Onset Of Obesity Research Articles

Smell Impairment in Stage I-II Obesity: Correlation with Biochemical Regulators and Clinical Aspects.

To evaluate the differences in olfactory sensitivity, nutritional habits, levels of modulators of feeding and smell, bioelectrical impedance analysis (BIA) measures and metabolic assays between two groups of participants with stage I and II obesity and reciprocal relationships between these parameters. Eighteen participants with stage I (11 female; mean age=54.3 ± 13.1 years) and 20 participants with stage II (10 female; mean age=54.5 ± 11.9) obesity underwent a food frequency questionnaire and Sniffin' Sticks® test battery, anthropometric parameters, and BIA measurements as well as metabolic assays (including plasma levels of leptin, insulin, ghrelin, glucose, insulin-like growth factor-1 [IGF-1] and usual laboratory parameters). The stage II obesity participants demonstrated significant higher levels of insulin and leptin and lower levels of ghrelin and IGF-1, a reduction in odor identification (OI) and in total olfactory score, and an increase in visceral and total fat percentage. Among a mosaic of multiple correlations, ghrelin was found to positively correlate with OI and leptin negatively with odor discrimination. The present study expands the notions positing the olfactory perception - and its connections with metabolic cues, foods habits and BIA measures - changes across the two most important obesity stages. This could ameliorate clinical and research deepening of obesity-related olfactory behavior with possible consequences on diagnosis, treatment and prevention of onset and development of obesity, thus opening possible future strategies involving multidisciplinary contributions. 3 Laryngoscope, 132:2028-2035, 2022.

Body Mass Index Trajectories From Childhood to Adulthood and Age at Onset of Overweight and Obesity: The Influence of Parents' Weight Status.

We investigated the influence of parents' weight status on their children's growth trajectories and its association with age at onset of overweight and obesity. We used 16,396 height and weight records from 3,284 youths from the Panel Study of Income Dynamics, followed across childhood into adulthood (United States, 1997-2017). Across age groups, we modeled body mass index trajectories (ages 5-32 years) according to parents' weight status, using mixed-effect models to estimate age at onset of overweight and obesity and proportion with obesity from childhood to adulthood. There were large differences in growth patterns according to parents' weight status: Children of parents with obesity had, on average, overweight at age 6 (95% confidence interval (CI): 5, 7) and steep growth trajectories until age 12; children of normal-weight parents had slower increases in body mass index, reaching overweight on average at age 25 (95% CI: 24, 27). By age 30, 30% (95% CI: 28, 31) of youths had obesity. Differences in early-life growth persisted into adulthood: 48% (95% CI: 45, 52) of adult children of parents with obesity had obesity versus 16% (95% CI: 14, 19) of those of normal-weight parents. Trajectories to unhealthy weight were heavily influenced by parents' weight status, especially before age 12, children of parents with obesity having overweight 19 earlier in life than children of normal-weight parents.

Childhood obesity and depression: 2020–2022

As obesity continues to remains an immense challenge to mitigate effectively, efforts to untangle its determinants continue, especially those that may exacerbate or impact childhood obesity, and its predictable and well established negative health impacts. Studied for many years in various spheres, the role played by depression has been discussed for some time in this regard, especially in light of COVID-19 pandemic imperatives and their long term mental health effects on youth. This mini review discusses some of these current ideas and related observations regarding, and whether more emphasis on fostering mental health among youth is indicated in efforts to effectively attenuate the onset and spread of childhood obesity into adulthood. Extracted from current literature, it is concluded that this is a topic of significance, but one requiring more acceptance and recognition, plus dedicated sustainable collaborative goals and supportive efforts.

The gene knockout of angiotensin II type 1a receptor improves high-fat diet-induced obesity in rat via promoting adipose lipolysis.

