The use of small ruminants, mainly sheep and goats, is increasing in biomedical research. Small ruminants are a desirable animal model due to their human-like anatomy and physiology. However, the large variability between studies and lack of baseline data on these animals creates a barrier to further research. This knowledge gap includes a lack of computed tomography (CT) scans for healthy subjects. Full body, contrast enhanced CT scans of caprine and ovine subjects were acquired for subsequent modeling studies. Scans were acquired from an ovine specimen (male, Khatadin, 30-35 kg) and caprine specimen (female, Nubian 30-35 kg). Scans were acquired with and without contrast. Contrast enhanced scans utilized 1.7 mL/kg of contrast administered at 2 mL/s and scans were acquired 20 seconds, 80 seconds, and 5 minutes post-contrast. Scans were taken at 100 kV and 400 mA. Each scan was reconstructed using a bone window and a soft tissue window. Sixteen full body image data sets are presented (2 specimens by 4 contrast levels by 2 reconstruction windows) and are available for download through the form located at: https://redcap.link/COScanData. Scans showed that the post-contrast timing and scan reconstruction method affected structural visualization. The data are intended for further biomedical research on ruminants related to computational model development, device prototyping, comparative diagnostics, intervention planning, and other forms of translational research.

Ovarian dysfunction increases risk for chronic diseases of aging including cardiovascular disease, depression, cognitive impairment, as well as bone and muscle loss which promote frailty. Psychosocial stress can disrupt ovarian function, and recent observations suggest that consumption of a Western Diet may also. Determination of causal relationships among diet, psychosocial stress, and ovarian physiology is difficult in humans. Long-tailed (a.k.a. cynomolgus) macaques (Macaca fascicularis) are an excellent translational model for the study of diet and psychosocial effects on ovarian physiology and aging-related processes. They have 28-day menstrual cycles with hormonal fluctuations like those of women, and similar physiologic responses to alterations and/or cessation of cyclicity. We examined ovarian function in 38 middle-aged socially housed females fed either a Western or Mediterranean diet for 31 months (approximate to a 9-year period for humans). During the last year, we examined cycle length and peak progesterone per cycle using blood sampling (3/week) and vaginal swabbing for menses (6/week). Repeated measures analysis revealed a circannual pattern consistent with increased menstrual cycle disturbance during the late Summer and early Fall (F(11,348)= 4.05 p < 0.001). In addition, both Western diet (F(1,34)= 3.99; p = 0.05) and the stress of low social status (F(1,34)= 3.99; p = 0.04) reduced mean progesterone levels. Thus, on average, subordinates in the Western group had the lowest average progesterone levels (10.02 ng/pl). Compared to Western diets, Mediterranean diets exhibited protective effects via menstrual cycle regularity. For dominant monkeys, consuming Mediterranean diets resulted in significantly greater likelihood of having regular menstrual cycles. Mediterranean diets also protected individuals from shorter than normal menstrual cycles. The relationships between diet and menstrual regularity were partially mediated by both adrenal reactivity and social isolation. This study demonstrates the additive negative effects of poor diet and psychosocial stress on ovarian physiology in mid-life and lays the groundwork for future investigations to uncover their impact on metabolic signatures of accelerated aging. The results also suggest that - compared to Western-style diets - a Mediterranean diet may exert a protective influence against ovarian dysfunction and its pathologic sequelae.

