Karen L. Sweazea

Glucose regulation in birds

Birds maintain higher plasma glucose concentrations (P(Glu)) than other vertebrates of similar body mass and, in most cases, appear to store comparatively very little glucose intracellularly as glycogen. In general, birds are insensitive to the regulation of P(Glu) by insulin. However, there appears to be no phylogenetic or dietary pattern in the avian response to exogenous insulin. Moreover, the high levels of P(Glu) do not appear to lead to significant oxidative stress as birds are longer-lived compared to mammals. Glucose is absorbed by the avian gastrointestinal tract by sodium-glucose co-transporters (SGLTs; apical side of cells) and glucose transport proteins (GLUTs; basolateral side of cells). In the kidney, both types of glucose transporters appear to be upregulated as no glucose appears in the urine. Data also indicate that the avian nervous system utilizes glucose as a metabolic substrate. In this review, we have attempted to bring together information from a variety of sources to portray how glucose serves as a metabolic substrate for birds by considering each organ system involved in glucose homeostasis.

Effects of Captivity and Body Condition on Plasma Corticosterone, Locomotor Behavior, and Plasma Metabolites in Curve-Billed Thrashers

The acute stress response involves the secretion of catabolic glucocorticoids, such as corticosterone (CORT) in birds, that mobilize intrinsic energy stores primarily through a gluconeogenic pathway involving fat breakdown, thus linking body condition and stress. We measured changes in CORT and gluconeogenic metabolites (triglycerides, free glycerols, glucose) during handling stress in curve-billed thrashers Toxostoma curvirostre from two habitats (urban vs. desert) that may differ in food abundance in the wild, in captivity, and in response to both food restriction and subsequent recovery. Urban thrashers were heavier and secreted more CORT than desert birds in the field, but differences did not persist in captivity. Decreased access to food resulted in decreased body mass and a diminished ability to elevate plasma CORT in response to handling stress. However, the opposite effect was observed as these birds recovered from food restriction. Plasma levels of glucose and triglycerides did not change with stress. Food restriction also increased locomotor activity, which likely further exacerbated energy loss. These observations suggest that body condition and stress differences between urban and desert birds may be related to differences in their relative energetic states, possibly due to food availability. Body condition may affect the extent to which an individual can elevate CORT and use free glycerol as energy during acute stress.

Unpredictable food availability induces metabolic and hormonal changes independent of food intake in a sedentary songbird

SUMMARY Environments often vary with regard to their temporal resource availability, but little is understood concerning how resource predictability impacts animals. The adaptive regulation hypothesis suggests that organisms act to conserve their current energetic state during periods of diminished food access and recuperate their energetic reserves (fat and muscle) during periods of greater food availability. In contrast, the chronic stress hypothesis suggests that variation in access to food can induce a prolonged stress response, resulting in maladaptive usage of energy reserves and increased behavioral activity. To distinguish between these hypotheses we compared the behavioral, hormonal and metabolic responses of captive curve-billed thrashers, Toxostoma curvirostre, fed varying amounts each day (variable group) with those of birds fed a constant amount every day (constant feeding group). Birds of both groups consumed, on average, a similar total amount of food during the course of the study, but birds in the variable feeding group lost mass and increased their circulating initial levels of the stress hormone corticosterone, showed evidence for increased secretion of a hypothalamic stress peptide, vasotocin, used greater amounts of fat and protein energy reserves, and were more behaviorally active than birds in the constant feeding group. Overall, these findings support the chronic stress hypothesis and suggest that birds such as thrashers may be particularly susceptible to the perception of unpredictable variation in food supplies independent of actual energetic constraints.

Comparison of mechanisms involved in impaired vascular reactivity between high sucrose and high fat diets in rats

BackgroundTo determine the effects of high sucrose diets on vascular reactivity. We hypothesized that similar to high fat diets (HFD), HSD feeding would lead to increased adiposity resulting in inflammation and oxidative stress-mediated impairment of vasodilation.MethodsMale Sprague-Dawley rats were fed control chow (Chow), HSD or HFD diets for 6 weeks. The role of inflammation and oxidative stress on impaired vasodilation were assessed in isolated mesenteric arterioles.ResultsHSD and HFD induced increased adiposity, oxidative stress and inflammation. HFD rats developed fasting hyperglycemia. Both HSD and HFD rats developed impaired glucose tolerance and hyperleptinemia. Nitric oxide (NO)-mediated vasodilation was significantly attenuated in both HSD and HFD rats but was normalized by treatment with antioxidants or anti-inflammatory drugs. Endothelial NO synthase (eNOS) protein expression was not affected by diet. Sensitivity to NO was reduced since NOS inhibition attenuated vasodilation in Chow rats but did not further impair vasodilation in HSD or HFD rats. Likewise, responsiveness to a NO donor was attenuated in both experimental groups.ConclusionsOxidative stress diminishes vasodilatory responsiveness in HSD and HFD rats through ROS-mediated scavenging of NO and decreased smooth muscle sensitivity to NO. Inflammation also plays a significant role in the impaired vasodilation.

