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2.
Braz J Biol ; 84: e264320, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35946729

RESUMO

Toxicological studies are essential for developing novel medications in pharmaceutical industries including ayurvedic preparation. Hence, the present study is aimed to evaluate acute and 28-days repeated dose oral toxicity of anti-obesity polyherbal granules (PHG) in Sprague Dawley rats by OECD guidelines No 425 and 407, respectively. In an acute oral toxicity study, a single dose of 2 g/kg PHG was administered to rats and mortality, body weight, and clinical observations were noted for fourteen days. However, in the subacute oral toxicity study, the PHG was administered orally at doses of 0.3, 0.5 and 1 g/kg daily for 28 days to rats. Food intake and body weight were recorded weekly. On the 29th day, rats were sacrificed and subjected to haematological, biochemical, urine, necropsy, and histopathological analysis. In an acute oral toxicity study, no treatment-related, mortality, behavioral changes, and toxicity were found throughout fourteen days. Likewise, in the sub-acute toxicity study, no mortality and toxic effects were found in haematology, biochemical, urine, necropsy and histopathological analysis in rats for 28 days of treatment with PHG. Based on these results, the LD50 of PHG was found to be greater than 2 g/kg and the no-observed-adverse-effect level (NOAEL) of PHG for rats was found to be 0.5 g/kg/day. Thus, anti-obesity polyherbal granules showed a good safety profile in animal studies and can be considered an important agent for the clinical management of obesity.


Assuntos
Obesidade , Animais , Peso Corporal , Relação Dose-Resposta a Droga , Nível de Efeito Adverso não Observado , Obesidade/induzido quimicamente , Ratos , Ratos Sprague-Dawley , Testes de Toxicidade Aguda/métodos
3.
Ecotoxicol Environ Saf ; 242: 113893, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35917711

RESUMO

Due to the highly evolved industrialization and modernization, air quality has deteriorated in most countries. As reported by the World Health Organization (WHO), air pollution is now considered as one of the major threats to global health and a principal risk factor for noncommunicable diseases. Meanwhile, the increasing worldwide prevalence of overweight and obesity is attracting more public attentions. Recently, accumulating epidemiological studies have provided evidence that overweight and obesity may be partially attributable to environmental exposure to air pollution. This review summarizes the epidemiological evidence for the correlation between exposure to various outdoor and indoor air pollutants (mainly particulate matter (PM), nitrogen oxides (NOx), ozone (O3), and polycyclic aromatic hydrocarbons (PAHs)) and overweight and obesity outcomes in recent years. Moreover, it discusses the multiple effects of air pollution during exposure periods throughout life and sex differences in populations. This review also describes the potential mechanism underlying the increased risk of obesity caused by air pollution, including inflammation, oxidative stress, metabolic imbalance, intestinal flora disorders and epigenetic modifications. Finally, this review proposes macro- and micro-measures to prevent the negative effects of air pollution exposure on the obesity prevalence.


Assuntos
Poluentes Atmosféricos , Poluição do Ar em Ambientes Fechados , Poluição do Ar , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/toxicidade , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Poluição do Ar em Ambientes Fechados/efeitos adversos , Poluição do Ar em Ambientes Fechados/análise , Monitoramento Ambiental , Feminino , Humanos , Masculino , Obesidade/induzido quimicamente , Obesidade/etiologia , Sobrepeso/epidemiologia , Sobrepeso/etiologia , Material Particulado/análise , Material Particulado/toxicidade
4.
Phys Med Rehabil Clin N Am ; 33(3): 719-732, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35989060

RESUMO

Environmental toxicant exposure, according to many researchers in the field, is the leading cause of chronic disease and premature death globally. For the purposes of this review, we will use obesity and type 2 diabetes as examples of toxicant-induced chronic diseases. Endocrine Disrupting chemicals (EDCs) such as phthalates and bisphenols, per- and polyfluoroalkyl substances (PFAS), and persistent organic pollutants (POPs) have been linked to increased risk for obesity and type 2 diabetes in both animal and large epidemiologic studies. These two conditions are well-documented examples of evidence for mechanisms of both adipose metabolism disruption and pancreatic cell dysfunction. The implications for health care directives to both identify, prevent, and treat these exposures are reviewed.


