Obese Research Articles

Transferrin receptor levels and its rare variant are associated with human obesity.

Iron homeostasis is critical for functional respiratory chain complex of mitochondrial, thus potentially contributing to fat biology and energy homeostasis. Transferrin receptor (Tfrc) binds to transferrin for extracellular iron uptake and is recently reported to be involved in brown fat development and functionality. However, whether TFRC levels and variants are associated with human obesity is unknown. To investigate the association of TFRC levels and variants with human obesity, fat biopsies were obtained from surgery. Exon-sequencing and genetic assessments were conducted of a case-control study. For TFRC levels assessment in fat biopsy, 9 overweight and 12 lean subjects were involved. For genetic study, obese (n = 1271) and lean subjects (n = 1455) were involved. TFRC levels were compared in abdominal mesenteric fat of pheochromocytoma patients versus control subjects, and overweight versus lean subjects. For genetic study, whole-exome sequencing of obese and matched control subjects were conducted and analyzed. In addition, the possible disruption in protein stability of TFRC variant was assessed by structural and molecular analysis. TFRC levels are increased in human browning adipose tissue and decreased in fat of overweight patients. Besides, TFRC levels are negatively correlated with body mass index and positively correlated with uncoupling protein 1 levels. Furthermore, a rare heterozygous missense variant p.I337V in TFRC shows a tendency to enrich in obese subjects. Structural and functional study reveals impaired protein stability of the TFRC variant compared to wild-type. Reduced TFRC levels and its rare variant p.I337V with protein instability are associated with human obesity.

Adipomyokines in children with obesity

Adipomyokines are synthesized and secreted into the bloodstream by cells of both muscle and adipose tissue. They can have both a negative metabolic effect, acting as pro-inflammatory adipokines in obesity, and a positive one, increasing in response to physical exertion in the form of myokines. To study the features of adipocytokine secretion in children with constitutionally exogenous obesity. The study included 80 patients: 60 adolescents aged 15 [13; 16] years with constitutionally exogenous obesity SDS BMI: 3.0 [2.6; 3.3] and 20 control group children aged 16 [15; 17] years without excess weight SDS BMI: -0.3 [-1.25; 0.33]. Commercial enzyme immunoassay kits were used to determine the level of adipomyokines. The compositional composition of the body was evaluated by bioimpedance analysis (InBody 770 analyzer, South Korea) in the morning, on an empty stomach. Statistical processing was carried out using STATISTICA v.12.0 (StatSoft Inc., USA). The results are presented in the form of median (Me) and quartiles (Q1; Q3) corresponding to 25 and 75 percentiles. The critical significance level (p) was assumed to be <0.05. Levels of IL-6 and irisin are statistically significantly higher in obese adolescents compared to the control group: 0.55 [0.226; 1.35] pg/ml vs 0.202 [0.128; 0.652] pg/ml (p=0.041) and 11.16 [6.6; 22.76] mcg/ml vs 7.36 [6.48; 9.68] mcg/ml (p=0.043), respectively. Concentrations of IL-6, myostatin and decorin increase with an increase in the degree of obesity: grade I vs III: 0.226 [0.224; 0.398] vs 0.80 [0.36; 1.81] pg/ml (p=0,0197), 25,85 [21,53; 28,23] vs 31.41 [24.36; 35.06] ng/ml (p=0.03), 4065.3 [3244.9; 5245.5] vs 5322.5 [4199.8; 7702.4] pg/ml (p=0.0376), respectively. In obese children, IL-6 levels positively correlate with BMI, SDS BMI and the amount of adipose tissue, and myostatin - with BMI and SDS BMI. The concentration of irisin in the blood serum is significantly higher in obese girls than in obese boys and healthy girls. Obese patients, compared with lean peers, are characterized by a statistically significantly higher content of both fat and lean mass. With the progression of obesity, there is a statistically significant increase in the ratio of fat to lean mass (I degree - 0.66 [0.56; 0.7], III - 0.78 [0.68; 0.98] (p=0.0073). Patients with obesity and normal body weight have different levels of adipomyokines. An increase in the level of IL-6 with the progression of obesity is directly related to an increase in the content of adipose tissue. Further study of the features of adipocytokine secretion, their relationship with the features of the body composition and metabolic complications in obesity is required.

