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Low-protein diets promote metabolic health in rodents and humans, and the benefits of low-protein diets are recapitulated by specifically reducing dietary levels of the three branched-chain amino acids (BCAAs), leucine, isoleucine, and valine. Here, we demonstrate that each BCAA has distinct metabolic effects. A low isoleucine diet reprograms liver and adipose metabolism, increasing hepatic insulin sensitivity and ketogenesis and increasing energy expenditure, activating the FGF21-UCP1 axis. Reducing valine induces similar but more modest metabolic effects, whereas these effects are absent with low leucine. Reducing isoleucine or valine rapidly restores metabolic health to diet-induced obese mice. Finally, we demonstrate that variation in dietary isoleucine levels helps explain body mass index differences in humans. Our results reveal isoleucine as a key regulator of metabolic health and the adverse metabolic response to dietary BCAAs and suggest reducing dietary isoleucine as a new approach to treating and preventing obesity and diabetes.

Low‐protein (LP) diets are associated with a decreased risk of diabetes in humans, and promote leanness and glycaemic control in both rodents and humans. While the effects of an LP diet on glycaemic control are mediated by reduced levels of the branched‐chain amino acids, we have observed that reducing dietary levels of the other six essential amino acids leads to changes in body composition. Here, we find that dietary histidine plays a key role in the response to an LP diet in male C57BL/6J mice. Specifically reducing dietary levels of histidine by 67% reduces the weight gain of young, lean male mice, reducing both adipose and lean mass without altering glucose metabolism, and rapidly reverses diet‐induced obesity and hepatic steatosis in diet‐induced obese male mice, increasing insulin sensitivity. This normalization of metabolic health was associated not with caloric restriction or increased activity, but with increased energy expenditure. Surprisingly, the effects of histidine restriction do not require the energy balance hormone Fgf21. Histidine restriction that was started in midlife promoted leanness and glucose tolerance in aged males but not females, but did not affect frailty or lifespan in either sex. Finally, we demonstrate that variation in dietary histidine levels helps to explain body mass index differences in humans. Overall, our findings demonstrate that dietary histidine is a key regulator of weight and body composition in male mice and in humans, and suggest that reducing dietary histidine may be a translatable option for the treatment of obesity. Key points: Protein restriction (PR) promotes metabolic health in rodents and humans and extends rodent lifespan.Restriction of specific individual essential amino acids can recapitulate the benefits of PR.Reduced histidine promotes leanness and increased energy expenditure in male mice.Reduced histidine does not extend the lifespan of mice when begun in midlife.Dietary levels of histidine are positively associated with body mass index in humans. [ABSTRACT FROM AUTHOR]

Abstract Background Evidence-based public health requires the existence of reliable information systems for priority setting and evaluation of interventions. Existing data systems in the United States are either too crude (e.g., vital statistics), rely on administrative data (e.g., Medicare) or, because of their national scope (e.g., NHANES), lack the discriminatory power to assess specific needs and to evaluate community health activities at the state and local level. This manuscript describes the rationale and methods of the Survey of the Health of Wisconsin (SHOW), a novel infrastructure for population health research. Methods/Design The program consists of a series of independent annual surveys gathering health-related data on representative samples of state residents and communities. Two-stage cluster sampling is used to select households and recruit approximately 800-1,000 adult participants (21-74 years old) each year. Recruitment and initial interviews are done at the household; additional interviews and physical exams are conducted at permanent or mobile examination centers. Individual survey data include physical, mental, and oral health history, health literacy, demographics, behavioral, lifestyle, occupational, and household characteristics as well as health care access and utilization. The physical exam includes blood pressure, anthropometry, bioimpedance, spirometry, urine collection and blood draws. Serum, plasma, and buffy coats (for DNA extraction) are stored in a biorepository for future studies. Every household is geocoded for linkage with existing contextual data including community level measures of the social and physical environment; local neighborhood characteristics are also recorded using an audit tool. Participants are re-contacted bi-annually by phone for health history updates. Discussion SHOW generates data to assess health disparities across state communities as well as trends on prevalence of health outcomes and determinants. SHOW also serves as a platform for ancillary epidemiologic studies and for studies to evaluate the effect of community-specific interventions. It addresses key gaps in our current data resources and increases capacity for etiologic, applied and translational population health research. It is hoped that this program will serve as a model to better support evidence-based public health, facilitate intervention evaluation research, and ultimately help improve health throughout the state and nation.