AimsThe renin-angiotensin system (RAS) is over-activated and the serum angiotensin II (Ang II) level increased in obese patients, while their correlations were incompletely understood. This study aims to explore the role of Ang II in diet-induced obesity by focusing on adipose lipid anabolism and catabolism.MethodsRat model of AT1aR gene knockout were established to investigate the special role of Ang II on adipose lipid metabolism. Wild-type (WT) and AT1aR gene knockout (AT1aR-/-) SD rats were fed with normal diet or high-fat diet for 12 weeks. Adipose morphology and adipose lipid synthesis and lipolysis were examined.ResultsAT1aR deficiency activated lipolysis-related enzymes and increased the levels of NEFAs and glycerol released from adipose tissue in high-fat diet rats, while did not affect triglycerides synthesis. Besides, AT1aR knockout promoted energy expenditure and fatty acids oxidation in adipose tissue. cAMP levels and PKA phosphorylation in the adipose tissue were significantly increased in AT1aR-/- rats fed with high-fat. Activated PKA could promote adipose lipolysis and thus improved adipose histomorphology and insulin sensitivity in high-fat diet rats.ConclusionsAT1aR deficiency alleviated adipocyte hypertrophy in high-fat diet rats by promoting adipose lipolysis probably via cAMP/PKA pathway, and thereby delayed the onset of obesity and related metabolic diseases.

Overnutrition Induced Cognitive Impairment: Insulin Resistance, Gut-Brain Axis, and Neuroinflammation.

Overnutrition-related obesity has become a worldwide epidemic, and its prevalence is expected to steadily rise in the future. It is widely recognized that obesity exerts negative impacts on metabolic disorders such as type 2 diabetes mellitus (T2DM) and cardiovascular diseases. However, relatively fewer reports exist on the impairment of brain structure and function, in the form of memory and executive dysfunction, as well as neurogenerative diseases. Emerging evidence indicates that besides obesity, overnutrition diets independently induce cognitive impairments via multiple mechanisms. In this study, we reviewed the clinical and preclinical literature about the detrimental effects of obesity or high-nutrition diets on cognitive performance and cerebral structure. We mainly focused on the role of brain insulin resistance (IR), microbiota-gut-brain axis, and neuroinflammation. We concluded that before the onset of obesity, short-term exposure to high-nutrition diets already blunted central responses to insulin, altered gut microbiome composition, and activated inflammatory mediators. Overnutrition is linked with the changes in protein expression in brain insulin signaling, leading to pathological features in the brain. Microbiome alteration, bacterial endotoxin release, and gut barrier hyperpermeability also occur to trigger mental and neuronal diseases. In addition, obesity or high-nutrition diets cause chronic and low-grade systematic inflammation, which eventually spreads from the peripheral tissue to the central nervous system (CNS). Altogether, a large number of unknown but potential routes interact and contribute to obesity or diet-induced cognitive impairment. The challenge for future research is to identify effective interventions involving dietary shifts and personalized therapy targeting the underlying mechanisms to prevent and improve cognition deficits.

Changes in the Incidence of Childhood Obesity.

Examine childhood obesity incidence across recent cohorts. We examined obesity incidence and prevalence across 2 cohorts of children in the United States 12 years apart using the Early Childhood Longitudinal Studies, parallel data sets following the kindergarten cohorts of 1998 and 2010 with direct anthropometric measurements at multiple time points through fifth grade in 2004 and 2016, respectively. We investigated annualized incidence rate and cumulative incidence proportion of obesity (BMI z-score ≥95th percentile based on Centers for Disease Control and Prevention weight-for-age z-scores). Among children who did not have obesity at kindergarten entry, there was a 4.5% relative increase in cumulative incidence of new obesity cases by end of fifth grade across cohorts (15.5% [14.1%-16.9%] vs 16.2% [15.0%-17.3%]), though annual incidence did not change substantially. The risk of incident obesity for children who had normal BMI at kindergarten entry stayed the same, but the risk of incident obesity among overweight kindergartners increased slightly. Social disparities in obesity incidence expanded: incidence of new cases during primary school among non-Hispanic Black children increased by 29% (95% confidence interval, 25%-34%), whereas risk for other race-ethnic groups plateaued or decreased. Children from the most socioeconomically disadvantaged households experienced 15% higher cumulative incidence across primary school in 2010 than 1998. Incidence of childhood obesity was higher, occurred at younger ages, and was more severe than 12 years previous; thus, more youths may now be at risk for health consequences associated with early onset of obesity.