Assuntos
Diabetes Mellitus Tipo 2 , Disruptores Endócrinos , Medicina Ambiental , Animais , Doença Crônica , Disruptores Endócrinos/toxicidade , Humanos , Obesidade/induzido quimicamente
5.
Nutrients ; 14(13)2022 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-35807946

RESUMO

Metabolic syndrome (MS) is a multifactorial disease entity and is not fully understood. Growing evidence suggests that early exposure to bisphenol A (BPA) is a significant risk factor for the development of metabolic diseases. BPA is a monomer used in the manufacturing of polycarbonate plastics, thermal receipt paper, and epoxy resins. Owing to its widespread use, BPA has been detected in human fluids and tissues, including blood, placental breast milk, and follicular fluid. In the present review, we aimed to review the impact of prenatal exposure to different doses of BPA on metabolic parameters as determined by in vivo and epidemiological studies. The PubMed, Scopus, and Web of Science electronic databases were searched to identify articles published during a period of 15 years from 2006 to 2021, and 29 studies met the criteria. Most studies demonstrated that prenatal exposure to low BPA concentrations correlated with alterations in metabolic parameters in childhood and an increased risk of metabolic diseases, such as obesity and type 2 diabetes mellitus (T2DM), in adulthood. Therefore, prenatal exposure to low doses of BPA may be associated with an increased risk of obesity and T2DM in a sex-specific manner.


Assuntos
Diabetes Mellitus Tipo 2 , Doenças Metabólicas , Efeitos Tardios da Exposição Pré-Natal , Adulto , Compostos Benzidrílicos/toxicidade , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Humanos , Masculino , Doenças Metabólicas/induzido quimicamente , Obesidade/induzido quimicamente , Obesidade/etiologia , Fenóis , Placenta , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente
6.
Obesity (Silver Spring) ; 30(8): 1659-1669, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35894081

RESUMO

OBJECTIVE: The study aimed to identify periods of heightened susceptibility to the effects of pre- and postnatal secondhand tobacco smoke (SHS) exposure on body composition at age 12 years. METHODS: The study used data from 217 children from the Health Outcomes and Measures of the Environment (HOME) Study, a prospective cohort in Cincinnati, Ohio. Using multiple informant models, the study estimated associations of maternal serum cotinine (16 and 26 weeks of pregnancy) and child serum cotinine concentrations (at age 12, 24, 36, and 48 months) with measures of body composition obtained with anthropometry and dual-energy x-ray absorptiometry at 12 years. We examined whether there were differences between these associations for pre- and postnatal exposure periods and potential effect measure modification by sex. RESULTS: Postnatal cotinine concentrations were associated with higher weight, BMI, body fat and lean mass, waist circumference, and visceral, android, and gynoid fat. Each 10-fold increase in postnatal cotinine was associated with 76% increased risk of overweight or obesity (95% CI: 1.13-2.75). Associations between prenatal concentrations and measures of body composition at 12 years were generally null. CONCLUSIONS: Postnatal exposure to SHS may increase adolescent adiposity and lean mass. Future studies should determine whether early-life exposures to SHS are associated with other cardiometabolic risk markers.


Assuntos
Poluição por Fumaça de Tabaco , Adolescente , Composição Corporal , Criança , Cotinina , Feminino , Humanos , Obesidade/induzido quimicamente , Gravidez , Estudos Prospectivos , Poluição por Fumaça de Tabaco/efeitos adversos , Circunferência da Cintura
7.
Chem Biol Interact ; 363: 110027, 2022 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-35780845

RESUMO

Tris (2-chloroethyl) phosphate (TCEP) is the most commonly detective organophosphate flame retardant in surroundings. TCEP is also evidenced as endocrine disrupting chemicals and has potential adverse effects on metabolic diseases. In this study, we hypothesized that metabolic diseases are adverse outcomes of TCEP exposure. Adult ICR mice was daily treated with TCEP (20 mg/kg and 60 mg/kg, higher than expected level in people) by gavage administration for 9 weeks. The results demonstrate that TCEP promoted body weight gain, hypertriglyceridemia, and hepatic steatosis, consistent with upregulation of hepatic lipogenesis-related gene expression. Moreover, TCEP altered the levels of several hepatic metabolites, especially bile acids and downregulated bile acid synthesis pathways. Intriguingly, we found a marked downregulation of the bile acid nuclear reporter, FXR, in TCEP-exposed livers. Mechanistically, TCEP directly interacted with FXR at Lys335 and Lys336. Further studies in this work elucidate the mechanisms of long-term TCEP exposure on hepatic steatosis and obesity in mice via FXR-mediated lipid accumulation. Our results provide insight into the possibility of intermediate TCEP exposure in causing metabolic diseases.


