Mfn2 is critical for brown adipose tissue thermogenic function.

Mitochondrial fusion and fission events, collectively known as mitochondrial dynamics, act as quality control mechanisms to ensure mitochondrial function and fine-tune cellular bioenergetics. Defective mitofusin 2 (Mfn2) expression and enhanced mitochondrial fission in skeletal muscle are hallmarks of insulin-resistant states. Interestingly, Mfn2 is highly expressed in brown adipose tissue (BAT), yet its role remains unexplored. Using adipose-specific Mfn2 knockout (Mfn2-adKO) mice, we demonstrate that Mfn2, but not Mfn1, deficiency in BAT leads to a profound BAT dysfunction, associated with impaired respiratory capacity and a blunted response to adrenergic stimuli. Importantly, Mfn2 directly interacts with perilipin 1, facilitating the interaction between the mitochondria and the lipid droplet in response to adrenergic stimulation. Surprisingly, Mfn2-adKO mice were protected from high-fat diet-induced insulin resistance and hepatic steatosis. Altogether, these results demonstrate that Mfn2 is a mediator of mitochondria to lipid droplet interactions, influencing lipolytic processes and whole-body energy homeostasis.

Both PD-1 ligands protect the kidney from ischemia reperfusion injury.

Acute kidney injury (AKI) is a common problem in hospitalized patients that enhances morbidity and mortality and promotes the development of chronic and end-stage renal disease. Ischemia reperfusion injury (IRI) is one of the major causes of AKI and is characterized by uncontrolled renal inflammation and tubular epithelial cell death. Our recent studies demonstrated that regulatory T cells (Tregs) protect the kidney from ischemia reperfusion-induced inflammation and injury. Blockade of programmed death-1 (PD-1) on the surface of Tregs, prior to adoptive transfer, negates their ability to protect against ischemic kidney injury. The present study was designed to investigate the role of the known PD-1 ligands, PD-L1 and PD-L2, in kidney IRI. Administration of PD-L1 or PD-L2 blocking Abs prior to mild or moderate kidney IRI significantly exacerbated the loss of renal function, renal inflammation, and acute tubular necrosis compared with mice receiving isotype control Abs. Interestingly, blockade of both PD-1 ligands resulted in worse injury, dysfunction, and inflammation than did blocking either ligand alone. Genetic deficiency of either PD-1 ligand also exacerbated kidney dysfunction and acute tubular necrosis after subthreshold ischemia. Bone marrow chimeric studies revealed that PD-L1 expressed on non-bone marrow-derived cells is critical for this resistance to IRI. Finally, blockade of either PD-1 ligand negated the protective ability of adoptively transferred Tregs in IRI. These findings suggest that PD-L1 and PD-L2 are nonredundant aspects of the natural protective response to ischemic injury and may be novel therapeutic targets for AKI.

ADHD and overweight in boys: cross-sectional study with birth weight as a controlled factor.

Population studies indicate a strong relationship between birth weight (BW) and body size in later life. However, BW as a variable was never accounted for in studies on the relationship between attention-deficit/hyperactivity disorder (ADHD) and overweight. This study aims to assess the relationship between ADHD and overweight with control of birth weight and other confounding factors. Prevalence of overweight was compared in clinical sample of 219 boys with ADHD and 396 boys without ADHD, aged 6-18 years. The following factors were controlled: BW, parents income and education level, place of residence, ADHD type, selected comorbid disorders and stimulant treatment. Overweight and obesity were diagnosed according to the criteria proposed by the International Obesity Task Force. Logistic regression analysis was used to estimate the association between ADHD and the prevalence of overweight and obesity. Boys with ADHD differed significantly from the control group in distribution of low BW (8.2 vs. 3.0 %, χ (2) = 8.23, p = 0.02). Low BW was associated with a lower prevalence of overweight than normal and high BW (0 vs. 12.14 %, χ (2) = 4.12, p = 0.04). Overweight was observed significantly more often in boys with ADHD (17.3 vs. 8.3 %, χ (2) = 11.23, p < 0.001) even after adjustment for BW and other variables (OR = 2.44, 95 % CI 1.38-4.29, p = 0.002) and after controlling for ADHD type, stimulant treatment and selected comorbid disorders. Independently to applied analysis, obesity was not associated with ADHD. Lower birth weight is over twice more often observed in boys with ADHD than in control group. Although this phenomenon may reduce the rate of overweight in the studied group, ADHD remains strongly associated with increased prevalence of overweight.

