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Aggressive and violent behaviour is a challenging psychiatric emergency to manage, especially among vulnerable categories such as patients with Intellectual Developmental Disorder. Although there is some evidence that clozapine may be useful as an anti-violence compound, its use is limited by common metabolic complications. An adult patient presented with obesity, type II diabetes mellitus, compulsive food intake, severe Intellectual Developmental Disorder, and a treatment-resistant aggressive behaviour. Clozapine was administered resulting in reduced aggressive behaviour. Unexpectedly, a reduction in the food craving as well as a sustained improvement in both anthropometric parameters and glycemic control were observed during the clozapine treatment. Our case report, describes these findings for the first time, highlighting the need for more clinical research to investigate both the efficacy of clozapine in the Intellectual Developmental Disorder populations and its long-term effects with special regard to the metabolic outcomes in this type of patients.

ABSTRACTMicrobial-based therapeutics in clinical practice are of considerable interest, and a recent study demonstrated fecal microbial transplantation (FMT) followed by dietary fiber supplements improved glucose homeostasis. Previous evidence suggests that donor and recipient compatibility and FMT protocol are key determinants, but little is known about the involvement of specific recipient factors. Using data from our recent randomized placebo-control phase 2 clinical trial in adults with obesity and metabolic syndrome, we grouped participants that received FMT from one of 4 donors with either fiber supplement into HOMA-IR responders (n = 21) and HOMA-IR non-responders (n = 8). We further assessed plasma bile acids using targeted metabolomics and performed subgroup analyzes to evaluate the effects of recipient parameters and gastrointestinal factors on microbiota engraftment and homeostatic model assessment of insulin resistance (HOMA2-IR) response. The baseline fecal microbiota composition at genus level of recipients could predict the improvements in HOMA2-IR at week 6 (ROC-AUC = 0.70). Prevotella was identified as an important predictor, with responders having significantly lower relative abundance than non-responders (p = .02). In addition, recipients displayed a highly individualized degree of microbial engraftment from donors. Compared to the non-responders, the responders had significantly increased bacterial richness (Chao1) after FMT and a more consistent engraftment of donor-specific bacteria ASVs (amplicon sequence variants) such as Faecalibacillus intestinalis (ASV44), Roseburia spp. (ASV103), and Christensenellaceae spp. (ASV140) (p

Long-acting dual amylin and calcitonin receptor agonists (DACRAs) are novel candidates for the treatment of type 2 diabetes and obesity due to their beneficial effects on body weight, glucose control, and insulin action. However, how the metabolic benefits are maintained after long-lasting treatment is unknown. This study investigates the long-term anti-obesity and anti-diabetic treatment efficacy of the DACRA KBP-336 alone and combined with the GLP-1 analog semaglutide. Zucker diabetic Sprague Dawley (ZDSD) rats with obesity and diabetes received KBP-336 (4.5 nmol/kg Q3D), semaglutide (50 nmol/kg Q3D), or the combination for 7 mo, and the treatment impact on body weight, food intake, glucose control, and insulin action was evaluated. Furthermore, serum levels of the cardiac fibrosis biomarker endotrophin were evaluated. KBP-336, semaglutide, and the combination lowered body weight significantly compared with the vehicle, with the combination inducing a larger and more sustained weight loss than either monotherapy. All treatments resulted in reduced fasting blood glucose levels and HbA1c levels and improved glucose tolerance compared with vehicle-treated rats. Furthermore, all treatments protected against lost insulin secretory capacity and improved insulin action. Serum levels of endotrophin were significantly lowered by KBP-336 compared with vehicle. This study shows the benefit of combining KBP-336 and semaglutide to obtain significant and sustained weight loss, as well as improved glucose control. Furthermore, KBP-336-driven reductions in circulating endotrophin indicate a clear reduction in the risk of complications. Altogether, KBP-336 is a promising candidate for the treatment of obesity and type 2 diabetes both alone and in combination with GLP-1 analogs. NEW & NOTEWORTHY These studies describe the benefit of combining dual amylin and calcitonin receptor agonists (DACRA) with semaglutide for long-term treatment of obesity and type 2 diabetes. Combination treatment induced sustained weight loss and improved glucose control. A DACRA-driven reduction in a serological biomarker of cardiac fibrosis indicated a reduced risk of complications. These results highlight DACRAs as a promising candidate for combination treatment of obesity and type 2 diabetes and related long-term complications.

