Acute metformin induces hyperglycemia in healthy adult mourning doves, Zenaida macroura.

Birds have the highest blood glucose among vertebrates. Several mechanisms may explain this including the lack of a functional insulin-responsive glucose transport protein, high glucagon concentrations, and reliance on lipid oxidation resulting in the production of gluconeogenic precursors. The hypothesis was that interruption of gluconeogenesis using the diabetes medication metformin would lower glucose concentrations in wild-caught birds. We captured two cohorts of adult mourning doves, Zenaida macroura, and acclimated them to captivity for two weeks. In this crossover study, cohort 1 was administered a single dose of one of the following oral treatments each week: metformin (150 or 300 mg/kg), glycogenolysis inhibitor (2.5 mg/kg 1,4-dideoxy-1,4-imino-D-arabinitol (DAB)), or water (50 µL). Whole blood glucose was measured using a glucometer at baseline, 30, 60, and 120 min following the oral doses. In contrast to mammals and chickens, 300 mg/kg metformin did not alter blood glucose (p > 0.05) whereas 150 mg/kg metformin increased blood glucose compared to water (p = 0.043). To examine whether 150 mg/kg metformin stimulated glycogenolysis, we co-administered 150 mg/kg metformin and 2.5 mg/kg DAB, which prevented the hyperglycemic response. Cohort 2 was administered the same treatments and the early response was examined (0, 5, 10, 15 min). Low-dose metformin increased blood glucose within 5 min (p = 0.039) whereas the high dose had no effect. DAB did not prevent the early response to metformin nor did it alter blood glucose concentrations when administered alone (p = 0.887). In conclusion, metformin increases endogenous blood glucose via glycogenolysis in healthy adult male mourning doves.

Past and future: Urbanization and the avian endocrine system.

Urban environments are evolutionarily novel and differ from natural environments in many respects including food and/or water availability, predation, noise, light, air quality, pathogens, biodiversity, and temperature. The success of organisms in urban environments requires physiological plasticity and adjustments that have been described extensively, including in birds residing in geographically and climatically diverse regions. These studies have revealed a few relatively consistent differences between urban and non-urban conspecifics. For example, seasonally breeding urban birds often develop their reproductive system earlier than non-urban birds, perhaps in response to more abundant trophic resources. In most instances, however, analyses of existing data indicate no general pattern distinguishing urban and non-urban birds. It is, for instance, often hypothesized that urban environments are stressful, yet the activity of the hypothalamus-pituitary-adrenal axis does not differ consistently between urban and non-urban birds. A similar conclusion is reached by comparing blood indices of metabolism. The origin of these disparities remains poorly understood, partly because many studies are correlative rather than aiming at establishing causality, which effectively limits our ability to formulate specific hypotheses regarding the impacts of urbanization on wildlife. We suggest that future research will benefit from prioritizing mechanistic approaches to identify environmental factors that shape the phenotypic responses of organisms to urbanization and the neuroendocrine and metabolic bases of these responses. Further, it will be critical to elucidate whether factors affect these responses (a) cumulatively or synergistically; and (b) differentially as a function of age, sex, reproductive status, season, and mobility within the urban environment. Research to date has used various taxa that differ greatly not only phylogenetically, but also with regard to ecological requirements, social systems, propensity to consume anthropogenic food, and behavioral responses to human presence. Researchers may instead benefit from standardizing approaches to examine a small number of representative models with wide geographic distribution and that occupy diverse urban ecosystems.

Systematic review of the impact of genistein on diabetes-related outcomes.

