Huanglian-Jiedu decoction promotes adipose thermogenesis in obese mice by suppressing the expression of HDAC3.

ETHNOPHARMACOLOGICAL RELEVANCE: Huanglian Jiedu Decoction (HLJDD) is an ancient formula of traditional Chinese medicine that is commonly utilized in a range of disorders, and it has been shown to have pharmacological effects on glucose and lipid metabolism. However, the specific mechanism of HLJDD for the treatment of obesity and related metabolic disorders remains to be further investigated. AIM OF THE STUDY: It has been thought that encouraging adipose thermogenesis to raise the body's energy expenditure is a useful tactic for improving metabolic abnormalities and losing weight. In this study, we investigated the ability and underlying mechanisms of HLJDD to regulate fat cell thermogenesis to improve energy expenditure in obesity. METHODS: The obese mouse model was established on a high-fat diet for 12 weeks. All mice were divided into NC, HFD, HFD with HLJDD of a low dose (2.25 g/kg/d), and HFD with HLJDD of a high dose (4.5 g/kg/d) groups and kept for 4 weeks. In vitro experiments were conducted to evaluate the effects of 5% and 10% HLJDD-containing serum on differentiated 3T3-L1 cells and HDAC3-knocking-down 3T3-L1 cells. RESULTS: The results showed that HLJDD treatment significantly improved glucose and insulin tolerance and decreased the adipocyte radius of WATs, as well as increased energy consumption in obese mice. Besides, HLJDD treatment dramatically increased the levels of thermogenic genes UCP-1 and PGC-1α while suppressing HDAC3 levels in WATs and 3T3-L1 adipocytes. Importantly, the effects of HLJDD on PGC-1α and UCP-1 were blocked in HDAC3 knockdown adipocytes. CONCLUSIONS: Therefore, these results suggest that HLJDD enhanced adipose thermogenesis and improved energy expenditure by inhibiting HDAC3, thereby increasing UCP-1 and PGC-1α expression. These findings amplified the mechanisms of HLJDD and its potential to treat obesity and related metabolic disorders.

The relationship between microRNAs and COVID-19 complications.

Over the past three years, since the onset of COVID-19, several scientific studies have concentrated on understanding susceptibility to the virus, the progression of the illness, and possible long-term complexity. COVID-19 is broadly recognized with effects on multiple systems in the body, and various factors related to society, medicine, and genetics/epigenetics may contribute to the intensity and results of the disease. Additionally, a SARS-CoV-2 infection can activate pathological activities and expedite the emergence of existing health issues into clinical problems. Forming easily accessible, distinctive, and permeable biomarkers is essential for categorizing patients, preventing the disease, predicting its course, and tailoring treatments for COVID-19 individually. One promising candidate for such biomarkers is microRNAs, which could serve various purposes in understanding diverse forms of COVID-19, including susceptibility, intensity, disease progression, outcomes, and potential therapeutic options. This review provides an overview of the most significant findings related to the involvement of microRNAs in COVID-19 pathogenesis. Furthermore, it explores the function of microRNAs in a broad span of effects that may arise from accompanying or underlying health status. It underscores the value of comprehending how diverse conditions, such as neurological disorders, diabetes, cardiovascular diseases, and obesity, interact with COVID-19.

Riesgo cardiovascular, dislipemias e indicación de estatinas en una población de obesos mórbidos

