BACKGROUND:Chronic pain, which affects over 50 million adults in the United States, has stimulated growing interest in natural and nutrition-based remedies as adjuncts to pharmacologic therapies. Evidence suggests that turmeric and related extracts (i.e., curcuminoids) may provide pain relief, albeit often at levels above dietary ranges, while piperine from black pepper exhibits bioenhancer characteristics of relevance with dietary exposures. OBJECTIVE:To test the effectiveness of dietarily relevant amounts of turmeric with and without black pepper on self-reported pain ratings among adults with chronic pain. METHODS:A randomized, crossover clinical trial tested the effectiveness of turmeric only (one of three amounts within culinary ranges) or turmeric with black pepper to influence pain in adults ≥ 40 years of age. Participants (n = 30, with moderate pain: 4-7 on 0-10-point scale) were enrolled in a 21-day trial, and an experience sampling methodology approach was used. Participants were prompted to report current pain using the numeric pain rating scale (NPRS; 0-10) via text message three times per day for the full study period. Data were averaged and analyzed via linear mixed effects models for repeated measurements. RESULTS:Pain ratings from baseline to week 3 were reduced and statistically significant (p < 0.001) but not statistically different between groups. The provided turmeric, both with and without black pepper, and varying amounts of turmeric (300 mg, 1 g, and 3 g, n = 10 participants/amount) did not show statistically significant differences in pain ratings (p = 0.157 and p = 0.338, respectively). CONCLUSIONS:Consuming dietarily relevant amounts of turmeric, either alone or with black pepper, appears to improve average pain ratings. This result suggests a feasible dietary option for further study of nutritional interventions for chronic pain management.

Social housing is desirable for the health and well-being of laboratory mice, as social interactions with conspecifics influence both behavioral and physiological outcomes. Although group housing benefits social species, it can introduce variability in mortality outcomes, and raise welfare concerns, particularly with the emergence of aggression or fluctuating cage densities. Despite this, few studies have evaluated how changes in the number of living cagemates over time are associated with survival, particularly in a sex-specific manner. We analyzed data from the National Institute on Aging’s Interventions Testing Program (ITP; n = 2635 UM-HET3 mice), across three research sites to assess whether housing density influenced longevity differently in male and female mice. Mice were housed in same-sex cages (median = 3 per cage) without reassignment after cagemate death. We applied Cox frailty models incorporating nested random effects for cage and site, with fixed effects for sex, treatment, and time-varying number of living cagemates to estimate hazard ratios, which allowed us to assess the instantaneous risk of death associated with changes in cagemate number. Results showed a significant main effect of the number of living cagemates on mortality and a significant interaction between sex and cagemate count, indicating sex-specific responses. Female mice exhibited a pronounced increase in mortality rate as cage density declined, suggesting a potential role of social buffering in longevity. These findings emphasize the importance of considering social housing dynamics, particularly for female mice, in both experimental design and animal welfare protocols.

Despite extensive research on life-extending interventions, rigorous statistical techniques to determine their impact on compression of morbidity (CoM) are rarely used. We present a case example of an analytical method for examining the effect of life-extending dietary interventions on CoM by comparing the rates of decline in vitality and survival toward the end of life. Using data from previous experimental studies in mice, we calculated the average rate of vitality decline by fitting exponential decay models to individual vitality trajectories and compared this rate with the rate of survival decline estimated from Cox proportional hazards model. The results showed that, surprisingly, the life-extending interventions failed to compress morbidity. Instead, the models suggested a potential expansion of morbidity with the interventions, particularly for chronic caloric restriction, as evidenced by a greater difference between the rates of vitality decline and survival decline in the intervention group than in the control group. The results further showed age-dependent effects, with interventions likely to demonstrate CoM at very old ages. These findings challenge the assumption that lifespan extension necessarily compresses morbidity, highlighting the need to consider lifespan, healthspan, and CoM as endpoints when evaluating anti-aging interventions. We do not claim that life-extending interventions categorically fail to achieve CoM; rather, we demonstrate how a rigorous statistical approach can be applied to test the CoM hypothesis. Our framework offers a valuable tool for future studies, and further refining this method will be crucial to determine under which circumstances lifespan extension leads to CoM. The potential to choose from multiple analyses of CoM calls for leadership in the geroscience community both to standardize the nomenclature so that different CoM analysis approaches can be communicated clearly and to establish a “default” CoM analysis for everyone to use in addition to their analyses of choice, thus facilitating comparisons and meta-analyses across studies.

