Adventure and Games for Diabetes Prevention

According to the Centers for Disease Control and Prevention, diabetes prevention represents a critical need for the health education curriculum, given the rise of the disease and its precondition for today’s youth. An active understanding of diabetes encourages young people to take control of the nutritional and exercise factors that keep the disease in check. When teachers use experiential activities, or “adventure” education, students perform tasks that illustrate conceptual content and reinforce learning. Research has found that current modalities to be successful but lacking the physicality to meet the recommendations of the American Heart Association and the Society of Health and Physical Educators. Games such as Toll Road Boogie; Tom and Jerry, or Insulin and Sugar; Wacky Receptor; and Tusker Monster, or Fat Cell Tag help children meet the 60 min of physical activity that are required most days of the week. This article offers several examples of how to design and implement games and incentives into lessons that are both enjoyable and illustrative of diabetes prevention-based education for ages 8 to 18.

Carnosic Acid Attenuates the Free Fatty Acid-Induced Insulin Resistance in Muscle Cells and Adipocytes

Elevated blood free fatty acids (FFAs), as seen in obesity, impair insulin action leading to insulin resistance and Type 2 diabetes mellitus. Several serine/threonine kinases including JNK, mTOR, and p70 S6K cause serine phosphorylation of the insulin receptor substrate (IRS) and have been implicated in insulin resistance. Activation of AMP-activated protein kinase (AMPK) increases glucose uptake, and in recent years, AMPK has been viewed as an important target to counteract insulin resistance. We reported previously that carnosic acid (CA) found in rosemary extract (RE) and RE increased glucose uptake and activated AMPK in muscle cells. In the present study, we examined the effects of CA on palmitate-induced insulin-resistant L6 myotubes and 3T3L1 adipocytes. Exposure of cells to palmitate reduced the insulin-stimulated glucose uptake, GLUT4 transporter levels on the plasma membrane, and Akt activation. Importantly, CA attenuated the deleterious effect of palmitate and restored the insulin-stimulated glucose uptake, the activation of Akt, and GLUT4 levels. Additionally, CA markedly attenuated the palmitate-induced phosphorylation/activation of JNK, mTOR, and p70S6K and activated AMPK. Our data indicate that CA has the potential to counteract the palmitate-induced muscle and fat cell insulin resistance.

Adipokines Profile and Inflammation Biomarkers in Prepubertal Population with Obesity and Healthy Metabolic State

(1) Background and aims: Obesity and high body max index (BMI) have been linked to elevated levels of inflammation serum markers such as C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), adiponectin, and resistin. It has been described that adipose tissue presents a high production and secretion of these diverse pro-inflammatory molecules, which may have local effects on the physiology of the fat cell and also systemic effects on other organs. Our aim was to evaluate the impact that lifestyle modifications, following a Mediterranean Diet (MedDiet) program and physical activity (PA) training, would have on inflammatory biomarkers in a metabolically healthy prepubertal population with obesity (MHOPp) from Malaga (Andalusia, Spain). (2) Methods: 144 MHOPp subjects (aged 5–9 years) were included in this study as they met ≤1 of the following criteria: waist circumference and blood pressure ≥ 90 percentile, triglycerides > 90 mg/dL, high-density lipoprotein cholesterol (HDL-c) < 40 mg/dL, or impaired fasting glucose (≥100 md/dL). Selected subjects followed a personalized intensive lifestyle modification. Anthropometric measurements, inflammation biomarkers, and adipokine profile were analyzed after 12 and 24 months of intervention. (3) Results: 144 MHOPp participants (75 boys—52% and 69 girls—48%; p = 0.62), who were 7.8 ± 1.4 years old and had a BMI 24.6 ± 3.3 kg/m2, were included in the study. After 24 months of MedDiet and daily PA, a significant decrease in body weight (−0.5 ± 0.2 SD units; p < 0.0001) and BMI (−0.7 ± 0.2 SD units; p < 0.0001) was observed in the total population with respect to baseline. Serum inflammatory biomarkers (IL-6, TNF-alpha, and CRP) after 24 months of intervention were significantly reduced. Adipokine profile (adiponectin and resistin) did not improve with the intervention, as adiponectin levels significantly decreased and resistin levels increased in all the population. Inflammatory biomarkers and adipokine profile had a significant correlation with anthropometric parameters, body composition, and physical activity. (5) Conclusions: After 24 months of lifestyle modification, our MHOPp reduced their Z-score of BMI, leading to an improvement of inflammatory biomarkers but inducing deterioration in the adipokine profile, which does not improve with MedDiet and physical activity intervention. An adequate education within the family about healthier habits is necessary to prevent and reduce an excessive increase in obesity in childhood.