Introducción: La obesidad se relaciona con un riesgo cardiovascular (RCV) elevado. Esto nos obliga a tomar conductas terapéuticas y prevencionistas. El objetivo de este trabajo es evaluar el riesgo cardiovascular en una población de obesos mórbidos y valorar la correcta indicación de estatinas. Metodología: Estudio transversal, descriptivo, observacional, con la población obesos mórbidos del Programa de Obesidad y Cirugía Bariátrica (POCB) del Hospital Maciel, desde noviembre del 2014 a marzo del 2020. El RCV se valoró con la calculadora de la organización panamericana de la salud. La indicación de estatinas se consideró según RCV o diagnóstico de dislipemia. Resultados: Se analizaron 478 pacientes, el 84.3% fueron mujeres, la mediana para la edad fue de 44 años, y para el IMC 50 kg/m2. Se calculó un RCV bajo para el 57% de los pacientes; y alto o muy alto para un 37%. La prevalencia de las dislipemias fue 84,3%, a predominio de hipercolesterolemia (33,7%) y dislipemia aterogénica (19,5%). El 60.6% (290) de los pacientes presenta indicación de tratamiento con estatinas, solo el 38.9%. (113) las recibe. El 38.1% (43) alcanzan los objetivos terapéuticos. Conclusiones : La obesidad presenta múltiples comorbilidades que aumentan el RCV, aun así se encuentra subestimada por las calculadoras de riesgo. Queda en evidencia un infratratamiento farmacológico de estos pacientes, no logrando los objetivos terapéuticos propuestos.

Introduction: Obesity is related to a high cardiovascular risk (CVR). This forces us to take therapeutic and preventive behaviors. The objective of this work is to evaluate cardiovascular risk in a morbidly obese population and assess the correct indication of statins. Methodology: Cross-sectional, descriptive, observational study, with the morbidly obese population of the Obesity and Bariatric Surgery Program (POCB) of the Maciel Hospital, from November 2014 to March 2020. CVR was assessed with the calculator of the Pan-American health organization. The indication for statins was considered according to CVR or diagnosis of dyslipidemia. Results: 478 patients were analyzed, 84.3% were women, the median age was 44 years, and the BMI was 50 kg/m2. A low CVR was calculated for 57% of patients; and high or very high for 37%. The prevalence of dyslipidemia was 84.3%, with a predominance of hypercholesterolemia (33.7%) and atherogenic dyslipidemia (19.5%). 60.6% (290) of patients have an indication for treatment with statins, only 38.9%. (113) receives them. 38.1% (43) achieved therapeutic objectives. Conclusions: Obesity presents multiple comorbidities that increase CVR, yet it is underestimated by risk calculators. Pharmacological undertreatment of these patients is evident, not achieving the proposed therapeutic objectives.

Introdução : A obesidade está relacionada a um alto risco cardiovascular (RCV). Isso nos obriga a adotar comportamentos terapêuticos e preventivos. O objetivo deste trabalho é avaliar o risco cardiovascular em uma população com obesidade mórbida e avaliar a correta indicação de estatinas. Metodologia: Estudo transversal, descritivo, observacional, com a população com obesidade mórbida do Programa de Obesidade e Cirurgia Bariátrica (POCB) do Hospital Maciel, no período de novembro de 2014 a março de 2020. O RCV foi avaliado com a calculadora da organização pan-americana de saúde. A indicação de estatinas foi considerada de acordo com RCV ou diagnóstico de dislipidemia. Resultados: Foram analisados ​​478 pacientes, 84,3% eram mulheres, a mediana de idade foi de 44 anos e o IMC foi de 50 kg/m2. Um RCV baixo foi calculado para 57% dos pacientes; e alto ou muito alto para 37%. A prevalência de dislipidemia foi de 84,3%, com predomínio de hipercolesterolemia (33,7%) e dislipidemia aterogênica (19,5%). 60,6% (290) dos pacientes têm indicação de tratamento com estatinas, apenas 38,9%. (113) os recebe. 38,1% (43) alcançaram objetivos terapêuticos. Conclusões: A obesidade apresenta múltiplas comorbidades que aumentam o RCV, mas é subestimada pelas calculadoras de risco. É evidente o subtratamento farmacológico destes pacientes, não atingindo os objetivos terapêuticos propostos.

Dietary apigenin ameliorates obesity-related hypertension through TRPV4-dependent vasorelaxation and TRPV4-independent adiponectin secretion.