Assuntos
Fígado Gorduroso , Retardadores de Chama , Doenças Metabólicas , Animais , Ácidos e Sais Biliares/química , Fígado Gorduroso/induzido quimicamente , Retardadores de Chama/metabolismo , Retardadores de Chama/toxicidade , Humanos , Lipídeos/química , Camundongos , Camundongos Endogâmicos ICR , Obesidade/induzido quimicamente , Organofosfatos/metabolismo , Organofosfatos/toxicidade , Fosfatos , Fosfinas
8.
Front Endocrinol (Lausanne) ; 13: 851035, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35813629

RESUMO

Background: The impact of glucagon-like peptide-1 receptor agonists on patients with heart failure has not been fully described. Our main objective was to evaluate the safety and clinical and glycemic efficacy of once-weekly semaglutide in obese patients with type 2 diabetes and heart failure. Methods: In this observational, retrospective, real-world study, we enrolled outpatients with type 2 diabetes, obesity, and heart failure who started semaglutide and were followed-up on at 3, 6, and 12 months. Results: A total of 136 patients were included. From baseline to 12 months, there was a significant improvement on the Kansas City Cardiomyopathy Questionnaire total symptom score (59.0 ± 24.1 vs 79.9 ± 28.4 points, p<0.01), a reduction in the proportion of patients with New York Heart Association functional class III (40.4% to 16.2%, p<0.01), and a reduction in N-terminal pro-brain natriuretic peptide levels (969.5 ± 653.5 vs 577.4 ± 322.1 pg/mL, p<0.01). Emergency department visits due to heart failure, hospitalizations due to heart failure, and all-cause hospitalizations also declined. Additionally, significant reductions in glycated hemoglobin (-1.4%) and body weight (-12.7 kilograms) were observed as well as a de-intensification of antidiabetic therapy. Moreover, semaglutide was safe and well-tolerated. Conclusion: In obese patients with type 2 diabetes and heart failure, the use of once-weekly semaglutide was safe and clinically efficacious, improving health and functional status. Nevertheless, more strong evidence on glucagon-like peptide-1 receptor agonists in heart failure is required.


Assuntos
Diabetes Mellitus Tipo 2 , Insuficiência Cardíaca , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Peptídeos Semelhantes ao Glucagon/uso terapêutico , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Obesidade/induzido quimicamente , Obesidade/complicações , Obesidade/tratamento farmacológico , Estudos Retrospectivos
9.
Trends Endocrinol Metab ; 33(9): 628-638, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35902330

RESUMO

Antipsychotics (APDs) represent a core treatment for severe mental disorders (SMEs). Providing symptomatic relief, APDs do not exert therapeutic effects on another clinically significant domain of serious mental disorders, cognitive impairment. Moreover, adverse metabolic effects (diabetes, weight gain, dyslipidemia, and increased cardiovascular risk) are common during treatment with APDs. Among pharmacological candidates reversing APD-induced metabolic adverse effects, glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1 RAs), approved for both diabetes and recently for obesity treatment, stand out due to their favorable effects on peripheral metabolic parameters. Interestingly, GLP-1 RAs are also proposed to have pro-cognitive effects. Particularly in terms of dual therapeutic mechanisms potentially improving both central nervous system (CNS) deficits and metabolic burden, GLP-1 RAs open a new perspective and assume a clinically advantageous position.