Fatty acid composition and genome-wide associations of a chickpea (Cicer arietinum L.) diversity panel for biofortification efforts

Chickpea is a nutritionally dense pulse crop with high levels of protein, carbohydrates, micronutrients and low levels of fats. Chickpea fatty acids are associated with a reduced risk of obesity, blood cholesterol, and cardiovascular diseases in humans. We measured four primary chickpea fatty acids; palmitic acid (PA), linoleic acid (LA), alpha-linolenic acid (ALA), and oleic acid (OA), which are crucial for human health and plant stress responses in a chickpea diversity panel with 256 accessions (Kabuli and desi types). A wide concentration range was found for PA (450.7–912.6 mg/100 g), LA (1605.7–3459.9 mg/100 g), ALA (416.4–864.5 mg/100 g), and OA (1035.5–1907.2 mg/100 g). The percent recommended daily allowances also varied for PA (3.3–6.8%), LA (21.4–46.1%), ALA (34.7–72%), and OA (4.3–7.9%). Weak correlations were found among fatty acids. Genome-wide association studies (GWAS) were conducted using genotyping-by-sequencing data. Five significant single nucleotide polymorphisms (SNPs) were identified for PA. Admixture population structure analysis revealed seven subpopulations based on ancestral diversity in this panel. This is the first reported study to characterize fatty acid profiles across a chickpea diversity panel and perform GWAS to detect associations between genetic markers and concentrations of selected fatty acids. These findings demonstrate biofortification of chickpea fatty acids is possible using conventional and genomic breeding techniques, to develop superior cultivars with better fatty acid profiles for improved human health and plant stress responses.

The obese brain: is it a matter of time?

Understanding how obesity rewires the brain, triggers neuroinflammation and neurodegeneration relies on research using animal models. There is, however, a disconnect between the timeline of human obesity and typical preclinical protocols. We emphasize here the need to adopt models of chronic obesity to study the pathophysiology of human obesity.

Prejudice among egalitarians: The case of values and weight bias

AbstractMany domains of research suggest that high favourability to social power and low favourability to egalitarian ideals predict more prejudice against other groups. In the present article, we describe theory and evidence suggesting that the relations between power, egalitarianism and prejudice may be reversed for one group: fat men. Using both implicit and explicit measures, we found across four studies (N = 602) that target gender moderated the relation between values and attitude toward fat people. For male targets, implicitly but not explicitly measured positivity toward power (over egalitarian) values predicted significantly more spontaneous positive attitudes toward fat (over slim) people. Further, implicit attitude toward power (over egalitarian) values predicted the time‐pressured decision to choose a fat male. Together, the implicit evaluation of values allows us to identify processes in inter‐group attitudes and behaviours that would not be possible to detect using explicit measures of values alone.

Glutamine Production by Glul Promotes Thermogenic Adipocyte Differentiation Through Prdm9-Mediated H3K4me3 and Transcriptional Reprogramming.

Thermogenic adipocytes have been extensively investigated due to their energy dissipating property and therapeutic potential for obesity and diabetes. Besides serving as fuel sources, accumulating evidence suggests that intermediate metabolites play critical roles in multiple biological processes. However, their role in adipocyte differentiation and thermogenesis remains unexplored. Here, we report that human and mouse obesity is associated with marked downregulation of glutamine synthetase (Glul) expression and activity in thermogenic adipose tissues. Glul is robustly upregulated during brown adipocyte (BAC) differentiation and in brown adipose tissue (BAT) upon cold exposure and Cl316,243 stimulation. Further genetic, pharmacologic, or metabolic manipulations of Glul and glutamine levels reveal that glutamine cell-autonomously stimulates BAC differentiation and function, BAT tissue remodeling, and improves systemic energy homeostasis in mice. Mechanistically, glutamine promotes transcriptional induction of adipogenic and thermogenic gene programs through histone modification-mediated chromatin remodeling. Among all the glutamine-regulated writer and eraser genes responsible for histone methylation and acetylation, only Prdm9, a histone lysine methyltransferase, is robustly induced during BAC differentiation. Importantly, Prdm9 inactivation by shRNA knockdown or a selective inhibitor attenuates glutamine-triggered adipogenic and thermogenic induction. Further, Prdm9 gene transcription is regulated by glutamine through the recruitment of C/EBPb to its enhancer region. This work reveals glutamine as a novel activator of thermogenic adipocyte differentiation and uncovers an unexpected role of C/EBPb-Prdm9-mediated H3K4me3 and transcriptional reprogramming in adipocyte differentiation and thermogenesis.