Diabetes is the eighth leading cause of death in the world and the prevalence is rising in low-income countries. Cardiovascular diseases are the leading cause of death worldwide, especially for individuals with diabetes. Although medications exist to treat symptoms of diabetes, lack of availability and high costs may deter their use by individuals with low incomes as well as those in low-income nations. Therefore, this systematic review was performed to determine whether genistein, a phytoestrogen found in soy products, could provide therapeutic benefits for individuals with diabetes. We searched PubMed and SCOPUS using the terms "genistein," "diabetes," and "glucose" and identified 33 peer-reviewed articles that met our inclusion criteria. In general, preclinical studies demonstrated that genistein decreases body weight and circulating glucose and triglycerides concentrations, whereas increasing insulin levels and insulin sensitivity. Genistein also delayed the onset of type 1 and type 2 diabetes. In contrast, clinical studies utilizing genistein generally reported no significant relationship between genistein and body mass, circulating glucose, glycated hemoglobin (A1C) concentrations, or onset of type 1 diabetes. However, genistein was found to improve insulin sensitivity and serum triglyceride concentrations and delayed the onset of type 2 diabetes. In summary, preclinical and clinical studies suggest that genistein may help delay the onset of type 2 diabetes and improve several symptoms associated with the disease. Although additional research is required to confirm these findings, the results highlighted in this review provide some evidence that genistein may offer a natural approach to mitigating some of the complications associated with diabetes.

An urban diet differentially alters the gut microbiome and metabolomic profiles compared with a seed diet in mourning doves.

Urbanization influences food quality and availability for many avian species, with increased access to human refuse and food subsidies in built environments. In relation to such nutritional intakes and their presumed impact on microbes harbored in the intestinal tract and metabolic profiles of host physiological systems, our overall knowledge of the role of gut microbiome (GM) and metabolomic expression in the avian host lags far behind our understanding of mammals. Therefore, the objective of this investigation was to examine the potential differential effect of an urban modeled versus control (i.e., bird seed) diet on the GM, the metabolic profiles of plasma, liver, adipose, kidney, and muscle tissues, and circulating endotoxin and inflammatory factors in urban-caught mourning doves (Zenaida macroura). We hypothesized that the urban diet would differently impact the profiles of the GM and tissue metabolomes and increase plasma lipopolysaccharide (LPS) and proinflammatory factors compared with animals fed a seed diet. After a 4-wk-diet period, contents of the large intestine were sequenced to profile the microbiome, metabolomic analyses were performed on plasma and tissue homogenates, and circulating LPS and inflammatory markers were assessed. The composition of the GM was significantly dissimilar between diets, with greater abundance of Erysipelatoclostridiaceae, Sanguibacteraceae, Oribacterium, and Sanguibacter and decreased circulating LPS in the urban-fed birds. These differences were largely not reflected in the surveyed metabolomes and plasma inflammatory markers. This research supports the notion that the microbial composition in urban doves is impacted by diet, though may only weakly associate with host physiology.

Effect of macronutrient and micronutrient manipulation on avian blood glucose concentration: A systematic review.

Animals with natural protections against diabetes complications may provide clues to improve human health. Birds are unique in their ability to avoid hyperglycemia-associated complications (e.g., glycation and oxidative stress) despite having naturally high blood glucose (BG) concentrations. This makes them useful models to elucidate strategies to prevent and/or treat diabetes-related complications in mammals. As diet plays a key role in BG concentration and diabetes risk, this systematic review aimed to summarize the effects of macro and micronutrient manipulation on avian BG. Three databases were searched (PubMed, SCOPUS, and Web of Science) for articles that met inclusion criteria: altered at least one nutrient and measured BG in at least one avian species. The search yielded 91 articles that produced 128 datasets (i.e., one nutrient manipulation in one sample). Across all macronutrient manipulations (n = 69 datasets), 62% reported no change in BG and 23% measured an increase (p < 0.001). Within the macronutrient groups (carbohydrate, lipid, protein, and mixed) most datasets showed no change in BG (67%, 62%, 52%, and 86%, respectively). Across micronutrient manipulations (n = 59 datasets), 51% demonstrated no change and 41% decreased BG (p < 0.001). While manipulations that altered vitamin intake largely produced no change in BG (62%), 48% of datasets examining altered mineral intake found no change and 46% decreased BG. Chromium was the most studied micronutrient (n = 24 datasets), where 67% of datasets reported a decrease in BG. These results suggest birds are largely able to maintain blood glucose homeostasis in response to altered nutrient intake indicative of dietary flexibility.