Objective:The association of food insecurity with dyslipidemia has not been firmly established. The main objective of this study was to assess whether food insecurity was associated with dyslipidemia. Method A population-based sample of 1,663 adults from the 2008-2011 Survey of the Health of Wisconsin was used. Food insecurity was defined as an affirmative response to either of the questions: (1) "In the last 12 months, have you been concerned about having enough food for you or your family?" (2) "In the last 12 months, have your food choices been limited because there wasn't enough money?" High total cholesterol was defined as total cholesterol (TC) > 240 mg/dL or taking prescribed lipid-lowering medication. Low high-density lipoprotein cholesterol (HDL-C) was defined as < 40 mg/dL in men and < 50 mg/dL in women. Results:Food insecurity was not associated with high TC either among men or women. Food insecurity was associated with a higher likelihood of low HDL-C among women (adjusted odds ratio [AOR]: 2.31 {95% confidence interval [CI]: 1.42, 3.76}), but not among men. Obesity appears to be a partial mediator of the association among women (P from the Sobel test = 0.01). Conclusion:These findings suggest that food insecurity may contribute to an increased risk of low HDL-C in women. [ABSTRACT FROM AUTHOR]

The amino acid composition of the diet has recently emerged as a critical regulator of metabolic health. Consumption of the branched-chain amino acid isoleucine is positively correlated with body mass index in humans, and reducing dietary levels of isoleucine rapidly improves the metabolic health of diet-induced obese male C57BL/6J mice. However, it is unknown how sex, strain, and dietary isoleucine intake may interact to impact the response to a Western Diet (WD). Here, we find that although the magnitude of the effect varies by sex and strain, reducing dietary levels of isoleucine protects C57BL/6J and DBA/2J mice of both sexes from the deleterious metabolic effects of a WD, while increasing dietary levels of isoleucine impairs aspects of metabolic health. Despite broadly positive responses across all sexes and strains to reduced isoleucine, the molecular response of each sex and strain is highly distinctive. Using a multi-omics approach, we identify a core sex- and strain- independent molecular response to dietary isoleucine, and identify mega-clusters of differentially expressed hepatic genes, metabolites, and lipids associated with each phenotype. Intriguingly, the metabolic effects of reduced isoleucine in mice are not associated with FGF21 - and we find that in humans plasma FGF21 levels are likewise not associated with dietary levels of isoleucine. Finally, we find that foods contain a range of isoleucine levels, and that consumption of dietary isoleucine is lower in humans with healthy eating habits. Our results demonstrate that the dietary level of isoleucine is critical in the metabolic and molecular response to a WD, and suggest that lowering dietary levels of isoleucine may be an innovative and translatable strategy to protect from the negative metabolic consequences of a WD., Competing Interests: DECLARATION OF INTERESTS DWL has received funding from, and is a scientific advisory board member of, Aeovian Pharmaceuticals, which seeks to develop novel, selective mTOR inhibitors for the treatment of various diseases.

