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1.
Nutrients ; 13(5)2021 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-34066330

RESUMO

Consumption of fructose has been associated with a higher risk of developing obesity and metabolic syndrome (MetS). The aim of this study was to examine the long-term effects of fructose compared to starch from high-amylose maize starch (HiMaize) at ad libitum feeding in a juvenile Göttingen Minipig model with 20% of the diet provided as fructose as a high-risk diet (HR, n = 15) and 20% as HiMaize as a lower-risk control diet (LR, n = 15). The intake of metabolizable energy was on average similar (p = 0.11) among diets despite increased levels of the satiety hormone PYY measured in plasma (p = 0.0005) of the LR pigs. However, after over 20 weeks of ad libitum feeding, no difference between diets was observed in daily weight gain (p = 0.103), and a difference in BW was observed only at the end of the experiment. The ad libitum feeding promoted an obese phenotype over time in both groups with increased plasma levels of glucose (p = 0.005), fructosamine (p < 0.001), insulin (p = 0.03), and HOMA-IR (p = 0.02), whereas the clinical markers of dyslipidemia were unaffected. When compared to the LR diet, fructose did not accelerate the progression of MetS associated parameters and largely failed to change markers that indicate a stimulated de novo lipogenesis.


Assuntos
Dieta da Carga de Carboidratos/efeitos adversos , Ingestão de Energia/fisiologia , Frutose/administração & dosagem , Síndrome Metabólica/etiologia , Obesidade/etiologia , Animais , Biomarcadores/sangue , Dieta da Carga de Carboidratos/métodos , Modelos Animais de Doenças , Dislipidemias/sangue , Metabolismo Energético/fisiologia , Amido/administração & dosagem , Suínos , Porco Miniatura , Ganho de Peso/efeitos dos fármacos , Zea mays
2.
Res Vet Sci ; 137: 186-193, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34000649

RESUMO

The objective of this study was to determine whether a phytogenic blend (PB), formulated based on organic acids, tannins, curcumin, and essential oils, could replace the antimicrobials commonly used as growth promoters in the poultry industry without compromising zootechnical performance, health, or meat quality. In addition, our goal was to report the anti-aflatoxin effect of this phytogenic blend. Four treatments were used: TC, or control; T250, T500, and T1000, representing test doses of 250, 500, 1000 mg PB/kg of feed, respectively, or a 34-day experiment (initial and growth phases). On day 22 of the study and age of the birds, 500 ppb of aflatoxin was included in the diet to represent an intestinal challenge and to evaluate the growth-promoting effects of PB. In the initial phase (up to 21 days), there were no differences between groups in weight gain, feed intake, or feed conversion. After adding an aflatoxin-contaminated feed, doses of 250 and 500 mg/kg minimized the adverse effects on feed consumption and feed conversion caused by aflatoxin; but 1000 mg/kg did not differ between groups. In birds that consumed PB (T250, T500, and T1000) compared to the control, there were the following changes: 1) lower counts of heterophiles, lymphocytes, and monocytes; 2) lower lipid peroxidation and high non-protein thiols levels in breast meat; 3) lower bacteria counts in broiler litter; and 4) lower ALT levels. Greater intestinal villus/crypt ratios were observed at T250 and T500. The dose of 250 mg/kg reduced saturated fatty acids and increased unsaturated fatty acids. The chemical-physical composition of the meat did not differ between treatments. The findings suggest that the addition of a PB has a high potential to improve performance for chickens in the growing stage and minimize the adverse effects of aflatoxicosis.


Assuntos
Aflatoxinas/antagonistas & inibidores , Ração Animal , Antibacterianos/farmacologia , Plantas Comestíveis , Produtos Avícolas , Ração Animal/análise , Animais , Galinhas/crescimento & desenvolvimento , Dieta/veterinária , Ingestão de Alimentos , Ácidos Graxos/farmacologia , Qualidade dos Alimentos , Masculino , Ganho de Peso/efeitos dos fármacos
3.
Diabetes Res Clin Pract ; 176: 108848, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33945841