Chronic psychosocial stress is associated with increased risk of many chronic diseases including type 2 diabetes mellitus. However, it is difficult to establish a causal relationship between stress and diabetes in human studies because stressors often are self-reported and may be distant in time from metabolic consequences. Macaques are useful models of the effects of chronic psychosocial stress on health and may develop obesity and diabetes similar to human beings. Thus, we studied the relationships between social subordination stress - a well-validated psychological stressor in macaques - and body composition and carbohydrate metabolism in socially housed, middle-aged female cynomolgus monkeys (Macaca fascicularis; n = 42). Following an 8-week baseline phase, the monkeys were fed a Western diet for 36 months (about equivalent to 10 human years). Social status was determined based on the outcomes of agonistic interactions (X¯= 33.3 observation hours/monkey). Phenotypes collected included plasma cortisol, body composition, circulating markers of glucose metabolism, activity levels, and heart rate variability measured as RMSSD (root of mean square of successive differences) and SDDN (standard deviation of beat to beat interval) after 1.5- and 3-years on diet. Mixed model analyses of variance revealed that aggression received, submissions sent, and cortisol were higher, and RMSSD and SDNN were lower in subordinates than dominants (social status: p < 0.05). After 3 years of Western diet consumption, fasting triglyceride, glucose and insulin concentrations, calculated insulin resistance (HOMA-IR), body weight and body fat mass increased in all animals (time: all p's < 0.05); however, the increase in fasting glucose and HOMA-IR was significantly greater in subordinates than dominants (time x social status: p's < 0.05). Impaired glucose metabolism, (glucose > 100 mg/dl) incidence was significantly higher in subordinates (23%) than dominants (0%) (Fisher's exact test, p < 0.05). These findings suggest that chronic psychosocial stress, on a Western diet background, significantly increases type 2 diabetes risk in middle-aged female primates.

Mounting evidence suggests that diet may influence risk for cognitive impairment and neurodegenerative disease, including Alzheimer’s disease. Nonhuman primates are important models of cognitive aging and Alzheimer’s disease‐like neuropathology given their complex central nervous systems and susceptibility to diet‐induced diseases. Diffusion magnetic resonance imaging (MRI) studies in humans report age‐related increases in mean diffusivity (MD) and decreases in fractional anisotropy (FA). Whether nonhuman primate models of Alzheimer’s disease‐like neuropathology show similar changes in diffusivity, and whether diet affects these changers is unknown. As such, the purpose of this study was to determine the longitudinal effects of diet (Mediterranean vs Western) and social subordination stress on diffusion MRI measures of white matter structural integrity in a nonhuman primate model of aging.

Dietary changes associated with industrialization increase the prevalence of chronic diseases, such as obesity, type II diabetes, and cardiovascular disease. This relationship is often attributed to an ‘evolutionary mismatch’ between human physiology and modern nutritional environments. Western diets enriched with foods that were scarce throughout human evolutionary history (e.g. simple sugars and saturated fats) promote inflammation and disease relative to diets more akin to ancestral human hunter-gatherer diets, such as a Mediterranean diet. Peripheral blood monocytes, precursors to macrophages and important mediators of innate immunity and inflammation, are sensitive to the environment and may represent a critical intermediate in the pathway linking diet to disease. We evaluated the effects of 15 months of whole diet manipulations mimicking Western or Mediterranean diet patterns on monocyte polarization in a well-established model of human health, the cynomolgus macaque ( Macaca fascicularis ). Monocyte transcriptional profiles differed markedly between diets, with 40% of transcripts showing differential expression (FDR < 0.05). Monocytes from Western diet consumers were polarized toward a more proinflammatory phenotype. The Western diet shifted the co-expression of 445 gene pairs, including small RNAs and transcription factors associated with metabolism and adiposity in humans, and dramatically altered behavior. For example, Western-fed individuals were more anxious and less socially integrated. These behavioral changes were also associated with some of the effects of diet on gene expression, suggesting an interaction between diet, central nervous system activity, and monocyte gene expression. This study provides new molecular insights into an evolutionary mismatch and uncovers new pathways through which Western diets alter monocyte polarization toward a proinflammatory phenotype.