Early and delayed puberty among Iranian children with obesity.

It has been hypothesized that puberty onset is disturbed as the children gain more weight. This study aimed to investigate the prevalence and risk factors of the puberty disturbances among children with obesity in Tehran, Iran. This study was performed as a cross-sectional study, investigating 168 children with obesity from Tehran, Iran, from March 2018 to February 2019. BMI percentile more than 95% was considered as the inclusion criteria. Seventy-eight (46.4%) of the assessed children were females. The mean weight, height, BMI were 89.65 (±11.01) kg, 169.88 (±8.32) centimeters and 31.13(±3.8) kg/m2, respectively. There was no difference between males and females regarding the early puberty (P=0.098), but delayed puberty was significantly higher among males (P=0.029). Our results indicated higher birth weight is associated with earlier onset of obesity in children (P=0.044). Our study demonstrated no association between obesity and early puberty in girls; however, boys with obesity had delayed puberty. We also found higher birth weight is associated with earlier onset of obesity, putting light on the importance of preventive interventions.

Metformin ameliorates olanzapine-induced disturbances in POMC neuron number, axonal projection, and hypothalamic leptin resistance

Antipsychotics have been widely accepted as a treatment of choice for psychiatric illnesses such as schizophrenia. While atypical antipsychotics such as aripiprazole are not associated with obesity and diabetes, olanzapine is still widely used based on the anticipation that it is more effective in treating severe schizophrenia than aripiprazole, despite its metabolic side effects. To address metabolic problems, metformin is widely prescribed. Hypothalamic proopiomelanocortin (POMC) neurons have been identified as the main regulator of metabolism and energy expenditure. Although the relation between POMC neurons and metabolic disorders is well established, little is known about the effects of olanzapine and metformin on hypothalamic POMC neurons. In the present study, we investigated the effect of olanzapine and metformin on the hypothalamic POMC neurons in female mice. Olanzapine administration for 5 days significantly decreased Pomc mRNA expression, POMC neuron numbers, POMC projections, and induced leptin resistance before the onset of obesity. It was also observed that coadministration of metformin with olanzapine not only increased POMC neuron numbers and projections but also improved the leptin response of POMC neurons in the olanzapine-treated female mice. These findings suggest that olanzapine-induced hypothalamic POMC neuron abnormality and leptin resistance, which can be ameliorated by metformin administration, are the possible causes of subsequent hyperphagia.

Gestational Nutrition as a Predisposing Factor to Obesity Onset in Offspring: Role for Involvement of Epigenetic Mechanism.

Maternal lifestyle has been implicated as a predisposing factor in the development of metabolic disorders in adulthood. This lifestyle includes the immediate environment, physical activity and nutrition. Maternal nutrition has direct influence on the developmental programming through biochemical alterations and can lead to modifications in the fetal genome through epigenetic mechanisms. Imbalance in basic micro or macro nutrients due to famine or food deficiency during delicate gestational periods can lead to onset of metabolic syndrome including obesity. A major example is the Dutch famine which led to a serious metabolic disorder in adulthood of affected infants. Notably due to gene variants, individualized responses to nutritional deficiencies are unconventional, therefore intensifying the need to study nutritional genomics during fetal programming. Epigenetic mechanisms can cause hereditary changes without changing the DNA sequence; the major mechanisms include small non-coding RNAs, histone modifications and most stable of all is DNA methylation. The significance association between obesity and DNA methylation is through regulation of genes implicated in lipid and glucose metabolism either directly or indirectly by hypomethylation or hypermethylation. Examples include CPT1A, APOA2, ADRB3 and POMC. Any maternal exposure to malnutrition or overnutrition that can affect genes regulating major metabolic pathways in the fetus, will eventually cause underlying changes that can predispose or cause the onset of metabolic disorder in adulthood. In this review, we examined the interaction between nutrition during gestation and epigenetic programming of metabolic syndrome.

