Risk factors for lower renal compensation after nephrectomy: an analysis of living kidney donors in an Amazonian cohort / Fatores de risco para menor compensação renal pós-nefrectomia: análise de doadores de rim vivo em uma coorte amazônica

Abstract Introduction: Living donor kidney transplantation is considered the ideal renal replacement therapy because it has a lower complication rate and allows an efficient response to the high demand for grafts in the healthcare system. Careful selection and adequate monitoring of donors is a key element in transplantation. Individuals at greater risk of developing kidney dysfunction after nephrectomy must be identified. Objective: To identify risk factors associated with a renal compensation rate (CR) below 70% 12 months after nephrectomy. Methods: This observational retrospective longitudinal study included living kidney donors followed up at the Lower Amazon Regional Hospital between 2016 and 2022. Data related to sociodemographic variables, comorbid conditions and kidney function parameters were collected. Results: The study enrolled 32 patients. Fourteen (43.75%) had a CR < 70% 12 months after kidney donation. Logistic regression found obesity (Odds Ratio [95%CI]: 10.6 [1.7-65.2]), albuminuria (Odds Ratio [95%CI]: 2.41 [1.2-4.84]) and proteinuria (Odds Ratio [95%CI]: 1.14 [1.03-1.25]) as risk factors. Glomerular filtration rate was a protective factor (Odds Ratio [95% CI]: 0.92 [0.85-0.99]). Conclusion: Obesity, albuminuria and proteinuria adversely affected short-term renal compensation rate. Further studies are needed to uncover the prognostic implications tied to these risk factors. Our findings also supported the need for careful individualized assessment of potential donors and closer monitoring of individuals at higher risk.

Resumo Introdução: O transplante de rim de doador vivo é considerado a terapia renal substitutiva ideal por oferecer menor taxa de complicações e possibilitar uma resposta eficiente à grande demanda por enxertos no sistema de saúde. A seleção criteriosa e o acompanhamento adequado dos doadores constituem um pilar fundamental dessa modalidade terapêutica, sendo essencial a identificação dos indivíduos em maior risco de disfunção renal pós-nefrectomia. Objetivo: Identificar fatores de risco para uma Taxa de Compensação (TC) da função renal inferior a 70% 12 meses após a nefrectomia. Métodos: Estudo observacional, retrospectivo e longitudinal conduzido com doadores de rim vivo acompanhados no Hospital Regional do Baixo Amazonas entre 2016 e 2022. Foram coletados dados correspondentes a variáveis sociodemográficas, comorbidades e parâmetros de função renal. Resultados: Foram incluídos 32 pacientes na amostra final. Destes, 14 (43,75%) obtiveram TC < 70% 12 meses após a doação. A regressão logística identificou a obesidade (Odds Ratio [IC95%]: 10.6 [1.7-65.2]), albuminúria (Odds Ratio [IC95%]: 2.41 [1.2-4.84]) e proteinúria (Odds Ratio [IC95%]: 1.14 [1.03-1.25]) como fatores de risco. A taxa de filtração glomerular atuou como fator de proteção (Odds Ratio [IC95%]: 0.92 [0.85-0.99]). Conclusão: Obesidade, albuminúria e proteinúria demonstraram impacto negativo na taxa de compensação renal em curto prazo, o que reitera a necessidade de estudos acerca das implicações prognósticas desses fatores. Além disso, reforça-se a necessidade de avaliação cuidadosa e individualizada dos possíveis doadores, com acompanhamento rigoroso, especialmente para indivíduos de maior risco.

Assessment of EN-RAGE, sRAGE, and its isoforms: cRAGE, esRAGE in obese patients treated by moderate caloric restriction combined with physical activity conducted in hospital condition.

