bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of Urbanization and Lower Light Exposure With Increased Body Mass Index
Authors: Constantino Débora Barroggi , Xavier Nicoli , Roenneberg Till , Hidalgo Maria , Pilz Luísa 
Published: May 2021

Abstract
Introduction: Light/dark cycles are the main synchronizing signal (zeitgeber) that entrain human’s internal clock to the 24h-days. Some aspects of urban environments, including irregular light exposure and weak zeitgebers, influence the circadian organization and thereby may have an impact on metabolism. Comparing communities at different levels of urbanization and with different histories of access to electricity might provide evidence to support associations previously found between disrupted patterns of light exposure and increased populational rates of overweight and obesity. The present study aimed to investigate whether living at a higher level of urbanization would be associated with higher body mass index (BMI). It was hypothesized that BMI is higher in urbanized communities, since their inhabitants have weaker zeitgebers, often associated with disrupted circadian rhythms. Methods: We conducted a cross-sectional study in Quilombolas communities, located in the south of Brazil. Subjects were categorized into 5 groups based on their communities’ stage of urbanization and history of access to electricity: from rural with no access to electricity to highly urbanized communities that have access to the grid. We used data from 134 participants aged 16 - 92 years old (63% women), who had 7 days of light exposure recordings collected using wrist-worn actimeters. We also collected anthropometric data to calculate BMI, which was then categorized as follows: ≥18.5 kg/m² to &lt;25 kg/m² = normal weight; ≥25 kg/m² to &lt; 30 kg-m² = overweight; ≥ 30 kg/m² = obesity. We used Shapiro-Wilk to test for normality, Kruskal-Wallis followed by Dunn to compare BMI between groups and Spearman to assess whether there was an association between patterns of light exposure and BMI. Results: Kruskal-Wallis/Dunn test showed a significant difference in BMI between the urban group and the rural ones (KW: X² = 11.987, p &lt; 0.001). Lower average light exposure between 7 am and 5 pm was significantly correlated with higher BMI (Spearman, r = - 0.296, p &lt; 0.001). Also, higher average light exposure at night (from 1 am to 6 am) was significantly correlated with higher BMI (Spearman, r = 0.256, p = 0.002). Conclusions: Our results support the hypothesis that low amplitudes of light exposure may be a risk factor contributing to the high prevalence of obesity worldwide. Studies have previously shown associations between BMI and social jetlag, suggesting the correlations found in our study may be related to higher levels of circadian misalignment, more often present where zeitgeber strength is lower, as in urban environments. Future research is needed to address causal relationships between light exposure and excessive body mass in humans. Provided light exposure is a risk factor for obesity, these results point to potential new targets for intervention and prevention strategies.
Clinically-Relevant Weight Loss is Achieved Independently of Early Weight Loss Response to Once-Weekly Subcutaneous Semaglutide 2.4 MG (STEP 4)
Authors: Mosenzon Ofri , Garvey W Timothy , Hesse Dan , Koroleva Anna , Kushner Robert F , Lim Soo , Lingvay Ildiko , Wallenstein Signe O R , Wadden Thomas A , Le Roux Carel W 
Published: May 2021

Abstract
Background: Semaglutide, a glucagon-like peptide-1 analogue, is being investigated in people with overweight or obesity. A post-hoc analysis of the STEP 4 trial was conducted to identify whether early weight loss is predictive of later weight loss with maintenance once-weekly subcutaneous (s.c.) semaglutide 2.4 mg.