Recent advances and health implications of dietary fasting regimens on the gut microbiome.

Calorie restriction is a primary dietary intervention demonstrated over many decades in cellular and animal models to modulate aging pathways, positively affect age-associated diseases and, in clinical studies, to promote beneficial health outcomes. Because long-term compliance with daily calorie restriction has proven problematic in humans several intermittent fasting regimens, including alternate day fasting and time-restricted feeding, have evolved revealing similar clinical benefits as calorie restriction. Despite significant research on the cellular and physiological mechanisms contributing to, and responsible for, these observed benefits, relatively little research has investigated the impact of these various fasting protocols on the gut microbiome (GM). Reduced external nutrient supply to the gut may beneficially alter the composition and function of a "fed" gut microflora. Indeed, the prevalent, obesogenic Western diet can promote deleterious changes in the GM, signaling intermediates involved in lipid and glucose metabolism, and immune responses in the gastrointestinal tract. This review describes recent preclinical and clinical effects of varying fasting regimens on GM composition and associated physiology. Although the number of preclinical and clinical interventions are limited, significant data thus far suggest fasting interventions impact GM composition and physiology. However, there are considerable heterogeneities of study design, methodological considerations, and practical implications. Ongoing research on the health impact of fasting regimens on GM modulation is warranted.

In silico evaluation of the downstream effect of mutated glucagon is consistent with higher blood glucose homeostasis in Galliformes and Strigiformes.

In contrast to mammals, glucagon is reported as a much more potent blood glucose modulator in birds. Interestingly, we have found p.Thr16Ser mutation, a variation in the highly conserved glucagon hormone, in Galliformes as well as Strigiformes. To check the effect of this mutation on the receptor binding of glucagon, we predicted the ancestral glucagon receptor sequence of all available Galliformes and Strigiformes species. Subsequently, we analysed their binding to the mutated and wild type glucagon (ancestral) by molecular dynamics simulation. At first, we made a model of ancestral glucagon receptor and ancestral mutated, and wild type glucagon in the order Galliformes and Strigiformes. Then we performed molecular dynamics for each Galliformes and Strigiformes receptor as well as each glucagon peptide, respectively. The final structures were used for docking simulation of glucagon to their receptors. The results of the docking simulations showed a stronger binding affinity of mutated glucagon to glucagon receptors. Afterward, we obtained blood glucose concentrations of all available Galliformes members, as well as all available members of its only taxonomic neighbour (order Anseriformes) in superorder Galloanserae. Interestingly the p.Thr16Ser mutation could finely cluster these two orders into two groups: higher blood glucose concentration (order Galliformes, 17.64 ± 1.66 mMol/L) and lower blood glucose concentration (order Anseriformes, 11.34 ± 1.11 mMol/L). Strigiformes which carry the mutated glucagon peptide show also high blood glucose concentrations (17.40 ± 1.51 mMol/L). Therefore, the results suggest this mutation, which leads to stronger binding affinity of mutated glucagon to its receptor, may be a driving force for higher blood glucose homeostasis in the related birds.

A four-week high fat diet does not alter plasma glucose or metabolic physiology in wild-caught mourning doves (Zenaida macroura).