BACKGROUND: Obesity-related hypertension is a major cardiovascular risk factor. Apigenin, a natural flavonoid in celery, induces vascular dilation via endothelial transient receptor potential channel vanilla 4 (TRPV4) channels. This study aimed to explore apigenin's potential to alleviate obesity-related hypertension in mice and its underlying mechanisms. METHODS: The C57BL/6 and TRPV4 knockout mice were fed a high-fat diet and subjected to dietary intervention with apigenin. Body weight and tail blood pressure of the mice were measured during the feeding. Vascular reactivity was assessed through a DMT wire myograph systems in vitro. The distribution and expression of adiponectin and pro-inflammatory markers in brown fat were detected. Injecting adeno-associated eight (AAV8) viruses into brown adipose tissue (BAT) to determine whether adiponectin is indispensable for the therapeutic effect of apigenin. Palmitic acid (PA) was used in mouse brown adipocytes to examine the detailed mechanisms regulating adiponectin secretion. RESULTS: Apigenin improved vasodilation and reduced blood pressure in obese mice, effects partly blocked in TRPV4 knockout. It also reduced weight gain independently of TRPV4. Apigenin increased adiponectin secretion from BAT; knockdown of adiponectin weakened its benefits. Apigenin downregulated Cluster of differentiation 38 (CD38), restoring Nicotinamide adenine dinucleotide+ (NAD+) levels and activating the NAD+/Sirtuin 1 (SIRT1) pathway, enhancing adiponectin expression. CONCLUSIONS: Our study indicates that dietary apigenin is suitable as a nonpharmaceutical intervention for obesity-related hypertension. In mechanism, in addition to improving vascular relaxation through the activation of endothelial TRPV4 channels, apigenin also directly alleviated adipose inflammation and increased adiponectin levels by inhibiting CD38.

Dietary protein defends lean mass and maintains the metabolic benefits of glucagon receptor agonism in mice.

OBJECTIVE: Glucagon has long been proposed as a component of multi-agonist obesity therapeutics due to its ability to induce energy expenditure and cause weight loss. However, chronic glucagon-receptor agonism has been associated with a reduction in circulating amino acids and loss of lean mass. Importantly, it is currently not known whether the metabolic benefits of glucagon can be maintained under contexts that allow the defence of lean mass. METHODS: We investigate the metabolic effects of the long-acting glucagon receptor agonist, G108, when administered to obese mice at low-doses, and with dietary protein supplementation. RESULTS: Dietary protein supplementation can only fully defend lean mass at a low dose of G108 that is sub-anorectic and does not reduce fat mass. However, in this context, G108 is still highly effective at improving glucose tolerance and reducing liver fat in obese mice. Mechanistically, liver RNA-Seq analysis reveals that dietary protein supplementation defends anabolic processes in low-dose G108-treated mice, and its effects on treatment-relevant glucose and lipid pathways are preserved. CONCLUSION: Glucagon-mediated energy expenditure and weight loss may be mechanistically coupled to hypoaminocidemia and lean mass loss. However, our data suggest that glucagon can treat MAFLD at doses which allow full defence of lean mass given sufficient dietary protein intake. Therefore, proportionate glucagon therapy may be safe and effective in targeting hepatocytes and improving in glycaemia and liver fat.

Examining the bidirectional longitudinal associations between body mass index and episodic memory following bariatric surgery.

BACKGROUND: The relationship between obesity and episodic memory (i.e., conscious memory for specific events) is hypothesized to be bidirectional. Indeed, studies have shown that metabolic and bariatric surgery (MBS) is associated with episodic memory improvement, and better memory is associated with better postsurgical weight-loss outcomes. However, direct tests of the hypothesized bidirectional association between episodic memory and body mass index (BMI) in MBS are lacking, as few studies have employed repeated, prospective assessments of memory in conjunction with bidirectional modeling techniques. OBJECTIVES: The present study used latent change score analysis to examine the bidirectional longitudinal associations between episodic memory and BMI in the 2 years following MBS. SETTING: University hospital; public practice. METHODS: Episodic memory function and BMI were assessed in adults prior to MBS, and at 1, 6, 12, 18, and 24-months postsurgery. RESULTS: A total of 124 participants (41% lost at 2-year follow-up) showed, on average, favorable weight-loss and episodic memory outcomes following MBS. Crucially, presurgery episodic memory predicted initial change in BMI at 1-month postsurgery, and postsurgery episodic memory at 1- and 6-months predicted change in BMI at 6- and 12-months postsurgery. No evidence was found for pre- and postsurgery BMI predicting changes in episodic memory. CONCLUSIONS: Results supported a unidirectional prospective relationship between episodic memory and weight change following MBS, such that better memory pre- and postsurgery predicted improved weight-loss outcomes. These findings highlight the likely importance of episodic memory function for weight change and support the potential benefit of targeting memory processes to improve weight-loss outcomes.