The effect of acute stress and long-term corticosteroid administration on plasma metabolites in an urban and desert songbird.

In response to stressful stimuli, animals activate the hypothalamic-pituitary-adrenal axis, which can result in transition to the “emergency life history stage.” A key adaptive characteristic of this life history stage is the mobilization of energy stores. However, few data are available on the metabolic response to acute stress in wild-caught, free-ranging birds. We quantified the effect of acute capture and restraint stress on plasma glucose, free fatty acid, and uric acid in free-ranging Abert’s towhees Melozone aberti. Furthermore, birds were caught from urban and desert localities of Phoenix, Arizona, to investigate potential effects of urban versus desert habitats on the corticosterone (CORT) and metabolic response to acute stress. Complementing work on free-ranging birds, captive towhees received CORT-filled Silastic capsules to investigate the response of urban and desert conspecifics to long-term CORT administration. We quantified the effect of CORT administration on baseline plasma glucose and uric acid, liver and pectoralis muscle glycogen stores, kidney phosphoenolpyruvate carboxykinase (PEPCK-C, a key gluconeogenic enzyme), and body mass. Acute stress increased plasma CORT and glucose and decreased plasma uric acid but had no effect on plasma free fatty acid. There was no difference between urban and desert localities in body mass, fat scores, and the response to acute stress. CORT administration decreased body mass but had no effect on glucose and uric acid, pectoral muscle glycogen, or kidney PEPCK-C. However, liver glycogen of CORT-treated urban birds increased compared with corresponding controls, whereas glycogen decreased in CORT-treated desert birds. This study suggests that Abert’s towhees principally mobilize glucose during acute stress but urban and desert towhees do not differ in their CORT and metabolic response to acute stress or long-term CORT administration.

Effects of carotenoid and vitamin E supplementation on oxidative stress and plumage coloration in house finches (Haemorhous mexicanus)

There has been much recent interest from both applied and basic scientists in the broad series of benefits that animals reap from acquiring high concentrations of dietary antioxidants, such as carotenoids and vitamins (e.g., vitamin E, or tocopherol). Most attention has been paid to separate effects of these compounds on, for example, coloration, health state, development, and vision, but because of possible interactions between these lipid-soluble molecules, we are in need of more studies that co-manipulate these substances and examine their possible synergistic impacts on animal physiology and phenotype. We capitalized on a model avian system (the house finch, Haemorhous mexicanus), where extensive information is available on the fitness roles of carotenoids, to test how variation in carotenoid and/or vitamin E concentrations in the diet impacts body accumulation of these compounds, factors related to oxidative damage (e.g., breast muscle and plasma oxidative-stress susceptibility, plasma nitric-oxide levels), and plumage color development. As in a previous study of ours on carotenoids and health in finches, we employed a 2×2 factorial experimental design on birds in both molting and non-molting conditions, to understand how seasonal shifts in carotenoid use (i.e., pigment incorporation into plumage) might alter the accumulation and roles of carotenoids and vitamins. As expected, lutein supplementation increased the level of circulating carotenoids in both experiments and the color of newly molted plumage. By contrast, vitamin E provisioning did not significantly affect plasma carotenoid levels or plumage coloration in either experiment. Interestingly, carotenoid provisioning decreased circulating vitamin E levels during molt, which suggests either molecular competition between carotenoids and tocopherol at the absorption/transport stages or that vitamin E serves as an antioxidant to offset harmful actions that carotenoids may have at very high concentrations. Finally, in both experiments, we found a reduction in breast-muscle oxidative damage for tocopherol-supplemented birds, which constitutes the first demonstration of a protective effect of vitamin E against oxidative stress in wild birds. Taken together, these findings provide an interesting contrast with our earlier work on season-specific physiological benefits of carotenoids in finches and point to complex associations between indicators of antioxidant and oxidative state in wild-caught animals.

Effects of High-intensity Interval Training and Moderate-intensity Continuous Training on Endothelial Function and Cardiometabolic Risk Markers in Obese Adults