The aim of this study was to determine the metabolic effects of a four-week 60% high-fat (HF) diet on mourning doves. Plasma glucose concentrations are, on average, 1.5-2 times higher in birds than in mammals of similar body mass, but birds have innate mechanisms that protect them from high blood glucose-associated pathologies normally developed in mammals. Elucidating these mechanisms may help develop therapeutics for treatment of human diabetes-related complications. A high fat (HF) diet is commonly used in rodents to investigate metabolic disease. We hypothesized that this diet in doves would elevate plasma glucose and alter metabolic physiology compared to the control (CON) diet. Following the four-week long diets, doves were euthanized, and we collected blood, liver, pectoralis muscles, and kidney samples. Contrary to the rodent-models, HF-fed birds did not have increased plasma glucose concentrations relative to CON-fed birds. Metabolomic analyses revealed no group differences in plasma, liver, pectoralis muscle, or kidney metabolites (FDR q-value>0.05 for all). Principal component analysis score plots of metabolites showed no separation between groups, and pathway analyses revealed no significantly altered metabolic pathways between groups (191 pathways across tissues, FDR q-value>0.05). Body mass, plasma uric acid, glucose, and insulin as well as liver and pectoralis muscle glycogen and triglycerides did not differ between groups (p > 0.05 for all). In conclusion, a four-week long high fat diet did not alter plasma glucose concentrations or metabolic physiology in mourning doves, indicating that these birds have mechanisms that allow them to avoid high fat diet-induced pathologies seen in mammals.

Fewer Exposed Lysine Residues May Explain Relative Resistance of Chicken Serum Albumin to In Vitro Protein Glycation in Comparison to Bovine Serum Albumin.

Protein glycation and formation of advanced glycation end products is associated with several diseases resulting from high blood glucose concentrations. Plasma albumin is directly exposed to circulating glucose concentrations and is therefore at greater risk of glycation than hemoglobin. As plasma glucose concentrations in birds are 1.5-2 times higher than mammals of similar mass, avian albumin may be particularly at risk of glycation. Thus, the goal of the present study was to compare the in vitro formation of glycated albumin in chicken serum albumin (CSA) and bovine serum albumin (BSA) exposed to a range of glucose concentrations over a 16-week period. The level of glycation for CSA and BSA was quantified using boronate affinity columns to separate glycated albumin from non-glycated albumin and calculating the difference in protein concentration of each sample. The results indicate that CSA is glycated to a lesser degree than BSA when the albumins are exposed to increasing concentrations of glucose (38.8-500 mM). This was most apparent at week sixteen (500 mM glucose) where BSA expressed a higher degree of glycation (37.8 ± 0.76%) compared to CSA (19.7 ± 1.06%, P < 0.05). Additionally, percent glycation at week sixteen was significantly higher than the glucose-free solutions for both BSA and CSA, indicating that glycation is glucose-dependent. Analyses of the protein structures suggest that the relative resistance of CSA to glycation may be due to fewer lysine residues and variations in protein folding that shield more lysine residues from the plasma. Moreover, comparisons of reconstructed ancestral albumin sequences show that the ancestor of birds had 6-8 fewer lysine residues compared to that of mammals.

Short communication: Levels of land use and land cover in Phoenix, Arizona are associated with elevated plasma triglycerides in the Gambel's Quail, Callipepla gambelii.

Gambel's Quail, Callipepla gambelii, are gregarious birds commonly found in the southwestern deserts of the United States and Northwestern Mexico. With expanding urbanization, these birds are often found in exurban and suburban areas where they have access to food sources that may differ from those used by birds living in rural habitats and, as a result, also differ morphologically and physiologically. To investigate this hypothesis, we compared the morphology and nutritional physiology of quail sampled at sites varying with respect to land use and cover. We hypothesized that quail living in more developed areas have access to a greater variety of and to more stable food resources, and predicted that morphology and nutritional physiology would be associated with degree of urbanization. We sampled adult birds at locations in the greater Phoenix metropolitan, Arizona (USA) area that vary with respect to land use and cover types. At the time of capture, birds were weighed and chest circumference was recorded. We also collected a blood sample from the jugular vein of each individual for analysis of plasma glucose, total proteins, triglycerides, and free glycerol. Consistent with the hypothesis, birds living in more developed environments had larger chest circumferences and higher circulating lipid concentrations than birds living in less developed areas, suggesting greater access to lipid-rich foods. In addition, the areal proportion of grass and lakes was negatively correlated to plasma free glycerol (r = -0.46, p = .031), and positively, but not significantly, correlated to plasma protein concentrations (r = 0.388, p = .073). These results suggest that quail living in areas with more grass have access to less dietary fats than urban birds. The findings are the first to indicate an association between urbanization and the morphology and nutritional physiology of Gambel's Quail, but further study using more and larger samples is needed before these findings can be generalized.