Ado-Mediated Depletion of Taurine Impairs Mitochondrial Respiratory Capacity and Alters the Chromatin Landscape of Inguinal Adipose Tissue.

Non-shivering thermogenesis (NST) has strong potential to combat obesity; however, a safe molecular approach to activate this process has not yet been identified. The sulfur amino acid taurine has the ability to safely activate NST and confer protection against obesity and metabolic disease in both mice and humans, but the mechanism of this action is unknown. In this study, we discover that a suite of taurine biosynthetic enzymes, especially that of cysteamine dioxygenase (ADO), significantly increases in response to β3 adrenergic signaling in inguinal adipose tissue (IWAT) in order to increase intracellular concentrations of taurine. We further show that ADO is critical for thermogenic mitochondrial respiratory function as its ablation in adipocytes significantly reduces taurine levels, which leads to declines in mitochondrial oxygen consumption rates. Finally, we demonstrate via assay for transposase-accessible chromatin with sequencing (ATAC-seq) that taurine supplementation in beige adipocytes has the ability to remodel the chromatin landscape to increase the chromatin accessibility and transcription of genes, such as glucose-6-phosphate isomerase 1 (Gpi1), which are critical for NST. Taken together, our studies highlight a potential mechanism for taurine in the activation of NST that can be leveraged toward the treatment of obesity and metabolic disease.

Melatonin the sleep hormone: could it be a future potential for the management of human obesity?

Melatonin the sleep hormone: could it be a future potential for the management of human obesity?

The effects of sodium butyrate supplementation on the expression levels of PGC-1α, PPARα, and UCP-1 genes, serum level of GLP-1, metabolic parameters, and anthropometric indices in obese individuals on weight loss diet: a study protocol for a triple-blind, randomized, placebo-controlled clinical trial

BackgroundObesity is a multifaceted disease characterized by an abnormal accumulation of adipose tissue. Growing evidence has proposed microbiota-derived metabolites as a potential factor in the pathophysiology of obesity and related metabolic conditions over the last decade. As one of the essential metabolites, butyrate affects several host cellular mechanisms related to appetite sensations and weight control. However, the effects of butyrate on obesity in humans have yet to be studied. Thus, the present study was aimed to evaluate the effects of sodium butyrate (SB) supplementation on the expression levels of peroxisome proliferator activated-receptor (PPAR) gamma coactivator-1α (PGC-1α), PPARα and uncoupling protein 1 (UCP1) genes, serum level of glucagon-like peptide (GLP1), and metabolic parameters, as well as anthropometric indices in obese individuals on a weight loss diet.MethodsThis triple-blind randomized controlled trial (RCT) will include 50 eligible obese subjects aged between 18 and 60 years. Participants will be randomly assigned into two groups: 8 weeks of SB (600 mg/day) + hypo-caloric diet or placebo (600 mg/day) + hypo-caloric diet. At weeks 0 and 8, distinct objectives will be pursued: (1) PGC-1α, PPARα, and UCP1 genes expression will be evaluated by real-time polymerase chain reaction; (2) biochemical parameters will be assayed using enzymatic methods; and (3) insulin and GLP1 serum level will be assessed by enzyme-linked immunosorbent assay kit.DiscussionNew evidence from this trial may help fill the knowledge gap in this realm and facilitate multi-center clinical trials with a substantially larger sample size.Trial registrationIranian Registry of Clinical Trials: IRCT20190303042905N2. Registered on 31 January 2021.

Loss of CtBP2 may be a mechanistic link between metabolic derangements and progressive impairment of pancreatic β cell function

The adaptive increase in insulin secretion in early stages of obesity serves as a safeguard mechanism to maintain glucose homeostasis that cannot be sustained, and the eventual decompensation of β cells is a key event in the pathogenesis of diabetes. Here we describe a crucial system orchestrated by a transcriptional cofactor CtBP2. In cultured β cells, insulin gene expression is coactivated by CtBP2. Global genomic mapping of CtBP2 binding sites identifies a key interaction between CtBP2 and NEUROD1 through which CtBP2 decompacts chromatin in the insulin gene promoter. CtBP2 expression is diminished in pancreatic islets in multiple mouse models of obesity, as well as human obesity. Pancreatic β cell-specific CtBP2-deficient mice manifest glucose intolerance with impaired insulin secretion. Our transcriptome analysis highlights an essential role of CtBP2 in the maintenance of β cell integrity. This system provides clues to the molecular basis in obesity and may be targetable to develop therapeutic approaches.