Abstract The rising incidence of health‐endangering obesity constantly calls for more effective treatments. Gastric intramural injection of botulinum neurotoxin A (BTX‐A) as a new modality carries great promise yet inconsistent therapeutic efficacy. A layer‐specific delivery strategy enabled by dissolving microneedles is hence pioneered to investigate the working site of BTX‐A and the resulting therapeutic effects. The drug‐loaded tips of the layer‐specific gastric paralysis microneedles (LGP‐MN) rapidly release and achieve uniform distribution of BTX‐A within the designated gastric wall layers. In an obesity rat model, the LGP‐MNs not only prove safer than conventional injection, but also demonstrate consistently better therapeutic effects with muscular layer delivery, including 16.23% weight loss (3.06‐fold enhancement from conventional injection), 55.20% slower gastric emptying rate, improved liver steatosis, lowered blood lipids, and healthier gut microbiota. Further hormonal study reveals that the elevated production of stomach‐derived glucagon‐like peptide‐1 due to the muscularis‐targeting LGP‐MN treatment is an important contributor to its unique glucose tolerance‐improving effect. This study provides clear indication of the gastric muscularis as the most favorable working site of BTX‐A for weight loss and metabolic improvement purposes, and meanwhile suggests that the LGP‐MNs could serve as a novel clinical approach to treat obesity and metabolic syndromes.

Background: Different metabolic/bariatric surgery approaches vary in their effect on weight loss and glucose levels, although the underlying mechanism is unclear. Studies have demonstrated that the gut microbiota might be an important mechanism of improved metabolism after metabolic/bariatric surgery., Aim: To investigate the relationship between the improvement in metabolic disturbances and the changes in gut microbiota after gastric or intestinal bypass., Methods: We performed sleeve gastrectomy (SG), distal small intestine bypass (DSIB) or sham surgery in nonobese rats with diabetes induced by 60 mg/kg streptozotocin (STZ-DM)., Results: The group comparisons revealed that both SG and DSIB induced a reduction in body weight and significant improvements in glucose and lipid metabolism in the STZ-DM rats. Furthermore, DSIB exhibited a stronger glucose-lowering and lipid-reducing effect on STZ-DM rats than SG. 16S ribosomal RNA gene sequencing revealed the gut abundance of some Lactobacillus spp. increased in both the SG and DSIB groups after surgery. However, the DSIB group exhibited a more pronounced increase in the gut abundance of Lactobacillus spp. compared to the SG group, with more Lactobacillus spp. types increased in the gut., Conclusion: The gut abundance of Lactobacillus was significantly correlated with the improvement in glycolipid metabolism and the change in serum fibroblast growth factor 21 levels., Competing Interests: Conflict-of-interest statement: All authors declare that there are no potential conflicts of interest., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Bariatric surgery induces significant weight loss, increases insulin sensitivity, and improves dyslipidemia. As one of the most widely performed bariatric surgeries, laparoscopic sleeve gastrectomy (LSG) is thought to improve the metabolic profile along with weight loss. The objective of this study was to evaluate longitudinal changes in the serum metabolite levels after LSG and elucidate the underlying mechanisms of metabolic improvement. Methods: Clinical metabolic parameters and serum samples were collected preoperatively and at 1, 3, and 6 months postoperatively from nine patients with obesity undergoing LSG. Serum metabolites were measured using a non-targeted metabolic liquid chromatography–mass spectrometry method. Results: During the 1, 3, and 6 months postoperative follow-up, the body mass index, HOMA-IR, and liver fat content showed a gradual descending trend. A total of 328 serum metabolites were detected, and 38 were differentially expressed. The up-regulated metabolites were mainly enriched in ketone body metabolism, alpha-linolenic acid and linoleic acid metabolism, pantothenate and CoA biosynthesis, glycerolipid metabolism, and fructose and mannose degradation, while the down-regulated metabolites were closely related to caffeine metabolism, oxidation of branched-chain fatty acids, glutamate metabolism, and homocysteine degradation. Notably, nine metabolites (oxoglutarate, 2-ketobutyric acid, succinic acid semialdehyde, phthalic acid, pantetheine, eicosapentaenoate, 3-hydroxybutanoate, oxamic acid, and dihydroxyfumarate) showed persistent differential expression at 1, 3, and 6 months follow-up. Some were found to be significantly associated with weight loss, insulin resistance improvement, and liver fat content reduction. Conclusions: This finding may provide a new perspective for revealing novel biomarkers and mechanisms of metabolic improvement in obesity and related comorbidities.