INTRODUCTION:Accurate assessment of body composition is critical for understanding health risks and developing appropriate interventions, particularly in underrepresented populations. The purpose of this study was to compare the body composition estimate (% body fat [%BF]) between dual-energy x-ray absorptiometry (DXA) and hydrodensitometry via hydrostatic weighing (HW) in a group of Hispanic pre-menopausal women. METHODOLOGY:Healthy Hispanic women (n=78, age: 22-51 years, BMI: 18.5-42.5) were measured for body composition by DXA and HW at a single lab visit. %BF from HW was calculated from body density using three commonly used adult-specific equations (2-component [2-C] Siri, 2-C Brozek, 3-component [3-C] Lohman) and a 2-C Hispanic-specific equation. Comparisons between the two methods (DXA and HW) were analyzed using paired t-tests, and linear regression and Bland-Altman plots were used to assess agreement between the two methods. RESULTS:%BF was significantly higher by DXA compared to all four HW equations (P < 0.01). Based on regression analyses the mean difference scores were not different from zero for all estimates of %BF. CONCLUSIONS:While DXA and HW are both common laboratory measures for determining %BF, given the time-efficiency, minimal participant effort, and high precision, %BF estimation by DXA appears to be an adequate and sufficient method of measurement of body composition in Hispanic women.

Objective: This study aimed to measure the potential relationships between sociodemographic characteristics, academic factors, body mass index (BMI), financial challenges, individual health behaviors, impact of COVID-19, and psychological well-being (PWB) among students. Participants: Undergraduate college students. Methods: Data from the National College Health Assessment III (American College Health Association [ACHA]) were used (n = 1,439). Differences in absolute values among PWB groups were analyzed using analysis of variance (ANOVA). To measure the influence of all factors combined on PWB, multiple regression analyses were performed. Results: Significant differences were observed in age, GPA, financial challenges, and individual health behaviors by PWB groups (p < .05). Being older, being female, having a higher GPA, being a full-time student, having a higher intake of vegetables, taking less time to fall asleep, and having lower stress levels were significantly positively associated with higher PWB scores (p < .05). Conclusions: Multiple considerations related to the academic environment and individual behaviors seem to influence PWB among college students.

Background Approximately 25% of college students reported a disability that can be any condition of the body or mind that makes it more difficult for the person to do certain activities. This may have an additional impact on psychosocial factors and health-related behaviors. Objective Evaluate differences in loneliness, resiliency, and health-related behaviors in students with and without disabilities. Study Design, Settings, Participants Data analysis was conducted from the National College Health Assessment from one university in Fall 2022. 829 of the 4,500 randomly sampled students completed the survey. Disability status was assessed through self-report and categorized into 4 groups; 1) individuals with no disability, 2) individuals with a cognitive disability, 3) individuals with a physical disability, and 4) individuals that have both a cognitive and physical disability. Measurable Outcome/Analysis Variables include resilience from the Connor Davidson Scale, loneliness using the UCLA scale, food intake, physical activity (PA), sleep, disability, and demographic characteristics (age, race, sex). To evaluate differences among students in health-related behaviors and resiliency Analysis of Covariance (ANCOVA) was used. To measure the likelihood of dietary intake and physical activity being less healthful with loneliness Adjusted Odds Ratio (AOR) was used. Results Majority of the sample were female (67.52%), full-time (85.38%), and had a GPA of “A” (55.30%). Mean age was 23 years (23.1±7.4). Significant differences were seen in loneliness (p=0.019) and well-being (p=0.016) among student groups. No significant differences were found in PA, resiliency, and food intake among student groups. There was no significant difference of the odds of having lower fruit (OR=2.53, 95% CI [0.46,13.76]), vegetable(OR=1.21, 95% CI [0.44,3.33]), meat/poultry (OR=1.78, 95% CI [0.76,4.16]), higher SSB intake (OR=1.01, 95% CI [0.98,1.04]), lower PA (OR=1.00, 95% CI [1.00,1.00]) with feeling lonely in student groups. Conclusions Students with disabilities showed higher loneliness but showed no differences in health-related behaviors. This analysis has provided insight for future interventions that can target increasing resiliency, reducing loneliness, and increasing healthful behaviors among students. Funding NIH