Improvement to an existing multi-level capacitated lot sizing problem considering setup carryover, backlogging, and emission control

This paper presents a multi-level, multi-item, multi-period capacitated lot-sizing problem. The lot-sizing problem studies can obtain production quantities, setup decisions and inventory levels in each period fulfilling the demand requirements with limited capacity resources, considering the Bill of Material (BOM) structure while simultaneously minimizing the production, inventory, and machine setup costs. The paper proposes an exact solution to Chowdhury et al. (2018)'s[1] developed model, which considers the backlogging cost, setup carryover & greenhouse gas emission control to its model complexity. The problem contemplates the Dantzig-Wolfe (D.W.) decomposition to decompose the multi-level capacitated problem into a single-item uncapacitated lot-sizing sub-problem. To avoid the infeasibilities of the weighted problem (WP), an artificial variable is introduced, and the Big-M method is employed in the D.W. decomposition to produce an always feasible master problem. In addition, Wagner & Whitin's[2] forward recursion algorithm is also incorporated in the solution approach for both end and component items to provide the minimum cost production plan. Introducing artificial variables in the D.W. decomposition method is a novel approach to solving the MLCLSP model. A better performance was achieved regarding reduced computational time (reduced by 50%) and optimality gap (reduced by 97.3%) in comparison to Chowdhury et al. (2018)'s[1] developed model.© 2023 Society of Manufacturing Engineers (SME). Published by Elsevier Ltd. All rights reserved.This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)Peer-review under responsibility of the Scientific Committee of the NAMRI/SME.

Compliance with Nutritional Recommendations and Gut Microbiota Profile in Galician Overweight/Obese and Normal-Weight Individuals.

Different research studies have identified specific groups or certain dietary compounds as the onset and progression of obesity and suggested that gut microbiota is a mediator between these compounds and the inflammation associated with pathology. In this study, the objective was to evaluate the dietary intake of 108 overweight (OW), obese (OB), and normal-weight (NW) individuals and to analyze their gut microbiota profile to determine changes and associations with Body Mass Index (BMI) and diet. When individuals were compared by BMI, significant differences in fiber and monounsaturated fatty acids (MUFAs) intake were observed, showing higher adequacy for the NW group. The analysis of gut microbiota showed statistical differences for 18 ASVs; Anaerostipes and Faecalibacterium decreased in the OW/OB group, whereas the genus Oscillospira increased; the genus was also found in the LEFSe analysis as a biomarker for OW/OB. Roseburia faecis was found in a significantly higher proportion of NW individuals and identified as a biomarker for the NW group. Correlation analysis showed that adequation to nutritional recommendation for fiber indicated a higher abundance of Prevotella copri, linearly correlated with F. prausnitzii, Bacteroides caccae, and R. faecis. The same correlation was found for the adequation for MUFAs, with these bacteria being more abundant when the intake was adjusted to or below the recommendations.