Research on enhancing the production of lipids, particularly polyunsaturated fatty acids that are considered important for health, has focused on improvement of metabolism as well as heterologous expression of biosynthetic genes in the oleaginous fungus Aspergillus oryzae. To date, the productivity and production yield of free fatty acids have been enhanced by 10-fold to 90-fold via improvements in metabolism and optimization of culture conditions. Moreover, the productivity of ester-type fatty acids present in triacylglycerols could be enhanced via metabolic improvement. Culturing A. oryzae in a liquid medium supplemented with non-ionic surfactants could also lead to the effective release of free fatty acids from the cells. The current review highlights the advancements made in this field so far and discusses the future outlook for research on lipid production using A. oryzae. I hope the contents are useful for researchers in this field to consider the strategy of increasing production of various valuable metabolites as well as lipids in A. oryzae.

Aggressive and violent behaviour is a challenging psychiatric emergency to manage, especially among vulnerable categories such as patients with Intellectual Developmental Disorder. Although there is some evidence that clozapine may be useful as an anti-violence compound, its use is limited by common metabolic complications. An adult patient presented with obesity, type II diabetes mellitus, compulsive food intake, severe Intellectual Developmental Disorder, and a treatment-resistant aggressive behaviour. Clozapine was administered resulting in reduced aggressive behaviour. Unexpectedly, a reduction in the food craving as well as a sustained improvement in both anthropometric parameters and glycemic control were observed during the clozapine treatment. Our case report, describes these findings for the first time, highlighting the need for more clinical research to investigate both the efficacy of clozapine in the Intellectual Developmental Disorder populations and its long-term effects with special regard to the metabolic outcomes in this type of patients. [ABSTRACT FROM AUTHOR]

Abstract Background and aim The role of dietary protein and glycemic index on insulin resistance (based on TyG index) within a nutritional program for weight loss and weight maintenance was examined. Methods This study analyzed 744 adults with overweight/obesity within the DIOGenes project. Patients who lost at least 8% of their initial weight (0–8 weeks) after a low-calorie diet (LCD) were randomly assigned to one of five ad libitum diets designed for weight maintenance (8–34 weeks): high/low protein (HP/LP) and high/low glycemic index (HGI/LGI), plus a control. The complete nutritional program (0–34 weeks) included both LCD plus the randomized diets intervention. The TyG index was tested as marker of body mass composition and insulin resistance. Results In comparison with the LP/HGI diet, the HP/LGI diet induced a greater BMI loss (p