Type 2 deiodinase p.Thr92Ala polymorphism does not affect the severity of obesity and weight loss after bariatric surgery

A single nucleotide polymorphism in the Type 2 deiodinase (DIO2) gene (p.Thr92Ala) was found to be associated with hypertension, type 2 diabetes mellitus (T2DM), insulin resistance, and body mass index (BMI). We retrospectively evaluated 182 patients to assess whether the DIO2 p.Thr92Ala was associated with severe obesity and response to bariatric surgery. Genomic DNA was extracted from peripheral blood leukocytes before surgery. Glycemic control parameters, cardiometabolic risk biomarkers (waist circumference, lipid assessment and blood pressure) and hormonal parameters were assessed at baseline and after surgery. Based on genotype evaluation, 78/182 (42.9%) patients were homozygous wild-type (Thr/Thr), 83/182 (45.6%) heterozygous (Thr/Ala), and 21/182 (11.5%) rare homozygous (Ala/Ala). Age at the time of the first evaluation in our Unit was significantly lower in patients with DIO2 p.Thr92Ala. No significant association was observed between DIO2 p.Thr92Ala and BMI, excess weight, waist circumference, Homa Index. The prevalence of comorbidities was not associated with allele distribution except for hypertension that was more frequent in wild-type patients (p = 0.03). After bariatric surgery, excess weight loss (EWL) % and remission from comorbidities occurred without differences according to genotypes. DIO2 p.Thr92Ala does not affect the severity of obesity and its complications, but it seems to determine an earlier onset of morbid obesity. The presence of polymorphism seems not to impact on the response to bariatric surgery, both in terms of weight loss and remission of comorbidities.

Profiling hypertrophic adipocytes in humans, from transcriptomics to diagnostics.

Obesity rates continue to rise worldwide, with a concomitant increase in co-morbidities, including metabolic disease, cardiovascular disease and cancer. The onset of obesity is most often characterized by an increase in the size of white adipose tissue fat cells (adipocyte hypertrophy) and secondary to this by adipocyte hyperplasia. Adipocyte hypertrophy is strongly linked to metabolic and cardiovascular disease with hypertrophy and not obesity per se, a predictor of type 2 diabetes.1 The contribution of visceral adipose tissue to these pathologies is even more pronounced.

1407-P: Deletion of the Abi3 Immune Gene Locus in Mice Results in Obesity and Systemic Metabolic Disruption

Obesity is a global epidemic that affects 13% of adults world-wide, and over 40% of adults in the United States. Further, obesity contributes substantially to global morbidity and mortality and acts as a major risk factor for type II diabetes, among many other diseases. Therefore, efforts to understand the pathobiology of obesity and generate novel methods of prevention are paramount. Recent findings suggest the importance of immune cells in the progression and onset of obesity, prominently including microglia, the immune cells of the central nervous system (CNS) , and peripheral macrophages. To this end, our project proposes to explore the role of these immune cells in the etiology and progression of obesity. Our laboratory found that deletion of the Abi3 gene locus, which is a gene primarily involved in the regulation of actin dynamics within immune cells, resulted in the induction of obesity in mice. Specifically, mice lacking Abi3 had increased body weight and body fat percentage compared to wild-type mice. Additionally, mice without Abi3 showed impaired glucose tolerance and insulin sensitivity, but no changes in acute energy expenditure or food intake. Further, through RNA-seq analysis, we observed that deletion of the Abi3 gene locus substantially altered the expression of immune genes in both the CNS and peripheral tissue. Through this study, we aimed to metabolically characterize mice with and without the Abi3 gene locus in order to discover the mechanisms by which this deletion alters central and peripheral immune cells to facilitate the onset of obesity. This and future studies will enable us to understand how perturbations to microglia and peripheral immune cells alter metabolic regulation to mediate susceptibility to metabolic disease. Disclosure D.C.Smith: None. H.Karahan: None. H.Wijeratne: None. M.Al amin: None. B.Mccord: None. Y.Moon: None. J.Kim: None. Funding Indiana University Diabetes and Obesity Research Training Program, DK064466