BACKGROUND: AGEs, their receptor (RAGE), and the extracellular newly identified receptor for AGEs product-binding protein (EN-RAGE) are implicated in the pathogenesis of inflammation. AIM: We analyzed serum EN-RAGE, soluble RAGE (sRAGE), and their isoforms: endogenous secretory - esRAGE and cleaved - cRAGE concentrations in lean controls (n = 74) and in patients with obesity (n = 71) treated for three weeks with moderate calorie restriction (CR) combined with physical activity in a hospital condition. METHODS: Using the ELISA method, serum sRAGE, esRAGE, and EN-RAGE were measured before and after CR. RESULTS: The serum level of sRAGE and esRAGE in patients with obesity was lower than that in non-obese individuals, contrary to cRAGE. EN-RAGE concentration was about three times higher in obese patients. Gradually, a rise in BMI resulted in sRAGE, esRAGE reduction, and EN-RAGE increase. The sRAGE concentration was sex-dependent, indicating a higher value in lean men. A moderate negative correlation was observed between BMI and all RAGE isoforms, whereas EN-RAGE displays a positive correlation. CR resulted in an expected decrease in anthropometric, metabolic, and proinflammatory parameters and EN-RAGE, but no RAGE isoforms. The ratio EN-RAGE/sRAGE was higher in obese humans than in control and was not modified by CR. CONCLUSION: Obesity decreases sRAGE and esRAGE and increases EN-RAGE concentration. Moderate CR and physical activity by decreasing inflammation reduces EN-RAGE but is insufficient to increase sRAGE and esRAGE to the extent observed in lean patients. EN-RAGE instead of sRAGE could be helpful to indicate a better outcome of moderate dietary intervention in obese subjects.

Impact of maternal body mass index (BMI) and the challenges of fetal echocardiography.

OBJECTIVES: Fetal echocardiography is the gold standard modality to detect suspected congenital heart disease (CHD). Accurate diagnosis and subsequent prognosis is even more challenging in the presence of a raised maternal body mass index (BMI). This retrospective study aimed to gain insight into the prevalence of obesity within the cohort of patients referred for fetal echocardiography. STUDY DESIGN/METHODS: Retrospective analysis of all pregnant patients referred to the Scottish National Fetal Cardiology Service between 2015 and 2021 due to a suspected fetal cardiac abnormality and examining the associated trends in maternal BMI and the Scottish Index of Multiple Deprivation (SIMD). RESULTS: BMI data were available for 962 (96.3%) of the 998 patients referred during the study period. Median BMI during the study period was 31. BMI range in the seven-year period was 16-63. There was no association between BMI group and year (P = 0.889). A median of 58% of patients referred were classified as overweight (BMI > 25 kg/m2), and only 37% were reported to have a BMI within normal limits. Referral BMI was relatively consistent in the seven years with no dramatic increase in the obese categories. Mean BMI in SIMD 5 (lowest level of deprivation), was significantly lower (P = 0.001), than in SIMD 1 (highest deprivation). CONCLUSIONS: People of child bearing age should be aware the potential limitations that a raised BMI may have upon diagnostic/screening accuracy impacting subsequent ability to provide accurate fetal cardiac diagnoses and prognostic fetal cardiac imaging.

The associations between neighborhood characteristics and childhood overweight and obesity in a national dataset.