A four-week white bread diet does not alter plasma glucose concentrations, metabolic or vascular physiology in mourning doves, Zenaida macroura.

Birds are an enigma: their plasma glucose concentration is 1.5-2 times higher than similar-sized mammals, yet they do not normally exhibit symptoms of diabetes. We hypothesized that feeding adult mourning doves a refined carbohydrate diet (white bread: WB) for four weeks would raise plasma glucose concentrations and alter metabolic pathways and endothelial function when compared to birds receiving a nutritionally-balanced diet (bird seeds: SD). Following the four-week long diets, birds were euthanized, and cardiac blood, liver, and pectoralis muscles were collected for metabolomics analyses and biochemical assays. Cranial tibial arteries were dissected to measure acetylcholine-mediated vasodilation. Contrary to the hypothesis, WB-fed birds did not have increased plasma glucose concentrations. Principle component analysis score plots suggest minimal differences between groups. However, we identified 15 changes in individual metabolite concentrations between diet groups that, although not statistically significant, are highly predictive (area under receive operating curve, AUROC>0.90; number of highly predictive metabolites: 5 of 123 in plasma, 4 of 92 in liver, and 6 of 92 in pectoralis muscle). Moreover, pathway analyses revealed no significantly altered metabolic pathways between groups. Biochemical assays revealed no significant group differences in plasma uric acid and insulin, or pectoralis muscle glycogen concentrations. However, hepatic glycogen concentration was 2.12-fold higher in the WB group than in control doves (p = .015). Diet type did not influence vasodilation. In conclusion, a four-week long white bread diet increased liver glycogen but did not alter plasma glucose concentrations, metabolic or vascular physiology in mourning doves.

Seasonal and elevational variation in glucose and glycogen in two songbird species.

Birds naturally maintain high glucose concentrations in the blood and tissues, even when relying on fat to meet the metabolic demands of flight or thermogenesis. One possibility is that high glucose levels might be needed to deal with these metabolic demands. Thus, we hypothesized that birds chronically exposed to colder temperatures and higher elevations have higher circulating glucose and tissue free glucose and glycogen compared to conspecifics living at warmer temperatures and lower elevations. Adult House Sparrows (Passer domesticus) and House Finches (Haemorhous mexicanus) were captured from Phoenix, AZ (340 m elevation), and Albuquerque, NM (1600 m elevation), during the summer and winter months. We measured plasma glucose, as well as free glucose and glycogen from multiple tissues. In general, high elevation and colder temperatures were associated with higher tissue glycogen and higher free glucose concentrations in the brain. These findings indicate that glucose and glycogen are subject to seasonal phenotypic flexibility as well as geographic variations that may relate to local food availability and abundance.

High glucose impairs acetylcholine-mediated vasodilation in isolated arteries from Mourning doves (Z. macroura).

Normal avian plasma glucose levels are 1.5-2 times greater than mammals of similar size. In mammals, hyperglycemia induces oxidative stress and impaired endothelium-dependent vasodilation. Prior work has shown that mourning doves have high levels of antioxidants and isolated vessels have low endogenous oxidative stress. Therefore, the hypothesis was that endothelium-dependent vasodilation of isolated avian arteries would not be impaired following acute exposure to high glucose. Isolated small resistance cranial tibial arteries (c. tibial) were cannulated and pressurized in a vessel chamber then incubated with either normal or high glucose (20mM vs. 30mM) for 1h at 41°C. Vessels were then pre-constricted to 50% of resting inner diameter with phenylephrine (PE) followed by increasing doses of acetylcholine (ACh; 10(-9) to 10(-5)M, 5min per step). Percent vasodilation was measured by tracking the inner diameter with edge-detection software. Contrary to our hypothesis, ACh-induced vasodilation was impaired with acute exposure to high glucose (p=0.013). The impairment was not related to increased osmolarity since vasodilation of arteries exposed to an equimolar combination of 20mM d-glucose and 10mM l-glucose was not different from controls (p=0.273). Rather, the impaired vasodilation was attributed to oxidative stress since superoxide levels were elevated 168±42% (p=0.02) and pre-exposure of arteries to the superoxide dismutase mimetic tiron (10mM) improved vasodilation (p<0.05). Therefore, isolated arteries from doves do not have endogenous mechanisms to prevent impaired vasodilation resulting from high glucose-mediated increases in oxidative stress.