1382-P: Novel Mechanisms to Reconvert Glucocorticoids into Pro-Metabolic Agents through Adiponectin

Adiponectin is the most abundant adipokine in our circulation and regulates inter-tissue communication like the adipose-muscle axis. Pharmacological modulation of this crosstalk is beneficial in promoting exercise tolerance in metabolic stress conditions like obesity. Endogenous glucocorticoids regulate metabolic function and stress response, but chronic daily intake of exogenous glucocorticoids produces or exacerbates metabolic stress. However, in stark contrast to daily intake, we discovered that intermittent regimens of glucocorticoids, e.g. once-weekly, improves exercise tolerance. However, the mechanisms underlying the differential regimen-specific effects of glucocorticoids in obesity remain unknown. Here we investigated the mechanisms differentiating once-weekly versus once-daily regimens of the same glucocorticoid prednisone in obesity. In mice with diet-induced obesity, once-weekly prednisone stimulated total and high-molecular weight adiponectin levels, improving exercise tolerance and energy expenditure. These effects were dependent upon adiponectin and were blocked by genetic ablation of the adipokine. Upregulation of Adipoq occurred through the adipose-specific glucocorticoid receptor (GR) , as this effect was blocked in mice with inducible GR ablation in adipose tissue. In contrast, once-daily prednisone decreased adiponectin levels through upregulation of known repressors of adiponectin expression in adipose tissue. The drug regimens remodeled in opposite ways also transcriptome and function in skeletal muscle after onset of obesity. Particularly, once-weekly prednisone treatment increased the muscle metabolic response to adiponectin through the CAMKK2-AMPK cascade. Our study demonstrates that intermittent glucocorticoids produce healthful metabolic remodeling in diet-induced obesity through direct upregulation of adiponectin expression in adipose tissue and adiponectin-dependent signaling in skeletal muscle. Disclosure M.Wintzinger: Employee; Cincinnati Children's Hospital. K.Miz: None. M.Panta: None. H.Durumutla: None. A.Pragasam: None. M.Quattrocelli: None. Funding National Institutes of Health grant DK121875National Institutes of Health grant HL158531CCHMC Trustee AwardCCHMC Heart Institute Translational Grant

210-LB: Central Regulation of Peripheral Adiposity by Nos1PVHNeurons

Within the CNS, the paraventricular nucleus of the hypothalamus (PVH) is critical for energy homeostasis, as developmental or mechanical lesions targeting the PVH lead to massive obesity. The PVH is composed of multiple cell types expressing an assortment of neuropeptides, receptors, and enzymes, including a subset of neurons expressing nitric oxide synthase-1 (Nos1PVH) . Nos1PVH neurons project to the nucleus of the solitary tract and the intermediolateral column of the spinal cord suggesting a neural substrate through which Nos1PVH neurons might directly modulate sympathetic output and energy balance [1]. To understand the necessity of Nos1PVH neurons in basal energy balance regulation, we bilaterally injected the PVH of Nos1-iCre mice with an AAV expressing a Cre-dependent tetanus toxin (Nos1TT) . Chronic silencing of the Nos1PVH resulted in acute onset of subcutaneous and visceral obesity without changes in food intake. Surprisingly, metabolic analyses indicated no significant changes in energy expenditure, although Nos1TT treated animals preferred to utilize fat as the predominant fuel source. Pair feeding experiments also confirmed that the obesity observed in Nos1TT animals was not secondary to increased caloric intake. Adipose tissues receive input from CNS cell groups that are part of the general SNS outflow from the brain [2, 3]. Analysis of subcutaneous white adipose tissue of Nos1TT animals revealed a significant decrease in tyrosine hydroxylase (TH) immunoactivity within WAT suggesting decreased capacity for sympathetic activation of lipolysis. These data indicate that Nos1PVH neurons regulate energy homeostasis possibly through changes in peripheral aspects of energy balance without the influence of energy consumption. Therefore, the main goal of this project is to clarify the physiological roles of Nos1PVH neurons in the regulation of peripheral adiposity, which may lead to the development of more refined anti-obesity therapies. 1. PMID: 25392498 2. PMID: 9688991 3. PMID: 15142857 Disclosure L. D. Faulkner: n/a. K. Lewis: None. T. H. Meek: Employee; Novo Nordisk. A. J. Mercer: Employee; Novo Nordisk. O. A. Macdougald: None. D. Olson: Research Support; AstraZeneca, Novo Nordisk A/S. Funding American Diabetes Association (7-21-PMF-020) ; Novo Nordisk A/S; National Institutes of Health (5R01DK104999-05)