Methods: STEP 4 was a randomized, double-blind, phase 3 withdrawal trial (NCT03548987). Adults aged ≥18 years with either body mass index (BMI) ≥27 kg/m2 with ≥1 weight-related comorbidity or BMI ≥30 kg/m2, without type 2 diabetes, underwent a 20-week run-in period. Participants reaching the maintenance dose of once-weekly s.c. semaglutide 2.4 mg at week 20 (regardless of weight loss achieved) were randomized 2:1 to semaglutide 2.4 mg or placebo, as adjunct to lifestyle intervention, for an additional 48 weeks. Percent change in body weight from week 0 to 68 was estimated using a mixed model for repeated measurements analysis with treatment, week 20 responder status, and the interaction between treatment and week 20 responder status as factors, and baseline body weight as a covariate, all nested within visit (based on the trial product estimand [treatment effect assuming treatment adherence and without use of rescue intervention] for the on-treatment period). Participants were considered responders if they achieved ≥5% weight loss at week 20. Whether the week 20 response to semaglutide predicted the achievement of clinically-relevant weight loss (≥5%) by week 68 was also assessed.
Results: In STEP 4, 902 participants initiated semaglutide at week 0, of whom 803 were randomized at week 20 (semaglutide: n=535, placebo: n=268; characteristics at week 0 for all randomized participants: mean age 46 years, body weight 107.2 kg, BMI 38.4 kg/m2; 79.0% female; 83.7% white). For the 88.0% of participants randomized to semaglutide and who were responders at week 20, mean body weight change from week 0 to 68 was -19.7%. For non-responders at week 20, mean body weight change was -6.4% with continued semaglutide vs -0.3% with switch to placebo. Of all participants randomized to semaglutide, 86.2% achieved a clinically-relevant weight loss (≥5%) at week 68. Being a responder at week 20 was highly predictive of achieving this outcome (positive predictive value: 96.4%), whereas being a non-responder at week 20 had limited predictive value (negative predictive value: 42.9%).
Conclusion: In the STEP 4 trial, the vast majority of participants who were randomized to the maintenance dose of once-weekly s.c. semaglutide 2.4 mg at week 20 had lost ≥5% body weight by week 68, with most achieving this by week 20. Overall weight loss with semaglutide was greater among early responders, but non-responders also achieved a clinically-relevant weight loss by week 68 if semaglutide treatment was continued.
How Personality and Unpredictability of Resources Impact Binge Eating Symptoms in Normal Weight Subjects: A Path Analysis
Authors: Weydmann Gibson , Eckhardt Joseane , Bizarro Lisiane , Friedman Rogerio 
Published: May 2021

Abstract
STUDIES ASSESSING SENSITIVITY TO ENVIRONMENTAL STIMULI INDICATE THAT SUBJECTS WITH BINGE EATING DISORDER (BED) ARE MORE PRONE TO REACT TO STRESSFUL SITUATIONS, AND MORE WILLING TO PURSUE IMMEDIATE REWARDS IN COMPARISON TO SUBJECTS WITHOUT BED. UNPREDICTABILITY OF FAMILY RESOURCES RELEVANT TO CHILD DEVELOPMENT INCREASES THE CHANCES OF EXTERNALIZING BEHAVIORS IN CHILDHOOD AND, COUPLED WITH PERSONALITY PROFILES LINKED TO BED, MAY INCREASE THE ODDS OF MANIFESTING BINGE EATING (BE) IN