity, and biomarker measures, we show that Shuar forager-horticulturalist children of Amazonian Ecuador are ~25% more physically active and, in association with immune activity, have ~20% greater resting energy expenditure than children from industrial populations. Despite these differences, Shuar children's total daily energy expenditure, measured using doubly labeled water, is indistinguishable from industrialized counterparts. Trade-offs in energy allocation between competing physiological tasks, within a constrained energy budget, appear to shape childhood phenotypic variation (e.g., patterns of growth). These trade-offs may contribute to the lifetime obesity and metabolic health disparities that emerge during rapid economic development.Item Open Access Disruption of STIM1-mediated Ca2+ sensing and energy metabolism in adult skeletal muscle compromises exercise tolerance, proteostasis, and lean mass.(Molecular metabolism, 2022-03) Wilson, Rebecca J; Lyons, Scott P; Koves, Timothy R; Bryson, Victoria G; Zhang, Hengtao; Li, TianYu; Crown, Scott B; Ding, Jin-Dong; Grimsrud, Paul A; Rosenberg, Paul B; Muoio, Deborah MObjective
Stromal interaction molecule 1 (STIM1) is a single-pass transmembrane endoplasmic/sarcoplasmic reticulum (E/SR) protein recognized for its role in a store operated Ca2+ entry (SOCE), an ancient and ubiquitous signaling pathway. Whereas STIM1 is known to be indispensable during development, its biological and metabolic functions in mature muscles remain unclear.Methods
Conditional and tamoxifen inducible muscle STIM1 knock-out mouse models were coupled with multi-omics tools and comprehensive physiology to understand the role of STIM1 in regulating SOCE, mitochondrial quality and bioenergetics, and whole-body energy homeostasis.Results
This study shows that STIM1 is abundant in adult skeletal muscle, upregulated by exercise, and is present at SR-mitochondria interfaces. Inducible tissue-specific deletion of STIM1 (iSTIM1 KO) in adult muscle led to diminished lean mass, reduced exercise capacity, and perturbed fuel selection in the settings of energetic stress, without affecting whole-body glucose tolerance. Proteomics and phospho-proteomics analyses of iSTIM1 KO muscles revealed molecular signatures of low-grade E/SR stress and broad activation of processes and signaling networks involved in proteostasis.Conclusion
These results show that STIM1 regulates cellular and mitochondrial Ca2+ dynamics, energy metabolism and proteostasis in adult skeletal muscles. Furthermore, these findings provide insight into the pathophysiology of muscle diseases linked to disturbances in STIM1-dependent Ca2+ handling.Item Open Access Energy recovery in individuals with knee osteoarthritis.(Osteoarthritis Cartilage, 2014-06) Sparling, TL; Schmitt, D; Miller, CE; Guilak, F; Somers, TJ; Keefe, FJ; Queen, RMOBJECTIVE: Pathological gaits have been shown to limit transfer between potential (PE) and kinetic (KE) energy during walking, which can increase locomotor costs. The purpose of this study was to examine whether energy exchange would be limited in people with knee osteoarthritis (OA). METHODS: Ground reaction forces during walking were collected from 93 subjects with symptomatic knee OA (self-selected and fast speeds) and 13 healthy controls (self-selected speed) and used to calculate their center of mass (COM) movements, PE and KE relationships, and energy recovery during a stride. Correlations and linear regressions examined the impact of energy fluctuation phase and amplitude, walking velocity, body mass, self-reported pain, and radiographic severity on recovery. Paired t-tests were run to compare energy recovery between cohorts. RESULTS: Symptomatic knee OA subjects displayed lower energetic recovery during self-selected walking speeds than healthy controls (P = 0.0018). PE and KE phase relationships explained the majority (66%) of variance in recovery. Recovery had a complex relationship with velocity and its change across speeds was significantly influenced by the self-selected walking speed of each subject. Neither radiographic OA scores nor subject self-reported measures demonstrated any relationship with energy recovery. CONCLUSIONS: Knee OA reduces effective exchange of PE and KE, potentially increasing the muscular work required to control movements of the COM. Gait retraining may return subjects to more normal patterns of energy exchange and allow them to reduce fatigue.Item Open Access Fueling for Performance.(Sports health, 2018-01) Bytomski, Jeffrey RCONTEXT:Proper nutrition is crucial for an athlete to optimize his or her performance for training and competition. Athletes should be able to meet their dietary needs through eating a wide variety of whole food sources. EVIDENCE ACQUISITION:PubMed was searched for relevant articles published from 1980 to 2016. STUDY DESIGN:Clinical review. LEVEL OF EVIDENCE:Level 4. RESULTS:An athlete should have both daily and activity-specific goals for obtaining the fuel necessary for successful training. Depending on the timing of their season, athletes may be either trying to gain lean muscle mass, lose fat, or maintain their current weight. CONCLUSION:An athlete will have different macronutrient goals depending on sport, timing of exercise, and season status. There are no specific athletic micronutrient guidelines, but testing should be considered for athletes with deficiency or injury. Also, some athletes who eliminate certain whole food groups (eg, vegetarian) may need to supplement their diet to avoid deficiencies.Item Open Access Metabolic programming and PDHK1 control CD4+ T cell subsets and inflammation.