We hypothesized that high-intensity interval training (HIIT) would be more effective than moderate-intensity continuous training (MICT) at improving endothelial function and maximum oxygen uptake (V̇o2 max) in obese adults. Eighteen participants [35.1 ± 8.1 (SD) yr; body mass index = 36.0 ± 5.0 kg/m(2)] were randomized to 8 wk (3 sessions/wk) of either HIIT [10 × 1 min, 90-95% maximum heart rate (HRmax), 1-min active recovery] or MICT (30 min, 70-75% HRmax). Brachial artery flow-mediated dilation (FMD) increased after HIIT (5.13 ± 2.80% vs. 8.98 ± 2.86%, P = 0.02) but not after MICT (5.23 ± 2.82% vs. 3.05 ± 2.76%, P = 0.16). Resting artery diameter increased after MICT (3.68 ± 0.58 mm vs. 3.86 ± 0.58 mm, P = 0.02) but not after HIIT (4.04 ± 0.70 mm vs. 4.09 ± 0.70 mm; P = 0.63). There was a significant (P = 0.02) group × time interaction in low flow-mediated constriction (L-FMC) between MICT (0.63 ± 2.00% vs. -2.79 ± 3.20%; P = 0.03) and HIIT (-1.04 ± 4.09% vs. 1.74 ± 3.46%; P = 0.29). V̇o2 max increased (P < 0.01) similarly after HIIT (2.19 ± 0.65 l/min vs. 2.64 ± 0.88 l/min) and MICT (2.24 ± 0.48 l/min vs. 2.55 ± 0.61 l/min). Biomarkers of cardiovascular risk and endothelial function were unchanged. HIIT and MICT produced different vascular adaptations in obese adults, with HIIT improving FMD and MICT increasing resting artery diameter and enhancing L-FMC. HIIT required 27.5% less total exercise time and ∼25% less energy expenditure than MICT.

High Fat Feeding Impairs Endothelin-1 Mediated Vasoconstriction Through Increased iNOS-derived Nitric Oxide

Rats fed a high fat diet develop increased adiposity and oxidative stress leading to impaired vasodilation. The purpose of the present study was to examine the effects of high fat-induced increases in adiposity and oxidative stress on vasoconstrictor reactivity of isolated mesenteric arteries. We hypothesized that rats with more adiposity would develop oxidative stress-potentiated increases in iNOS-derived nitric oxide leading to diminished vasoconstriction. Male Sprague-Dawley rats were fed either a control (Chow) or high fat diet for 6 weeks. The roles of oxidative stress and iNOS in the impaired vasoconstrictor responses to endothelin-1 were characterized in small mesenteric arteries. Rats fed the HFD developed significantly more adiposity compared to Chow rats. Plasma levels of nitric oxide and the inflammatory factor tumor necrosis factor α were significantly higher in high fat fed rats compared to Chow rats (nitric oxide: 95.36±19.3 vs. 38.96±6.7 μM; tumor necrosis factor α: 598±111.4 vs. 292±71.8 pg/ml, respectively). Despite exhibiting elevated systolic blood pressure compared to Chow rats (153.5±2.4 vs. 137.5±2.7 mm Hg), endothelin-1 mediated vasoconstriction was impaired in isolated mesenteric arteries from high fat fed rats but was normalized by individual or combined inhibition of nitric oxide synthase, iNOS, or oxidative stress. Therefore, oxidative stress and iNOS are involved in the attenuation of endothelin-1 mediated vasoconstriction observed in isolated mesenteric arteries from high fat fed rats.

Stress hormone concentration in Rocky Mountain populations of the American pika (Ochotona princeps)

We developed and validated techniques for non-invasive measurement of physiological stress in the American pika, a climate sensitive sentinel species. Results deomnstrate baseline stress hormone levels for pikas, and establish a basis for future research to determine whether local habitat variables specifically related to climate can explain levels of stress.

Impaired myogenic tone in mesenteric arteries from overweight rats

BackgroundRats fed high fat (HFD) or high sucrose (HSD) diets develop increased adiposity as well as impaired vasodilatory responsiveness stemming from oxidative stress. Moreover, HFD rats become hypertensive compared to either control (Chow) or HSD fed rats, suggesting elevated vascular tone. We hypothesized that rats with increased adiposity and oxidative stress demonstrate augmented pressure-induced vasoconstriction (i.e. myogenic tone) that could account for the hypertensive state.MethodsMale Sprague-Dawley rats were fed Chow, HFD or HSD for 6 weeks. The effects of oxidative stress and endogenous nitric oxide on myogenic responses were examined in small mesenteric arteries by exposing the arteries to incremental intraluminal pressure steps in the presence of antioxidants or an inhibitor of nitric oxide synthase, LNNA (100 μM).ResultsContrary to the hypothesis, rats fed either HSD or HFD had significantly impaired myogenic responses despite similar vascular morphology and passive diameter responses to increasing pressures. Vascular smooth muscle (VSM) calcium levels were normal in HFD arteries suggesting that diminished calcium sensitivity was responsible for the impaired myogenic response. In contrast, VSM calcium levels were reduced in HSD arteries but were increased with pre-exposure of arteries to the antioxidants tiron (10 mM) and catalase (1200 U/mL), also resulting in enhanced myogenic tone. These findings show that oxidative stress impairs myogenic tone in arteries from HSD rats by decreasing VSM calcium. Similarly, VSM calcium responses were increased in arteries from HFD rats following treatment with tiron and catalase, but this did not result in improved myogenic tone. Nitric oxide is involved in the impaired myogenic response in HFD, but not HSD, rats since inhibition with LNNA resulted in maximal myogenic responses at lower intraluminal pressures and VSM calcium levels, further implicating reduced calcium sensitivity in the impaired response.ConclusionThe impaired myogenic responses observed in isolated arteries from HSD and HFD rats are attributed to changes in VSM calcium signaling.