Protocol for the LIFEH project: a prospective observational study to explore lifestyle among people living with HIV experiencing weight gain, looking beyond antiretroviral therapy.

INTRODUCTION: Weight gain, together with the onset of overweight and obesity, is a relevant emerging health issue among people living with HIV (PLWH). A large body of literature recognises this issue as a part of the secondary effects of some antiretroviral therapy (ART), but little is known about the role of lifestyle. In order to assess the role of modifiable aspects of lifestyle in addition to ART on the onset of overweight and obesity, we designed a prospective observational study among PLWH. METHODS AND ANALYSIS: This is a prospective observational study among PLWH aged 18-65 years attending the Clinic of Infectious Diseases of Spedali Civili, Brescia, Italy, and on ART for at least 24 months. According to the sample size computation, 175 PLWH will be enrolled. PLWH willing to participate in the study are invited to a scheduled clinical visit to collect anthropometric measures, dietary habits and physical activity levels. During the visit, standardised and validated questionnaires are administered regarding emotional distress, food insecurity, use of food supplements, sleep quality, smoking habit and alcohol consumption/risk of addiction. After the interviews, bioimpedance analysis is performed and blood pressure and heart rate are assessed. After 12 months from baseline, each participant will be asked to participate in a further visit, with the same assessments as at baseline. The primary objective of the study is to assess the role of the modifiable factors of lifestyle in the onset of overweight and/or obesity among on-treatment PLWH experiencing weight gain, focusing on diet and physical activity. ETHICS AND DISSEMINATION: The study research protocol and informed consent procedures were approved by Ethics Committee of Brescia Province (Italy) on 23 May 2023 (NP5892). Informed consent will be obtained from participants. Results will be submitted for publication in international peer-reviewed journals and summaries will be provided annually to the funders.

The autophagy-repressive tissue hormone DBI/ACBP (diazepam binding inhibitor, acyl-CoA binding protein) suppresses anorexia.

DBI/ACBP (diazepam binding inhibitor, acyl-CoA binding protein) is produced by multiple cell types and detectable in blood plasma. DBI acts on GABRA (gamma-aminobutyric acid type A receptor) complexes containing GABRG2 (gamma-aminobutyric acid type A receptor, subunit gamma 2) to inhibit macroautophagy/autophagy and hence can be considered as an "autophagy checkpoint". In patients with poor-prognosis anorexia nervosa, as well as in mice developing stress-induced anorexia, circulating DBI levels are reduced. Using a chemical-genetic system that makes it possible to control DBI secretion by hepatocytes, we showed that increasing DBI levels suffices to prevent anorexia induced by chronic restraint stress or chemotherapy with cisplatin, doxorubicin or paclitaxel in mice. At the mechanistic level, DBI administration acts through GABRA outside of the central nervous system and reduces the plasma levels of anorexigenic factors such as GDF15 (growth differentiation factor 15) and LCN2 (lipocalin 2), as well as anorexigenic signaling via the LCN2 receptor MC4R (melanocortin 4 receptor) in the hypothalamus. Accordingly, DBI supplementation stimulates food intake and normalizes whole body weight, body composition and metabolism in mouse models of anorexia. This normalization extends to the liver transcriptome and metabolome. Altogether, it appears that enhancing DBI levels constitutes a promising strategy for combating anorexia.

Lower urinary tract symptoms among normal-weight, overweight, and obese palestinians: a study of prevalence and impact on the quality of life.