Background: Time-restricted eating (TRE) manages weight effectively, but choosing how long and what time window remain debatable. Although an 8:00 a.m. to 16:00 p.m. time frame is reported to show positive results in most weight loss trial, its safety and efficacy in overweight and obese women with polycystic ovary syndrome (PCOS) is uncertain. This randomized controlled trial is conducted to evaluate the safety and efficacy of TRE in specific populations. Objective: This study aims to assess the 6-month effects of TRE on weight change, metabolic improvement, reproductive recovery, and health-related quality of life in overweight and obese women with polycystic ovary syndrome (PCOS), compared to those who did not receive TRE. Methods: This randomized controlled trial will enroll 96 overweight and obese women with polycystic ovary syndrome (PCOS), who will be randomly assigned to either a TRE group (with an eating window from 8:00 a.m. to 16:00 p.m.) or a control group (without eating time restrictions), with 49 participants in each group. Evaluators and data analysts will remain blinded to group allocation throughout the study. The primary outcomes, including changes in weight and body mass index (BMI), will be assessed weekly. Secondary outcomes, encompassing alterations in sex hormones, metabolic parameters, body composition, sleep quality, quality of life, anxiety, and depression, will be evaluated monthly. Compliance and safety will be continuously monitored throughout the study. Additionally, a 6-month follow-up will be conducted at the end of the trial to assess the long-term effects of TRE. Statistical analysis will include the Anderson-Darling test for normality, T-test/Wilcoxon test based on distribution, mixed-effects models for assessing time/group effects, Cox model for time-to-event analysis, repeated ANOVA for change analysis, and sensitivity analysis. All tests will be conducted using appropriate software, with a significance level set at P<0.05. Missing data will be imputed. Discussion: The purpose of this study protocol is to further evaluate the effects of TRE in overweight and obese women with PCOS through a randomized controlled trial (RCT). Findings from this study are expected to provide new dietary intervention strategies for overweight and obese PCOS participants. Ethics and dissemination: This study has received ethics approval from the Medical Ethics Committee of the University of South China (Number: NHHL027). Participants are included after signing informed consent. Results will be submitted for publication in peer-reviewed journals. Trail registration: Trail registration number:ChiCTR2400086815. [ABSTRACT FROM AUTHOR]

Introduction: Intermittent fasting (IF) has emerged as a popular dietary intervention for its potential health benefits, including weight management, metabolic improvement, and reduced risk of chronic diseases. The practice alternates periods of eating and fasting, influencing physiological processes and offering an alternative to traditional calorie-restrictive diets. Purpose of Work: This paper aims to investigate the efficacy of IF as a revolutionary approach to maintaining health and mitigating the risks associated with chronic diseases. By analyzing contemporary research, the paper seeks to elucidate the underlying mechanisms and broader health implications of IF. State of Knowledge: Existing studies suggest that IF positively affects metabolic markers, enhances insulin sensitivity, and promotes autophagy--a cellular repair mechanism crucial for longevity and disease prevention. Emerging evidence links IF to improved cardiovascular health, reduced inflammation, and enhanced cognitive functions. However, variability in outcomes due to age, gender, and fasting protocols highlights the need for tailored approaches and further research. Material and methods: The research methodology entailed establishing the study aims, undertaking a systematic review of the literature, and implementing a structured process to screen pertinent studies. The investigation involved a comprehensive search across scientific databases, including PubMed and Google Scholar. Summary: Intermittent fasting represents a transformative paradigm in health and nutrition science. While preliminary findings are promising, more robust longitudinal studies are required to establish standardized protocols and validate its therapeutic potential across diverse populations. This paper underscores the promise of IF as a strategic tool in the prevention and management of chronic diseases. [ABSTRACT FROM AUTHOR]

Background: Epidemics and pandemics have been shown to have widespread effects on health systems. Diabetes is a condition of particular risk during national emergencies such as the COVID-19 pandemic. The aim of this study is to determine the influence of COVID-19 in the patient's diabetes quality management. Methods: We conducted a retrospective multicenter cohort study. Data from type 2 diabetes patients living in Sevilla were included into the study. The study was divided into two observation periods, before and during COVID-19. Metabolic status was assessed using the levels of hemoglobin A1c (A1C) measured during the pre- and COVID-19 period. The time interval between sequential A1C tests were also measured. We as well identified the locations where the burden of diabetes quality management is clustered and their relation with demographic and economic factors. Results: We included a total of 106,336 patients from four different hospitals. A significant number patients have worsened their quality management during COVID-19. During the first year of the pandemic, 72,235 patients did not have any hemoglobin A1c (A1C) control. By the time of data extraction, the time between A1C controls was significantly increased by 309 days (from 211 to 520). In addition, 34,001 patients who had A1C control during the COVID-19 period did not reveal a deterioration of their metabolic status. They showed a small but significant metabolic improvement indicated by reduced A1C levels from 52 mmol/mol to 51 mmol/mol. Just like the other group, these patients showed a significant increase of 29 days (from 195 to 224) between A1C controls. COVID-19 increased the substantial clustering for diabetes quality management in specific locations, mostly along the rural southeastern area of Sevilla and these variations were associated with economic and socio-demographic variants. Conclusions: Our study highlighted the great impact of the COVID-19 in diabetes quality management exacerbating the previous inequities and disparities. Our results highlight the need for urgent patient intervention in the areas with high burdens of poorer quality management. [ABSTRACT FROM AUTHOR]

