Benefits of calorie restriction in mice are mediated via energy imbalance, not absolute energy or protein intake.

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.

Reducing the residue of retractions in evidence synthesis: ways to minimise inappropriate citation and use of retracted data.

The incorporation of publications that have been retracted is a risk in reliable evidence synthesis. Retraction is an important mechanism for correcting the literature and protecting its integrity. Within the medical literature, the continued citation of retracted publications occurs for a variety of reasons. Recent evidence suggests that systematic reviews and meta-analyses often unwittingly cite retracted publications which, at least in some cases, may significantly impact quantitative effect estimates in meta-analyses. There is strong evidence that authors of systematic reviews and meta-analyses may be unaware of the retracted status of publications and treat them as if they are not retracted. These problems are difficult to address for several reasons: identifying retracted publications is important but logistically challenging; publications may be retracted while a review is in preparation or in press and problems with a publication may also be discovered after the evidence synthesis is published. We propose a set of concrete actions that stakeholders (eg, scientists, peer-reviewers, journal editors) might take in the near-term, and that research funders, citation management systems, and databases and search engines might take in the longer term to limit the impact of retracted primary studies on evidence syntheses.

Sex and Race Differences in Obesity-Related Genetic Susceptibility and Risk of Cardiometabolic Disease in Older US Adults.

Importance: The fat mass and obesity-associated gene (FTO) is associated with obesity phenotypes, but the association is inconsistent across populations. Within-population differences may explain some of the variability observed. Objective: To investigate sex differences in the association between FTO single-nucleotide variants (SNVs) and obesity traits among self-identified non-Hispanic Black and non-Hispanic White US adults, to examine whether the SNVs were associated with cardiometabolic diseases, and to evaluate whether obesity mediated the association between FTO SNVs and cardiometabolic diseases. Design, Setting, and Participants: This cross-sectional study used data from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, a US population-based cohort study with available genetic data (assayed in 2018) and phenotypic data at baseline (enrolled 2003-2007). Participants were aged 45 to 98 years at baseline. Data were analyzed from October 2021 to October 2022. Exposures: Eleven SNVs in the FTO gene present among both Black and White participants. Main Outcomes and Measures: Objectively measured obesity indicators (body mass index and waist-to-height ratio), objectively measured and/or self-reported cardiometabolic diseases (hypertension, stroke history, heart disease, and diabetes), and self-reported social-economic and psychosocial status. Results: A total of 10 447 participants (mean [SD] age, 64.4 [9.7] years; 5276 [55.8%] women; 8743 [83.7%] Black and 1704 [16.3%] White) were included. In the White group, 11 FTO SNVs were significantly associated with obesity, hypertension, and diabetes using linear models (eg, body mass index: ß = 0.536; 95% CI, 0.197-0.875), but none of the FTO SNVs were associated with obesity traits in the Black group. White males had a higher risk of obesity while White females had a higher risk of hypertension and diabetes. However, 1 FTO SNV (rs1121980) was associated with a direct increase in the risk of heart disease in Black participants not mediated by obesity (c' = 0.145 [SE, 0.0517]; P = .01). Conclusions and Relevance: In this cross-sectional study of obesity phenotypes and their association with cardiometabolic diseases, the tested FTO SNVs reflected sex differences in White participants. Different patterns of associations were observed among self-identified Black participants. Therefore, these results could inform future work discovering risk alleles or risk scores unique to Black individuals or further investigating genetic risk in all US residents.

The effect of a pharmaceutical ghrelin agonist on lifespan in C57BL/6J male mice: A controlled experiment.

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.

Science dialogue mapping of knowledge and knowledge gaps related to the effects of dairy intake on human cardiovascular health and disease.