BACKGROUND: This study was conducted to assess the prevalence of lower urinary tract symptoms (LUTS) among non-obese and obese Palestinians. The study also aimed to assess the effects of LUTS on the quality of life of obese and non-obese Palestinians. METHODS: This was a cross-sectional study that was conducted among normal-weight, overweight, and obese Palestinians using the King Health Questionnaire. The data collected from participants were entered and analyzed using SPSS (version 22). RESULTS: In this study, data were collected from 378 participants. The median age of the participants was 42.0 [30.0, 55.0] years, and the median body mass index was 27.1 [24.0, 30.8] kg/m2. Of the participants, 149 (39.4%) were overweight and 112 (29.6%) were obese. The prevalence of urinary hesitancy, incomplete emptying, urgency, nocturia, urgency, urge incontinence, stress incontinence, nocturnal enuresis, intercourse incontinence, bladder pain, number of urinations/24 h, and number of urinations/night was significantly higher among obese participants. Similarly, role limitations, physical/social limitation, personal relationships, emotions, and sleep/energy were affected significantly higher in obese compared to nonobese participants. CONCLUSION: Higher prevalence of LUTS among obese patients compared to nonobese patients was observed among the Palestinians. Obese patients reported significantly higher deterioration of the quality of life as a result of LUTS compared to nonobese patients. Urologists, nutritionists, public health specialists, and other healthcare providers should consider measures to reduce LUTS among obese patients and improve their quality of life.

The discriminatory capability of anthropometric measures in predicting reproductive outcomes in Chinese women with PCOS.

OBJECTIVE: Obesity is a common feature in women with polycystic ovary syndrome (PCOS) and potentially significantly influences reproductive function. However, opinions are divided as to which factor is a more appropriate obesity predictor of reproductive outcomes. The aim of this study was to investigate the discriminatory capability of anthropometric measures in predicting reproductive outcomes in Chinese women with PCOS. METHODS: A total of 998 women with PCOS from PCOSAct were included. Logistic regression models were used to compute the odds ratios (ORs) and 95% confidence interval (95% CIs) to assess the effect of anthropometric measures, including body mass index (BMI), waist circumference (WC), hip circumference (HC), the waist‒hip ratio (WHR) and the waist‒height ratio (WHtR), on reproductive outcomes. The discrimination abilities of the models were assessed and compared based on the area under the receiver operating characteristic curve (AUC), Akaike's information criterion (AIC) and integrated discrimination improvement (IDI). RESULTS: Among PCOS women, there was a graded association between anthropometric measures and predicted reproductive outcomes across quintiles of anthropometric measures, including a linear association among WHR, BMI and reproductive outcomes and among waist circumference, WHtR and live birth, pregnancy, and ovulation. However, only a linear association was noted between the hip and ovulation. C-statistic comparisons and IDI analyses revealed a trend towards a significant superiority of BMI for ovulation and WHR for live birth, pregnancy and conception in the models. Combining obesity variables improved discrimination in the multivariable models for reproductive outcomes. CONCLUSIONS: Our findings support that BMI is a better predictor of ovulation and that the WHR is a better predictor of live birth, pregnancy and conception, whereas the combination of obesity variables contributes to the discrimination of reproduction.

Relationship between systemic biomarker of lipid peroxidation 4-hydroxynonenal and lipidomic profile of morbidly obese patients undergoing bariatric surgery.

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.

Healthy Lifestyle and Cardiac Rehabilitation for Weight Loss.

PURPOSE OF REVIEW: Considerable current interest is directed at pharmacological agents for producing significant weight loss. However, healthy lifestyle choices can also lead to clinically meaningful weight loss and improvements in cardiovascular disease (CVD) risk factors. RECENT FINDINGS: In this review, we summarize the recent research from our PROmoting Successful Weight Loss in Primary CarE in Louisiana (PROPEL) randomized controlled trial and review previous data on the potential benefits of cardiac rehabilitation and exercise training (CRET) programs to produce weight loss and improvements in CVD risk factors. Although obesity medications are becoming extremely attractive for secondary and even primary CVD prevention, high-intensity non-pharmacological therapies with healthy lifestyle choices reviewed herein can also lead to substantial health improvements in patients with obesity, including improvements in body weight and other body composition parameters as well as overall CVD risk.

Actein ameliorates diet-induced obesity through the activation of AMPK-mediated white fat browning.