Is Health Education among the Decisive Factors for the Diet Quality of Pregnant Women in Poland?

Health education (HE), an educational process that leads to increased nutritional awareness and improved health, is one of the factors influencing diet quality (DQ) during pregnancy. The aim was to evaluate the DQ of pregnant women and its determinants considering their HE. The study included 122 pregnant women aged 20-40 years. DQ was assessed using the Kom-PAN® questionnaire and the Pro-Healthy Diet Index (pHDI). Data collected included dietary habits, socio-demographic data, education level, place of residence, and maternal lifestyle-related characteristics, namely, pre-pregnancy weight, trimester of pregnancy, and pre-pregnancy and pregnancy physical activity (PA). Weekly energy expenditure was determined using the Polish version of the PPAQ questionnaire. HE at school more than tripled the odds of a higher DQ. Women in their second trimester were 54% more likely to have a higher DQ than women in their third trimester of pregnancy. Undertaking pre-pregnancy PA increased the odds of a higher DQ 2.5 times. Comparative analyses performed in a group of women with HE (HEG, n = 33) and without HE (nHEG, n = 89) showed better DQ in the former, but this was still unsatisfactory in health-promoting properties. The results obtained showed that the HE and trimester of pregnancy and pre-pregnancy Pa influenced DQ in pregnant women.

Assessment of Biochemical Parameters in 8- and 9-Year-Old Children with Excessive Body Weight Participating in a Year-Long Intervention Program.

Childhood obesity represents a significant challenge both clinically and socio-economically. This study aimed to assess specific biochemical parameters, particularly glucose, insulin and lipid profile, before and after a year-long intervention program in 8- and 9-year-old children with excessive body weight living in Szczecin, Poland from 2016 to 2018. The research comprised two phases: screening in elementary schools and intervention in the outpatient clinic of the clinical Pomeranian Medical University hospital. Out of 11,494 8- to 9-year-olds in Szczecin, 42.54% (4890) participated in the screening. In the intervention phase, 515 children were examined. Anthropometric measurements were recorded at each visit, and blood samples were collected during the first and fourth visits. In the statistical analysis, the Kolmogorov-Smirnov, t-Student and ANOVA tests were employed (with statistical significance when p ≤ 0.05). Results highlighted a significant proportion of children exhibiting disruptions in carbohydrate and lipid metabolism. A total of 8.6% of participants had elevated total cholesterol, 9.7% had reduced HDL, 13.4% had elevated LDL, and 21.2% had elevated triglycerides. Initially, abnormal fasting glucose was detected in 4.7% of children, and elevated insulin levels in 3.1%. Metabolic disorders persisted post-intervention despite BMI improvement. The results emphasize the necessity for prolonged programs with frequent follow-ups targeting weight normalization in children.

Effects of 12-Month Interdisciplinary Interventions in 8- and 9-Year-Old Children with Excess Body Weight.

Childhood obesity remains one of the most serious medical challenges of the 21st century. The aim of the study was to obtain epidemiological data on the prevalence of overweight and obesity among 8- and 9-year-old children in Szczecin, and to evaluate the effectiveness of medical intervention in the form of a year of interdisciplinary work with children with excess body weight. The study consisted of two main stages: I-screening, II-intervention. The program was implemented for three consecutive years, starting in 2016-2018. The entire population of 8-9-year-olds in Szczecin is 11,494 children. In the screening part of the study, 4890 children took part, whose parent agreed to participate (42.54%). In the intervention part of the study, we analyzed a group of 515 children. Children were further divided into subgroups according to the number of visits completed. Anthropometric parameters were measured on each visit. The prevalence of overweight and obesity in the screened population was 16.9% and 6.4%, respectively. Statistically significant changes were observed in BMI (Body Mass Index) percentiles and BMI z-scores, as well as WHR (Waist-Hip Ratio) during the one year observation time. The best effects were achieved by the 3rd visit (for the first 6 months of the program). Thereafter, the effects diminished due to the longer interval between the 3rd and 4th visits (6 months). There is the need for long-term programs for the prevention of excessive body weight in children and adolescents with frequent checkpoints.