Fatquant: An automated image analysis tool for identification of fat cells in heterogeneous hematoxylin and eosin tissue sections.

Hematoxylin and eosin (H and E) is one of the common histological staining techniques that provides information on the tissue cytoarchitecture. Adipose (fat) cells accumulation in pancreas has been shown to impact beta cell survival and its endocrine function. The current automated tools available for fat analysis are suited for white adipose tissue which is homogeneous and easier to segment unlike heterogeneous tissues such as pancreas where fat cells continue to play critical physiopathological functions. In the current study, we present an automated fat analysis tool, Fatquant, where mathematical formula to calculate diagonal of a square drawn inside circle is utilized for identification and analysis of fat cells in heterogeneous H and E tissue sections. Using histological images of pancreas from a publicly available database, we show an area accuracy overlap of 89-93% between manual versus automated algorithm based fat cell detection.

Transcriptome Analysis of Umbilical Cord Mesenchymal Stem Cells Revealed Fetal Programming Due to Chorioamnionitis

Although chorioamnionitis (CAM) has been demonstrated to be associated with numerous short- and long-term morbidities, the precise mechanisms remain unclear. One of the reasons for this is the lack of appropriate models for analyzing the relationship between the fetal environment and chorioamnionitis and fetal programming in humans. In this study, we aimed to clarify the fetal programming caused by CAM using the gene expression profiles of UCMSCs.. From nine preterm neonates with CAM (n=4) or without CAM (n=5), we established UCMSCs.The gene expression profiles obtained by RNA-seq analysis revealed distinctive changes in the CAM group USMSCs. The UCMSCs in the CAM group had a myofibroblast-like phenotype with significantly increased expression levels of myofibroblast-related genes, including α-smooth muscle actin (p<0.05). In the pathway analysis, the genes involved in DNA replication and G1 to S cell cycle control were remarkably decreased, suggesting that cellular proliferation was impaired, as confirmed by the cellular proliferation assay (p<0.01 ~ 0.05). Pathway analysis revealed that genes related to white fat cell differentiation were significantly increased. Our results could explain the long-term outcomes of patients who were exposed to CAM and revealed that UCMSCs could be an in vitro model of fetal programming affected by CAM.

Adipose Tissue Inflammation is Not Related to Adipose Insulin Resistance in Humans

The role of adipose tissue (AT) inflammation on AT function in humans is unclear. We tested whether AT macrophage (ATM) content, cytokine gene expression and senescent cell burden (markers of AT inflammation) predict AT insulin resistance measured as the insulin concentration that suppresses lipolysis by 50% (IC₅₀). We studied 86 volunteers with normal weight or obesity at baseline, and a subgroup of 25 volunteers with obesity before and after weight loss. There was a strong, positive relationship between IC₅₀and abdominal subcutaneous and femoral fat cell size (FCS). The positive, univariate relationships between IC₅₀and abdominal AT inflammatory markers: CD68, CD14, CD206 ATM/100 adipocytes, senescent cells, IL-6 and TNF-α mRNA were not significant after adjustment for FCS. A 10% weight loss significantly reduced IC₅₀, however, there was no reduction in adipose ATM content, senescent cells or cytokine gene expression. Our study suggests that commonly used markers of AT inflammation are not causally linked to AT insulin resistance, whereas FCS is a strong predictor of AT insulin resistance with respect to lipolysis.