Children's sleep quality and duration are important to overall development, health, and wellbeing. However, measuring children's sleep is challenging, especially in situations where objective assessment is impractical. This study aimed to assess age and proxy effects in comparing subjective sleep duration with objective measures, in a community-based sample of Wisconsin children (aged 6-17 years), recruited from 2014-2017. The sample participants had a mean age of 11.4 (standard deviation, 3.3) years and 52% of them were male. We used linear mixed effects models to test for age effects in proxy- and self-report groups separately, and a quasiexperimental regression discontinuity approach to compare subjective sleep duration with objective actigraphy estimates across proxy- and self-report groups. We found evidence of systematic overestimation of sleep duration when using subjective measurements but did not find evidence of age effects in either group. Based on these analyses, we found evidence of differential overestimation by proxy- or self-report condition. Proxy reporters overestimated sleep duration by 2.3 hours (95% confidence interval: 2.2, 2.4), compared with 1.0 hour (95% confidence interval: 0.7, 1.2) for self-reporters. These findings suggest that proxy- versus self-reporting conditions are an important consideration when designing a study, and that it might be beneficial to reduce the age at which children self-report., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: To analyze overall prescription medication use patterns among study participants in a representative statewide sample of Wisconsin adults., Methods: We analyzed data on 1572 participants from the 2008-2010 cycles of the Survey of the Health of Wisconsin (SHOW). SHOW is a statewide population-based survey that collects health information, including prescription medications, from 21 to 74 year olds. Prescription medication use was examined according to demographic and socioeconomic characteristics., Result: Almost 55% of participants reported using at least 1 medication in the past month and 14% reported using at least 5 medications. The top 5 medications reported were lisinopril, hydrochlorothiazide, simvastatin, levothyroxine, and metoprolol. Overall prescription medication use increased significantly with age. Medication use was greater among females, former smokers, adults with body mass index (BMI) ≥ 30, or with low family income, and non-hispanic blacks. Adults having health insurance, drug coverage, or a regular source of care were more likely to report medication use., Conclusion: The prevalence of prescription medication use in a general population sample in Wisconsin was high. Age, gender, race, BMI, family income, smoking history, health insurance, prescription drug coverage, and having a regular source of health care were associated with prescription medication use.

Background: Food insecurity is a public health concern estimated to affect 18 million American households nationally, which can result in chronic nutritional deficiencies and other health risks. The relationships between food insecurity and specific demographic and geographic factors in Wisconsin are not well documented. The goals of this paper are to investigate sociodemographic and geographic features associated with food insecurity in a representative sample of Wisconsin adults., Methods: This study used data from the Survey of the Health of Wisconsin (SHOW). SHOW annually collects health-related data on a representative sample of Wisconsin residents. Between 2008-2012, 2,947 participants were enrolled in the SHOW study. The presence of food insecurity was defined based on the participant's affirmative answer to the question "In the last 12 months, have you been concerned about having enough food for you or your family?", Results: After adjustment for age, race, and gender, 13.2% (95% CI, 10.8%-15.1%) of participants reported food insecurity, 56.7% (95% CI, 50.6%-62.7%) of whom were female. Food insecurity did not statistically differ by region (P = 0.30). The adjusted prevalence of food insecurity in the urban core, other urban, and rural areas was 14.1%, 6.5%, and 10.5%, respectively. These differences were not statistically significant (P = 0.13) and, for urban core and rural areas, persisted even when accounting for level of economic hardship in the community., Conclusions: The prevalence of food insecurity is substantial, affecting an estimated 740,000 or more Wisconsin residents. The prevalence was similarly high in all urbanicity levels and across all state public health regions in Wisconsin. Food insecurity is a common problem with potentially serious health consequences affecting populations across the entire state.

Background: Studies have shown that laws banning smoking in public places reduce exposure to secondhand smoke, but the impact of such laws on exposure to smoke outside the home and on household smoking policies has not been well documented. The goal of this study was to evaluate the effects of 2009 Wisconsin Act 12, a statewide smoke-free law enacted in July 2010, among participants in the Survey of the Health of Wisconsin (SHOW)., Methods: Smoking history and demographic information was gathered from 1341 survey participants from 2008 to 2010. Smoking behaviors of independent samples of participants surveyed before and after the legislation was enacted were compared., Results: The smoking ban was associated with a reduction of participants reporting exposure to smoke outside the home (from 55% to 32%; P<0.0001) and at home (13% to 7%; P=0.002). The new legislation was associated with an increased percentage of participants with no-smoking policies in their households (from 74% to 80%; P=.04). The results were stronger among participants who were older, wealthier, and more educated., Conclusion: Smoke-free legislation appears to reduce secondhand smoke exposure and to increase no-smoking policies in households. Further research should be conducted to see if these effects are maintained.