Contributing factors to postural stability in Prader-Willi syndrome

BackgroundPrader-Willi Syndrome (PWS) is a rare neurodevelopmental disorder affecting multiple functional parameters. This study examined postural stability and associated gait and neuromuscular factors in young adults with PWS. MethodsParticipants included 10 adults with PWS [7 M/3F; Body Fat % 40.61 ± 7.79]; ten normal weight (NW) adults [7 M/3F; Body Fat % 23.42 ± 7.0]; ten obese (OB) adults [7 M/3F; Body Fat % 42.40 ± 5.62]. Participants completed the Sensory Organization Test (SOT)®. Condition (C) specific and a composite equilibrium score (CES) were calculated (maximum = 100). Quadriceps strength was assessed using an isokinetic dynamometer. Three-dimensional gait analyses were completed along a 10 m walkway using a motion capture system and two force plates. A gait stability ratio (GSR) was computed from gait speed and step length (steps/m). ResultsThe PWS group had lower scores for C1, C3, C4 and CES compared to the NW (p < .039 for all) and lower scores for C4 and CES than the OB (p < .019 for both) groups, respectively. In C5 (eyes closed, sway-referenced support) and C6 (sway-referenced vision and support), 33.3% of participants with PWS fell during the first trial in both conditions (X2 [2] 7.436, p = .024) and (X2 [2] 7.436, p = .024) but no participant in the other groups fell. Those with PWS showed higher GSR than participants with NW (p = .005) and those with obesity (p = .045). ConclusionIndividuals with PWS had more difficulty maintaining standing balance when relying on information from the somatosensory (C3), visual-vestibular (C4) and vestibular systems (C5, C6). A more stable walk was related to shorter steps, slower velocity and reduced peak quadriceps torque. Participation in multisensory activities that require appropriate prioritization of sensory system(s) input for controlling balance in altered sensory environments should be routinely included. In addition, exercises targeting muscular force and power should be included as part of exercise programming in PWS.

Highly recruited brown adipose tissue does not in itself protect against obesity

ObjectiveThe possibility to counteract the development of obesity in humans by recruiting brown or brite/beige adipose tissue (and thus UCP1) has attracted much attention. Here we examine if a diet that can activate diet-induced thermogenesis can exploit pre-enhanced amounts of UCP1 to counteract the development of diet-induced obesity. MethodsTo investigate the anti-obesity significance of highly augmented amounts of UCP1 for control of body energy reserves, we physiologically increased total UCP1 amounts by recruitment of brown and brite/beige tissues in mice. We then examined the influence of the augmented UCP1 levels on metabolic parameters when the mice were exposed to a high-fat/high-sucrose diet under thermoneutral conditions. ResultsThe total UCP1 levels achieved were about 50-fold higher in recruited than in non-recruited mice. Contrary to underlying expectations, in the mice with highly recruited UCP1 and exposed to a high-fat/high-sucrose diet the thermogenic capacity of this UCP1 was completely inactivate. The mice even transiently (in an adipostat-like manner) demonstrated a higher metabolic efficiency and fat gain than did non-recruited mice. This was accomplished without altering energy expenditure or food absorption efficiency. The metabolic efficiency here was indistinguishable from that of mice totally devoid of UCP1. ConclusionsAlthough UCP1 protein may be available, it is not inevitably utilized for diet-induced thermogenesis. Thus, although attempts to recruit UCP1 in humans may become successful as such, it is only if constant activation of the UCP1 is also achieved that amelioration of obesity development could be attained.

An adiposity force induces obesity in humans independently of a normal energy balance system-a thought experiment.

Obesity in humans represents a cumulative retention of a tiny fraction of total energy intake as fat, which is accompanied by growth of the metabolically active, energy-demanding, lean body mass. Since the energy balance regulation operates irrespective of the excess fat storage, availability of the required energy supplies is a permissive condition for obesity development. It occurs predominantly among people genetically predisposed and/or living with social or mental challenges. I propose a theory in which the body responds to social disruptions as threats of a future lack of food by an adiposity force building a reserve of energy independent of the regulation of the energy balance. It is based on the assumption that our evolutionary development required collaboration in gathering and sharing of food, combined with precautionary measures against anticipated failing food supplies. Social challenges are perceived as such threats, which activate the adiposity force through the brain to instigate the growth of fat and lean mass by neuro-hormonal signalling. If both perceived social threats and food abundance continue, the adiposity force pushes the fat accretion process to continue without inhibition by feedback signals from the fat mass, eventually leading to more obesity, and more so among the genetically predisposed. This article is part of a discussion meeting issue 'Causes of obesity: theories, conjectures and evidence (Part I)'.

Endothelial-derived FABP4 constitutes the majority of basal circulating hormone and regulates lipolysis-driven insulin secretion.