Assuntos
Antipsicóticos , Diabetes Mellitus Tipo 2 , Antipsicóticos/efeitos adversos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Peptídeo 1 Semelhante ao Glucagon/uso terapêutico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Humanos , Hipoglicemiantes/uso terapêutico , Obesidade/induzido quimicamente , Obesidade/tratamento farmacológico , Aumento de Peso
10.
Life Sci ; 306: 120825, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-35870619

RESUMO

As obesity prevalence increases, more and more drugs that assist with weight loss have been developed. Numerous weight loss drugs had been approved, but many have also been withdrawn based on their lack of efficacy as well as safety concerns. Initial approaches in developing weight loss drugs was by increasing physiological energy expenditure and suppressing the appetite. Subsequently, as more physiological mechanisms for weight gain has been unearthed, drugs targeting newly discovered receptors and/or enzymes have been introduced with improved safety profiles and fewer psychological adverse events. Additionally, drugs targeting hunger or satiety signaling have been actively studied, and have shown increased adoption by physicians. Studies have also evaluated drugs that target metabolic tissues-such as adipose tissue or muscle-to promote weight loss, however to-date nothing has carried on into clinical practice. Starting with a brief history of early obesity treatments, this review evaluates current weight loss pharmaceutical options based on their duration of therapy status.


Assuntos
Fármacos Antiobesidade , Fármacos Antiobesidade/uso terapêutico , Metabolismo Energético , Humanos , Obesidade/induzido quimicamente , Aumento de Peso , Redução de Peso
11.
Gen Comp Endocrinol ; 327: 114098, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-35878704

RESUMO

Obesity has become a very important public health problem and is increasing globally. Genetics, individual and environmental factors play roles in the etiology of this complex disorder. Recently, several environmental pollutants have been suggested to have obesogenic activities. Peroxisome proliferator activating receptor gamma (PPARγ), uncoupling protein-1 (UCP1) and their expression in white adipose tissue (WAT) and brown adipose tissue (BAT) play key roles in adipogenesis. UCP3 and irisin were reported to play roles in non-shivering thermogenesis. Our primary aim was to investigate obesogenic effects of hexachlorobenzene (HCB), dichlorodiphenyltrichloroethane (DDT) and dichlorodiphenyldichloroethylene (DDE) in rats. In addition, thermoregulatory effects of HCB, DDT and DDE were also investigated by analyzing the levels of Ucp3 and irisin. Thirty-two adult male Sprague-Dawley rats were randomly divided into four groups as control, HCB, DDT and DDE. Animals were administered with organochlorine pesticides (OCPs; 5 mg/kg bw) by oral gavage every other day for five weeks. At the end of the experimental period, the animals were sacrificed, BAT and WAT samples were collected to analyze Pparγ, Ucp1 and Ucp3 levels. Moreover, skeletal muscle samples were collected to examine Ucp3 and irisin levels. Serum glucose, cholesterol and triglyceride levels were also determined. Body weight and core temperature of the animals were not significantly affected by any of the OCP administration. Serum glucose, cholesterol and triglyceride levels were similar among the experimental groups. Pparγ expression was significantly elevated by HCB administration only in WAT (p < 0.05). On the other hand, both Pparγ and Ucp1 expressions were diminished in WAT and BAT (p < 0.01) by DDT treatment, while in WAT, DDE significantly decreased Pparγ expression without altering its expression in BAT (p < 0.001). Ucp3 and irisin levels in skeletal muscle were not altered. Our findings show that both DDT and DDE reduce the browning of WAT by suppressing white adipocytes and thus may have obesogenic activity in male rats without altering thermoregulation. In addition, HCB, DDT and DDE-induced alterations in expression of Pparγ and Ucp1 in WAT implicates differential regulation of adipogenic processes.


Assuntos
DDT , Diclorodifenil Dicloroetileno , Hexaclorobenzeno , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco , Animais , Peso Corporal , DDT/metabolismo , DDT/toxicidade , Diclorodifenil Dicloroetileno/metabolismo , Diclorodifenil Dicloroetileno/toxicidade , Fibronectinas/genética , Glucose/metabolismo , Hexaclorobenzeno/metabolismo , Hexaclorobenzeno/toxicidade , Masculino , Obesidade/induzido quimicamente , PPAR gama/genética , PPAR gama/metabolismo , Ratos , Ratos Sprague-Dawley , Triglicerídeos/metabolismo
12.
Gen Hosp Psychiatry ; 78: 58-67, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35863294