Nicotinamide riboside kinase 1 protects against diet and age-induced pancreatic ß-cell failure.

OBJECTIVE: Disturbances in NAD+ metabolism have been described as a hallmark for multiple metabolic and age-related diseases, including type 2 diabetes. While alterations in pancreatic ß-cell function are critical determinants of whole-body glucose homeostasis, the role of NAD+ metabolism in the endocrine pancreas remains poorly explored. Here, we aimed to evaluate the role of nicotinamide riboside (NR) metabolism in maintaining NAD+ levels and pancreatic ß-cell function in pathophysiological conditions. METHODS: Whole body and pancreatic ß-cell-specific NRK1 knockout (KO) mice were metabolically phenotyped in situations of high-fat feeding and aging. We also analyzed pancreatic ß-cell function, ß-cell mass and gene expression. RESULTS: We first demonstrate that NRK1, the essential enzyme for the utilization of NR, is abundantly expressed in pancreatic ß-cells. While NR treatment did not alter glucose-stimulated insulin secretion in pancreatic islets from young healthy mice, NRK1 knockout mice displayed glucose intolerance and compromised ß-cells response to a glucose challenge upon high-fat feeding or aging. Interestingly, ß cell dysfunction stemmed from the functional failure of other organs, such as liver and kidney, and the associated changes in circulating peptides and hormones, as mice lacking NRK1 exclusively in ß-cells did not show altered glucose homeostasis. CONCLUSIONS: This work unveils a new physiological role for NR metabolism in the maintenance of glucose tolerance and pancreatic ß-cell function in high-fat feeding or aging conditions.

Pro-Healthy Diet Properties and Its Determinants among Aging Masters Athletes.

Qualitative dietary assessments are not common in aging athletes. Therefore, this study aimed to evaluate diet quality and its determinants among aging masters athletes. Eighty-six participants of the 8th World Masters Indoor Athletics Championships were enrolled in the study (age range 36-65 years). Three subgroups were distinguished to represent countries with different eating habits. Body composition was measured by bioelectrical impedance. Eating habits and diet quality were assessed using the Dietary Habits and Nutrition Beliefs Questionnaire (KomPAN®, Warszawa, Poland), and the Pro-healthy Diet Index (pHDI-10). Dietary quality determinants were identified by a multiple regression model conducted for each subgroup separately (Great Britain, France, and Poland). The results showed that none of the subgroups adhered to the reference intake of products with beneficial health outcomes. This was particularly noticeable in the insufficient consumption of whole grain products, dairy, and fish. The fish and vegetables consumption frequency significantly differentiated the eating habits of the studied groups. Diet quality determinants varied depending on the group. However, in each of them, fruit consumption was one of the components of a good-quality diet. The obtained results can be used by institutions providing health education among the elderly to develop an appropriate strategy aimed at changing inappropriate eating habits.

The Predictors of Obesity among Urban Girls and Boys Aged 8-10 Years-A Cross-Sectional Study in North-Western Poland.

BACKGROUND: Children worldwide are increasingly becoming overweight and obese and developing related health problems, including hypertension, lipid disorders, abnormal glucose tolerance, type 2 diabetes, and secondary psychological disorders. The aim of the study was to determine sociodemographic risk factors that predict an increase in BMI in children at an early school age. MATERIAL AND METHOD: The study covered 4972 children aged 8-10 years, including boys (N = 2461) and girls (N = 2511). Measurements of basic anthropometric indicators were used, such as body height, body weight, body composition, and physical fitness. The criteria developed by the International Obesity Task Force (IOTF) were adopted. Sociodemographic features were analyzed based on a diagnostic survey. IBM SPSS Statistics v.25 (Mineral Midrange SA, Warsaw, Poland) and IBM SPSS Amos software (Mineral Midrange SA, Warsaw, Poland) were used to perform descriptive statistics, the Kolmogorov-Smirnov test, Pearson's chi-square test, Student's t-test, and the Mann-Whitney U test. The statistical significance index was assumed to be p < 0.05, while p < 0.01 was taken as an indicator of a trend which was not completely statistically significant. RESULTS: Both the children and their parents had mainly moderate BMI. A total of 78.7% of children were within the weight norm. Among girls, extreme obesity was two times more frequent than extreme underweight. The examined boys were significantly taller, heavier, and had a higher BMI than girls. There were significant differences between boys and girls in BMI; however, gender alone accounted for less than 1% variance. The influence of parents' characteristics was much greater, increasing the explained variance to 10%. Body weight of mothers and fathers (p < 0.001), mother's height (p < 0.01) and both parents' level of education (p < 0.001) were detected as significant predictors of children's BMI. CONCLUSIONS: The analysis of selected sociodemographic and health factors determining the BMI of the child population indicates the need for preventive action and health promotion both among children and their parents.