1066-P: Association of T2D Subgroups with MCI/Dementia

Objectives: To assess whether T2D subgroups are associated with MCI/dementia, and whether the Action for Health in Diabetes (Look AHEAD) intensive lifestyle intervention (ILI) differs in prevention of MCI/dementia by T2D subgroup. Methods: Included 3760 participants (73% of original cohort after death and attrition) with T2D and overweight/obesity randomized to years of ILI or diabetes support and education. We characterized T2D subgroups at randomization using k-means clustering methods and data on age of T2D diagnosis, BMI, waist circumference, and HbA1c. We estimated marginal probabilities for prevalent MCI/dementia 10-13 years post-randomization by T2D subgroup with adjustment for cohort attrition and covariates (Table) and assessed for differential effects of ILI on MCI/dementia by T2D subgroup. Results: T2D subgroups were characterized by (1) older and (2) younger age at T2D onset, (3) high HbA1c, and (4) severe obesity (Table) . Prevalence of MCI/dementia was 8.4% and differed by T2D subgroup. After adjustment, rate of MCI/dementia was highest for the severe obesity and lowest for the younger onset subgroups. There were no differences in MCI/dementia rates between intervention arms for any T2D subgroup (interaction p-value=0.84) . Conclusions: T2D subgroups differ in rate of MCI/dementia, with the highest rate for a subgroup of participants with severe obesity. Lifestyle intervention did not modify rate of MCI/dementia in any T2D subgroup. Disclosure M.Bancks: None. J.Lovato: None. A.Balasubramanyam: None. M.Coday: None. K.C.Johnson: None. M.Munshi: Consultant; Sanofi. C.J.Rebello: None. L.E.Wagenknecht: None. M.Espeland: None.

313-OR: A Cytoskeleton-Based Mechanism Regulates Lipid Metabolism and Energy Homeostasis in Brown Adipose Tissue

Genetic variants in ANK2, encoding ankyrin-B (AnkB) , increase risk of obesity and type 2 diabetes in humans. We previously concluded that AnkB deficiency in white (WAT) and brown (BAT) adipose tissue (AT) of mice (AT-AnkB KO) led to lipotoxicity, WAT hypertrophy, and insulin resistance associated with age and consumption of a high-fat diet. These metabolic deficits were caused by impairments in glucose transporter GLUT4 endocytosis in WAT due to AnkB deficiency. Additionally, we found that AT-AnkB KO mice had decreased energy expenditure and lipid accumulation in BAT prior to the onset of obesity suggesting a potential role of AnkB in BAT. However, the role of AnkB in BAT and its contribution to metabolic homeostasis through BAT has not been elucidated. We investigated the role of AnkB in mice conditionally lacking AnkB in BAT (BAT-AnkB KO) . Based on histological and transmission electron microscopy analysis, we found that young (4-month-old) BAT-AnkB KO mice have enlarged lipid droplets, lipid accumulation, and decreased mitochondrial content in BAT with no changes in BAT size, body weight, or body composition. Consistent with these findings, primary brown adipocytes from BAT-AnkB KO mice exhibited lipid accumulation suggesting that AnkB may regulate lipid homeostasis in BAT in a cell-autonomous manner. Similar to our previous findings, young BAT-AnkB KO mice also had decreases in oxygen consumption and energy expenditure. These mice also exhibit minimal changes in glucose handling and insulin tolerance at 4-months of age. Proteomic-MS analysis was performed on AnkB associated proteins from BAT which revealed that GLUT4 as well as a number of critical regulators of lipid metabolism form complexes with AnkB in BAT. In combination with this data, we will present our latest findings in gene expression of genes regulating lipid metabolism and mitochondrial function as well as cellular assays in brown adipocytes that may highlight metabolic pathways regulated by AnkB in BAT. Disclosure A.Aguillard: None. J.Arricastres: None. J.Tzeng: None. D.Lorenzo: None. Funding American Diabetes Association (1-19-JDF-081)