BACKGROUND: National child obesity rates continue to climb. While neighborhood factors are known to influence childhood weight, more work is needed to further our understanding of these relationships and inform intervention and policy approaches reflective of complex real-world contexts. METHODS: To evaluate the associations between neighborhood components and childhood overweight/obesity, we analyzed sequential, cross-sectional data from the National Survey of Children's Health collected annually between 2016 and 2021. To characterize the complexity of children's neighborhood environments, several interrelated neighborhood factors were examined: amenities, detractions, support, and safety. We used ordinal logistic regression models to evaluate the associations between these exposures of interest and childhood weight status, adjusting for potential confounders. RESULTS: Our analytic sample contained 96,858 children representing a weighted population of 28,228,799 children ages 10-17 years. Child weight status was healthy in 66.5%, overweight in 16.8%, and obese in 17.2%. All four neighborhood factors were associated with child weight status. The odds of overweight or obesity generally increased with a decreasing number of amenities and increasing number of detractions, with the highest adjusted odds ratio seen with no amenities and all three possible detractions (1.71; 95% confidence interval [1.31, 2.11]). CONCLUSIONS: Multiple factors within a child's neighborhood environment were associated with child weight status in this sample representative of the U.S. population aged 10-17 years. This suggests the need for future research into how policies and programs can support multiple components of a healthy neighborhood environment simultaneously to reduce rates of childhood overweight/obesity. WHAT'S NEW: In a national sample of 96,858 children ages 10-17 years, the odds of child overweight/obesity were highest in neighborhoods reported by parents as being unsafe, unsupportive, having multiple detractions (e.g. vandalism), and having no amenities (e.g. playgrounds).

Assessing the causal relationship of birth weight and childhood obesity on osteoarthritis: a Mendelian randomization study.

Obesity is associated with osteoarthritis (OA), but few studies have used fetal origin to explore the association. Our study aims to disentangle the causality between birth weight, childhood obesity, and adult OA using Mendelian randomization (MR). We identified single nucleotide polymorphisms (SNPs) related to birth weight (n = 298,142) and childhood obesity (n = 24,160) from two genome-wide association studies contributed by the Early Growth Genetics Consortium. Summary statistics of OA and its phenotypes (knee, hip, spine, hand, thumb, and finger OA) from the Genetics of Osteoarthritis Consortium (n = 826,690) were used to estimate the effects of SNPs on OA. Multivariable MR (MVMR) was conducted to investigate the independent effects of exposures. It turned out that genetically predicted standard deviation increase in birth weight was not associated with OA. In contrast, there was a marginally positive effect of childhood obesity on total [odds ratio (OR) = 1.07, 95% confidence interval (CI) = 1.00, 1.15 using IVW], knee (OR = 1.13, 95% CI = 1.05, 1.22 using weighted median), hip (OR = 1.13, 95% CI = 1.04, 1.24 using IVW), and spine OA (OR = 1.12, 95% CI = 1.03, 1.22 using IVW), but not hand, thumb, or finger OA. MVMR indicated a potential adulthood body mass index-dependent causal pathway between childhood obesity and OA. In conclusion, no association of birth weight with OA was suggested. Childhood obesity, however, showed a causality with OA in weight-bearing joints, which seems to be a general association of obesity with OA.

Efficacy of Glucagon-like Peptide-1 Receptor Agonists in Overweight/Obese and/or T2DM Adolescents: A Meta-analysis Based on Randomized Controlled Trials.

Objective: This meta-analysis aimed to investigate the effect of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on blood glucose and weight in overweight/obese and/or type 2 diabetes mellitus (T2DM) adolescents aged <18 years. Methods: Herein, we searched PubMed, Embase, Web of Science, and Cochrane Library for all randomized controlled trials (RCTs) comparing GLP-1RAs with placebo in overweight/obese and/or T2DM adolescents and extracted relevant data up to August 2023 for meta-analysis. Results: Fourteen RCTs were included in the meta-analysis with a total of 1262 participants. Results revealed that the GLP-1RAs group had a more significant reduction in glycosylated hemoglobin A1c (HbA1c; risk difference (RD)=-0.34%, P<0.001) than the control group. However, there was no difference in fasting blood glucose (FPG; RD=-2.07mg/dL, P=0.065) between the two groups. Nonetheless, the experimental group that administered exenatide showed a no significant reduction in HbA1c (P=0.253) and FPG (P=0.611) between the two groups. The GLP-1RAs group had a more significant decline in body weight (RD=-4.28kg, P=0.002) and BMI (RD=-1.63kg/m2, P=0.002) compared to the control group. The experimental group was adopted with liraglutide (RD=-2.31kg, P=0.038) or exenatide (RD=-2.70kg, P<0.001). Compared to the control group, the experimental group had a more significant drop in body weight than the control group. But for the experimental group that received liraglutide, the BMI had a no significant reduction between the two groups (RD=-0.81kg/m2, P=0.260). For the experimental group that was adopted with exenatide, BMI revealed a more significant decline in the intervention group than in the control group (RD=-1.14kg/m2, P<0.001). Conclusion: This study showed that GLP-1RAs reduced HbA1c, FPG, and weight loss in overweight/obese and/or T2DM adolescents. Liraglutide is better than exenatide in terms of glucose reduction. Nevertheless, in terms of weight control, exenatide is better than liraglutide.