RESUMO

AIMS: To evaluate efficacy and safety of Gla-300 with Gla-100 in a patient-level meta-analysis among large East Asian patients with type 2 diabetes mellitus (T2DM). METHODS: A patient level meta-analysis of three EDITION studies with similar design and endpoints were conducted over 6-months treatment period. The analysis included 547 patients treated with Gla-300 and 348 patients treated with Gla-100. RESULTS: Over 6-month treatment period, mean change in HbA1c was similar for Gla-300 [Least square (LS) mean, (SE): -1.13 (0.05) % and Gla-100: -1.14 (0.05) %], showing non-inferiority of Gla-300 to Gla-100 (LS mean difference: 0.02%, 95% CI: -0.08 to 0.11). Gla-300 was associated with reduced risk of hypoglycemic event (confirmed ≤ 3.9 mmol/L or severe) vs Gla-100 at any time of day or at night (00:00-05:59 h). The event rates of hypoglycemia were consistently lower with Gla-300 than Gla-100. Severe hypoglycemia was rare in both treatment groups. Weight gain was minimal in both treatment groups. CONCLUSION: Gla-300 provides comparable glycemic control to Gla-100 in East Asian patients with broad clinical spectrum of T2DM, with consistently less hypoglycemia at any time of the day and night.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Controle Glicêmico/métodos , Insulina Glargina/administração & dosagem , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático , Ensaios Clínicos Fase III como Assunto/estatística & dados numéricos , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/etnologia , Relação Dose-Resposta a Droga , Extremo Oriente/etnologia , Feminino , Hemoglobina A Glicada/análise , Hemoglobina A Glicada/efeitos dos fármacos , Hemoglobina A Glicada/metabolismo , Controle Glicêmico/efeitos adversos , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/epidemiologia , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Insulina Glargina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto/estatística & dados numéricos , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Ganho de Peso/efeitos dos fármacos , Ganho de Peso/etnologia
4.
Lancet Oncol ; 22(7): e303-e313, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33891888

RESUMO

The growing availability of more effective therapies has contributed to an increased survival of patients with breast cancer. In hormone receptor-positive early disease, increased survival is strongly correlated with the use of adjuvant endocrine therapy, but this therapy can cause side-effects that have major consequences in terms of treatment adherence and patients' quality of life. In premenopausal breast cancer survivors, these side-effects might be even more prominent due to the abrupt suppression of oestrogen associated with the most intense endocrine therapies. An important ambition of cancer care in the 21st century is to recover pre-cancer quality of life and emotional and social functions, which is only possible through the mitigation of the side-effects of anticancer treatments. This Review presents a comprehensive summary of the efficacy and safety data of the available interventions (hormonal and non-hormonal pharmacological strategies, non-pharmacological approaches, and complementary and alternative medicine) to control selected side-effects associated with adjuvant endocrine therapy (hot flashes, sexual dysfunction, weight gain, musculoskeletal symptoms, and fatigue), providing updated, evidence-based approaches for their management.


Assuntos
Antineoplásicos Hormonais/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/terapia , Quimioterapia Adjuvante , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/fisiopatologia , Medicina Baseada em Evidências , Fadiga/induzido quimicamente , Fadiga/terapia , Feminino , Fogachos/induzido quimicamente , Fogachos/terapia , Humanos , Menopausa Precoce , Doenças Musculoesqueléticas/induzido quimicamente , Doenças Musculoesqueléticas/terapia , Qualidade de Vida , Medição de Risco , Fatores de Risco , Disfunções Sexuais Fisiológicas/induzido quimicamente , Disfunções Sexuais Fisiológicas/terapia , Resultado do Tratamento , Ganho de Peso/efeitos dos fármacos
5.
Food Funct ; 12(8): 3552-3561, 2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33900305

RESUMO

Consumption of milk-derived whey proteins has been demonstrated to have insulin-sensitizing effects in mice and humans, in part through the generation of bioactive whey peptides. While whey peptides can prevent insulin resistance in vitro, it is unclear whether consumption of whey peptides can prevent obesity-induced metabolic dysfunction in vivo. We sought to determine whether whey peptides consumption can protect from high fat (HF) diet-induced obesity and dysregulation of glucose homeostasis. Male C57BL/6J mice were fed either a low or HF diet for 13 weeks. HF diet fed mice were provided drinking water with no addition (control), undigested whey protein isolate (WPI, 1 mg ml-1) or whey protein hydrolysate (WPH, 1 mg ml-1) throughout the diet regimen. Mice consuming WPH gained more body weight and were more glucose intolerant compared to those consuming WPI or water only. Despite increased body weight gain, perigonadal adipose tissue weight and lipid accumulation were unchanged. However, excess lipids accumulated ectopically in the liver and skeletal muscle in mice consuming WPH, which was associated with elevated inflammatory markers systemically and in adipose tissue, liver, and skeletal muscle. In skeletal muscle, mitochondrial fat oxidation and electron transport chain proteins were decreased with WPH consumption, indicative of mitochondrial dysfunction. Taken together, our results demonstrate that WPH, but not WPI, exacerbates HF-induced body weight gain and impairs glucose homeostasis, which is accompanied by increased inflammation, ectopic fat accumulation and mitochondrial dysfunction. Thus, our results argue against the use of dietary whey peptide supplementation as a preventative option against HF diet-induced metabolic dysfunction.