(J Clin Invest, 2015-01) Gerriets, Valerie A; Kishton, Rigel J; Nichols, Amanda G; Macintyre, Andrew N; Inoue, Makoto; Ilkayeva, Olga; Winter, Peter S; Liu, Xiaojing; Priyadharshini, Bhavana; Slawinska, Marta E; Haeberli, Lea; Huck, Catherine; Turka, Laurence A; Wood, Kris C; Hale, Laura P; Smith, Paul A; Schneider, Martin A; MacIver, Nancie J; Locasale, Jason W; Newgard, Christopher B; Shinohara, Mari L; Rathmell, Jeffrey CActivation of CD4+ T cells results in rapid proliferation and differentiation into effector and regulatory subsets. CD4+ effector T cell (Teff) (Th1 and Th17) and Treg subsets are metabolically distinct, yet the specific metabolic differences that modify T cell populations are uncertain. Here, we evaluated CD4+ T cell populations in murine models and determined that inflammatory Teffs maintain high expression of glycolytic genes and rely on high glycolytic rates, while Tregs are oxidative and require mitochondrial electron transport to proliferate, differentiate, and survive. Metabolic profiling revealed that pyruvate dehydrogenase (PDH) is a key bifurcation point between T cell glycolytic and oxidative metabolism. PDH function is inhibited by PDH kinases (PDHKs). PDHK1 was expressed in Th17 cells, but not Th1 cells, and at low levels in Tregs, and inhibition or knockdown of PDHK1 selectively suppressed Th17 cells and increased Tregs. This alteration in the CD4+ T cell populations was mediated in part through ROS, as N-acetyl cysteine (NAC) treatment restored Th17 cell generation. Moreover, inhibition of PDHK1 modulated immunity and protected animals against experimental autoimmune encephalomyelitis, decreasing Th17 cells and increasing Tregs. Together, these data show that CD4+ subsets utilize and require distinct metabolic programs that can be targeted to control specific T cell populations in autoimmune and inflammatory diseases.Item Open Access Persistent hypermetabolism and longitudinal energy expenditure in critically ill patients with COVID-19.(Critical care (London, England), 2020-09-28) Whittle, John; Molinger, Jeroen; MacLeod, David; Haines, Krista; Wischmeyer, Paul E; LEEP-COVID Study GroupItem Open Access Skeletal muscle mitochondrial fragmentation and impaired bioenergetics from nutrient overload are prevented by carbon monoxide.(American journal of physiology. Cell physiology, 2020-10) Gasier, Heath G; Dohl, Jacob; Suliman, Hagir B; Piantadosi, Claude A; Yu, TianzhengNutrient excess increases skeletal muscle oxidant production and mitochondrial fragmentation that may result in impaired mitochondrial function, a hallmark of skeletal muscle insulin resistance. This led us to explore whether an endogenous gas molecule, carbon monoxide (CO), which is thought to prevent weight gain and metabolic dysfunction in mice consuming high-fat diets, alters mitochondrial morphology and respiration in C2C12 myoblasts exposed to high glucose (15.6 mM) and high fat (250 µM BSA-palmitate) (HGHF). Also, skeletal muscle mitochondrial morphology, distribution, respiration, and energy expenditure were examined in obese resistant (OR) and obese prone (OP) rats that consumed a high-fat and high-sucrose diet for 10 wk with or without intermittent low-dose inhaled CO and/or exercise training. In cells exposed to HGHF, superoxide production, mitochondrial membrane potential (ΔΨm), mitochondrial fission regulatory protein dynamin-related protein 1 (Drp1) and mitochondrial fragmentation increased, while mitochondrial respiratory capacity was reduced. CO decreased HGHF-induced superoxide production, Drp1 protein levels and mitochondrial fragmentation, maintained ΔΨm, and increased mitochondrial respiratory capacity. In comparison with lean OR rats, OP rats had smaller skeletal muscle mitochondria that contained disorganized cristae, a normal mitochondrial distribution, but reduced citrate synthase protein expression, normal respiratory responses, and a lower energy expenditure. The combination of inhaled CO and exercise produced the greatest effect on mitochondrial morphology, increasing ADP-stimulated respiration in the presence of pyruvate, and preventing a decline in resting energy expenditure. These data support a therapeutic role for CO and exercise in preserving mitochondrial morphology and respiration during metabolic overload.Item Restricted Whole body mechanics of stealthy walking in cats.(PLoS One, 2008) Bishop, Kristin L; Pai, Anita K; Schmitt, DanielThe metabolic cost associated with locomotion represents a significant part of an animal's metabolic energy budget. Therefore understanding the ways in which animals manage the energy required for locomotion by controlling muscular effort is critical to understanding limb design and the evolution of locomotor behavior. The assumption that energetic economy is the most important target of natural selection underlies many analyses of steady animal locomotion, leading to the prediction that animals will choose gaits and postures that maximize energetic efficiency. Many quadrupedal animals, particularly those that specialize in long distance steady locomotion, do in fact reduce the muscular contribution required for walking by adopting pendulum-like center of mass movements that facilitate exchange between kinetic energy (KE) and potential energy (PE). However, animals that are not specialized for long distance steady locomotion may face a more complex set of requirements, some of which may conflict with the efficient exchange of mechanical energy. For example, the "stealthy" walking style of cats may demand slow movements performed with the center of mass close to the ground. Force plate and video data show that domestic cats (Felis catus, Linnaeus, 1758) have lower mechanical energy recovery than mammals specialized for distance. A strong negative correlation was found between mechanical energy recovery and diagonality in the footfalls and there was also a negative correlation between limb compression and diagonality of footfalls such that more crouched postures tended to have greater diagonality. These data show a previously unrecognized mechanical relationship in which crouched postures are associated with changes in footfall pattern which are in turn related to reduced mechanical energy recovery. Low energy recovery was not associated with decreased vertical oscillations of the center of mass as theoretically predicted, but rather with posture and footfall pattern on the phase relationship between potential and kinetic energy. An important implication of these results is the possibility of a tradeoff between stealthy walking and economy of locomotion. This potential tradeoff highlights the complex and conflicting pressures that may govern the locomotor choices that animals make.