Tryptophan Metabolism Is Associated with BMI and Adipose Tissue Mass and Linked to Metabolic Disease in Pediatric Obesity

The obesity epidemic has contributed to an escalating prevalence of metabolic diseases in children. Overnutrition leads to increased tryptophan uptake and availability. An association between the induction of the tryptophan catabolic pathway via indoleamine 2,3-dioxygenase (IDO) activity and obesity-related inflammation has been observed. This study aimed to investigate the impact of pediatric obesity on tryptophan metabolism and the potential relationship with metabolic disease. In this prospective cohort study, plasma kynurenine, tryptophan, and serotonin levels were measured by ELISA, and IDO activity was estimated by calculating the kynurenine/tryptophan ratio in a clinically characterized population with severe obesity (BMI ≥ 97th percentile) aged 9 to 19 (n = 125). IDO activity and its product kynurenine correlated with BMI z-score and body fat mass, whereas concentrations of serotonin, the alternative tryptophan metabolite, negatively correlated with these measures of adiposity. Kynurenine and tryptophan, but not serotonin levels, were associated with disturbed glucose metabolism. Tryptophan concentrations negatively correlated with adiponectin and were significantly higher in prediabetes and metabolically unhealthy obesity. In conclusion, BMI and body fat mass were associated with increased tryptophan catabolism via the kynurenine pathway and decreased serotonin production in children and adolescents with severe obesity. The resulting elevated kynurenine levels may contribute to metabolic disease in obesity.

The Global Spread of Severe Obesity in Toddlers, Children and Adolescents – a Systematic Review & Meta Analysis

Introduction: Severe obesity among children and adolescents has emerged as a public health concern in multiple places around the world. Methods: We searched the Medline database for articles on severe obesity rates in children published between January 1960 and January 2020. For studies with available prevalence rates for an early and a more recent time period, the relative increase in prevalence was imputed. Results: In total, 874 publications were identified, of which 38 contained relevant epidemiological data. Rates of severe obesity varied significantly according to age, gender, geographic area, and the definition of severe obesity. The highest rates of class II and III obesity in the US according to the Centers of Disease Control cutoff were 9.5% and 4.5%, respectively. Seventeen studies reported prevalence rates in at least two time periods. Data for 9,190,718 individuals showed a 1.71 (95%CI, 1.53-1.90) greater odds for severe obesity in 2006-2017 (N=5,029,584) vs. 1967-2007 (N=4,161,134). In an analysis limited to studies from 1980s’ with a minimum follow-up of 20 years, a 9.16(95%CI, 7.76-10.80) greater odds for severe obesity in recent vs. earlier time was found. An analysis limited to studies from 2000, with a follow-up of 5-15 years, a 1.09 (95%CI, 0.99-1.20) greater odds was noted when comparing (2011-2017; N=4,991,831) vs. (2000-2011; N=4,134,340). Conclusion: Severe pediatric obesity is escalating with a marked increase from the1980’s and a slower rate from 2000.

Impairment of gut microbial biotin metabolism and host biotin status in severe obesity: effect of biotin and prebiotic supplementation on improved metabolism

ObjectivesGut microbiota is a key component in obesity and type 2 diabetes, yet mechanisms and metabolites central to this interaction remain unclear. We examined the human gut microbiome’s functional composition in healthy metabolic state and the most severe states of obesity and type 2 diabetes within the MetaCardis cohort. We focused on the role of B vitamins and B7/B8 biotin for regulation of host metabolic state, as these vitamins influence both microbial function and host metabolism and inflammation.DesignWe performed metagenomic analyses in 1545 subjects from the MetaCardis cohorts and different murine experiments, including germ-free and antibiotic treated animals, faecal microbiota transfer, bariatric surgery and supplementation with biotin and prebiotics in mice.ResultsSevere obesity is associated with an absolute deficiency in bacterial biotin producers and transporters, whose abundances correlate with host metabolic and inflammatory phenotypes. We found suboptimal circulating biotin levels in severe obesity and altered expression of biotin-associated genes in human adipose tissue. In mice, the absence or depletion of gut microbiota by antibiotics confirmed the microbial contribution to host biotin levels. Bariatric surgery, which improves metabolism and inflammation, associates with increased bacterial biotin producers and improved host systemic biotin in humans and mice. Finally, supplementing high-fat diet-fed mice with fructo-oligosaccharides and biotin improves not only the microbiome diversity, but also the potential of bacterial production of biotin and B vitamins, while limiting weight gain and glycaemic deterioration.ConclusionStrategies combining biotin and prebiotic supplementation could help prevent the deterioration of metabolic states in severe obesity.Trial registration numberNCT02059538.