Caloric restriction (CR) results in reduced energy and protein intake, raising questions about protein restriction's contribution to CR longevity benefits. We kept ad libitum (AL)-fed male C57BL/6J mice at 27°C (AL27) and pair-fed (PF) mice at 22°C (22(PF27)). The 22(PF27) group was fed to match AL27 while restricted for calories due to cold-induced metabolism. The 22(PF27) mice had significantly lower body weight, lean mass, fat mass, leptin, IGF-1, and TNF-α levels than AL27 mice (p<0.001 for all). Manipulations over ~11 weeks resulted in significant differences in body temperature, physical activity, and expression of key genes linked to hunger in the hypothalamus. Survival was significantly greater in 22(PF27) compared to AL27 overall (p<0.001). CR in the context of equivalent energy and protein intake resulted in hormonal, metabolic, and physiological benefits and extended longevity. Hence, energy imbalance, rather than low energy or protein intake per se, mediates the benefits of CR.

Abstract Immunotherapies are the standard of care for patients with renal cancer, yet their effects on renal tumor antigen-specific CD8 T cell responses and their subsequent ability to modulate the renal tumor microenvironment remain difficult to evaluate. In order to address this gap in the field, we developed a novel murine model to examine tumor-antigen specific CD8 T cell immune responses in orthotopic renal cancer utilizing a new cell line, Renca-tERK-LUC. Parental Renca cells were transduced with a lentivirus expressing the naturally-occurring, mutated tERK peptide found in CMS5 fibrosarcoma cells to create Renca-tERK-LUC tumor cells. The tERK mutation consists of a one base pair change that creates an Sfc1 site, so it can be detected by RT-PCR followed by restriction enzyme digestion. Our data show that Renca-tERK-LUC cells express tERK at high levels and grow progressively in control BALB/c mice, but are rejected in DUC Thy1.1 mice, which contain endogenous TCR transgenic CD8+ T cells specific for tERK peptide/MHC I complexes. We then performed adoptive transfers of 5 × 105 DUC Thy1.1 T cells into mice with established, orthotopic Renca-tERK-LUC tumors to evaluate: 1) the effects of immunotherapy on tumor-antigen-specific T cell responses; and 2) the effects of tumor-antigen-specific T cells on the broader renal tumor microenvironment. Our data indicate that the transfer of relatively low numbers of tumor antigen-specific CD8+ T cells induces transcriptomic and cellular changes in the tumor microenvironment in both the presence and absence of immunotherapy. Defining the parameters surrounding tumor-antigen-specific T cell responses and their ability to modulate the renal tumor microenvironment under the influence of clinically relevant immunotherapeutic intervention has the potential to increase the understanding of immunity to renal tumors, which could ultimately prove beneficial for renal cancer patients. Citation Format: Holly Stephens, Elizabeth Elkins, Francesca Dempsey, Zoey Swalley, Jing Li, Jianqing Zhang, Richard Kirkman, Bo-Ruei Chen, Zachary Roberts, Sunil Sudarshan, Barry Sleckman, Hubert Tse, Daniel L. Smith, Lyse A. Norian. Adoptive transfer of tumor antigen-specific T cells alters the renal tumor microenvironment in the presence and absence of immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 110.