Dairy has been described as everything from a superfood to a poison; yet, arguments, assumptions, and data justifying these labels are not always clear. We used an issue-based information system, "dialogue mapping™," to summarize scientific points of a live panel discussion on the putative effects of dairy on cardiovascular diseases (CVD) from a day-long session among experts in nutrition and CVD. Dialogue mapping captures relations among ideas to explicitly, logically, and visually connect issues/questions, ideas, pro/con arguments, and agreements, even if discussed at different times. Experts discussed two propositions: for CVD risk, consumption of full-fat dairy products 1) should be minimized, in part because of their saturated fat content, or 2) need not be minimized, despite their saturated fat content. The panel discussed the dairy-CVD relation through blood lipids, diabetes, obesity, energy balance, blood pressure, dairy bioactives, biobehavioral components, and other putative causal pathways. Associations and effects reported in the literature have varied by fat content of dairy elements considered, study design, intake methods, and biomarker versus disease outcomes. Two conceptual topics emerged from the discussion: 1) individual variability: whether recommendations should be targeted only to those at high CVD risk; 2) quality of evidence: whether data on dairy-CVD relations are strong enough for reliable conclusions-positive, negative, or null. Future procedural improvements for science dialog mapping include using singular rather than competing propositions for discussion.

CITY Health II - using entertainment education and social media to reduce HIV among emerging adults: A protocol paper for the Beat HIVe project.

BACKGROUND: Despite multiple efforts to reduce HIV rates among African American young adults, a significant racial disparity persists and continues to grow among this population. New approaches are needed to reach this at-risk group and engage them in prevention efforts. The Community Influences Transitions of Youth Health (CITY Health II) study aims to increase HIV preventive behaviors to decrease HIV rates among 18-25 year old African American emerging adults living in resource-poor southern urban communities. METHODS: CITY Health II is a 5-year HIV prevention study that evaluates the efficacy of a peer-driven entertainment education intervention compared to an attention-control intervention using a cluster randomized trial design. Participants were recruited through respondent-driven sampling (RDS) to participate in a social media intervention. We enlisted eight musicians and groups to help us create an entertaining and educational web-based video series, "The Beat HIVe", for study participants to view on smartphones and share with peers on social media. Data collection interviews at baseline, 3-month, and 6-month follow-up assessed socio-demographics, risk and protective behaviors, social networks, and peer norms. Analyses will determine if participation is associated with improved HIV-related outcomes; examine whether intervention changes are mediated by perceived social norms and outcome expectations; determine whether intervention benefits vary by sociodemographic characteristics related to mediators, intervention outcome, or level of engagement; and examine the relationship between participant dose of intervention and outcomes. DISCUSSION: Outcomes will inform ways to engage African American emerging adults through entertainment education and other strategies for increasing optimal sexual health behaviors. TRIAL REGISTRATION: NCT04320186.

Exceptional Reported Effects and Data Anomalies Merit Explanation from "A randomized controlled trial of coordination exercise on cognitive function in obese adolescents" by.

We read the recent article in Psychology of Sport and Exercise by Liu et al. ("A randomized controlled trial of coordination exercise on cognitive function in obese adolescents") with great interest. Our interest in the article stemmed from the extraordinary differences in obesity-related outcomes reported in response to a rope-jumping intervention. We requested the raw data from the authors to confirm the results and, after the journal editors reinforced our request, the authors graciously provided us with their data. We share our evaluation of the original data herein, which includes concerns that weight and BMI loss by the intervention appears extraordinary in both magnitude and aspects of the distributions. We request that the authors address our findings by providing explanations of the extraordinary data or correcting any errors that may have occurred in the original report, as appropriate.

Biobehavioural approaches to prevention and treatment: A call for implementation science in obesity research.

Much progress has been made in the last 30 years in understanding the causes and mechanisms that contribute to obesity, yet widely available and successful strategies for prevention and treatment remain elusive at population levels. This paper discusses the biobehavioural framework and provides suggestions for applying it to enable greater progress in the science of obesity prevention and treatment, including an increased focus on implementation of science strategies. The objective is to promote a re-evaluation of current views about preventing and treating obesity within a unified biobehavioural framework. Further integration of research exploring how both behavioural and biological components interact is a critical step forward.

A Systematic Scoping Review of Surgically Manipulated Adipose Tissue and the Regulation of Energetics and Body Fat in Animals.