Adipose Tissue Inflammation is Not Related to Adipose Insulin Resistance in Humans

The role of adipose tissue (AT) inflammation on AT function in humans is unclear. We tested whether AT macrophage (ATM) content, cytokine gene expression and senescent cell burden (markers of AT inflammation) predict AT insulin resistance measured as the insulin concentration that suppresses lipolysis by 50% (IC₅₀). We studied 86 volunteers with normal weight or obesity at baseline, and a subgroup of 25 volunteers with obesity before and after weight loss. There was a strong, positive relationship between IC₅₀and abdominal subcutaneous and femoral fat cell size (FCS). The positive, univariate relationships between IC₅₀and abdominal AT inflammatory markers: CD68, CD14, CD206 ATM/100 adipocytes, senescent cells, IL-6 and TNF-α mRNA were not significant after adjustment for FCS. A 10% weight loss significantly reduced IC₅₀, however, there was no reduction in adipose ATM content, senescent cells or cytokine gene expression. Our study suggests that commonly used markers of AT inflammation are not causally linked to AT insulin resistance, whereas FCS is a strong predictor of AT insulin resistance with respect to lipolysis.

A unique adipocyte progenitor population promotes age-related adiposity

The average fat mass in adults increases dramatically with age, and older people often suffer from visceral obesity and related adverse metabolic disorders. Unfortunately, how aging leads to fat accumulation is poorly understood. It is known that fat cell (adipocyte) turnover is very low in young mice, similar to that in young humans. Here, we find that mice mimic age-related fat expansion in humans. In vivo lineage tracing shows that massive adipogenesis (the generation of new adipocytes), especially in the visceral fat, is triggered during aging. Thus, in contrast to most types of adult stem cells that exhibit a reduced ability to proliferate and differentiate, the adipogenic potential of adipocyte progenitor cells (APCs) is unlocked by aging. In vivo transplantation and 3D imaging of transplants show that APCs in aged mice cell-autonomously gain high adipogenic capacity. Single-cell RNA sequencing analyses reveal that aging globally remodels APCs. Herein, we identify a novel committed preadipocyte population that is age-specific (CP-A), existing both in mice and humans, with a global activation of proliferation and adipogenesis pathways. CP-A cells display high proliferation and adipogenesis activity, both in vivo and in vitro. Macrophages may regulate the remodeling of APCs and the generation of CP-A cells during aging. Together, these findings define a new fundamental mechanism involved in fat tissue aging and offer prospects for preventing and treating age-related metabolic disorders.

A Distinctive NAFLD Signature in Adipose Tissue from Women with Severe Obesity

Development and severity of nonalcoholic fatty liver disease (NAFLD) have been linked to obesity and white adipose tissue (WAT) dysfunction plays a key role in this relation. We compared the main features of subcutaneous (SAT) and visceral WAT (VAT) tissue dysfunction in 48 obese women without (Ob) and with NAFLD (Ob-NAFLD) undergoing bariatric surgery and matched for age, BMI and T2D status. Fat cell area, adipocyte size distribution, the degree of histological fibrosis and the mRNA expression of adipokines and genes implicated in inflammation, adipogenesis, angiogenesis, metabolism and extracellular matrix remodeling were measured by RT-qPCR in both fat depots. Ob-NAFLD group showed higher TG and lower HDL circulating levels, increased VAT fat cell area and similar WAT fibrosis in comparison with Ob group. A sPLS-DA was performed in order to identify the set of genes that better characterize the presence of NAFLD. Finally, we build a multinomial logistic model including seven genes that explained 100% of the variance in NAFLD and correctly predicted 100% of cases. Our data support the existence of distinctive NAFLD signatures in WAT from women with severe obesity. A better understanding of these pathways may help in future strategies for the prevention and treatment of NAFLD.