RESUMO

BACKGROUND: Schizophrenia and antipsychotic use are associated with clinically significant weight gain and subsequent increased mortality. Despite weight loss medications (WLMs) licensed by regulatory bodies (FDA, EMA, and MHRA) being available, current psychiatric guidelines recommend off-label alternatives, which differ from non-psychiatric guidelines for obesity. OBJECTIVE: Evaluate the efficacy of licensed WLMs on treating antipsychotic-induced weight gain (AIWG) and obesity in schizophrenia and psychosis (OSP). METHOD: A literature search was conducted using Medline, EMBASE, PsycINFO and Cochrane Library online databases for human studies using licensed WLMs to treat AIWG and OSP. RESULTS: Three RCTs (two liraglutide, one naltrexone-bupropion), one unpublished open-label trial (naltrexone-bupropion), and seven observational studies (five liraglutide, one semaglutide, one multiple WLMs) were identified. Results for liraglutide showed statistically significant improvement in weight, BMI, waist circumference, HbA1c, cholesterol, and LDL readings on meta-analysis. Evidence was mixed for naltrexone-bupropion with no detailed studies conducted for setmelanotide, or stimulants. CONCLUSION: Evidence is strongest for liraglutide compared to other licensed WLMs. The findings, particularly the inclusion of human trial data, provide evidence for liraglutide use in treating AIWG and OSP, which would better align psychiatric practice with non-psychiatric practices around obesity. The findings also identify continued literature gaps regarding other licensed WLMs.


Assuntos
Antipsicóticos , Transtornos Psicóticos , Esquizofrenia , Antipsicóticos/efeitos adversos , Bupropiona/efeitos adversos , Humanos , Liraglutida/efeitos adversos , Naltrexona/uso terapêutico , Obesidade/induzido quimicamente , Obesidade/tratamento farmacológico , Transtornos Psicóticos/tratamento farmacológico , Esquizofrenia/tratamento farmacológico , Aumento de Peso
13.
BMJ Open ; 12(6): e058899, 2022 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-35667725

RESUMO

INTRODUCTION: Obese men with prostate cancer have an increased risk of biochemical recurrence, metastatic disease and mortality. For those undergoing androgen deprivation therapy (ADT), substantial increases in fat mass are observed in the first year of treatment. Recently, we showed that a targeted supervised clinic-based exercise and nutrition intervention can result in a substantial reduction in fat mass with muscle mass preserved in ADT-treated patients. However, the intervention needs to be accessible to all patients and not just those who can access a supervised clinic-based programme. The purpose of this study was to evaluate the efficacy of telehealth delivered compared with supervised clinic-based delivered exercise and nutrition intervention in overweight/obese patients with prostate cancer. METHODS AND ANALYSIS: A single-blinded, two-arm parallel group, non-inferiority randomised trial will be undertaken with 104 overweight/obese men with prostate cancer (body fat percentage ≥25%) randomly allocated in a ratio of 1:1 to a telehealth-delivered, virtually supervised exercise and nutrition programme or a clinic-based, face-to-face supervised exercise and nutrition programme. Exercise will consist of supervised resistance and aerobic exercise performed three times a week plus additional self-directed aerobic exercise performed 4 days/week for the first 6 months. Thereafter, for months 7-12, the programmes will be self-managed. The primary endpoint will be fat mass. Secondary endpoints include lean mass and abdominal aortic calcification, anthropometric measures and blood pressure assessment, objective measures of physical function and physical activity levels, patient-reported outcomes and blood markers. Measurements will be undertaken at baseline, 6 months (post intervention), and at 12 months of follow-up. Data will be analysed using intention-to-treat and per protocol approaches. ETHICS AND DISSEMINATION: Ethics approval has been obtained from the Edith Cowan University Human Research Ethics Committee (ID: 2021-02157-GALVAO). Outcomes from the study will be published in academic journals and presented in scientific and consumer meetings. TRIAL REGISTRATION NUMBER: ACTRN12621001312831.


Assuntos
Neoplasias da Próstata , Telemedicina , Antagonistas de Androgênios/uso terapêutico , Exercício Físico , Terapia por Exercício/métodos , Humanos , Masculino , Obesidade/induzido quimicamente , Obesidade/complicações , Obesidade/terapia , Sobrepeso/induzido quimicamente , Sobrepeso/complicações , Sobrepeso/terapia , Neoplasias da Próstata/complicações , Neoplasias da Próstata/terapia , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Redução de Peso
14.
Am J Ther ; 29(4): e410-e424, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35687055