Gender Difference and Changes in the Prevalence of Obesity Over Time in Children Under 12 Years Old: A Meta-analysis.

Objective: Evaluating changes over time in the odds of obesity according to sex. Methods: PubMed, Embase, Cochrane Library, and China National Knowledge Database were searched for relevant studies. Full-text studies evaluating the influence of sex on obesity were analyzed. We used R 3.4.3 to assess the impact of results in the selected studies, calculated pooled prevalence and odds ratio (OR) with their respective 95% confidence intervals (CIs). P<0.10 and I2>50% indicated high heterogeneity, and the random-effects model was used, otherwise, the fixed-effects model was used. Results: The included studies reported the prevalence of obesity in children covering 1987-2017 intervals. The pooled prevalence of obesity in boy and girl groups were 0.13 (95% CI: 0.08, 0.20) and 0.10 (95% CI: 0.07, 0.13). In the analysis of the boy group, the pooled OR in earlier time (1987-2013) vs. recent time (2011-2017) was 0.98 (95% CI: 0.76, 1.26). The estimated OR for girls in earlier vs. recent time was 1.01 (95% CI: 0.80, 1.28). In the analysis of studies with follow-up period ≥ 10 years, the pooled OR for obesity in earlier vs. recent time period was 0.99 (95% CI: 0.76, 1.30). For those with follow-up period < 10 years, the pooled OR in earlier vs. recent time period was 0.94 (95% CI: 0.57, 1.54). Conclusions: Comprehensive measurements are required to control obesity among children albeit with nonsignificant gender difference and time trend for obesity rates in children.

Anti-adipogenesis and anti-obesity potential of alliin mediated by modulating glycolipid metabolism via activating PPARγ signaling.

Garlic exhibits hypolipidemic, hypoglycemic, and cardiovascular benefits. The inconsistent results of garlic preparations on adipogenesis have caused more confusion in the public and academia. The compounds responsible for the anti-adipogenesis effect of garlic remain unknown. The present study aimed to verify the real anti-adipogenesis and anti-obesity component in garlic and explored its possible effects in metabolic syndrome. We verified the real anti-adipogenesis and anti-obesity components of garlic in 3T3-L1 preadipocytes and a 10-week-high fat diet (HFD)-induced obese mice. In vitro, two water-soluble and four typical lipid-soluble compounds of garlic were tested for their anti-adipogenesis. Then, the water-soluble compound, alliin, and two processing methods produced garlic oils, were evaluated in vivo study. Mice received oral administration of alliin (25 mg/kg) and garlic oils (15 mg/kg) daily for 8 weeks. Serum lipids, parameters of obesity, and indicators involved in regulating glycolipid metabolism were examined. Our findings confirmed that both water-soluble and lipid-soluble organosulfur compounds of garlic contributed to garlic's anti-adipogenesis effect, in which water-soluble sulfides, especially alliin, exhibited greater potency. Alliin possessed potent effects of anti-obesity and improvement in glucose and lipid metabolism in HFD-induced obese mice. Alliin mediated these effects partly attributed to its modulation of enzymatic activities within glycolipid metabolism and activating PPARγ signaling pathway. In contrast to odorous lipid-soluble sulfides, alliin is odorless, stable, and safe, and is an ideal nutraceutical or even medicinal candidates for the treatment of metabolic diseases. Alliin could be used to standardize the quality of garlic products.