OBJECTIVE: Surgical manipulations of adipose tissue by removal, or partial lipectomy, have demonstrated body fat compensation and recovered body weight, suggesting that the body is able to resist changes to body composition. However, the mechanisms underlying these observations are not well understood. The purpose of this scoping review is to provide an update on what is currently known about the regulation of energetics and body fat after surgical manipulations of adipose tissue in small mammals. METHODS: PubMed and Scopus were searched to identify 64 eligible studies. Outcome measures included body fat, body weight, food intake, and circulating biomarkers. RESULTS: Surgeries performed included lipectomy (72%) or transplantation (12%) in mice (35%), rats (35%), and other small mammals. Findings suggested that lipectomy did not have consistent long-term effects on reducing body weight and fat because regain occurred within 12 to 14 weeks post surgery. Hence, biological feedback mechanisms act to resist long-term changes of body weight or fat. Furthermore, whether this weight and fat regain occurred because of "passive" and "active" regulation under the "set point" or "settling point" theories cannot fully be discerned because of limitations in study designs and data collected. CONCLUSIONS: The regulation of energetics and body fat are complex and dynamic processes that require further studies of the interplay of genetic, physiological, and behavioral factors.

Love with No Exceptions: A Statewide Faith-Based, University-Community Partnership for Faith-Based HIV Training and Assessment of Needs in the Deep South.

This project established a faith-based, university-community partnership with the African Methodist Episcopal (AME) church in Alabama to develop a statewide training model to address HIV knowledge and stigma, promote discussion and generate action plans to address HIV in the Deep South. A community-engaged research team consisting of church leadership and university researchers developed and implemented the model, "Love with No Exceptions." Mixed methods were used to evaluate the model delivered in 3-h sessions in five state regions (N = 146 clergy and laity). The majority of participants reported feeling better prepared to serve those living with or affected by HIV and would implement education and awareness activities in their churches. Participants' HIV knowledge increased from pre- to post-training. Stigma-related attitudes showed minor changes from baseline. These results reflect that partnerships between academic institutions and churches can deliver promising steps towards impactful HIV education in the Deep South.

Effect of Food Predictability on Life Span in Male Mice.

The purpose of this study is to compare the effect of unpredictable (U) or predictable (P) food delivery on health and longevity in mice. From 2 months of age until end of life, singly-housed male C57BL/6 mice were fed a semisynthetic diet either ad libitum (AL), or as imposed meals delivered as small pellets at either P or U times, frequencies, or amounts. The total daily food consumed by all groups was the same. The AL group gained body weight faster than either P or U groups, and had ~12% shorter median life span compared with either P or U groups. Bimonthly noninvasive body composition determinations showed that the differences in body weights were due to differences in fat and lean mass. Postmortem examinations revealed that the organ pathologies were similar in all groups, but a larger fraction of P and U mice were euthanized due to end-of-life suffering. There were no systematic differences in outcome measures between P and U groups suggesting that, within the range studied, the temporal pattern of food delivery did not have a significant metabolic effect.

Issues with data and analyses: Errors, underlying themes, and potential solutions.

Some aspects of science, taken at the broadest level, are universal in empirical research. These include collecting, analyzing, and reporting data. In each of these aspects, errors can and do occur. In this work, we first discuss the importance of focusing on statistical and data errors to continually improve the practice of science. We then describe underlying themes of the types of errors and postulate contributing factors. To do so, we describe a case series of relatively severe data and statistical errors coupled with surveys of some types of errors to better characterize the magnitude, frequency, and trends. Having examined these errors, we then discuss the consequences of specific errors or classes of errors. Finally, given the extracted themes, we discuss methodological, cultural, and system-level approaches to reducing the frequency of commonly observed errors. These approaches will plausibly contribute to the self-critical, self-correcting, ever-evolving practice of science, and ultimately to furthering knowledge.

Body Mass Index and Subjective Social Status: The Coronary Artery Risk Development in Young Adults Study.

OBJECTIVE: Subjective social status (SSS), or perceived social status, may explain, in part, the relationship between socioeconomic status (SES) and obesity. The objective of this study was to test whether SSS mediates the relationship between two indicators of SES (income and education) and body mass index (BMI). METHODS: A cross-sectional, structural equation path analysis was applied to the Coronary Artery Risk Development in Young Adults (CARDIA) study (n = 2,624). The analysis tested whether SSS (MacArthur scale), education, and income were associated with BMI at the year 20 examination (adjusting for sex, age, and race), and it was hypothesized that the associations of education and income with BMI would be at least partly mediated by SSS. RESULTS: SSS had a significant direct effect on BMI (-0.21, P = 0.018). Education had a significant direct relationship with SSS (0.11, P < 0.001) and a small but significant indirect relationship with BMI through SSS (-0.02, P = 0.022). Although income did not have a significant direct relationship with BMI, it did have a significant indirect relationship through SSS (b = -0.05, P = 0.019). CONCLUSIONS: Results are consistent with the hypothesized model in which SSS partially mediates the relationship between SES indicators and BMI.