Obesity as a mortality risk factor in the medical ward: a case control study

Background Research regarding the association between severe obesity and in-hospital mortality is inconsistent. We evaluated the impact of body mass index (BMI) levels on mortality in the medical wards. The analysis was performed separately before and during the COVID-19 pandemic. Methods We retrospectively retrieved data of adult patients admitted to the medical wards at the Mount Sinai Health System in New York City. The study was conducted between January 1, 2011, to March 23, 2021. Patients were divided into two sub-cohorts: pre-COVID-19 and during-COVID-19. Patients were then clustered into groups based on BMI ranges. A multivariate logistic regression analysis compared the mortality rate among the BMI groups, before and during the pandemic. Results Overall, 179,288 patients were admitted to the medical wards and had a recorded BMI measurement. 149,098 were admitted before the COVID-19 pandemic and 30,190 during the pandemic. Pre-pandemic, multivariate analysis showed a “J curve” between BMI and mortality. Severe obesity (BMI > 40) had an aOR of 0.8 (95% CI:0.7–1.0, p = 0.018) compared to the normal BMI group. In contrast, during the pandemic, the analysis showed a “U curve” between BMI and mortality. Severe obesity had an aOR of 1.7 (95% CI:1.3–2.4, p < 0.001) compared to the normal BMI group. Conclusions Medical ward patients with severe obesity have a lower risk for mortality compared to patients with normal BMI. However, this does not apply during COVID-19, where obesity was a leading risk factor for mortality in the medical wards. It is important for the internal medicine physician to understand the intricacies of the association between obesity and medical ward mortality.

Predictors of Post-Exercise Energy Intake in Adolescents Ranging in Weight Status from Overweight to Severe Obesity

Exercise may sensitize individuals with overweight and obesity to appetitive signals (e.g., hunger and fullness cues), overriding trait eating behaviors that contribute to overeating and obesity, such as uncontrolled eating. The objective of the current study was to measure predictors of objective ad libitum energy intake at a laboratory-based, post-exercise test-meal in adolescents ranging in weight status from overweight to severe obesity. We hypothesized that appetitive states, rather than appetitive traits, would be the strongest predictors of energy intake at a post-exercise test-meal, after controlling for body size. At Baseline, 30 adolescents (ages 10–16 years, 50% female (F), 43% non-Hispanic white (NHW), 83% with obesity (OB)) completed state and trait appetite measures and an ad libitum dinner meal following intensive exercise. Nineteen of those participants (47% F, 32% NHW, 79% OB) completed identical assessments two years later (Year 2). Energy intake (kcal) at each time point was adjusted for fat-free mass index (i.e., body size). Adjusted energy intake was reliable from Baseline to Year 2 (ICC = 0.84). Multiple pre-meal appetite ratings were associated with test-meal energy intake. In stepwise linear regression models, pre-meal prospective food consumption was the strongest and only significant predictor of test-meal energy intake at both Baseline (R2 = 0.25, p = 0.005) and Year 2 (R2 = 0.41, p = 0.003). Baseline post-exercise energy intake was associated with weight change over two years (R2 = 0.24, p = 0.04), but not with change in fat mass (p = 0.11). Appetitive traits were not associated with weight or body composition change (p > 0.22). State appetite cues were the strongest predictors of post-exercise energy intake, independent of body size. Future studies should examine whether long-term exercise programs enhance responsiveness to homeostatic appetite signals in youth with overweight and obesity, with a goal to reduce excess energy intake and risk for weight gain over time.

Obesity, preoperative weight loss, and telemedicine before total joint arthroplasty: a review

The preoperative period prior to elective total joint arthroplasty (TJA) is a critical time for lifestyle interventions since a scheduled surgery may help motivate patients to lose weight. Weight loss may reduce complications associated with obesity following TJA and enable patients with severe obesity (body mass index [BMI] > 40 kg/m2) to become eligible for TJA, as many institutions use a 40 kg/m2 cut-off for offering surgery. A comprehensive review was conducted to (1) provide background on complications associated with obesity following TJA, (2) synthesize prior research on the success rate of patients losing weight after being denied TJA for severe obesity, (3) discuss bariatric surgery before TJA, and (4) propose mobile health telemedicine weight loss interventions as potential weight loss methods for patients preoperatively.It is well established that obesity increases complications associated with TJA. In total knee arthroplasty (TKA), obesity increases operative time, length of stay, and hospitalization costs as well as the risk of deep infection, revision, and component malpositioning. Obesity may have an even larger impact on complications associated with total hip arthroplasty (THA), including wound complications and deep infection. Obesity also increases the risk of hip dislocation, aseptic loosening, and venous thromboembolism after THA.Synthesis of the only two studies (n = 417), to our knowledge, that followed patients denied TJA for severe obesity demonstrated that only 7% successfully reduced their BMI below 40 kg/m2 via lifestyle modifications and ultimately underwent TJA. Unfortunately, bariatric surgery may only increase certain post-TKA complications including death, pneumonia, and implant failure, and there is limited research on preoperative weight loss via lifestyle modification. A review of short-term mobile health weight loss interventions that combined personalized counseling with self-monitoring via a smartphone app found about 5 kg of weight loss over 3-6 months. Patients with severe obesity have more weight to lose and may have additional motivation to do so before TJA, so weight loss results may differ by patient population. Research is needed to determine whether preoperative mobile health interventions can help patients become eligible for TJA and produce clinically significant weight loss sufficient to improve postoperative outcomes.