BACKGROUND: Targeting white adipose tissue (WAT) browning to increase systemic energy expenditure is a promising therapeutic strategy to combat obesity. Actein from Actaea cimicifuga L. has recently been reported to ameliorate high fat-induced hepatic steatosis. However, the effect of actein on diet-induced obesity merits more and further investigation. PURPOSE: We aimed to examine the anti-obesity potential of actein and unravel its actions on WAT browning. METHODS: The effect of actein on diet-induced obesity was evaluated using a high-fat diet model in C57BL/6 mice. Systemic energy expenditure of mice was measured with a combined indirect calorimetry system. Quantitative real-time PCR analyses were performed to investigate the mRNA levels of genes involved in thermogenesis, browning, and lipolysis. The protein levels were assessed by Western blot. Moreover, WAT explants and a transwell co-culture system consisting of SVFs and adipocytes were constructed to study the mechanisms of actein on promoting WAT browning and lipolysis. RESULTS: At a dosage of 5 mg/kg/d, actein not only protected mice against diet-induced obesity and insulin resistance, but also reversed pre-established obesity and glucose intolerance in mice. Meanwhile, actein facilitated systemic energy expenditure by activating WAT lipolysis and browning. Further, mechanistic studies revealed that actein indirectly induced epididymal adipocyte lipolysis and directly promoted a white-to-beige conversion of subcutaneous adipocytes by activating the AMPK signaling. CONCLUSION: Actein ameliorated diet-induced obesity and was discovered as a natural lead compound directly targeting white-to-beige conversion of subcutaneous adipocytes, suggesting the potential of developing new therapies for obesity and associated metabolic disorders.

Lead-in calorie restriction enhances the weight-lowering efficacy of incretin hormone-based pharmacotherapies in mice.

OBJECTIVES: The potential benefits of combining lifestyle changes with weight loss pharmacotherapies for obesity treatment are underexplored. Building on recent clinical observations, this study aimed to determine whether "lead-in" calorie restriction before administering clinically approved weight loss medications enhances the maximum achievable weight loss in preclinical models. METHODS: Diet-induced obese mice (DIO) were exposed to 7 or 14 days of calorie restriction before initiating treatment with semaglutide (a glucagon-like peptide-1 receptor (GLP-1R) agonist), tirzepatide (a GLP-1R/glucose insulinotropic peptide receptor (GIPR) co-agonist), or setmelanotide (a melanocortin-4 receptor (MC4R) agonist). Follow-up assessments using indirect calorimetry determined the contributions of energy intake and expenditure linked to consecutive exposure to dieting followed by pharmacotherapy. RESULTS: Calorie restriction prior to treatment with semaglutide or tirzepatide enhanced the weight loss magnitude of both incretin-based therapies in DIO mice, reflected by a reduction in fat mass and linked to reduced energy intake and a less pronounced adaptive drop in energy expenditure. These benefits were not observed with the MC4R agonist, setmelanotide. CONCLUSIONS: Our findings provide compelling evidence that calorie restriction prior to incretin-based therapy enhances the achievable extent of weight loss, as reflected in a weight loss plateau at a lower level compared to that of treatment without prior calorie reduction. This work suggests that more intensive lifestyle interventions should be considered prior to pharmacological treatment, encouraging further exploration and discussion of the current standard of care.

Hidradenitis suppurativa and its association with obesity, smoking, and diabetes mellitus: A systematic review and meta-analysis.

Our meta-analysis aimed to quantify the association between Hidradenitis suppurativa (HS) and several risk factors including obesity, smoking, and type 2 diabetes mellitus (T2DM). We searched PubMed, Scopus, Embase, Web of Science, and cumulative index to nursing and allied health literature for articles reporting either the odds ratio (OR) or the numbers of HS cases associated with obesity, smoking, or T2DM, and including HS negative controls. Risk of bias was assessed against the risk of bias in non-randomized studies of interventions tool. Data synthesis was done using the random effects model with heterogeneity being evaluated with I2 statistic. Twenty-three studies with a total of 29 562 087 patients (average age of 36.6 years) were included. Ten studies relied on country-level data, while six studies collected their data from HS clinics. The analysis showed a significant association between HS and female sex (OR 2.34, 95% CI 1.89-2.90, I2 = 98.6%), DM (OR 2.78, 95% CI 2.23-3.47, I2 = 98.9%), obesity (OR 2.48, 95% CI 1.64-3.74, I2 = 99.9%), and smoking (OR 3.10 95% CI 2.60-3.69, I2 = 97.1%). Our meta-analysis highlights HS links to sex, DM, obesity, and smoking, with emphasis on holistic management approach. Further research is needed on molecular mechanisms and additional risk factors for improved patient care.