Research on enhancing the production of lipids, particularly polyunsaturated fatty acids that are considered important for health, has focused on improvement of metabolism as well as heterologous expression of biosynthetic genes in the oleaginous fungus Aspergillus oryzae. To date, the productivity and production yield of free fatty acids have been enhanced by 10-fold to 90-fold via improvements in metabolism and optimization of culture conditions. Moreover, the productivity of ester-type fatty acids present in triacylglycerols could be enhanced via metabolic improvement. Culturing A. oryzae in a liquid medium supplemented with non-ionic surfactants could also lead to the effective release of free fatty acids from the cells. The current review highlights the advancements made in this field so far and discusses the future outlook for research on lipid production using A. oryzae. I hope the contents are useful for researchers in this field to consider the strategy of increasing production of various valuable metabolites as well as lipids in A. oryzae. [ABSTRACT FROM AUTHOR]

Obesity is characterized by fat accumulation, impaired metabolism and oxidative stress, frequently associated with lipid peroxidation and generation of bioactive 4-hydroxynonenal (4-HNE). This study aimed to evaluate the impact of bariatric surgery-induced weight loss on lipid peroxidation and associated perturbations in lipid profile. Plasma samples of twenty obese individuals before and 6 months after bariatric surgery were collected in addition to samples of ten healthy controls. HILIC-LC-MS/MS platform was used to characterize phospholipid profile, while lipid peroxidation markers 15-F2t-IsoP, 10-F4t-NeuroP and reactive aldehyde 4-HNE were quantified by RP-LC-MS/MS and GC-MS, respectively. Six months post-surgery lipid peroxidation markers decreased significantly and the BMI of morbidly obese patients decreased by 13 on average. Lipidomics analysis, identified 117 phospholipid species from seven classes, and showed obesity-associated lipidome perturbations, particularly in ether-linked phosphatidylethanolamines (PEo). A total of 45 lipid species were found to be significantly altered with obesity, while 10 lipid species correlated with lipid peroxidation markers. Sample pairwise analyses indicated an interesting link between 4-HNE and the amount of two PEos, PEo (38:2) and PEo (36:2). The results indicate that weight loss-induced improvement of redox homeostasis together with changes in lipid metabolites may serve as markers of metabolic improvement. However, further studies are needed to understand the role of obesity-induced oxidative stress on ether lipid biosynthesis and lipidome perturbations, as well as the impact of bariatric surgery on metabolic improvement. [Display omitted] • Plasma levels of 4-hydroxynonenal, 15-F2t-IsoP and 10-F4t-NeuroP are elevated in obesity. • Weight loss in obese individuals results in a decrease of lipid peroxidation markers. • Lipidomics revealed distinct phospholipidome signatures between obese and lean individuals. • Weight loss causes a shift in the plasma phospholipidome toward the lipidome of the lean cohort. • Wight loss induced decrease in 4-hydroxynonenal negatively correlates with specific ether lipids. [ABSTRACT FROM AUTHOR]