Food processing according to the NOVA classification is not associated with glycemic index and glycemic load: results from an analysis of 1995 food items.

BACKGROUND: Ultraprocessed foods (UPFs) comprise most calories in the United States diet. Glycemic index (GI) and glycemic load (GL) are measures of the quality and quantity of carbohydrates in food based on their effect on postprandial blood glucose. Diets high in UPFs and GI/GL are associated with chronic metabolic diseases but the relationship between them is unclear. OBJECTIVES: Our objective was to examine the GI and GL of foods assigned to NOVA food processing groups. We hypothesized that GI and GL would be lowest in minimally processed foods (MPFs) compared to processed food (PRF) and UPF (with no difference between PRF and UPF). METHODS: GI and GL values produced by healthy individuals for 1995 food items were collated from published sources. Food items were manually coded by processing levels according to NOVA classification. In addition, as the effects of processing on glycemic potential may vary between types of foods, food items were coded into 8 groups (beans, nuts, and seeds; beverages; dairy; fats and sweets; fruit; grains; fish, meat, and poultry; and vegetables). Multilevel linear modeling was used to determine significance with an α value of 0.05. RESULTS: The effect of food processing on GI and GL was contrary to our hypothesis as means did not differ significantly across processing levels: GI-MPF: 54.1 ± 19.5, PRF: 53.2 ± 18.9, UPF: 49.3 ± 18.1 (P = 0.712); GL-MPF: 17.1 ± 10.3, PRF: 15.8 ± 12.4, UPF; 11.5 ± 7.9 (P = 0.890). Within food groups, there was no significant association between processing level and GI (P = 0.184), but GL was inversely associated with grains and vegetables (P < 0.001). CONCLUSIONS: Across analyzed foods, GI and GL do not differ between processing levels, whereas GL was lower in ultraprocessed grains and vegetables than MPF. Any potential adverse outcomes associated with UPF are unlikely to be related to effects on glycemia. This project was preregistered at the Open Science Framework (OSF) Registries through the Center for Open Science as 10.17605/OSF.IO/PJWG9.

Gut microbiome remodeling and metabolomic profile improves in response to protein pacing with intermittent fasting versus continuous caloric restriction.

The gut microbiome (GM) modulates body weight/composition and gastrointestinal functioning; therefore, approaches targeting resident gut microbes have attracted considerable interest. Intermittent fasting (IF) and protein pacing (P) regimens are effective in facilitating weight loss (WL) and enhancing body composition. However, the interrelationships between IF- and P-induced WL and the GM are unknown. The current randomized controlled study describes distinct fecal microbial and plasma metabolomic signatures between combined IF-P (n = 21) versus a heart-healthy, calorie-restricted (CR, n = 20) diet matched for overall energy intake in free-living human participants (women = 27; men = 14) with overweight/obesity for 8 weeks. Gut symptomatology improves and abundance of Christensenellaceae microbes and circulating cytokines and amino acid metabolites favoring fat oxidation increase with IF-P (p < 0.05), whereas metabolites associated with a longevity-related metabolic pathway increase with CR (p < 0.05). Differences indicate GM and metabolomic factors play a role in WL maintenance and body composition. This novel work provides insight into the GM and metabolomic profile of participants following an IF-P or CR diet and highlights important differences in microbial assembly associated with WL and body composition responsiveness. These data may inform future GM-focused precision nutrition recommendations using larger sample sizes of longer duration. Trial registration, March 6, 2020 (ClinicalTrials.gov as NCT04327141), based on a previous randomized intervention trial.