Identifying effective treatment(s) for sarcopenia and sarcopenic obesity is of paramount importance as the global population advances in age and obesity continues to be a worldwide concern. Evidence has shown that a ketogenic diet can be beneficial for the preservation of muscle quality and function in older adults, but long-term adherence is low due in part to the high-fat (≥80%), very low carbohydrate (<5%) composition of the diet. When provided in adequate amounts, exogenous ketone esters (KEs) can increase circulating ketones to concentrations that exceed those observed during prolonged fasting or starvation without significant alterations in the diet. Ketone esters first emerged in the mid-1990s and their use in preclinical and clinical research has escalated within the past 10-15 years. We present findings from a narrative review of the existing literature for a proposed hypothesis on the effects of exogenous ketones as a therapeutic for preservation of skeletal muscle and function within the context of sarcopenic obesity and future directions for exploration. Much of the reviewed literature herein examines the mechanisms of the ketone diester (R,S-1,3-butanediol diacetoacetate) on skeletal muscle mass, muscle protein synthesis, and epigenetic regulation in murine models. Additional studies are needed to further examine the key regulatory factors producing these effects in skeletal muscle, examine convergent and divergent effects among different ketone ester formulations, and establish optimal frequency and dosing regimens to translate these findings into humans.

Objective: The objective of this study was to investigate body composition changes with weight cycling (WC) among adult C57BL/6J mice with diet-induced obesity. Methods: A total of 555 single-housed mice were fed a high-fat diet ad libitum (AL) from 8 to 43 weeks of age. The 200 heaviest mice of each sex were randomized to the following four groups: ever obese (EO, continued AL feeding); obese weight loser (OWL, calorie-restricted); obese weight loser moderate (OWLM, body weight halfway between EO and OWL); and WC (diet restricted to OWL followed by AL refeeding cycles). Body weight and composition data were collected. Linear regression was used to calculate residuals between predicted and observed fat mass. Linear mixed models were used to compare diet groups. Results: Although weight loss and regain resulted in changes in body weight and composition, fat mass, body weight, and relative body fat were not significantly greater for the WC group compared with the EO group. During long-term calorie restriction, males (but not females) in the OWLM group remained relatively fatter than the EO group. Conclusions: WC did not increase body weight or relative fat mass for middle-aged, high-fat diet-fed adult mice. However, long-term moderate calorie restriction resulted in lower body weight but greater "relative" fat in male mice.

Investigators traditionally use randomized designs and corresponding analysis procedures to make causal inferences about the effects of interventions, assuming independence between an individual's outcome and treatment assignment and the outcomes of other individuals in the study. Often, such independence may not hold. We provide examples of interdependency in model organism studies and human trials and group effects in aging research and then discuss methodologic issues and solutions. We group methodologic issues as they pertain to (1) single-stage individually randomized trials; (2) cluster-randomized controlled trials; (3) pseudo-cluster-randomized trials; (4) individually randomized group treatment; and (5) two-stage randomized designs. Although we present possible strategies for design and analysis to improve the rigor, accuracy and reproducibility of the science, we also acknowledge real-world constraints. Consequences of nonadherence, differential attrition or missing data, unintended exposure to multiple treatments and other practical realities can be reduced with careful planning, proper study designs and best practices.

Mitochondrial diseases represent a spectrum of disorders caused by impaired mitochondrial function, ranging in severity from mortality during infancy to progressive adult-onset disease. Mitochondrial dysfunction is also recognized as a molecular hallmark of the biological ageing process. Rapamycin, a drug that increases lifespan and health during normative ageing, also increases survival and reduces neurological symptoms in a mouse model of the severe mitochondrial disease Leigh syndrome. The Ndufs4 knockout (Ndufs4−/−) mouse lacks the complex I subunit NDUFS4 and shows rapid onset and progression of neurodegeneration mimicking patients with Leigh syndrome. Here we show that another drug that extends lifespan and delays normative ageing in mice, acarbose, also suppresses symptoms of disease and improves survival of Ndufs4−/− mice. Unlike rapamycin, acarbose rescues disease phenotypes independently of inhibition of the mechanistic target of rapamycin. Furthermore, rapamycin and acarbose have additive effects in delaying neurological symptoms and increasing maximum lifespan in Ndufs4−/− mice. We find that acarbose remodels the intestinal microbiome and alters the production of short-chain fatty acids. Supplementation with tributyrin, a source of butyric acid, recapitulates some effects of acarbose on lifespan and disease progression, while depletion of the endogenous microbiome in Ndufs4−/− mice appears to fully recapitulate the effects of acarbose on healthspan and lifespan in these animals. To our knowledge, this study provides the first evidence that alteration of the gut microbiome plays a significant role in severe mitochondrial disease and provides further support for the model that biological ageing and severe mitochondrial disorders share underlying common mechanisms. Alterations in the gut microbiome, as a result of treatment with the anti-diabetic drug acarbose or with antibiotics, are shown to extend healthspan and lifespan in a mouse model of Leigh syndrome.