Marrow Adipocyte Senescence in the Pathogenesis of Bone Loss.

PURPOSE OF REVIEW: Beyond aging, senescent cells accumulate during multiple pathological conditions, including chemotherapy, radiation, glucocorticoids, obesity, and diabetes, even earlier in life. Therefore, cellular senescence represents a unifying pathogenic mechanism driving skeletal and metabolic disorders. However, whether senescent bone marrow adipocytes (BMAds) are causal in mediating skeletal dysfunction has only recently been evaluated. RECENT FINDINGS: Despite evidence of BMAd senescence following glucocorticoid therapy, additional evidence for BMAd senescence in other conditions has thus far been limited. Because the study of BMAds presents unique challenges making these cells difficult to isolate and image, here we review issues and approaches to overcome such challenges, and present advancements in isolation and histological techniques that may help with the future study of senescent BMAds. Further insights into the roles of BMAd senescence in the pathogenesis of skeletal dysfunction may have important basic science and clinical implications for human physiology and disease.

[The role of the musculoadipose status in the assessment of the risk profile before liver transplantation]. / Die Rolle des muskuloadipösen Status bei der Beurteilung des Risikoprofils vor Lebertransplantation.

Sarcopenia and sarcopenic obesity worsen the prognosis after liver transplantation; however, the assessment of body composition is not yet considered in the evaluation prior to liver transplantation to estimate the risk profile of the recipient. Prehabilitation, which includes the nutritional supplementation and physiotherapy, represents a recent focus of interest in clinical transplantation research. This article gives an overview of the recent knowledge about the role of the musculoadipose status and the available methods for the estimation in the assessment of the recipient's risk profile.

An Australian Football Themed Health Behaviour Change Intervention for Men With Cardiovascular Disease is Feasible and Acceptable: Results From a Feasibility Randomised Trial.

BACKGROUND: Physical activity (PA) and weight management are critical for cardiovascular disease (CVD) secondary prevention. However, PA adherence during or after cardiac rehabilitation is low. Here, we assess the feasibility and acceptability of the Australian football-themed Aussie Fans in Training (Aussie-FIT) program and associated trial procedures when adapted for men with CVD. METHOD: A pragmatic randomised control trial, with waitlist control arm, and follow-up measures at 3 and 6 months. Men with a CVD diagnosis and body mass index ≥25 kg/m2 were recruited from community and clinical settings, and randomised, following baseline measures of health and health behaviours. The intervention arm attended 12 face-to-face football-themed education and PA sessions. Feasibility (recruitment, retention, attendance, and adherence to trial procedures) was assessed via mixed methods. RESULTS: A total of 74% (64/86) of participants expressing interest met the eligibility criteria. Of those, 49 men (mean age=61.4, standard deviation=9.5, mean body mass index=31.3, standard deviation=4.2) were randomised. Program attendance rates (87% attended ≥80% of sessions) and retention (92%) were high. Trial retention at the primary end point (3 months) was high (86%) and at the 6-month follow-ups reduced to 67%. Program and trial procedures were acceptable, except for the request to visit a pathologist for the blood draw. CONCLUSIONS: Using a football theme and setting may be a feasible way to engage men with CVD in health behaviour change. Given the existing pilot evidence for men at risk of CVD, and that recruitment rates were under the target, trialling a program for men with or at risk of CVD is recommended.

The healthcare costs of increased body mass index-evidence from The Trøndelag Health Study.