Assuntos
Obesidade/metabolismo , Ganho de Peso/efeitos dos fármacos , Proteínas do Soro do Leite/farmacologia , Animais , Dieta Hiperlipídica , Modelos Animais de Doenças , Glucose/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Distribuição Aleatória , Proteínas do Soro do Leite/administração & dosagem
6.
Food Funct ; 12(9): 4221-4230, 2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-33876796

RESUMO

One polysaccharide, designated as WPEP-A, was isolated from Passiflora edulis Sims peel and its hypoglycemic effects on diabetic db/db mice were evaluated. Physicochemical characterization showed that WPEP-A was composed of galactose, glucose, xylose, rhamnose, galacturonic acid and glucuronic acid with a molecular weight of 9.51 × 104 Da. We observed an inhibition in weight gain and blood glucose levels. Glucose tolerance and insulin tolerance improved after the administration of WPEP-A. In addition, our data showed increased antioxidant enzyme activities. Furthermore, the levels of serum insulin and triglyceride decreased with the recovery of liver damage. Meanwhile, positive changes in short chain fatty acid content were observed, and the mRNA levels of glucagon-like peptide 1 receptor, glucagon and prohormone convertase 3 were up-regulated in the intestinal tract. In summary, our results showed that WPEP-A had hypoglycemic activity and improved intestinal function in diabetic mice, which may contribute to the attenuation of the hypoglycemia effects.


Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Passiflora/química , Polissacarídeos/química , Polissacarídeos/farmacologia , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Glicemia/análise , Carboidratos da Dieta/farmacologia , Ácidos Graxos Voláteis/metabolismo , Glucagon/genética , Receptor do Peptídeo Semelhante ao Glucagon 1/genética , Insulina/sangue , Mucosa Intestinal/metabolismo , Camundongos , Polissacarídeos/isolamento & purificação , Pró-Proteína Convertase 1/genética , Triglicerídeos/sangue , Regulação para Cima , Ganho de Peso/efeitos dos fármacos
7.
Nutrients ; 13(5)2021 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-33921980

RESUMO

Iron-fortified formulas and iron drops (both usually ferrous sulfate, FS) prevent early life iron deficiency, but may delay growth and adversely affect neurodevelopment by providing excess iron. We used a rat pup model to investigate iron status, growth, and development outcomes following daily iron supplementation (10 mg iron/kg body weight, representative of iron-fortified formula levels) with FS or an alternative, bioavailable form of iron, ferrous bis-glycinate chelate (FC). On postnatal day (PD) 2, sex-matched rat litters (n = 3 litters, 10 pups each) were randomly assigned to receive FS, FC, or vehicle control until PD 14. On PD 15, we evaluated systemic iron regulation and CNS mineral interactions and we interrogated iron loading outcomes in the hippocampus, in search of mechanisms by which iron may influence neurodevelopment. Body iron stores were elevated substantially in iron-supplemented pups. All pups gained weight normally, but brain size on PD 15 was dependent on iron source. This may have been associated with reduced hippocampal oxidative stress but was not associated with CNS mineral interactions, iron regulation, or myelination, as these were unchanged with iron supplementation. Additional studies are warranted to investigate iron form effects on neurodevelopment so that iron recommendations can be optimized for all infants.


Assuntos
Sistema Nervoso Central/crescimento & desenvolvimento , Suplementos Nutricionais , Compostos Ferrosos/farmacologia , Glicina/farmacologia , Quelantes de Ferro/farmacologia , Ferro/metabolismo , Ferro/farmacologia , Animais , Animais Recém-Nascidos , Sistema Nervoso Central/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Homeostase/efeitos dos fármacos , Ferro/sangue , Bainha de Mielina/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley , Oligoelementos/análise , Ganho de Peso/efeitos dos fármacos
8.
Int J Mol Sci ; 22(7)2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33807173

RESUMO

Mealworms (Tenebrio molitor larva) are an edible insect and a protein-rich food; however, research on mealworms as a substitute protein is insufficient. In this study, mealworm fermentation extract (TMP) was assessed as a replacement for soy protein (SP) in a control diet (CON) or a high-fat diet (HFD) of mice for 12 weeks. TMP substitution reduced body weight, body weight gain, body fat mass (perirenal and mesenteric), fat size, glucose intolerance, and insulin resistance compared to the HFD-SP group. TMP alleviated hepatic steatosis (lipid contents and lipid droplets) in high-fat-fed mice and down-regulated the PPARγ, CD36, and DGAT2 gene levels. Proteomic analysis showed that a HFD for 12 weeks up-regulated 20 proteins and down-regulated 17 proteins in mice fed SP. On the other hand, TMP reversed the protein profiles. TMP significantly down-regulated KHK, GLO1, ATP5H, SOD, and DDAH1 and up-regulated DLD, Mup1, CPS1, Ces3b, PDI, and HYOU1 compared to the HFD-SP group. These proteins are involved in the glucose, lipid, and amino acid metabolism, as well as in oxidative stress and endoplasmic reticulum stress. Thus, substituting SP for TMP helped improve HFD-induced obesity, steatosis, and insulin resistance in mice. These results suggest that TMP is a potential substitute for commonly used protein sources.