Objectives: The purpose of this study was to evaluate food insecurity on body mass index (BMI) and dietrelated behaviors among college students and whether psychological well-being (PWB) and stress levels mediate this relationship.Study design: This was a cross-sectional study. Methods: Data from 1439 students from the American College Health Association National College Health Assessment III (Fall 2020) were used. Food security status was evaluated by the USDA Six-Item Short Form. PWB was measured using the Diener Flourishing Scale. Diet-related behaviors included the average servings of fruits, vegetables, and sugar-sweetened beverages consumed per day. Stress was measured by self-reported levels. Regression model analysis evaluated the influence of food security status, PWB, and stress levels on BMI. PWB and stress were also tested as mediators in the relationship between food insecurity and BMI.Results: Among our sample of college students, 44.54% (n = 641) were food insecure, and 55.46% (n = 798) were food secure. Multiple regression analysis showed that higher food insecurity, older age, full-time enrollment status, and fifth-year student status were positively associated with a higher BMI score (P < 0.05). Results from mediation models revealed that PWB, but not stress, mediated the relationship between food security and BMI among Black/African American students. Regarding diet-related behaviors, high stress levels mediated the relationship between food insecurity and sugar-sweetened beverage intake among students.Conclusions: Food insecurity appears to influence BMI in college students. This relationship seems to be mediated by disrupted PWB and a higher intake of sugar-sweetened beverages due to stress.(c) 2023 The Author(s). Published by Elsevier Ltd on behalf of The Royal Society for Public Health. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4. 0/).

Interventions for animal lifespan extension like caloric restriction (CR) have identified physiologic and biochemical pathways related to hunger and energy-sensing status as possible contributors, but mechanisms have not been fully elucidated. Prior studies using ghrelin agonists show greater food intake but no effect on lifespan in rodent models. This experiment in male C57BL/6J mice tested the influence of ghrelin agonism for perceived hunger, in the absence of CR, on longevity. Mice aged 4 weeks were allowed to acclimate for 2 weeks prior to being assigned (N = 60/group). Prior to lights off daily (12:12 cycle), animals were fed a ghrelin agonist pill (LY444711; Eli Lilly) or a placebo control (Ctrl) until death. Treatment (GhrAg) animals were pair-fed daily based on the group mean food intake consumed by Ctrl (ad libitum feeding) the prior week. Results indicate an increased lifespan effect (log-rank p = 0.0032) for GhrAg versus placebo Ctrl, which weighed significantly more than GhrAg (adjusted for baseline weight). Further studies are needed to determine the full scope of effects of this ghrelin agonist, either directly via increased ghrelin receptor signaling or indirectly via other hypothalamic, systemic, or tissue-specific mechanisms.

Aging is accompanied by increased susceptibility to infections including with viral pathogens resulting in higher morbidity and mortality among the elderly. Significant changes in host metabolism can take place following virus infection. Efficient immune responses are energetically costly, and viruses divert host molecular resources to promote their own replication. Virus-induced metabolic reprogramming could impact infection outcomes, however, how this is affected by aging and impacts organismal survival remains poorly understood. RNA virus infection of Drosophila melanogaster with Flock House virus (FHV) is an effective model to study antiviral responses with age, where older flies die faster than younger flies due to impaired disease tolerance. Using this aged host-virus model, we conducted longitudinal, single-fly respirometry studies to determine if metabolism impacts infection outcomes. Analysis using linear mixed models on Oxygen Consumption Rate (OCR) following the first 72-hours post-infection showed that FHV modulates respiration, but age has no significant effect on OCR. However, the longitudinal assessment revealed that OCR in young flies progressively and significantly decreases, while OCR in aged flies remains constant throughout the three days of the experiment. Furthermore, we found that the OCR signature at 24-hours varied in response to both experimental treatment and survival status. FHV-injected flies that died prior to 48- or 72-hours measurements had a lower OCR compared to survivors at 48-hours. Our findings suggest the host’s metabolic profile could influence the outcome of viral infections.