The objective of this study was to increase understanding of the complex interactions between diet, obesity, and the gut microbiome of adult female non-human primates (NHPs). Subjects consumed either a Western (n=15) or Mediterranean (n=14) diet designed to represent human dietary patterns for 31 months. Body composition was determined using CT, fecal samples were collected, and shotgun metagenomic sequencing was performed. Gut microbiome results were grouped by diet and adiposity. Diet was the main contributor to gut microbiome bacterial diversity. Adiposity within each diet was associated with subtle shifts in the proportional abundance of several taxa. Mediterranean diet-fed NHPs with lower body fat had a greater proportion of Lactobacillus animalis than their higher body fat counterparts. Higher body fat Western diet-fed NHPs had more Ruminococcus champaneliensis and less Bacteroides uniformis than their low body fat counterparts. Western diet-fed NHPs had significantly higher levels of Prevotella copri than Mediterranean diet NHPs. Western diet-fed subjects were stratified by P. copri abundance (P. copriHIGH versus P. copriLOW), which was not associated with adiposity. Overall, Western diet-fed animals in the P. copriHIGH group showed greater proportional abundance of B. ovatus, B. faecis, P. stercorea, P. brevis, and Faecalibacterium prausnitzii than those in the Western P. copriLOW group. Western diet P. copriLOW subjects had a greater proportion of Eubacterium siraeum. E. siraeum negatively correlated with P. copri proportional abundance regardless of dietary consumption. In the Western diet group, Shannon diversity was significantly higher in P. copriLOW when compared to P. copriHIGH subjects. Furthermore, gut E. siraeum abundance positively correlated with HDL plasma cholesterol indicating that those in the P. copriLOW population may represent a more metabolically healthy population. Untargeted metabolomics on urine and plasma from Western diet-fed P. copriHIGH and P. copriLOW subjects suggest early kidney dysfunction in Western diet-fed P. copriHIGH subjects. In summary, the data indicate diet to be the major influencer of gut bacterial diversity. However, diet and adiposity must be considered together when analyzing changes in abundance of specific bacterial taxa. Interestingly, P. copri appears to mediate metabolic dysfunction in Western diet-fed NHPs.

INTRODUCTION:Associations between diet, psychosocial stress, and neurodegenerative disease, including Alzheimer's disease (AD), have been reported, but causal relationships are difficult to determine in human studies. METHODS:We used structural magnetic resonance imaging in a well-validated non-human primate model of AD-like neuropathology to examine the longitudinal effects of diet (Mediterranean vs Western) and social subordination stress on brain anatomy, including global volumes, cortical thicknesses and volumes, and 20 individual regions of interest (ROIs). RESULTS:Western diet resulted in greater cortical thicknesses, total brain volumes, and gray matter, and diminished cerebrospinal fluid and white matter volumes. Socially stressed subordinates had smaller whole brain volumes but larger ROIs relevant to AD than dominants. DISCUSSION:The observation of increased size of AD-related brain areas is consistent with similar reports of mid-life volume increases predicting increased AD risk later in life. While the biological mechanisms underlying the findings require future investigation, these observations suggest that Western diet and psychosocial stress instigate pathologic changes that increase risk of AD-associated neuropathology, whereas the Mediterranean diet may protect the brain.

Persistent psychological stress increases the risk of many chronic diseases of aging. Little progress has been made to effectively reduce stress responses or mitigate stress effects suggesting a need for better understanding of factors that influence stress responses. Limited evidence suggests that diet may be a factor in modifying the effects of stress. However, long-term studies of diet effects on stress reactive systems are not available, and controlled randomized clinical trials are difficult and costly. Here we report the outcomes of a controlled, randomized preclinical trial of the effects of long-term consumption (31 months, ~ equivalent to 9 human years) of Western versus Mediterranean - like diets on behavioral and physiological responses to acute (brief social separation) and chronic (social subordination) psychosocial stress in 38 adult, socially-housed, female cynomolgus macaques. Compared to animals fed a Western diet, those fed the Mediterranean diet exhibited enhanced stress resilience as indicated by lower sympathetic activity, brisker and more overt heart rate responses to acute stress, more rapid recovery, and lower cortisol responses to acute psychological stress and adrenocorticotropin (ACTH) challenge. Furthermore, age-related increases in sympathetic activity and cortisol responses to stress were delayed by the Mediterranean diet. Population level diet modification in humans has been shown to be feasible. Our findings suggest that population-wide adoption of a Mediterranean-like diet pattern may provide a cost-effective intervention on psychological stress and promote healthy aging with the potential for widespread efficacy.