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.

Intermittent fasting and protein pacing are superior to caloric restriction for weight and visceral fat loss.

OBJECTIVE: This study compared intermittent fasting and protein pacing (IF-P) versus a heart-healthy caloric restriction (CR) diet, matched for energy intake and physical activity energy expenditure, on body weight, total and visceral fat mass, and cardiometabolic health outcomes in adults with obesity. METHODS: IF-P (n = 21) and CR (n = 20) were assessed pre- (week 0), mid- (week 5), and post- (week 9) intervention. RESULTS: Both groups reduced (p < 0.05) weight, total and visceral fat mass, blood pressure and lipids, and desire to eat food and increased proportion of fat-free mass. IF-P resulted in greater (p < 0.05) reductions in weight (-9% vs. -5%), total (-16% vs. -9%) and visceral (-33% vs. -14%) fat mass, and desire to eat (-17% vs. 1%) and increased fat-free mass percent (6% vs. 3%) compared with CR. These improvements were despite similar weekly total energy intake (IF-P, 9470 ± 550 vs. CR, 9095 ± 608 kcal/wk; p = 0.90) and physical activity energy expenditure (IF-P, 300 ± 150 vs. CR, 350 ± 200 kcal/d; p = 0.79). CONCLUSIONS: IF-P and CR optimize weight loss, body composition, cardiometabolic health, and hunger management, with IF-P providing greater benefits.

The relationship between diet, plasma glucose, and cancer prevalence across vertebrates.

Could diet and mean plasma glucose concentration (MPGluC) explain the variation in cancer prevalence across species? We collected diet, MPGluC, and neoplasia data for 160 vertebrate species from existing databases. We found that MPGluC negatively correlates with cancer and neoplasia prevalence, mostly of gastrointestinal organs. Trophic level positively correlates with cancer and neoplasia prevalence even after controlling for species MPGluC. Most species with high MPGluC (50/78 species = 64.1%) were birds. Most species in high trophic levels (42/53 species = 79.2%) were reptiles and mammals. Our results may be explained by the evolution of insulin resistance in birds which selected for loss or downregulation of genes related to insulin-mediated glucose import in cells. This led to higher MPGluC, intracellular caloric restriction, production of fewer reactive oxygen species and inflammatory cytokines, and longer telomeres contributing to longer longevity and lower neoplasia prevalence in extant birds relative to other vertebrates.

Mitochondrial function in sparrow pectoralis muscle.

Flying birds couple a high daily energy turnover with double-digit millimolar blood glucose concentrations and insulin resistance. Unlike mammalian muscle, flight muscle predominantly relies on lipid oxidation during locomotion at high fractions of aerobic capacity, and birds outlive mammals of similar body mass by a factor of three or more. Despite these intriguing functional differences, few data are available comparing fuel oxidation and free radical production in avian and mammalian skeletal muscle mitochondria. Thus we isolated mitochondria from English sparrow pectoralis and rat mixed hindlimb muscles. Maximal O(2) consumption and net H(2)O(2) release were measured in the presence of several oxidative substrate combinations. Additionally, NAD- and FAD-linked electron transport chain (ETC) capacity was examined in sonicated mitochondria. Sparrow mitochondria oxidized palmitoyl-l-carnitine 1.9-fold faster than rat mitochondria and could not oxidize glycerol-3-phosphate, while both species oxidized pyruvate, glutamate and malate-aspartate shuttle substrates at similar rates. Net H(2)O(2) release was not significantly different between species and was highest when glycolytic substrates were oxidized. Sonicated sparrow mitochondria oxidized NADH and succinate over 1.8 times faster than rat mitochondria. The high ETC catalytic potential relative to matrix substrate dehydrogenases in sparrow mitochondria suggests a lower matrix redox potential is necessary to drive a given O(2) consumption rate. This may contribute to preferential reliance on lipid oxidation, which may result in lower in vivo reactive oxygen species production in birds compared with mammals.