The plant product quinic acid activates Ca2+ -dependent mitochondrial function and promotes insulin secretion from pancreatic beta cells.

BACKGROUND AND PURPOSE: Quinic acid (QA) is an abundant natural compound from plant sources which may improve metabolic health. However, little attention has been paid to its effects on pancreatic beta-cell functions, which contribute to the control of metabolic health by lowering blood glucose. Strategies targeting beta-cell signal transduction are a new approach for diabetes treatment. This study investigated the efficacy of QA to stimulate beta-cell function by targeting the basic molecular machinery of metabolism-secretion coupling. EXPERIMENTAL APPROACH: We measured bioenergetic parameters and insulin exocytosis in a model of insulin-secreting beta-cells (INS-1E), together with Ca2+ homeostasis, using genetically encoded sensors, targeted to different subcellular compartments. Islets from mice chronically infused with QA were also assessed. KEY RESULTS: QA triggered transient cytosolic Ca2+ increases in insulin-secreting cells by mobilizing Ca2+ from intracellular stores, such as endoplasmic reticulum. Following glucose stimulation, QA increased glucose-induced mitochondrial Ca2+ transients. We also observed a QA-induced rise of the NAD(P)H/NAD(P)+ ratio, augmented ATP synthase-dependent respiration, and enhanced glucose-stimulated insulin secretion. QA promoted beta-cell function in vivo as islets from mice infused with QA displayed improved glucose-induced insulin secretion. A diet containing QA improved glucose tolerance in mice. CONCLUSIONS AND IMPLICATIONS: QA modulated intracellular Ca2+ homeostasis, enhancing glucose-stimulated insulin secretion in both INS-1E cells and mouse islets. By increasing mitochondrial Ca2+ , QA activated the coordinated stimulation of oxidative metabolism, mitochondrial ATP synthase-dependent respiration, and therefore insulin secretion. Bioactive agents raising mitochondrial Ca2+ in pancreatic beta-cells could be used to treat diabetes.

Endogenous nicotinamide riboside metabolism protects against diet-induced liver damage.

Supplementation with the NAD+ precursor nicotinamide riboside (NR) ameliorates and prevents a broad array of metabolic and aging disorders in mice. However, little is known about the physiological role of endogenous NR metabolism. We have previously shown that NR kinase 1 (NRK1) is rate-limiting and essential for NR-induced NAD+ synthesis in hepatic cells. To understand the relevance of hepatic NR metabolism, we generated whole body and liver-specific NRK1 knockout mice. Here, we show that NRK1 deficiency leads to decreased gluconeogenic potential and impaired mitochondrial function. Upon high-fat feeding, NRK1 deficient mice develop glucose intolerance, insulin resistance and hepatosteatosis. Furthermore, they are more susceptible to diet-induced liver DNA damage, due to compromised PARP1 activity. Our results demonstrate that endogenous NR metabolism is critical to sustain hepatic NAD+ levels and hinder diet-induced metabolic damage, highlighting the relevance of NRK1 as a therapeutic target for metabolic disorders.

The NAD-Booster Nicotinamide Riboside Potently Stimulates Hematopoiesis through Increased Mitochondrial Clearance.