RESUMO

BACKGROUND: Innovations in drug therapy for obesity have had a limited impact on the body mass index, prevalence of medical complications, quality of life, and work potential of a substantial majority of affected persons. STUDY QUESTION: What are the milestones of the changes in the expert approach to the pharmacological management of obesity in the past century? STUDY DESIGN: To determine the changes in the experts' approach to the management of obesity, as presented in a widely used textbook in the United States. DATA SOURCES: The primary sources were chapters describing the management of obesity in the 26 editions of Cecil Textbook of Medicine published from 1927 through 2020. Secondary sources were publications retrieved from Medline that clarified technical issues related to the development, regulatory approval, and use of the drugs mentioned in the Cecil Textbook of Medicine. RESULTS: Pharmacological interventions aimed at increasing caloric expenditures through thermogenesis were recommended from 1927 through 1943. Thyroid extracts were prescribed even in the absence of demonstrated hypothyroidism or decreased basal metabolic rate throughout this period. Dinitrophenol was mentioned in 1937, but was banned soon thereafter. Appetite suppression with amphetamine was considered useful from 1943 through 1988, after which the drug was replaced with other centrally acting molecules, such as fenfluramine in 1988, sibutramine in 2000, and rimonabant in 2008, which were in turn withdrawn because of major adverse effects. In the past decade, obesity has been treated with the appetite suppressants phentermine-topiramate, bupropion-naltrexone, lorcaserin, and liraglutide, and with orlistat, a drug promoting fat malabsorption. The change in weight produced by these drugs is generally modest and transient. CONCLUSIONS: The pharmacological management of obesity has remained frustratingly inefficient. The reasons for the relative lack of success may reside in the ever-growing access to dense, palatable, and relatively inexpensive food, coupled with the decrease in energy expenditure created by a sedentary lifestyle.


Assuntos
Fármacos Antiobesidade , Fármacos Antiobesidade/efeitos adversos , Prova Pericial , Humanos , Obesidade/induzido quimicamente , Obesidade/tratamento farmacológico , Orlistate/uso terapêutico , Qualidade de Vida , Estados Unidos
15.
Eur J Nutr ; 61(7): 3597-3611, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35643872

RESUMO

PURPOSE: To assess the effects of enriched seafood sticks with postbiotic and bioactive compounds on CMD risk factors and the gut microbiota in abdominally obese individuals. METHODS: Randomized, double-blind, parallel, placebo-controlled trial with abdominally obese individuals. Participants (n = 120) consumed 50 g/day of enriched seafood sticks containing SIAP: (1010 colony forming units (CFUs) of heat-inactivated B. animalis subsp. lactis CECT8145, 370 mg/day omega 3 and 1.7 g/day inulin), or 50 g/day of placebo seafood sticks for 12 weeks. At 12 weeks, an acute single-dose study of 4 h was performed. RESULTS: Sustained SIAP2 consumption significantly decreased the insulin by - 5.25 mg/dL and HOMA-IR (homeostatic Model Assessment of Insulin Resistance) by - 1.33. In women, SIAP2 consumption significantly decreased the pulse pressure (PP) by - 4.69 mmHg. Gut microbiota analysis showed a negative association between glycemic parameter reduction and Alistipes finegoldii and Ruminococcaceae, and between PP reduction and Prevotella 9-ASV0283 and Christensenellaceae. In the acute single dose-study 4-h, SIAP2 consumption produced a lower increase in the postprandial circulating triglyceride levels [23.9 (7.03) mg/dL (mean [standard error])] than the observed with placebo [49.0 (9.52)] mg/dL. CONCLUSION: In abdominally obese individuals, enriched seafood sticks induce a potential protection against type 2 diabetes development by the reduction in the insulin and HOMA-IR; and in cardiovascular disease, in women, by the PP reduction. These effects are accompanied by partial changes in the gut microbiota composition. The enriched seafood sticks reduce the atherogenic triglyceride postprandial concentrations. Our results support the use of enriched seafood sticks as a complementary strategy in the management of CMD risk factors. REGISTRATION NUMBER OF CLINICAL TRIAL: ( www. CLINICALTRIALS: gov ): NCT03630588 (August 15, 2018).