The interaction of dietary macronutrients in the control of growth, body composition, health, and longevity has received renewed attention. The protein leverage hypothesis proposes an inverse relationship between dietary protein levels and obesity development (low protein promoting high obesity), although the majority of laboratory studies have utilized a design modulating the protein amount within a single dietary protein source composition. We investigated whether varying the levels of dietary protein amount and sources would have impacts on growth and body composition using the Zebrafish Danio rerio model. At 28 d postfertilization, Zebrafish were fed 1 of 12 dietary treatments for 12 weeks. Diets contained different protein sources (fish protein hydrolysate [FPH], soy protein isolate [SOY], casein [CAS], or a mixture of all three sources including wheat gluten [MIX]). Sources were formulated at three protein concentrations (18, 33, or 48% as fed, substituted with wheat starch for caloric balance). Body length, height, and weight were measured over time and at termination. Contributions of macronutrients to growth and body fat outcomes were estimated by LASSO (least absolute shrinkage and selection operator) regression. Male and female length, height, and weight increased significantly in response to increasing dietary protein. Male and female fish fed SOY or FPH had the highest amount of body lipid at all protein concentrations relative to those fed CAS or MIX. Relative body lipid was highest in fish that were fed the lowest protein concentration. These data suggest an important role of macronutrient balances, including dietary protein amount and source, in relation to the protein: energy (carbohydrate and lipid) ratio on growth and body composition outcomes. These outcomes may ultimately reflect metabolic alterations that can lead to confounding interpretations of health and disease status. Furthermore, these data reinforce the need to consider and report dietary composition in establishing rigorous and reproducible nutritional guidelines for Zebrafish.

Exogenous ketone ester supplementation provides a means to increase circulating ketone concentrations without the dietary challenges imposed by ketogenic diets. Our group has shown that oral R,S-1,3, butanediol diacetoacetate (BD-AcAc 2 ) consumption results in body weight loss or maintenance with moderate increases in circulating ketones. We have previously shown a diet consisting of 25% BD-AcAc 2 can maintain lean body mass (LBM) and induce fat mass (FM) loss in young, healthy male mice, but the underlying mechanisms are still unknown. Therefore, the purpose of this study was to determine if a diet consisting of 25% BD-AcAc 2 (ketone ester, KE) would alter body composition, transcriptional regulation, the proteome, and the lipidome of skeletal muscle in aged mice. We hypothesized that the KE group would remain weight stable with improvements in body composition compared to controls, resulting in a healthy aging phenotype. Male C57BL/6J mice ( n = 16) were purchased from Jackson Laboratories at 72 weeks of age. After 1 week of acclimation, mice were weighed and randomly assigned to one of two groups ( n = 8 per group): control (CON) or KE. A significant group by time interaction was observed for body weight ( P < 0.001), with KE fed mice weighing significantly less than CON. FM increased over time in the control group but was unchanged in the KE group. Furthermore, LBM was not different between CON and KE mice despite KE mice weighing less than CON mice. Transcriptional analysis of skeletal muscle identified 6 genes that were significantly higher and 21 genes that were significantly lower in the KE group compared to CON. Lipidomic analysis of skeletal muscle identified no differences between groups for any lipid species, except for fatty acyl chains in triacylglycerol which was 46% lower in the KE group. Proteomics analysis identified 44 proteins that were different between groups, of which 11 were lower and 33 were higher in the KE group compared to CON. In conclusion, 72-week-old male mice consuming the exogenous KE, BD-AcAc 2 , had lower age-related gains in body weight and FM compared to CON mice. Furthermore, transcriptional and proteomics data suggest a signature in skeletal muscle of KE-treated mice consistent with markers of improved skeletal muscle regeneration, improved electron transport chain utilization, and increased insulin sensitivity.