Anemarrhena asphodeloides Bunge total saponins lower lipid via modulating MAOA activity to enhance defense mechanisms in mice and C. elegans.

ETHNOPHARMACOLOGICAL RELEVANCE: Within Anemarrhena asphodeloides Bunge (AAB), the pivotal bioactive constituents are identified as Anemarrhena asphodeloides Bunge total saponins (ABS). In traditional pharmacology, ABS has exhibited notable anti-inflammatory, hypoglycemic, and cardioprotective properties. Despite these observed effects, the specific protective mechanisms of ABS against metabolic diseases and improving the endocrine system remain largely uncharted. AIM TO STUDY: This work intends to shed light on the effects and intrinsic mechanisms of ABS on metabolic diseases. MATERIALS AND METHODS: The characterization of ABS components was achieved through High-Performance Liquid Chromatography/Mass Spectrometry (HPLC/MS). To evaluate ABS's anti-inflammatory efficacy, mouse macrophages underwent analysis using the Griess method. Induced differentiation of mouse fibroblasts was assessed through Oil Red O staining. In an obesity model with C57BL/6 N mice, ABS administration prompted measurements of glucose and insulin tolerance. Western blot analysis quantified lipolysis and anti-inflammatory protein expression. Nile red staining gauged body fat content in C. elegans post-ABS treatment. The mechanism of ABS action was elucidated through mRNA sequencing, further validated using RNA interference technology, and nematode mutants. RESULTS: ABS showcased the ability to diminish Nitric Oxide (NO) production in inflammatory macrophages and shrink adipocyte lipid droplets. In mice experiments, ABS was effective in alleviating fat accumulation and affecting serum lipid metabolism in diabetic mice. It enhanced oral glucose tolerance and insulin tolerance while increasing lipolysis-associated protein expression. ABS notably reduced fat content in C. elegans. Mechanistically, ABS downregulated NOD-like receptor thermal protein domain associated protein 3 (NLRP3) and monoamine oxidase A (MAOA) expression while enhancing UGT, ilys-2, and ilys-3. Lipolysis emerged as a pivotal pathway for ABS in the therapeutic intervention of metabolic diseases. CONCLUSIONS: Our investigation has revealed that ABS exert a role in combating metabolic diseases by enhancing the body's defense mechanisms. ABS activate the NLRP3-neurotransmitter-visceral adipose pathway in mice, thereby bolstering resistance and diminishing fat accumulation. In C. elegans, ABS downregulated the expression of MAOA, bolstered resistance, and augmented glucuronidase activity, consequently leading to a reduction in fat content.

A review of metabolic and microbial influences on women with polycystic ovarian syndrome.

INTRODUCTION: Polycystic Ovary Syndrome (PCOS) is a prevalent endocrine and metabolic disorder affecting reproductive-aged women worldwide. Characterized by irregular menstruation, signs of hyperandrogenism, polycystic ovaries via ultrasound ovarian dysfunction. AREA COVERED: The review delves into the intricate pathophysiological mechanisms underlying the syndrome. Dysregulation of the hypothalamic-pituitary-ovarian axis, IR, obesity, and hyperandrogenism contribute to anovulation and follicular dysfunction which is associated with gut dysbiosis, bile metabolites, and an unhealthy diet. Metabolomics and genomics analyses offer insights into the metabolism of bile acids (BAs) and gut microbiota dysbiosis in PCOS. BAs, crucial for metabolic regulation, are influenced by microbes, impacting hormonal balance. Disruptions in gut microbiota contribute to hormonal dysregulation. Interconnected pathways involving BAs and gut microbiota are pivotal in PCOS. Therapeutic implications include a healthy diet, exercise, and interventions targeting gut microbiota modulation and BAs metabolite to alleviate PCOS symptoms and improve metabolic health. CONCLUSION: PCOS requires a multifaceted, multidisciplinary approach for effective management, including lifestyle changes, medications, and emerging therapies. Tailored strategies considering individual needs and personalized treatment plans are crucial for successful PCOS management. Despite existing knowledge, comprehensive investigations are needed to bridge research gaps and discern the interconnected pathways linking the development of PCOS and the gut-bile axis which are interconnected with metabolic disorders and the development of PCOS. Gut microbiota and hormonal regulation offer promising avenues for innovative therapeutic strategies aimed at addressing the root causes of PCOS and improving patient outcomes.