Assuntos
Diabetes Mellitus Tipo 2 , Ácidos Graxos Ômega-3 , Microbioma Gastrointestinal , Fatores de Risco Cardiometabólico , Diabetes Mellitus Tipo 2/induzido quimicamente , Método Duplo-Cego , Ácidos Graxos Ômega-3/farmacologia , Feminino , Temperatura Alta , Humanos , Insulina , Inulina/efeitos adversos , Obesidade/induzido quimicamente , Alimentos Marinhos , Triglicerídeos
16.
Food Res Int ; 157: 111197, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35761521

RESUMO

Improved gut microbes and nutritious metabolites have been considered as the mediators of health benefits from indigestible polysaccharides, but their role in the anti-obesity effect of polysaccharides from Cordyceps militaris (CMP) remains elusive. This study aims to explore the potential mediators of the anti-obesity effects of CMP in high-fat diet (HFD)-fed mice using 16S rRNA sequencing and untargeted metabolomics analysis. The results showed that CMP supplementation in HFD-fed mice reduced body weight, fat accumulation, pro-inflammatory cytokine levels, and impaired glucose tolerance as well as gut barrier. Moreover, the CMP reversed the HFD-induced gut microbiota dysbiosis, as indicated by the elevated population of Alloprevotella, Parabacteroides, Butyricimonas, and Alistipes; and decreased population of Negativebacillus, in addition to altered levels of metabolites, such as brassicasterol and 4'-O-methylkanzonol W. Notably, CMP prevented obesity in association with the altered gut microbes and metabolites. These findings suggest that CMP may serve as a potential prebiotic agent to modulate specific gut microbes and related metabolites, which play a critical role in its preventing obesity-related diseases.


Assuntos
Cordyceps , Microbioma Gastrointestinal , Animais , Bacteroidetes , Citidina Monofosfato/efeitos adversos , Dieta Hiperlipídica/efeitos adversos , Camundongos , Obesidade/induzido quimicamente , Obesidade/prevenção & controle , Polissacarídeos/farmacologia , RNA Ribossômico 16S/genética
17.
Endocrine ; 77(1): 57-62, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35524875

RESUMO

PURPOSE: Prader-Willi syndrome (PWS) is characterised by childhood-onset hyperphagia and obesity however limited data are available to guide treatment of obesity in this population. We aimed to evaluate the safety, tolerability, and efficacy of intensive medical weight loss interventions (very-low-energy diets [VLED] and/or pharmacotherapy) in individuals with PWS attending a specialist obesity management service. METHODS: A retrospective audit was undertaken of individuals with PWS attending the Austin Health Weight Control Clinic between January 2010-April 2021. Main outcome measures were weight outcomes, duration of use, and adverse effects. RESULTS: Data were available for 18 patients, of whom 15 were treated with intensive weight loss interventions. Median (interquartile range, IQR) age at baseline was 20 years (19-32) with median body weight 90 kg (75-118) and BMI 37 kg/m2 (30-51). Median weight loss during VLED (n = 7) was 14 kg (1-20 kg) over 60 weeks. Median weight loss with phentermine-topiramate (n = 7) was 17 kg (IQR 9-19 kg) over 56 weeks. Median weight loss with liraglutide 0.6-3 mg (n = 7), prescribed with topiramate in 3 individuals, was 9 kg (2-14 kg) over 96 weeks. Naltrexone-bupropion resulted in weight loss in 2 of 4 individuals. Thirteen individuals achieved ≥10% weight loss but only 5 individuals maintained ≥10% weight loss at last follow-up. Five individuals discontinued pharmacotherapy due to adverse effects. CONCLUSIONS: VLED and pharmacotherapy can achieve substantial weight loss in some individuals with PWS though non-adherence results in substantial weight regain. Adverse effects were ascribed to phentermine and topiramate, whereas liraglutide was well-tolerated in this population.


Assuntos
Síndrome de Prader-Willi , Criança , Humanos , Liraglutida/uso terapêutico , Obesidade/induzido quimicamente , Obesidade/complicações , Obesidade/terapia , Fentermina/efeitos adversos , Síndrome de Prader-Willi/complicações , Síndrome de Prader-Willi/tratamento farmacológico , Estudos Retrospectivos , Topiramato/uso terapêutico , Redução de Peso
18.
Int J Biol Macromol ; 213: 234-246, 2022 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-35605721