Increased left ventricular (LV) myocardial extracellular volume fraction (ECVF) measured by cardiac magnetic resonance (CMR) is now a recognized consequence of anthracycline chemotherapy ([1][1],[2][2]). It remains unknown, however, whether elevated ECVF may be attributable to an expansion of the LV

Abstract Diet modifications are some of the most well-established aging interventions. For decades we have known that caloric restriction can dramatically increase lifespan and healthspan in organisms ranging from yeast to primates. More recently, other dietary modifications, including varying nutrient composition, have been experimentally shown to alter healthspan and lifespan. However, limitations inherent in human trials, such as diet adherence and heterogeneity of other lifestyle factors, mitigate our ability to identify the mechanisms through which diet alters healthspan and lifespan. Here, we conducted a randomized, long-term, whole-diet manipulation in a nonhuman primate, where cynomolgus macaques consumed either a Mediterranean or Western diet for 15 months. We hypothesized that individuals fed a Western diet would exhibit accelerated rates of cellular and physiological aging relative to their Mediterranean-fed counterparts. Indeed, we found that Western diet-fed animals exhibited increases in physiological measures that also increase with age, including body weight, fasting insulin, and triglycerides. Animals eating a Mediterranean diet, on the other hand, had a more sensitive and tuned autonomic response, and reduced HPA responses to an acute stress challenge. Probing further, we found that diet strongly affected monocyte function, altering the expression of 40% of expressed genes, leading to a more proinflammatory monocyte phenotype in Western diet fed animals. Experiments are underway to explore effects of diet on other markers of biological aging. Together, these data provide the first controlled evidence that Western and Mediterranean diets can alter aging-associated function in a species with clear biological similarity and relevance to humans.

Background: Western diets are associated with increased incidences of obesity, hypertension, diabetes, and hypercholesterolemia, whereas Mediterranean diets, richer in polyphenols, monounsaturated fats, fruits, vegetables, poultry, and fish, appear to have cardiometabolic health benefits. Previous work has included population-based studies with limited evidence for causation or animal studies focused on single macro-or micronutrients; therefore, primate animal models provide an opportunity to determine potential mechanisms underlying the effects of dietary patterns on health and disease. Objective: The aim of this study was to determine the effects of whole dietary patterns, either a Western or Mediterranean diet, on skeletal muscle mitochondrial bioenergetics in cynomolgus macaques. Methods: In this study, 22 adult female cynomolgus macaques (similar to 11-14 y by dentition) were fed either a Western or Mediterranean diet for 30 mo. The Western diet was designed to mimic the diet of a middle-aged American woman and the Mediterranean diet included key aspects of Mediterranean diets studied in humans, such as plant-based proteins and fat, complex carbohydrates, and fiber. Diets were matched on macronutrient composition (16% protein, 54% carbohydrate, and 31% fat) and cholesterol content. Skeletal muscle was collected for high-resolution respirometry, citrate synthase activity, and western blot measurements. Pearson correlation analysis between respirometry measures and measures of carbohydrate metabolism was also performed. Results: We found that consumption of a Western diet resulted in significantly higher mitochondrial respiration with fatty acid oxidation (FAO) (53%), FAO + complex I (52%), complex I + II (31%), max electron transport system (ETS) (31%), and ETS rotenone sensitive (31%) than did consumption of a Mediterranean diet. In addition, measures of respiration in response to fatty acids were significantly and positively correlated with both insulin resistance and plasma insulin concentrations. Conclusions: This study highlights the importance of dietary composition in mitochondrial bioenergetics and that diet can influence skeletal muscle mitochondrial respiration independently of other factors such as macronutrient composition.