BACKGROUND: Earlier studies have estimated the impact of increased body mass index (BMI) on healthcare costs. Various methods have been used to avoid potential biases and inconsistencies. Each of these methods measure different local effects and have different strengths and weaknesses. METHODS: In the current study we estimate the impact of increased BMI on healthcare costs using nine common methods from the literature: multivariable regression analyses (ordinary least squares, generalized linear models, and two-part models), and instrumental variable models (using previously measured BMI, offspring BMI, and three different weighted genetic risk scores as instruments for BMI). We stratified by sex, investigated the implications of confounder adjustment, and modelled both linear and non-linear associations. RESULTS: There was a positive effect of increased BMI in both males and females in each approach. The cost of elevated BMI was higher in models that, to a greater extent, account for endogenous relations. CONCLUSION: The study provides solid evidence that there is an association between BMI and healthcare costs, and demonstrates the importance of triangulation.

Early Adverse Respiratory Outcomes in Obese Pediatric Tonsillectomy Patients.

OBJECTIVE: To determine if body mass index (BMI) is predictive of adverse respiratory events (ARE) in the obese pediatric population undergoing tonsillectomy. STUDY DESIGN: Case series with chart review. SETTING: Single institution academic otolaryngology practice. METHODS: All patients 3 to 12 years old with BMI ≥95th percentile that underwent tonsillectomy March 1, 2011 to July 15, 2020 were included. The study excluded patients with comorbidities that warranted admission independent of BMI, including Trisomy 21, gross developmental delay, neuromuscular disorders, and congenital heart disease. Perioperative AREs following tonsillectomy were recorded. AREs were defined as postoperative desaturation (SpO2 < 90%), intubation, continuous positive airway pressure (CPAP), or new O2 requirement for >2 hours. RESULTS: Eighteen patients (8%) had at least 1 ARE. There were no children age 5 and older with a BMI 95th percentile to 98.9th percentile who had an early adverse respiratory outcome. Preoperative polysomnogram (PSG) metrics, obstructive apnea-hypopnea index (oAHI), and oxygen saturations (SpO2) nadir was significantly different between patients with and without AREs (mean oAHI 54.3 vs 17.4, P = .02; mean SpO2 nadir 73.1% vs 84.5%, P = .05). There was no significant difference in the BMI z score (2.88 vs 2.45, P = .09) between groups. CONCLUSION: AREs requiring inpatient management are uncommon in obese children after tonsillectomy. BMI is a poor independent indication for admission except at BMI extremes. We found significantly higher oAHI and lower SpO2 nadir on PSG indicate a higher risk for AREs and can guide admission postoperatively. There may be a subset of obese tonsillectomy patients who can be safely discharged home on the day of surgery.

Apixaban plasma concentrations in patients with obesity.

PURPOSE: Routine therapeutic drug monitoring of apixaban is currently not recommended but may however be warranted in some situations and for some patient groups to provide better and safer treatment. Due to limited data on apixaban concentrations in different subpopulations, it is still unclear which group of patients could possibly gain from monitoring. The purpose of this study was to examine apixaban exposure in patients with obesity compared with normal-weight patients. METHODS: Forty patients with obesity (mean BMI 39.4 kg/m2) and 40 controls with normal weight (mean BMI 23.4 kg/m2), treated with apixaban 5 mg twice daily were included. The patients were matched for age, sex, and renal function. Trough and peak apixaban concentrations were measured with LC‒MS/MS methodology. RESULTS: The median trough concentrations in patients with obesity (58.7, range 10.7-200.7 ng/ml) were slightly higher than those in patients with normal weight (52.0, range 31.0-150.9 ng/ml) (p < 0.05). Notably, the variability in trough concentration was considerably higher in patients with obesity. Peak concentrations were similar in both groups, with a median of 124.5 ng/ml (range 82.0-277.5) and 113.5 ng/ml (range 75.5-334.6) in patients with obesity and normal weight, respectively. CONCLUSION: Apixaban exposure did not vary substantially between obese and normal weight matched controls, implying that general dose adjustments are not required. However, vast interindividual variability was observed in patients with obesity, suggesting that measuring the concentrations could be valuable for specific patients. Further research is needed to identify which specific patients may benefit from this approach.

Ceftriaxone reverses diet-induced deficits in goal-directed control.