Fatty acid binding protein 4 (FABP4) is a lipid chaperone secreted from adipocytes upon stimulation of lipolysis. Circulating FABP4 levels strongly correlate with obesity and metabolic pathologies in experimental models and humans. While adipocytes have been presumed to be the major source of hormonal FABP4, this question has not been addressed definitively in vivo. We generated mice with Fabp4 deletion in cells known to express the gene - adipocytes (Adipo-KO), endothelial cells (Endo-KO), myeloid cells (Myeloid-KO), and the whole body (Total-KO) - to examine the contribution of these cell types to basal and stimulated plasma FABP4 levels. Unexpectedly, baseline plasma FABP4 was not significantly reduced in Adipo-KO mice, whereas Endo-KO mice showed ~87% reduction versus WT controls. In contrast, Adipo-KO mice exhibited ~62% decreased induction of FABP4 responses to lipolysis, while Endo-KO mice showed only mildly decreased induction, indicating that adipocytes are the main source of increases in FABP4 during lipolysis. We did not detect any myeloid contribution to circulating FABP4. Surprisingly, despite the nearly intact induction of FABP4, Endo-KO mice showed blunted lipolysis-induced insulin secretion, identical to Total-KO mice. We conclude that the endothelium is the major source of baseline hormonal FABP4 and is required for the insulin response to lipolysis.

Effects of synbiotic supplementation on intestinal microbiota composition in children and adolescents with exogenous obesity: (Probesity-2 trial)

IntroductionGut microbiota manipulation may be a potential therapeutic target to reduce host energy storage. There is limited information about the effects of probiotics/synbiotics on intestinal microbiota composition in children and adolescents with obesity. The objective of this randomized double-blind placebo-controlled trial was to test the effects of a multispecies synbiotic on intestinal microbiota composition in children and adolescents with exogenous obesity.MethodChildren with exogenous obesity were managed with a standard diet and increased physical activity and were randomly allocated into two groups at a ratio of 1:1; the 1st group received synbiotic supplementation (probiotic mixture including Lactobacillus acidophilus, Lacticaseibacillus. rhamnosus, Bifidobacterium bifidum, Bifidobacterium longum, Enterococcus faecium (total 2.5 × 109 CFU/sachet) and fructo-oligosaccharides (FOS; 625 mg/sachet) for 12 weeks; the 2nd group received placebo once daily for 12 weeks. Fecal samples were obtained before and at the end of the 12-week intervention to characterize the changes in the gut microbiota composition. Detailed metagenomic and bioinformatics analyses were performed.ResultsBefore the intervention, there were no significant differences in alpha diversity indicators between the synbiotic and placebo groups. After 12 weeks of intervention, the observed taxonomic units and Chao 1 were lower in the synbiotic group than at baseline (p < 0.001 for both). No difference for alpha diversity indicators was observed in the placebo group between baseline and 12 weeks of intervention. At the phylum level, the intestinal microbiota composition of the study groups was similar at baseline. The major phyla in the synbiotic group were Firmicutes (66.7%) and Bacteroidetes (18.8%). In the synbiotic group, the Bacteroidetes phylum was higher after 12 weeks than at baseline (24.0% vs. 18.8%, p < 0.01). In the synbiotic group, the Firmicutes/Bacteroidetes ratio was 3.54 at baseline and 2.75 at 12 weeks of intervention (p < 0.05). In the placebo group, the Firmicutes/Bacteroidetes ratio was 4.70 at baseline and 3.54 at 12 weeks of intervention (p < 0.05). After 12 weeks of intervention, the Firmicutes/Bacteroidetes ratio was also lower in the synbiotic group than in the placebo group (p < 0.05). In the synbiotic group, compared with the baseline, we observed a statistically significant increase in the genera Prevotella (5.28–14.4%, p < 0.001) and Dialister (9.68–13.4%; p < 0.05). Compared to baseline, we observed a statistically significant increase in the genera Prevotella (6.4–12.4%, p < 0.01) and Oscillospira (4.95% vs. 5.70%, p < 0.001) in the placebo group. In the synbiotic group, at the end of the intervention, an increase in Prevotella, Coprococcus, Lachnospiraceae (at the genus level) and Prevotella copri, Coprococcus eutactus, Ruminococcus spp. at the species level compared to baseline (predominance of Eubacterium dolichum, Lactobacillus ruminis, Clostridium ramosum, Bulleidia moorei) was observed. At the end of the 12th week of the study, when the synbiotic and placebo groups were compared, Bacteroides eggerthi species were dominant in the placebo group, while Collinsella stercoris species were dominant in the synbiotic group.ConclusionThis study is the first pediatric obesity study to show that a synbiotic treatment is associated with both changes intestinal microbiota composition and decreases in BMI. Trial identifier: NCT05162209 (www.clinicaltrials.gov).