ADULTHOOD. THIS STUDY AIMED TO INVESTIGATE WHETHER PERSONALITY AND UNPREDICTABILITY OF RESOURCES INTERACT TO PREDICT BE SYMPTOMS IN YOUNG ADULTS, EVEN BEFORE THE ONSET OF OBESITY. THE SAMPLE CONSISTED OF 257 ADULTS (AGES 20.73 ± 1.78 YEARS, MEAN ± SD), MOSTLY WHITE (N = 233), UNDERGRADUATES (N = 236), AND WITH A BMI OF 21.84 ± 1.68 KG/M². PERSONALITY WAS STUDIED USING THE BIS AND BAS SCALES THAT ASSESS, RESPECTIVELY, AVOIDANCE OF AVERSIVE STIMULI AND CONFLICT SITUATIONS, AND APPROACH TO AND DESIRE OF REWARD STIMULI. UNPREDICTABILITY OF NURTURE AND CARE, FINANCIAL RESOURCES, AND MEAL AVAILABILITY WERE ASSESSED USING THE FAMILY UNPREDICTABILITY SCALE (FU). BE SYMPTOMS WERE ASSESSED USING THE BINGE EATING SCALE (BES). A PATH ANALYSIS MODEL WAS USED TO ANALYZE THE DATA. PERSONALITY FACTORS WERE TREATED AS PRINCIPAL PREDICTORS, FU AS MEDIATORS, AND BE SYMPTOMS AS THE DEPENDENT/OUTCOME VARIABLE. GENDER, BMI, AND SOCIOECONOMIC STATUS WERE INCLUDED IN THE MODEL AS COVARIATES. AN EXCELLENT MODEL FIT WAS OBTAINED, [χ² (31) = 26.588, P = 0.692; RMSEA &lt; 0.01; CFI = 1.000; TFI = 1.041], AND THE FINAL MODEL EXPLAINED 20.1% OF BE VARIANCE. THE POSITIVE EFFECTS OVER BE VARIANCE SUGGEST THAT FEMALE PARTICIPANTS (β = 0.180) WITH A HIGHER TENDENCY TO SEEK FOR IMMEDIATE REWARDS (BAS SUBSCALE, β = 0.205) AND AVOID CONFLICT SITUATIONS (BIS SCALE, β = 0.304), AND WITH A BMI CLOSER TO 25 KG/M² (β = 0.130) SCORED HIGHER IN BES. ONLY ONE FU FACTOR WAS RELATED TO BE, WITH MARGINAL SIGNIFICANT RESULTS (NURTURE AND CARE, β = 0.145, P = 0.056). HIGHER POSITIVE REACTIONS TO BRIEF REWARDS - ANOTHER BAS SUBSCALE - WERE NEGATIVELY (β = − 0.123) RELATED TO BE SYMPTOMS, REPRESENTING A PROTECTIVE FACTOR. THE OBSERVED EFFECTS OF PERSONALITY AND GENDER ARE CONSONANT WITH THE AFFECT REGULATION THEORY OF EATING DISORDERS, AS BE MIGHT BE AN IMPULSIVE STRATEGY TO REGULATE EMOTION IN FEMALE PATIENTS WITH GENETICALLY INFLUENCED PERSONALITY TRAITS LINKED TO STRESS VULNERABILITY AND REWARD SENSITIVITY. RESPONSIVENESS TO BRIEF REWARDS IS A PROTECTIVE FACTOR FOR DEPRESSIVE SYMPTOMS LINKED ALSO TO HEALTHY BEHAVIORS, AND IT MAY HELP PATIENTS TO PLAN AND ENGAGE IN STRATEGIES TO PREVENT BE. LONGITUDINAL MONITORING OF THESE PARTICIPANTS MAY ANSWER WHETHER PERSONALITY PROFILES IMPACT WEIGHT GAIN AND ADHERENCE TO WEIGHT REDUCTION INTERVENTIONS IN THE FUTURE.
Incidence of Insulin Resistance in Obese Adolescent of Type-2 Diabetes Mellitus Patients
Authors: Javaid Farrukh , Khurshid Rukhshan , Ashraf Huma , Mazhar Abeera , Amir Lubna 
Published: May 2021

Abstract
Background: Insulin resistance is a reduced response of tissue to insulin-mediated action on cells. It may be due to many reasons, including the surplus of adipose tissue, which cause a resistance of insulin. Aims and Objectives: To find the incidence of insulin resistance in obese adolescent of type-2 diabetes mellitus patients.
Material and Methods: The study involved 50 adolescents aged 14–20 years old. Adolescents with BMI &gt; 26.0 Kg/m2 were included in the study. Levels of fasting blood sugar, Hb A1c and serum insulin were estimated. The index of Homeostatic model assessment for insulin resistance or HOMA-IR was calculated. The cut-off value of HOMA-IR was &gt; 3.16 for both genders.