Investigations into the causative role that western dietary patterns have on obesity and disease pathogenesis have speculated that quality and quantity of dietary fats and/or carbohydrates have a predictive role in the development of these disorders. Standard reference diets such as the AIN-93 rodent diet have historically been used to promote animal health and reduce variation of results across experiments, rather than model modern human dietary habits or nutrition-related pathologies. In rodents high-fat diets (HFDs) became a classic tool to investigate diet-induced obesity (DIO). These murine diets often relied on a single fat source with the most DIO consistent HFDs containing levels of fat up to 45-60% (kcal), higher than the reported human intake of 33–35% (kcal). More recently, researchers are formulating experimental animal (pre-clinical) diets that reflect mean human macro- and micronutrient consumption levels described by the National Health and Nutrition Examination Survey (NHANES). These diets attempt to integrate relevant ingredient sources and levels of nutrients; however, they most often fail to include high-fructose corn syrup (HFCS) as a source of dietary carbohydrate. We have formulated a modified Standard American Diet (mSAD) that incorporates relevant levels and sources of nutrient classes, including dietary HFCS, to assess the basal physiologies associated with mSAD consumption. Mice proffered the mSAD for 15 weeks displayed a phenotype consistent with metabolic syndrome, exhibiting increased adiposity, fasting hyperglycemia with impaired glucose and insulin tolerance. Metabolic alterations were evidenced at the tissue level as crown-like structures (CLS) in adipose tissue and fatty acid deposition in the liver, and targeted 16S rRNA metagenomics revealed microbial compositional shifts between dietary groups. This study suggests diet quality significantly affects metabolic homeostasis, emphasizing the importance of developing relevant pre-clinical diets to investigate chronic diseases highly impacted by western dietary consumption patterns.

Background Epidemiologic observations suggest increased potato consumption correlates with weight gain, adiposity, and diabetes risk, whereas nut consumption is associated with weight control and metabolic health. Randomized controlled trial (RCT) data indicate humans respond to changes in energy intake in single dietary components and compensate for extra energy consumed. Objectives We completed an RCT testing whether increased daily potato consumption influences energy balance [specifically, fat mass (FM)] compared with calorie-matched almond consumption. Methods A 30-d RCT of 180 adults prescribed calorie-matched (300 kcal/d, n = 60 participants/group) than consumed 1 of the following: 1) almonds (almond group), 2) French fries (potato group), or 3) French fries with herb/spices mix (potato + herb/spices group). Baseline and 30-d FM were measured by DXA (primary outcome), with secondary outcomes including body weight and carbohydrate metabolism markers [glycated hemoglobin (HbA1c), fasting blood glucose and insulin, HOMA-IR)]. A subset of 5 participants/group participated in a postprandial meal-based tolerance test. Results A total of 180 participants were randomly assigned [gender: 67.8% female; mean +/- SD age: 30.4 +/- 8.7 y; BMI (in kg/m(2)): 26.1 +/- 4.2; and weight: 75.6 +/- 15.4 kg], with 12 dropouts and 3 terminations. No significantly different FM changes were observed between almond and potato consumption [combined +/- herb/spices; mean +/- SE almond: 230.87 +/- 114.01 g; potato: 123.73 +/- 86.09 g; P = 0.443], fasting glucose (P = 0.985), insulin (P = 0.082), HOMA-IR (P = 0.080), or HbA1c (P = 0.269). Body weight change was not significantly different in the potato groups combined compared with the almond group (P = 0.116), but was significantly different among the 3 groups (P = 0.014; almond: 0.49 +/- 0.20 kg; potato: -0.24 +/- 0.20 kg; potato + herb/spices: 0.47 +/- 0.21 kg). In meal tests, significantly lower post-prandial glucose and insulin responses to almonds compared with potatoes were observed (P = 0.046, P = 0.006, respectively), with potato + herb/spices having intermediate effects. Conclusion There were no significant differences in FM or in glucoregulatory biomarkers after 30 d of potato consumption compared with almonds. Results do not support a causal relation between increased French fried potato consumption and the negative health outcomes studied. This trial was registered at clinicaltrials.gov as NCT03518515.