It has been recently shown that increased oxidative phosphorylation, as reflected by increased mitochondrial activity, together with impairment of the mitochondrial stress response, can severely compromise hematopoietic stem cell (HSC) regeneration. Here we show that the NAD+-boosting agent nicotinamide riboside (NR) reduces mitochondrial activity within HSCs through increased mitochondrial clearance, leading to increased asymmetric HSC divisions. NR dietary supplementation results in a significantly enlarged pool of progenitors, without concurrent HSC exhaustion, improves survival by 80%, and accelerates blood recovery after murine lethal irradiation and limiting-HSC transplantation. In immune-deficient mice, NR increased the production of human leucocytes from hCD34+ progenitors. Our work demonstrates for the first time a positive effect of NAD+-boosting strategies on the most primitive blood stem cells, establishing a link between HSC mitochondrial stress, mitophagy, and stem-cell fate decision, and unveiling the potential of NR to improve recovery of patients suffering from hematological failure including post chemo- and radiotherapy.

Perinatal Risk Factors and ADHD in Children and Adolescents: A Hierarchical Structure of Disorder Predictors.

OBJECTIVE: The aim of the study was to hierarchically assess the predictive power of low and high birth weight, pre-term and post-term birth, and low Apgar score as the risk factors for ADHD. METHOD: The data of 132 boys diagnosed with ADHD and 146 boys from control group, aged 6 to 18 years, have been analyzed. The boys were categorized according to term of birth, birth weight, and Apgar score. CART method (Classification and Regression Trees) was used for assessment of the relationship between perinatal factors and the risk of ADHD. RESULTS: Low Apgar score (21.97% vs. 13.01%) and post-term birth (12.12% vs. 0.68%) were more frequent in the sample than in the control group. CART method additionally indicated low birth weight as associated with the risk of ADHD. Among analyzed risk factors, Apgar score had the highest predictive value. CONCLUSION: The decreased Apgar score is the most important perinatal risk factor of ADHD. Research results also indicated a high significance of post-term birth in predicting the disorder.

Assessment pf physical fitness of 8 and 9-year-old children from Szczecin,Poland, involved in the obesity prevention program - pilot study.

INTRODUCTION: Increasing incidence of excess weight and poor physical fitness of children validates the need for preventive actions. The Szczecin municipality (gmina Szczecin) runs the "Odwazna ósemka" ("The Brave Eight") program - Prevention of excess weight and obesity in 8 and 9-year-old children attending elementary school in Szczecin, Poland. AIM: The assessment of physical fitness as well as the prevalence and intensity of excess body weight and blood pressure rates among the 8 and 9-year-old children attending elementary school in Szczecin, Poland. MATERIAL AND METHODS: Between 6th December 2016 and 3rd December 2017, 3407 8 and 9-year-old children were examined (1757 girls and 1650 boys). BMI (Body Mass Index) as well as WHR (Waist Hip Ratio) were calculated. All the children were assessed according to criteria established by the International Obesity Task Force (IOTF). The examination included basic anthropometric measurements, such as: body height and weight, waist and hip circumference, blood pressure, body constitution analysis, and physical fitness assessment. RESULTS: Excess body weight was diagnosed in 822 patients, which is 24.1% of the examined population. 369 patients were diagnosed with elevated blood pressure (10.8%). Very poor physical fitness - test abandoned before the completion (HR>180/min), was diagnosed in 151 children (4.5%), very poor physical fitness was diagnosed in 234 children (7%), poor physical fitness was diagnosed in 827 children (24.9%), sufficient physical fitness was diagnosed in 961 children (29.2%), good physical fitness was diagnosed in 650 children (19.5%), very good physical fitness was diagnose in 428 children (12.8%) and excellent in 70 children (2.1%). CONCLUSION: The fact of unsatisfactory physical fitness and excess body weight in children from Szczecin is unsettling. There is ceratainly a need for preventive measures in the broad sense.

Nicotinamide riboside kinases display redundancy in mediating nicotinamide mononucleotide and nicotinamide riboside metabolism in skeletal muscle cells.