Results: It was observed that the values of BMI and level of fasting blood sugar of first degree relatives of diabetics was significantly higher as compared to their controls. Levels of both blood HbA1c and serum insulin were increased but significant difference was observed only in case of serum insulin when compared with their controls.
Conclusion: Obesity in adolescents of first degree relatives of diabetics shows a major reason of insulin resistance. The incidence of insulin resistance in obese adolescents signals a perturbing trend for the burden of type 2 diabetes in our country.
A Novel Variant of the SH2B1 Gene in an Obese Child With Type 2 Diabetes
Authors: Morillo Mariaester Makacio , Ukarapong Supamit , Seeherunvong Tossaporn 
Published: May 2021

Abstract
Obesity in children and adolescents is at epidemic levels in the United States and creates high risk for comorbidities later in life. Childhood obesity is thought to be the result of behavioral and nutritional problems. Although genetic factors may play a role in the etiology of obesity, monogenic forms of obesity are rare. We present a child with obesity, behavioral problems, leptin resistance, and type 2 diabetes who also carries a mutation of Sarcoma Homologous 2B adapter protein 1 (SH2B1). The subject was evaluated at 13 7/12 years old. He had polyphagia, learning disability, aggressive behavior and marked obesity. At ages 9,11, and 13 years respectively, his BMI was 9%, 16%, and 52% above the 95th percentile. At 13 7/12 years old, his height was at the 80th percentile and BMI was 66% above the 95th percentile. He had marked acanthosis nigricans and he was prepubertal. Fasting blood glucose and insulin levels were 116 mg/dl and 592 mIU/L, respectively. Hemoglobin A1c was 6.5% and metformin therapy was initiated for type 2 diabetes. Fasting leptin level (41.5 ng/mL) was markedly elevated indicating leptin resistance. DNA methylation study excluded Prader-Willi syndrome. DNA sequencing indicated a novel heterozygous c.1555G&gt;T variant of SH2B1 gene, which is predicted to result in the amino acid substitution p. Asp519Tyr. The analysis by PolyPhen-2 and MutationTaster predicts that the variant is a pathogenic mutation affecting protein functions. SH2B1 interacts with JAK2 and may play a role in insulin signaling. Pathogenic heterozygous variants in SH2B1 have been associated with obesity, insulin resistance and maladaptive behavior phenotypes (Pearce et al, 2014). Sh2b1-null mice develop severe leptin resistance, obesity, and type 2 diabetes. Our report underscores the importance of investigating monogenic causes of obesity in subjects who present severe obesity, diabetes, and behavioral problems. Additional studies are needed to determine the association between this novel mutation and the clinical features of this patient.
The Use of Liraglutide in Obese Patients With COVID-19: A Case Report
Authors: Hanada Taliê Zanchetta Buani , Knack Rafael Silvestre , Knack Renata Silvestre 
Published: May 2021

Abstract
Introduction: In December 2019, a new type of coronavirus was discovered in Wuhan, China, characterized by a picture of atypical pneumonia composed of fever, dry cough and progressive dyspnea. Autopsy analyzes of patients with Covid-19 were performed, and hyperactivation of cytotoxic T cells was observed, suggesting an increase in humoral-type immunological signaling, where interleukin 6 (IL-6) is a mediator present that can fit as a potential critical agent for exacerbation of inflammatory conditions. In addition, not only interleukin-6, but also serum C-reactive protein (CRP) and ferritin have been recognized as strong predictors of COVID-19 severity. Recent studies have shown that the use of liraglutide has antioxidant and anti-inflammatory effects in vitro. Thus, the present case report discusses the possible anti-inflammatory properties of the antidiabetic drug liraglutide (Saxenda), in Covid-19. Clinical Case: JCMS, 45 years, male, married, obese grade 2 (BMI: 38.2), sought medical service on August 18, 2020, bringing a positive result of the RT-PCR test for Covid-19, performed in last day. The patient was in good general condition, reporting mild headache and adynamia. He was prescribed to start a treatment with Saxenda (6mg/ml - started 0.6mg/day at week 1, with a gradual increase up to 3mg/day at week 5); Jardiance (25mg / day); Fluimicil (600mg); Ivermectin (6mg) and Colchicine (0.5mg every 12 hours). In addition, collection of laboratory tests was requested. Examination results: IL6: &lt;1.5 pg/mL; Ferritin: 819 ng/ml; C-reactive protein: 5.1mg/L. On August 24, the patient was tachycardic (HR 120–140 bpm) associated with headache and fever (38 °C). Azithromycin (500mg), dexamethasone (4mg) and dipyrone (1g) were prescribed. Collection of laboratory tests was requested. Examination results: IL6: 9.3 pg/mL; Ferritin: 1085 ng/ml; C-reactive protein:23.9mg/L. On September 3, the patient was in good general condition, eupneic, afebrile, with no complaints to declare. On September 6, the collection of laboratory tests was requested. Examination results: IL6: &lt;1.5 pg/mL; Ferritin: 687 ng/ml; C-reactive protein: 1.7mg/L. Conclusion: Based on the described report, it is possible to observe a good clinical and laboratory evolution of the patient with Covid-19 who, among the drugs used, made use of liraglutida. Diabetes and obesity are considered significant risk factors for morbidity and mortality by COVID-19, since they are a condition of low-grade chronic inflammation and in these conditions, inflammatory markers such as CRP, IL-6 and ferritin have strong signs of alteration. Thus, the possible beneficial effect of the administration of liraglutide in obese patients is highlighted, as a potential anti-inflammatory effect, especially in the COVID-19 era.
Cholesterol-Free Ketogenic Diet Administration Ameliorates Experimental Metabolic Syndrome
Authors: Agosti Emanuela , Alessia Provera , Gadipudi Laila L , Ramavath Naresh N , Antonio Colasanto , Raineri Davide , Chiocchetti Annalisa , Arlorio Marco , Coisson Jean D , Caputo Marina , Reano Simone , Filigheddu Nicoletta , Albano Emanuele , Sutti Salvatore , Prodam Flavia 
Published: May 2021

Abstract
Background and Aims: Metabolic syndrome (MetS) is a pathologic condition characterized by abdominal obesity, insulin resistance, hypertension, and dyslipidemia. The prevalence of MetS parallels the rise of obesity rate reaching pandemic proportions due to the increased consumption of high-calories-high-fat-high-carbohydrates low-fibers diet associated with a sedentary lifestyle. MetS is associated with a plethora of comorbidities as non-alcoholic fatty liver disease (NAFLD). Noteworthy, NAFLD is considered the hepatic manifestation of MetS, and it can further progress to non-alcoholic steatohepatitis (NASH) that, in its turn, can evolve to cirrhosis and hepatocellular carcinoma (HCC). Despite the clinical relevance of NAFLD/NASH, however, effective therapy is still lacking. Lifestyle changes, including diet and physical activity, are so far the most effective interventions in NAFLD. Referring to nutritional approaches, however, there is not a definitive agreement concerning the dietary regimen to introduce into clinical practice. In this study, we investigated the capacity of a cholesterol-free ketogenic diet (KD) to improve pathological parameters associated with experimental MetS. Methods: MetS was induced in C57BL/6 mice by feeding with a cholesterol-enriched western diet (WD) up to 16 weeks followed by the switching to KD for further 8 weeks. WD and KD were chemical characterized through GC and SD-PAGE analysis. Results: KD administration in MetS mice significantly improved the liver pathological manifestations by lowering the gene expression of pro-inflammatory/fibrogenetic markers such as CCl2, IL-12, CD11b, OPN, Gal-3, TGF-β and α1-procollagen. Furthermore, KD feeding decreased the hepatic content of triglycerides and the hepatocellular damage, as testified by the reduction in ALT release. These observations were further supported by the histological analyses that revealed a significant amelioration in the extent of steatosis, necro-inflammation, and collagen fibers deposition, as confirmed by the Sirius-red staining in KD-fed mice. Interestingly, KD reduced the splenomegaly observed in WD-fed mice suggesting a reduction in chronic systemic inflammation. Finally, KD feeding ameliorated WD-induced muscle atrophy as confirmed by the recovery of the gastrocnemius mass. Microbiota analyses are ongoing. Conclusion: Altogether these results suggest that cholesterol-free ketogenic diet administration might represent a potential therapeutic strategy for MetS.