75-OR: IL-6R (Trans Signaling) Is a Major Modulator of Reverse Cholesterol Transport in Lipid-Laden Macrophages

The onset of obesity is vastly associated with low levels of high-density lipoprotein cholesterol (HDL-C) , which predisposes to cardiovascular diseases. Recently, mounting evidence indicates that IL-6 plays a key role in metabolism, especially in lipid metabolic homeostasis. Yet, the precise nature of the HDL/IL-6 dynamics has not been fully elucidated. Therefore, we evaluated the expression of IL-6 in circulatory monocytes of the individuals with various body mass index and we also determined their lipid profile. Our data show that monocytic IL-6 expression was found to be negatively associated with HDL-C levels in obese individuals and positively associated with C-reactive protein and other monocytic pro-inflammatory markers. Mechanistically, chemical inhibition or genetic silencing of IL-6 receptor gp130/IL-6ST gene induced severe upregulation of intracellular lipid accumulation in THP-1 transformed macrophages that was found to be further augmented under fatty acid rich culture conditions. Moreover, analysis of the genes involved in lipid and cholesterol metabolism showed up-regulation of the LDLR along with a remarkable inhibition of ATP Binding Cassette (ABC) Subfamily transporters ABCG1 and ABCB1. We also found that the macrophages lacking gp130/IL-6 receptors had very low beta-oxidation genes expression (CPT1A and CPT2) , however, with no effect on triglyceride synthesis genes expression (DGAT, ACACA, FASN and Srebp1c) . In conclusion, our data support a role for IL-6 receptor signaling pathways in lipid alteration and cholesterol efflux which may have potential as a therapeutic target for metabolic syndrome. Disclosure F.Alrashed: None. F.Alzaqqah: None. A.Al madhoun: None. R.Alqabandi: None. S.T.Sindhu: None. F.Almulla: None. R.Ahmad: None. Funding (KFAS) (Grant #: RA AM 2016-007)

Adipocyte Size, Adipose Tissue Fibrosis, Macrophage Infiltration and Disease Risk Are Different in Younger and Older Individuals with Childhood and Adulthood Onset Obesity