The Impact of Obesity on Perioperative Outcomes for Children Undergoing Appendectomy for Acute Appendicitis: A Systematic Review.

Today, the prevalence of obesity in the pediatric population has increased dramatically. Acute appendicitis (AA) is the most common surgical condition among pediatric patients. We aimed to investigate the impact of obesity on postoperative outcomes in terms of operative time (OT), length of stay (LOS), surgical site infection (SSI), overall complications, adverse events, and mortality in children undergoing appendectomy for acute appendicitis. An extensive search of the literature in PubMed and Google Scholar was conducted to evaluate the outcomes of normal weight (NW), overweight (OW), and obese (OB) children who underwent appendectomy. Although no statistically significant differences were noted in perioperative outcomes and overall postoperative complications between OW/OB and NW children in the majority of the included studies, prolonged OT and LOS and SSI were found in some studies. Moreover, no differences in terms of readmissions and ED visits were recorded. We conclude that the impact of obesity on postoperative outcomes for children undergoing appendectomy for AA is unclear, and, therefore, no safe conclusions can be drawn with the currently available data. Due to the lack of high-quality studies, further research is required to optimize the surgical approach and prevent unwarranted complications.

Determining the metabolic effects of dietary fat, sugars and fat-sugar interaction using nutritional geometry in a dietary challenge study with male mice

The metabolic effects of sugars and fat lie at the heart of the “carbohydrate vs fat” debate on the global obesity epidemic. Here, we use nutritional geometry to systematically investigate the interaction between dietary fat and the major monosaccharides, fructose and glucose, and their impact on body composition and metabolic health. Male mice (n = 245) are maintained on one of 18 isocaloric diets for 18–19 weeks and their metabolic status is assessed through in vivo procedures and by in vitro assays involving harvested tissue samples. We find that in the setting of low and medium dietary fat content, a 50:50 mixture of fructose and glucose (similar to high-fructose corn syrup) is more obesogenic and metabolically adverse than when either monosaccharide is consumed alone. With increasing dietary fat content, the effects of dietary sugar composition on metabolic status become less pronounced. Moreover, higher fat intake is more harmful for glucose tolerance and insulin sensitivity irrespective of the sugar mix consumed. The type of fat consumed (soy oil vs lard) does not modify these outcomes. Our work shows that both dietary fat and sugars can lead to adverse metabolic outcomes, depending on the dietary context. This study shows how the principles of the two seemingly conflicting models of obesity (the “energy balance model” and the “carbohydrate insulin model”) can be valid, and it will help in progressing towards a unified model of obesity. The main limitations of this study include the use of male mice of a single strain, and not testing the metabolic effects of fructose intake via sugary drinks, which are strongly linked to human obesity.

The muscle-enriched myokine Musclin impairs beige fat thermogenesis and systemic energy homeostasis via Tfr1/PKA signaling in male mice

Skeletal muscle and thermogenic adipose tissue are both critical for the maintenance of body temperature in mammals. However, whether these two tissues are interconnected to modulate thermogenesis and metabolic homeostasis in response to thermal stress remains inconclusive. Here, we report that human and mouse obesity is associated with elevated Musclin levels in both muscle and circulation. Intriguingly, muscle expression of Musclin is markedly increased or decreased when the male mice are housed in thermoneutral or chronic cool conditions, respectively. Beige fat is then identified as the primary site of Musclin action. Muscle-transgenic or AAV-mediated overexpression of Musclin attenuates beige fat thermogenesis, thereby exacerbating diet-induced obesity and metabolic disorders in male mice. Conversely, Musclin inactivation by muscle-specific ablation or neutralizing antibody treatment promotes beige fat thermogenesis and improves metabolic homeostasis in male mice. Mechanistically, Musclin binds to transferrin receptor 1 (Tfr1) and antagonizes Tfr1-mediated cAMP/PKA-dependent thermogenic induction in beige adipocytes. This work defines the temperature-sensitive myokine Musclin as a negative regulator of adipose thermogenesis that exacerbates the deterioration of metabolic health in obese male mice and thus provides a framework for the therapeutic targeting of this endocrine pathway.