Hepatic GH Receptor Signaling Directly Suppresses Hepatic Steatosis and De Novo Lipogenesis, Independent of Changes in Plasma IGF1 and Insulin
Authors: Vazquez Borrego Maria del Carmen , Moreno Mercedes del Rio , Sarmento-Cabral Andre , Mahmood Mariyah , Subbaiah Papasani V , Yakar Shoshana , Cordoba-Chacon Jose , Puchowicz Michelle , Kineman Rhonda D 
Published: May 2021

Abstract
A reduction in GH, as well as IGF1, is associated with non-alcoholic fatty liver disease (NAFLD). However, the relative contribution of changes in circulating GH and IGF1, to hepatic triglyceride accumulation (steatosis), remains to be clearly defined. To study the direct actions of GH on hepatocyte metabolism, we have utilized a mouse model of adult-onset, hepatocyte-specific, GHR knockdown (aHepGHRkd; 10–12 week-old, GHRfl/fl male mice, treated with AAV8-TBGp-Cre). In this and previous reports, we have observed that aHepGHRkd male mice rapidly develop steatosis (after 7 days) associated with enhanced de novo lipogenesis (DNL; measured by deuterated H2O labeling, 10h after 0800h food removal), and low ketone levels, suggestive of reduced hepatic β-oxidation. Of note, aHepGHRkd also reduces plasma IGF1 levels to &gt;80% of GHR-intact controls (GHRfl/fl mice treated with AAV8-TBGp-Null), leading to a rise in GH, due to loss of IGF1 negative feedback to the pituitary/hypothalamus. This reciprocal shift in IGF1/GH is associated with an increase in insulin levels. Therefore, it is possible that the steatosis that develops in aHepGHRkd mice is the consequence of systemic insulin resistance supplying excess substrates (glucose and NEFA) for hepatic lipogenesis. However, inconsistent with this theory is the fact that glucose and NEFA levels are not altered after aHepGHRkd. To tease out the indirect (perhaps driven by high insulin levels) vs. direct effects of GH on hepatocyte lipid accumulation, male aHepGHRkd mice were injected with a vector expressing rat IGF1 (AAV8-TBGp-rIGF1). Reconstitution of hepatocyte IGF1 in aHepGHRkd mice, raised plasma IGF1 and normalized GH, insulin and ketone levels, but hepatic steatosis and DNL remained greater than that of GHR-intact controls, indicating GH directly suppresses hepatic fat accumulation. RNAseq analysis of livers from aHepGHRkd mice showed expression of genes related to carbohydrate metabolism (Gck, Khk) and fatty acid synthesis (Fasn, Srebf1, Usf1), processing (Scd1) and uptake (Cd36) were increased, while genes related to gluconeogenesis (Pck1, Fbp1, G6pc) were reduced. Remarkably, IGF1 reconstitution had no major impact on the hepatic transcriptome of aHepGHRkd mice, with the exception of reducing the expression of Srebf1, consistent with the reduction in circulating insulin levels. Interestingly, carbohydrate-responsive element-binding protein (CHREBP) levels, but not mRNA levels, were greater in aHepGHRkd mice with or without IGF1 reconstitution, consistent with upregulation of CHREBP target genes (Khk and Fasn among others). Taken together, these results suggest GH directly regulates steatosis, at least in part, by suppressing carbohydrate-driven DNL, where additional studies are underway to test this hypothesis.