RATIONALE: Obesity is associated with numerous health risks and ever-increasing rates are a significant global concern. However, despite weight loss attempts many people have difficulty maintaining weight loss. Previous studies in animals have shown that chronic access to an obesogenic diet can disrupt goal-directed behavior, impairing the ability of animals to flexibly adjust food-seeking behavior following changes in the value of earned outcomes. Changes in behavioral control have been linked to disruption of glutamate transmission in the dorsal medial striatum (DMS), a region critical for the acquisition and expression of goal-directed behavior. OBJECTIVES: The goal of this study was to test whether ceftriaxone, a beta-lactam antibiotic shown elsewhere to upregulate the expression of the glutamate transporter GLT-1, would improve goal-directed control following long-term exposure to an obesogenic diet. METHODS: Male and female rats were given access to either standard chow or chow plus sweetened condensed milk (SCM) for 6 weeks. Access to SCM was ended and rats received daily injections of either ceftriaxone or saline for 6 days. Rats were then trained to press a lever to earn a novel food reward and, finally, were assessed for sensitivity to outcome devaluation. Histological analyses examined changes to GLT-1 protein levels and morphological changes to astrocytes, within the DMS. RESULTS: We found that ceftriaxone robustly restored goal-directed behavior in animals following long-term exposure to SCM. While we did not observe changes in protein levels of GLT-1 in the DMS, we observed that SCM induced changes in the morphology of astrocytes in the DMS, and that ceftriaxone mitigated these changes. CONCLUSIONS: These results demonstrate that long-term access to a SCM diet impairs goal-directed behavior while also altering the morphology of astrocytes in the DMS. Furthermore, these results suggest that ceftriaxone administration can reverse the impairment of goal-directed behavior potentially through its actions on astrocytes in decision-making circuitry.

Updates on Rare Genetic Variants, Genetic Testing, and Gene Therapy in Individuals With Obesity.

PURPOSE OF REVIEW: The goal of this paper is to aggregate information on monogenic contributions to obesity in the past five years and to provide guidance for genetic testing in clinical care. RECENT FINDINGS: Advances in sequencing technologies, increasing awareness, access to testing, and new treatments have increased the utilization of genetics in clinical care. There is increasing recognition of the prevalence of rare genetic obesity from variants with mean allele frequency < 5% -new variants in known genes as well as identification of novel genes- causing monogenic obesity. While most of these genes are in the leptin melanocortin pathway, those in adipocytes may also contribute. Common variants may contribute either to higher lifetime tendency for weight gain or provide protection from monogenic obesity. While specific genetic mutations are rare, these segregate in individuals with early-onset severe obesity; thus, collectively genetic etiologies are not as rare. Some genetic conditions are amenable to targeted treatment. Research into the discovery of novel genetic causes as well as targeted treatment is growing over time. The utility of therapeutic strategies based on the genetic risk of obesity is an advancing frontier.

The different roles of homocysteine metabolism in hypertension among normal-weight and obese patients with obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with hypertension. However, the differential mechanisms underlying OSA-related hypertension between normal-weight vs. obese patients is limited. METHODS: We studied 92 patients with OSA and 24 patients with continuous positive airway pressure (CPAP) treatment. Blood pressure (BP) was measured twice during awake and continuously monitored during sleep. Obesity was defined as body mass index ≥28 kg/m2. Serum metabolite levels were assessed by metabolomics. RESULTS: Among 59 normal-weight and 33 obese patients, 651 and 167 metabolites showed differences between hypertension and normotension or were associated with systolic and diastolic BP (SBP, DBP) after controlling confounders. These metabolites involved 16 and 12 Kyoto Encyclopedia of Genes and Genomes enrichment pathways in normal-weight and obese patients respectively, whereas 6 pathways overlapped. Among these 6 overlapping pathways, 4 were related to homocysteine metabolism and 2 were non-specific pathways. In homocysteine metabolism pathway, 13 metabolites were identified. Interestingly, the change trends of 7 metabolites associated with SBP (all interaction-p≤0.083) and 8 metabolites associated with DBP (all interaction-p≤0.033) were opposite between normal-weight and obese patients. Specifically, increased BP was associated with down-regulated folate-dependent remethylation and accelerated transsulfuration in normal-weight patients, whereas associated with enhanced betaine-dependent remethylation and reduced transsulfuration in obese patients. Similar findings were observed in ambulatory BP during sleep. After CPAP treatment, baseline low homocysteine levels predicted greater decrease in DBP among normal-weight but not obese patients. CONCLUSIONS: Mechanisms in OSA-related hypertension differ between normal-weight and obese patients, which are explained by different changes in homocysteine metabolism.