Epigallocatechin gallate enhances sympathetic heart rate variability and decreases blood pressure in obese subjects: a randomized control trial.

This study aimed to investigate effects of epigallocatechin gallate (EGCG) on blood pressure (BP) and autonomic nervous system, indicated by 5-min heart rate variability (HRV) measurement in obese subjects, and determine correlations of BP with metabolic factors. In a double-blind, randomized controlled trial, obese subjects (n = 30) were randomly allocated to receive 150 mg EGCG (n = 15) or placebo (n = 15) twice a day without dietary restrictions. After 8-week EGCG treatment, systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) significantly decreased, while the low-frequency (LF) to high-frequency power (HF) ratio (LF/HF ratio) significantly increased (P < 0.05 all), indicating a shift toward sympathetic dominance, either directly or indirectly after BP lowering. SBP had positive correlations with obesity parameters, leptin, insulin, and insulin resistance but had a negative correlation with insulin sensitivity. DBP was positively correlated with age and HF in normalized unit, but negatively correlated with height and LF in ms2. High-density lipoprotein cholesterol (HDL-C) was negatively correlated with SBP, DBP, and MAP reflecting its protective effect against elevated BP. In conclusion, the 8-week EGCG treatment decreased BP and increased the LF/HF ratio, reflecting increased sympathetic activity, either a direct EGCG effect or an indirect compensatory response following BP reduction.

Adipocyte derived exosomes promote cell invasion and challenge paclitaxel efficacy in ovarian cancer.

BACKGROUND: Epithelial ovarian cancer (EOC) is the deadliest gynaecological cancer with high mortality rates driven by the common development of resistance to chemotherapy. EOC frequently invades the omentum, an adipocyte-rich organ of the peritoneum and omental adipocytes have been implicated in promoting disease progression, metastasis and chemoresistance. The signalling mechanisms underpinning EOC omentum tropism have yet to be elucidated. METHODS: Three-dimensional co-culture models were used to explore adipocyte-EOC interactions. The impact of adipocytes on EOC proliferation, response to therapy and invasive capacity was assessed. Primary adipocytes and omental tissue were isolated from patients with ovarian malignancies and benign ovarian neoplasms. Exosomes were isolated from omentum tissue conditioned media and the effect of omentum-derived exosomes on EOC evaluated. Exosomal microRNA (miRNA) sequencing was used to identify miRNAs abundant in omental exosomes and EOC cells were transfected with highly abundant miRNAs miR-21, let-7b, miR-16 and miR-92a. RESULTS: We demonstrate the capacity of adipocytes to induce an invasive phenotype in EOC populations through driving epithelial-to-mesenchymal transition (EMT). Exosomes secreted by omental tissue of ovarian cancer patients, as well as patients without malignancies, induced proliferation, upregulated EMT markers and reduced response to paclitaxel therapy in EOC cell lines and HGSOC patient samples. Analysis of the omentum-derived exosomes from cancer patients revealed highly abundant miRNAs that included miR-21, let-7b, miR-16 and miR-92a that promoted cancer cell proliferation and protection from chemotherapy when transfected in ovarian cancer cells. CONCLUSIONS: These observations highlight the capacity of omental adipocytes to generate a pro-tumorigenic and chemoprotective microenvironment in ovarian cancer and other adipose-related malignancies.