OBJECTIVE: Augmenting nicotinamide adenine dinucleotide (NAD+) availability may protect skeletal muscle from age-related metabolic decline. Dietary supplementation of NAD+ precursors nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) appear efficacious in elevating muscle NAD+. Here we sought to identify the pathways skeletal muscle cells utilize to synthesize NAD+ from NMN and NR and provide insight into mechanisms of muscle metabolic homeostasis. METHODS: We exploited expression profiling of muscle NAD+ biosynthetic pathways, single and double nicotinamide riboside kinase 1/2 (NRK1/2) loss-of-function mice, and pharmacological inhibition of muscle NAD+ recycling to evaluate NMN and NR utilization. RESULTS: Skeletal muscle cells primarily rely on nicotinamide phosphoribosyltransferase (NAMPT), NRK1, and NRK2 for salvage biosynthesis of NAD+. NAMPT inhibition depletes muscle NAD+ availability and can be rescued by NR and NMN as the preferred precursors for elevating muscle cell NAD+ in a pathway that depends on NRK1 and NRK2. Nrk2 knockout mice develop normally and show subtle alterations to their NAD+ metabolome and expression of related genes. NRK1, NRK2, and double KO myotubes revealed redundancy in the NRK dependent metabolism of NR to NAD+. Significantly, these models revealed that NMN supplementation is also dependent upon NRK activity to enhance NAD+ availability. CONCLUSIONS: These results identify skeletal muscle cells as requiring NAMPT to maintain NAD+ availability and reveal that NRK1 and 2 display overlapping function in salvage of exogenous NR and NMN to augment intracellular NAD+ availability.

Circadian and Feeding Rhythms Orchestrate the Diurnal Liver Acetylome.

Lysine acetylation is involved in various biological processes and is considered a key reversible post-translational modification in the regulation of gene expression, enzyme activity, and subcellular localization. This post-translational modification is therefore highly relevant in the context of circadian biology, but its characterization on the proteome-wide scale and its circadian clock dependence are still poorly described. Here, we provide a comprehensive and rhythmic acetylome map of the mouse liver. Rhythmic acetylated proteins showed subcellular localization-specific phases that correlated with the related metabolites in the regulated pathways. Mitochondrial proteins were over-represented among the rhythmically acetylated proteins and were highly correlated with SIRT3-dependent deacetylation. SIRT3 activity being nicotinamide adenine dinucleotide (NAD)+ level-dependent, we show that NAD+ is orchestrated by both feeding rhythms and the circadian clock through the NAD+ salvage pathway but also via the nicotinamide riboside pathway. Hence, the diurnal acetylome relies on a functional circadian clock and affects important diurnal metabolic pathways in the mouse liver.

NRK1 controls nicotinamide mononucleotide and nicotinamide riboside metabolism in mammalian cells.

NAD+ is a vital redox cofactor and a substrate required for activity of various enzyme families, including sirtuins and poly(ADP-ribose) polymerases. Supplementation with NAD+ precursors, such as nicotinamide mononucleotide (NMN) or nicotinamide riboside (NR), protects against metabolic disease, neurodegenerative disorders and age-related physiological decline in mammals. Here we show that nicotinamide riboside kinase 1 (NRK1) is necessary and rate-limiting for the use of exogenous NR and NMN for NAD+ synthesis. Using genetic gain- and loss-of-function models, we further demonstrate that the role of NRK1 in driving NAD+ synthesis from other NAD+ precursors, such as nicotinamide or nicotinic acid, is dispensable. Using stable isotope-labelled compounds, we confirm NMN is metabolized extracellularly to NR that is then taken up by the cell and converted into NAD+. Our results indicate that mammalian cells require conversion of extracellular NMN to NR for cellular uptake and NAD+ synthesis, explaining the overlapping metabolic effects observed with the two compounds.

Mfn1 Deficiency in the Liver Protects Against Diet-Induced Insulin Resistance and Enhances the Hypoglycemic Effect of Metformin.