Relationship between metabolic syndrome and depression: A study based on Rafsanjan Youth Cohort Study.

BACKGROUND: Depressed people are susceptible to metabolic syndrome ression and metabolic syndrome in the Rafsanjan Youth Cohort Study in 2021. METHODS: In this cross-sectional study, the data of 3005 young people aged 15-35 under the coverage of urban and rural health centers was investigated in the enrollment stage of the Rafsanjan Youth Cohort Study as a part of the prospective epidemiological research studies in IrAN (PERSIAN). Data was collected using face-to-face interview and electronic questionnaires of the Rafsanjan Youth Cohort Study. RESULTS: Age of the youth was 25.78 ±â€¯6.06 years, 56 % (n = 1682) were female. The prevalence of metabolic syndrome (MetS) was 7.7 % (95 % CI: 6.8 %-8.8 %) and the prevalence of depression was 11.1 % (95 % CI: 10.0 %-12.3 %). Depression did not have a significant impact on the odds ratio of developing MetS in young people (P = 0.604). The odds ratio (OR) of MetS increases by 1.057 times with increasing age (95 % CI for OR: 1.020-1.094). This OR is also 1.715 times higher in married young people than in unmarried Youth (95 % CI for OR: 1.715-2.692) and 0.196 times lower in young people with medium and high MET index than in young people with low MET index (95 % CI for OR: 0.048-0.811). LIMITATIONS: Inability to determine a causal relationship between MetS and depression. CONCLUSION: Due to the growing trend of components of MetS among the young population, this issue needs to be addressed in future policies and planning for prevention and control as a health priority.

NPYR modulation: Potential for the next major advance in obesity and type 2 diabetes management?

The approval of the glucagon-like peptide 1 (GLP-1) mimetics semaglutide and liraglutide for management of obesity, independent of type 2 diabetes (T2DM), has initiated a resurgence of interest in gut-hormone derived peptide therapies for the management of metabolic diseases, but side-effect profile is a concern for these medicines. However, the recent approval of tirzepatide for obesity and T2DM, a glucose-dependent insulinotropic polypeptide (GIP), GLP-1 receptor co-agonist peptide therapy, may provide a somewhat more tolerable option. Despite this, an increasing number of non-incretin alternative peptides are in development for obesity, and it stands to reason that other hormones will take to the limelight in the coming years, such as peptides from the neuropeptide Y family. This narrative review outlines the therapeutic promise of the neuropeptide Y family of peptides, comprising of the 36 amino acid polypeptides neuropeptide Y (NPY), peptide tyrosine-tyrosine (PYY) and pancreatic polypeptide (PP), as well as their derivatives. This family of peptides exerts a number of metabolically relevant effects such as appetite regulation and can influence pancreatic beta-cell survival. Although some of these actions still require full translation to the human setting, potential therapeutic application in obesity and type 2 diabetes is conceivable. However, like GLP-1 and GIP, the endogenous NPY, PYY and PP peptide forms are subject to rapid in vivo degradation and inactivation by the serine peptidase, dipeptidyl-peptidase 4 (DPP-4), and hence require structural modification to prolong circulating half-life. Numerous protective modification strategies are discussed in this regard herein, alongside related impact on biological activity profile and therapeutic promise.