RESUMO

Guava is a popular fruit consumed worldwide with beneficial effects in regulation of glucose and lipid metabolism. Although polysaccharides are a major phytochemical component of guava, to date, the alleviative effects of polysaccharides from the guava fruit against diet-induced obesity remain unclear. The relationship between the anti-obesity effects of guava polysaccharide (GP) and gut microbiota is unknown. In current study, seven-week-old C57BL/6 mice were fed high-fat diet (HFD) supplemented with GP (100 mg/kg) by oral gavage for 11 weeks. GP supplementation alleviated HFD-induced body weight gain and visceral obesity, and reduced serum cholesterol, triglyceride, and LDL-C levels. In addition, GP ameliorated insulin resistance and prevented hepatic lipid accumulation and meta-inflammation in both liver and adipose tissues in obese mice. Remarkably, GP treatment restored the Firmicutes/Bacteroidetes ratio, induced growth of beneficial bacteria including Clostridium XlVa, Parvibacter, and Enterorhabdus, and decreased in inflammation-related bacteria Mucispirillum in mice fecal samples, accompanied with enhanced production of colonic short chain fatty acids especially butyric acid. However, the metabolic benefits of GP diminished in antibiotics-treated HFD-fed mice. Overall, GP improved metabolic profiles in HFD-induced obese mice via the mediation of gut microbiota-dependent pathways. GP might be developed and utilized as prebiotics in nutraceutical and food industry.


Assuntos
Microbioma Gastrointestinal , Psidium , Animais , Dieta Hiperlipídica/efeitos adversos , Inflamação , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/induzido quimicamente , Obesidade/etiologia , Polissacarídeos/efeitos adversos
19.
Am J Physiol Endocrinol Metab ; 323(1): E80-E091, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35575233

RESUMO

Obesogens are synthetic, environmental chemicals that can disrupt endocrine control of metabolism and contribute to the risk of obesity and metabolic disease. Bisphenol A (BPA) is one of the most studied obesogens. There is considerable evidence that BPA exposure is associated with weight gain, increased adiposity, poor blood glucose control, and nonalcoholic fatty liver disease in animal models and human populations. Increased usage of structural analogs of BPA has occurred in response to legislation banning their use in some commercial products. However, BPA analogs may also cause some of the same metabolic impairments because of common mechanisms of action. One key effector that is altered by BPA and its analogs is serotonin, however, it is unknown if BPA-induced changes in peripheral serotonin pathways underlie metabolic perturbations seen with BPA exposure. Upon ingestion, BPA and its analogs act as endocrine-disrupting chemicals in the gastrointestinal tract to influence serotonin production by the gut, where over 95% of serotonin is produced. The purpose of this review is to evaluate how BPA and its analogs alter gut serotonin regulation and then discuss how disruption of serotonergic networks influences host metabolism. We also provide evidence that BPA and its analogs enhance serotonin production in gut enterochromaffin cells. Taken together, we propose that BPA and many BPA analogs represent endocrine-disrupting chemicals that can influence host metabolism through the endogenous production of gut-derived factors, such as serotonin.


Assuntos
Disruptores Endócrinos , Serotonina , Animais , Compostos Benzidrílicos/toxicidade , Disruptores Endócrinos/toxicidade , Obesidade/induzido quimicamente , Fenóis/toxicidade
20.
Biosci Biotechnol Biochem ; 86(8): 1095-1105, 2022 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-35641089

RESUMO

Physical inactivity due to prolonged sedentary behavior induces obesity. Therefore, we investigated whether housing mice in small cages to mimic sedentary behavior induced obesity and whether dietary oleamide (cis-9,10-octadeceneamide) suppressed the induced obesity. A single oral administration of oleamide (50 mg/kg) to mice resulted in the accumulation of the exogenous oleamide in abdominal visceral fat. Next, mice were housed in small cages and oleamide (50 mg/kg/d) was orally administered for 12 weeks. Housing mice in small cages impaired glucose tolerance and increased food efficiency. It also increased body weight and abdominal fat mass. Dietary oleamide improved the impairment and inhibited their increase in mice housed in small cages. Furthermore, dietary oleamide suppressed the mRNA expression of inflammation-related factors in the abdominal fat of mice housed in small cages. Hence, these results indicate that although housing mice in small cages induces obesity and increases abdominal fat mass, dietary oleamide suppresses the obesity.


Assuntos
Habitação , Obesidade , Animais , Dieta Hiperlipídica/efeitos adversos , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/induzido quimicamente , Obesidade/tratamento farmacológico , Ácidos Oleicos/farmacologia
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