Objective: We have previously shown that early intestinal adaptation precedes and relates to metabolic improvement in humans after Roux‐en‐Y gastric bypass surgery (RYGB). We hypothesized that intestinal adaptation would persist at the 1‐year postoperative time point and that gene expression (GE) signatures would relate to type 2 diabetes remission, providing insight into potential mechanisms for intestinally mediated metabolic improvement after RYGB. Methods: We determined GE by RNA sequencing in jejunum (Roux limb [RL]) collected from 28 patients before and 12 months after RYGB. Results: Global GE from paired baseline and 1‐year jejunal samples did not separate according to clinical phenotype (type 2 diabetes remission, sustained weight loss). In general, GE was consistent with persistent RL remodeling, and microvilli were elongated by 39%. Remodeling was not attenuated in patients with lack of diabetes remission or with weight regain. Patients with diabetes remission demonstrated greater jejunal activation of lipogenesis‐related pathways driven by RXR, LXR, and SREBP. Conclusions: RL adaptation is a key feature of RYGB in all patients, likely reflecting the dramatic alterations to gastrointestinal anatomy, but jejunal lipogenesis appears to be more strongly activated in those patients with diabetes remission. Further study is needed to understand whether these pathways may drive metabolic remission after RYGB. [ABSTRACT FROM AUTHOR]

Bariatric surgery is vital for sustainable weight loss and metabolic improvement in obese individuals, but its effects on gut microbiota and their role in these benefits require further investigation. Investigate the temporal changes in gut microbiota in obese patients undergoing bariatric surgery (gastric sleeve gastrectomy or Roux-en-Y Gastric Bypass (RYGB)) compared to healthy controls, aiming to understand their role in weight loss and metabolic health improvement. A case-control study included 30 obese patients aged 65–95 undergoing bariatric surgery, and 18 matched healthy controls. Selection criteria were based on age, race, BMI, history of antibiotics, probiotics, and prebiotics usage. Stool samples were collected at baseline, three months, and six months post-surgery for DNA extraction and quantitative real-time PCR analysis to assess gut microbiota changes. Physical activity and dietary intake were evaluated using standardized questionnaires. Statistical analyses were performed using R. Post-surgery, patients showed significant reductions in weight and BMI, with changes in dietary habits and physical activity. Quantitative real-time PCR analysis revealed substantial alterations in bacterial groups such as Bacteroides and Fusobacterium. However, some groups showed no significant changes, indicating a complex interaction between gut microbiota and bariatric surgery. Notable correlations were found between body weight, BMI, and specific bacterial groups like the C. cluster IV and Lactobacillus, particularly in RYGB patients. Bariatric surgery significantly alters gut microbiota, aiding weight loss and metabolic regulation in obese patients. Understanding these changes is crucial for developing effective obesity management strategies, requiring further research to optimize outcomes. [ABSTRACT FROM AUTHOR]

Background: Obesity is a growing health concern in China, closely linked to metabolic disorders such as type 2 diabetes. Laparoscopic Sleeve Gastrectomy (LSG) is effective in promoting weight loss and improving metabolic outcomes. Emerging evidence highlights the role of gut microbiota in metabolic regulation, yet the specific alterations in gut microbiota and their association with metabolic changes post-surgery in Chinese patients remain unclear. Understanding these shifts could provide key insights into optimizing treatment strategies for metabolic improvement following bariatric surgery. Methods: Stool samples and clinical data were collected from 30 obese patients before and 6 months after surgery. The composition of the gut microbiota was analyzed through 16S rRNA sequencing, and Spearman correlation analysis was used to determine the association between gut microbiota and clinical indicators. Results: The analysis of 30 patients showed a significant decrease in Body Mass Index (BMI) (36.75 ± 4.09 kg/m2 vs 26.37 ± 3.47 kg/m2, p < 0.0001). Glucose metabolism, including Hemoglobin A1C levels, improved significantly (6.05 ± 0.96 vs 5.05 ± 0.25, p < 0.0001), and liver function as well as serum lipid levels were also notably improved. LSG increased the richness and composition of gut microbiota in obese patients post-surgery. These changes in gut microbiota were closely associated with improved clinical metabolic parameters. Conclusion: LSG not only significantly reduces body weight while also alleviating metabolic syndrome and comorbidities by altering gut microbiota. [ABSTRACT FROM AUTHOR]