Background Endometriosis is the growth of uterine lining (endometrium) outside of the uterus. In other chronic inflammatory diseases, mitochondrial dysfunction is suspected of playing a role in disease pathogenesis. However, little is known about endometriosis mitochondrial function or its effects on tissue metabolism. The objectives of this study were to analyze mitochondrial function in nonhuman primate (NHP) endometrium and endometriosis tissue and to identify the metabolic features of these tissues that may contribute to disease. Methods Mitochondrial function in endometriosis tissue and endometrium was measured using mitochondrial respirometry analysis to determine if changes in oxidative phosphorylation exist in endometrium and endometriosis tissue compared to control endometrium from clinically healthy NHPs. Targeted metabolomics and multidimensional statistical analysis were applied to quantify key metabolites in energy and amino acid biosynthesis pathways. Results Mitochondrial respirometry assays showed endometrium from NHPs with endometriosis had reduced complex II-mediated oxygen consumption rates (OCR) across all energy states (basal, p = 0.01; state 3, p = 0.02; state 3u, p = 0.04; state 4o, p = 0.008) and endometriosis tissue had reduced state 3, complex I-mediated OCR (p = 0.02) and respiratory control rates (p = 0.01) compared to normal endometrium. Targeted metabolomics performed on tissue revealed carnitine (p = 0.001), creatine phosphate (p = 0.01), NADH (p = 0.0001), FAD (p = 0.001), tryptophan (p = 0.0009), and malic acid (p = 0.005) were decreased in endometriosis tissue compared to normal endometrium samples. FAD (p = 0.004), tryptophan (p = 0.0004) and malic acid (p = 0.03) were significantly decreased in endometrium from NHPs with endometriosis compared to normal endometrium. Significant metabolites identified in endometriosis and endometrium samples from animals with endometriosis were part of amino acid biosynthesis or energy metabolism pathways. Conclusions Here, endometrial mitochondrial energy production and metabolism were decreased in endometrium and endometriosis tissue. Decreased mitochondrial energy production may be due to oxidative stress-induced damage to mitochondrial DNA or membranes, a shift in cell metabolism, or decreased energy substrate; however, the exact cause remains unknown. Additional research is needed to determine the implications of reduced mitochondrial energy production and metabolism on endometriosis and endometrium.

ObesityVolume 27, Issue 10 p. 1554-1554 Letter to the Editor Response to “Two Bad Diets for Monkeys” Carol A. Shively, Corresponding Author Carol A. Shively cshively@wakehealth.edu orcid.org/0000-0002-1536-2288 Section of Comparative Medicine, Department of Pathology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA Correspondence: Carol A. Shively (cshively@wakehealth.edu)Search for more papers by this authorSusan E. Appt, Susan E. Appt Section of Comparative Medicine, Department of Pathology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USASearch for more papers by this authorMara Z. Vitolins, Mara Z. Vitolins Department of Epidemiology and Prevention, Wake Forest School of Medicine, Winston-Salem, North Carolina, USASearch for more papers by this authorBeth Uberseder, Beth Uberseder Section of Comparative Medicine, Department of Pathology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USASearch for more papers by this authorKristofer T. Michalson, Kristofer T. Michalson Section of Comparative Medicine, Department of Pathology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USASearch for more papers by this authorMarnie G. Silverstein-Metzler, Marnie G. Silverstein-Metzler Section of Comparative Medicine, Department of Pathology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USASearch for more papers by this authorThomas C. Register, Thomas C. Register Section of Comparative Medicine, Department of Pathology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USASearch for more papers by this author Carol A. Shively, Corresponding Author Carol A. Shively cshively@wakehealth.edu orcid.org/0000-0002-1536-2288 Section of Comparative Medicine, Department of Pathology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA Correspondence: Carol A. Shively (cshively@wakehealth.edu)Search for more papers by this authorSusan E. Appt, Susan E. Appt Section of Comparative Medicine, Department of Pathology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USASearch for more papers by this authorMara Z. Vitolins, Mara Z. Vitolins Department of Epidemiology and Prevention, Wake Forest School of Medicine, Winston-Salem, North Carolina, USASearch for more papers by this authorBeth Uberseder, Beth Uberseder Section of Comparative Medicine, Department of Pathology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USASearch for more papers by this authorKristofer T. Michalson, Kristofer T. Michalson Section of Comparative Medicine, Department of Pathology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USASearch for more papers by this authorMarnie G. Silverstein-Metzler, Marnie G. Silverstein-Metzler Section of Comparative Medicine, Department of Pathology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USASearch for more papers by this authorThomas C. Register, Thomas C. Register Section of Comparative Medicine, Department of Pathology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USASearch for more papers by this author First published: 17 August 2019 https://doi.org/10.1002/oby.22587 Disclosure: The authors declared no conflict of interest. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume27, Issue10October 2019Pages 1554-1554 RelatedInformation