Mitochondrial function can be influenced by mitochondrial shape and connectivity with other cellular organelles through fusion and fission processes. Disturbances in mitochondrial architecture and mitochondrial fusion-related genes are observed in situations of type 2 diabetes and obesity, leading to a highly fissioned mitochondrial network. To directly test the effect of reduced mitochondrial fusion on hepatic metabolism, we generated mice with a liver-specific deletion of the Mfn1 gene (Mfn1LKO) and monitored their energy homeostasis, mitochondrial function, and susceptibility to diet-induced insulin resistance. Livers from Mfn1LKO mice displayed a highly fragmented mitochondrial network. This was coupled to an enhanced mitochondrial respiration capacity and a preference for the use of lipids as the main energy source. Although Mfn1LKO mice are similar to control mice fed a low-fat diet, they are protected against insulin resistance induced by a high-fat diet. Importantly, Mfn1 deficiency increased complex I abundance and sensitized animals to the hypoglycemic effect of metformin. Our results suggest that targeting Mfn1 could provide novel avenues to ameliorate glucose homeostasis in obese patients and improve the effectiveness of metformin.

Attention-Deficit/Hyperactivity Disorder is Related to Decreased Weight in the Preschool Period and to Increased Rate of Overweight in School-Age Boys.

OBJECTIVE: Previous studies have associated attention-deficit/hyperactivity disorder (ADHD) with growth deviations and obesity. However, available data regarding the growth of children with ADHD in their early childhood are insufficient. Therefore, we aimed to examine whether there are differences in body size between preschool boys with and without ADHD. METHODS: The study used cross-sectional and retrospective longitudinal data concerning 112 boys with ADHD and a community-based sample of 308 boys without ADHD. The groups were homogeneous in terms of socioeconomic status, place of residence, term of birth, and birth weight. The average age of diagnosis was 8.3 years, and none of boys had been treated with stimulants before they were 7 years of age. Comparisons were made at the ages of 2, 4, and 6 years, for World Health Organization (WHO)-norm-standardized height, weight, body mass index (BMI), prevalence of underweight, overweight, and obesity. Separate analysis were made for the cross-sectional measurements of current body size. RESULTS: Boys with ADHD at the age of 2 had significantly lower z scores for weight (t=-1.98, p=0.04) and BMI (t=-2.09, p=0.04), and at the age of 4 for weight (t=-2.05, p=0.04) than the boys from the control group. A significantly lower percentage of overweight/obesity was observed in boys with ADHD at the age of 2 in comparison with the control group. At the age of 6, boys with ADHD were underweight more often. Cross-sectional analysis of current body size showed that boys with ADHD had lower z scores for height (t=-3.08, p=0.002) and higher z scores (t=3.13, p=0.002) for BMI. Overweight was more frequent in this group. CONCLUSIONS: Preschool boys with ADHD (age of 2-6 years) have a tendency toward lower body weight than their peers. But in subsequent phases of development, they are shorter and more frequently overweight than boys without ADHD, when place of residence, socioeconomic status, term of birth, birth weight, comorbid conditions, and treatment are controlled.

SIRT1 enhances glucose tolerance by potentiating brown adipose tissue function.

OBJECTIVE: SIRT1 has been proposed to be a key signaling node linking changes in energy metabolism to transcriptional adaptations. Although SIRT1 overexpression is protective against diverse metabolic complications, especially in response to high-fat diets, studies aiming to understand the etiology of such benefits are scarce. Here, we aimed to identify the key tissues and mechanisms implicated in the beneficial effects of SIRT1 on glucose homeostasis. METHODS: We have used a mouse model of moderate SIRT1 overexpression, under the control of its natural promoter, to evaluate glucose homeostasis and thoroughly characterize how different tissues could influence insulin sensitivity. RESULTS: Mice with moderate overexpression of SIRT1 exhibit better glucose tolerance and insulin sensitivity even on a low fat diet. Euglycemic-hyperinsulinemic clamps and in-depth tissue analyses revealed that enhanced insulin sensitivity was achieved through a higher brown adipose tissue activity and was fully reversed by housing the mice at thermoneutrality. SIRT1 did not influence brown adipocyte differentiation, but dramatically enhanced the metabolic transcriptional responses to ß3-adrenergic stimuli in differentiated adipocytes. CONCLUSIONS: Our work demonstrates that SIRT1 improves glucose homeostasis by enhancing BAT function. This is not consequent to an alteration in the brown adipocyte differentiation process, but as a result of potentiating the response to ß3-adrenergic stimuli.