Analysis of the time and workers needed to conduct systematic reviews of medical interventions using data from the PROSPERO registry.

OBJECTIVES: To summarise logistical aspects of recently completed systematic reviews that were registered in the International Prospective Register of Systematic Reviews (PROSPERO) registry to quantify the time and resources required to complete such projects. DESIGN: Meta-analysis. DATA SOURCES AND STUDY SELECTION: All of the 195 registered and completed reviews (status from the PROSPERO registry) with associated publications at the time of our search (1 July 2014). DATA EXTRACTION: All authors extracted data using registry entries and publication information related to the data sources used, the number of initially retrieved citations, the final number of included studies, the time between registration date to publication date and number of authors involved for completion of each publication. Information related to funding and geographical location was also recorded when reported. RESULTS: The mean estimated time to complete the project and publish the review was 67.3 weeks (IQR=42). The number of studies found in the literature searches ranged from 27 to 92 020; the mean yield rate of included studies was 2.94% (IQR=2.5); and the mean number of authors per review was 5, SD=3. Funded reviews took significantly longer to complete and publish (mean=42 vs 26 weeks) and involved more authors and team members (mean=6.8 vs 4.8 people) than those that did not report funding (both p<0.001). CONCLUSIONS: Systematic reviews presently take much time and require large amounts of human resources. In the light of the ever-increasing volume of published studies, application of existing computing and informatics technology should be applied to decrease this time and resource burden. We discuss recently published guidelines that provide a framework to make finding and accessing relevant literature less burdensome.

Comparisons of Fatty Acid Taste Detection Thresholds in People Who Are Lean vs. Overweight or Obese: A Systematic Review and Meta-Analysis.

Given the increasing evidence that supports the ability of humans to taste non-esterified fatty acids (NEFA), recent studies have sought to determine if relationships exist between oral sensitivity to NEFA (measured as thresholds), food intake and obesity. Published findings suggest there is either no association or an inverse association. A systematic review and meta-analysis was conducted to determine if differences in fatty acid taste sensitivity or intensity ratings exist between individuals who are lean or obese. A total of 7 studies that reported measurement of taste sensations to non-esterified fatty acids by psychophysical methods (e.g.,studies using model systems rather than foods, detection thresholds as measured by a 3-alternative forced choice ascending methodology were included in the meta-analysis. Two other studies that measured intensity ratings to graded suprathreshold NEFA concentrations were evaluated qualitatively. No significant differences in fatty acid taste thresholds or intensity were observed. Thus, differences in fatty acid taste sensitivity do not appear to precede or result from obesity.

Re: Errors in Zhao et al (2015), Impact of enteral nutrition on energy metabolism in patients with Crohn's disease.

We report invalidating errors related to the statistical approach in the analysis and data inconsistencies in a published single cohort study of patients with Crohn's disease. We provide corrected calculations from the available data and request that a corrected analysis be provided by the authors. These errors should be corrected.

Common scientific and statistical errors in obesity research.

This review identifies 10 common errors and problems in the statistical analysis, design, interpretation, and reporting of obesity research and discuss how they can be avoided. The 10 topics are: 1) misinterpretation of statistical significance, 2) inappropriate testing against baseline values, 3) excessive and undisclosed multiple testing and "P-value hacking," 4) mishandling of clustering in cluster randomized trials, 5) misconceptions about nonparametric tests, 6) mishandling of missing data, 7) miscalculation of effect sizes, 8) ignoring regression to the mean, 9) ignoring confirmation bias, and 10) insufficient statistical reporting. It is hoped that discussion of these errors can improve the quality of obesity research by helping researchers to implement proper statistical practice and to know when to seek the help of a statistician.