ObjectivesThe timing of obesity onset and age have been shown to affect the risk of obesity-related comorbidities, although the impact of each of these factors on markers of adipose tissue function remains unclear. The aim of this study is to determine whether differences in regional adipose tissue characteristics vary with age and age of obesity onset, and whether these differences are associated with the markers of cardiometabolic health.MethodsAdipose tissue samples were from 80 female bariatric surgery candidates who were classified by age of obesity onset and age into 4 groups: 1) younger adults (<40 y) with childhood-onset obesity (< 18 y) (Childhood-Young); 2) younger adults with adulthood-onset obesity (>18 y) (Adulthood-Young); 3) older adults (>55 y) with childhood-onset obesity (Childhood-Old); and 4) older adults with adulthood-onset obesity (Adulthood-Old). Adipocyte diameter, adipose tissue fibrosis and macrophage infiltration were determined in subcutaneous (SAT) and visceral adipose tissue (VAT). Clinical parameters were obtained from participants’ medical records.ResultsVisceral adipocyte size in the Childhood-Young group was the smallest of all the groups. Age affected visceral infiltration of M1-like cells in both older groups, whereas onset, specifically childhood-onset, was related to visceral infiltration of M2-like cells in the Childhood-Old group. Fibrosis accumulation in SAT and VAT varied with age and onset, particularly in the Childhood-Old group having the lowest fibrosis levels. Markers of cardiometabolic health (fasting glucose, glycated hemoglobin, total, HDL- and LDL-cholesterol and triglyceride concentrations) were positively and well associated with adipose tissue characteristics of the Childhood-Old group but not of the Adulthood-Young group.ConclusionsOlder adults with childhood onset obesity, who had the greatest duration of obesity exposure, were particularly vulnerable to the cardiometabolic effects associated with perturbations in adipose tissue characteristics. These results, suggest that age and age of obesity onset may have independent and cumulative effects on obesity pathology.Funding SourcesSylvia Santosa holds a Canada Research Chair – Tier 2 in Clinical Nutrition. This research is also supported by a Discovery Grant from The Natural Science and Engineering Research Council of Canada.

Childhood obesity and mindfulness

Obesity, a largely intractable health condition with incalculable health, financial, emotional, physical, and social costs and ramifications remains an immense challenge to mitigate effectively, especially if this condition has evolved unabated since early childhood. Moreover, multiple intervention approaches designed to prevent or mitigate childhood obesity, and its predictable and well established negative health impacts, while studied intently and widely applied to aid efforts to foster the attainment of a healthy weight status across the lifespan, have generally failed to eliminate this growing global epidemic and its detrimental consequences for the individual, as well as society. Alternately, interventions that can limit the onset of obesity, or help to reduce this where present, including efforts to contain depression, anxiety, stress, and emotional and/or externally stimulated eating behaviors, would appear highly desirable and of high personal and social significance. Studied for many years in various spheres, mindfulness based strategies are being and have been discussed for some time in this regard. This mini review discusses some of these ideas and related observations regarding, and whether more emphasis on ensuring mindfulness based actions are possible and should not be ignored in efforts to effectively attenuate selected correlates of the global obesity burden. Extracted from current literature, it is concluded that this is a field of significant promise, but one requiring not only more long-term research, but possible novel ecologically oriented integrated mindful and collaborative thoughtful family, school, community, and policy intervention efforts, along with dedicated sustainable collaborative goals and supportive efforts.

Relationship between a near Melanocortin-4 receptor gene variant and puberty timing in children is vague unlike obesity.

Obesity is a complicated phenomenon which is a combination of genetic, environmental, and psychological factors. Genetic factors of obesity play an important role in individual risk. It is well known that obese children have disturbed puberty timing. To the best of our knowledge, no study has been performed to investigate the association between MC4R gene mutation and puberty timing. This study was performed as a cross-sectional study evaluating the near MC4R rs17782313 variation in 60 obese children and 98 healthy non obese children. Weight, height, BMI ( Body Mass Index ), BMI z-score (BMIz), family history of diabetes mellitus and obesity, the age of the obesity onset, overeating behavior, type of obesity (central or general) and puberty stage were evaluated in 60 obese children. The average age of the participants was 14.87 (+/- 1.3) years, with average weight and BMI of 90.77 (+/-12.2) Kg and 31.72 (+/-4.35) Kg/m2, respectively. Compared to healthy non obese patients, those with C-T genotype (C-T Vs. T-T and C-C) had higher odds of obesity than those with T-T and C-C genotype (p < 0.0001) while genotype TT showed significant protective effect (p = 0.0007). The heterozygote individuals (CT) have a higher BMIz than homozygote ones (CC and TT) (2.8 vs. 2.5 Kg/m2, p = 0.04). children with CT genotype have 5.1 increased risk of obesity. While genotype TT showed significant obesity protective effect. We did not find association of this polymorphism with either childhood eating disorders or puberty. It is recommended to perform a cohort study in a larger sample. The online version contains supplementary material available at 10.1007/s40200-022-01011-5.