Assuntos
Insetos Comestíveis/metabolismo , Obesidade/dietoterapia , Tenebrio/metabolismo , Animais , Peso Corporal/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Fígado Gorduroso/metabolismo , Fermentação , Intolerância à Glucose/metabolismo , Resistência à Insulina/fisiologia , Larva/metabolismo , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Proteínas/metabolismo , Ganho de Peso/efeitos dos fármacos
9.
Expert Opin Drug Metab Toxicol ; 17(6): 655-664, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33896324

RESUMO

Introduction: Antipsychotic medications are used to treat a number of conditions in children and adolescents. While side effect profiles from second generation antipsychotics (SGAs) may differ from older antipsychotics, they do not come without risk. Knowing which children may be at higher risk for specific outcomes is important clinical information for prescribers. Common side effects and toxicities of SGAs in children include movement disorders, weight gain, and hormonal changes. There are also rare, but potentially dangerous adverse events including neuroleptic malignant syndrome, hypersensitivity and suicidal ideation.Areas covered: This review will summarize and comment on clinical, pharmacological, and genetic factors having evidence as predictors of SGA-associated side effects and toxicities in children.Expert opinion: Observations across studies note that older children and those that do not respond early in treatment may be more at risk for movement disorders, while younger, antipsychotic naive children are at increased risk for weight gain. Relatively fewer studies have looked at pharmacogenetic relationships, although variations in pharmacokinetic and pharmacodynamic genes hold promise to advance drug dosing or selection strategies. Future efforts to assimilate multiple clinical, pharmacological, and genetic factors to facilitate predictive analytics and clinical decision support for prescribers will advance precision care to patients.


Assuntos
Antipsicóticos/efeitos adversos , Transtornos Mentais/tratamento farmacológico , Farmacogenética , Adolescente , Fatores Etários , Antipsicóticos/administração & dosagem , Criança , Discinesia Induzida por Medicamentos/etiologia , Humanos , Ganho de Peso/efeitos dos fármacos
10.
Nutrients ; 13(3)2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33652751

RESUMO

This study aimed to investigate the effects of two commercially available fish oils (FOs) containing different proportions of two omega-3 fatty acids (FA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), on the metabolic and endocrine dysfunctions of white adipose tissue resulting from obesity. Male C57BL/6J mice, 8 weeks old, received a control or high-fat diet (CO and HF groups, with 9% and 59% energy from fat, respectively) for 8 weeks. The next 8 weeks, the HF group was subdivided into HF, HF+FO/E (HF+5:1 EPA:DHA), and HF+FO/D (HF+5:1 DHA:EPA). Supplementation was performed by gavage, three times a week. All groups that received the HF diet had lower food and caloric intake, but a higher fat intake, body weight (BW) gain, glucose intolerance, and a significant increase in inguinal (ING), retroperitoneal (RP), and epididymal (EPI) adipose tissues when compared to the CO group. Additionally, HF and HF+FO/D groups showed insulin resistance, adipocyte hypertrophy, increased lipolysis and secretion of TNF-α, resistin and IL-10 adipokines by ING and RP adipocytes, and adiponectin only by the HF+FO/D group in ING adipocytes. All of these effects were completely reversed in the HF+FO/E group, which also showed partial reversion in BW gain and glucose intolerance. Both the HF+FO/E and HF+FO/D groups showed a reduction in ING and RP adipose depots when compared to the HF group, but only HF+FO/E in the EPI depot. HF+FO/E, but not HF+FO/D, was able to prevent the changes triggered by obesity in TNF-α, Il-10, and resistin secretion in ING and RP depots. These results strongly suggest that different EPA:DHA ratios have different impacts on the adipose tissue metabolism, FO being rich in EPA, but not in DHA, and effective in reversing the changes induced by obesity.


Assuntos
Ácido Eicosapentaenoico/farmacologia , Óleos de Peixe/farmacologia , Alimentos Fortificados , Síndrome Metabólica/terapia , Obesidade/terapia , Adipócitos/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Ácidos Docosa-Hexaenoicos/farmacologia , Resistência à Insulina/fisiologia , Masculino , Síndrome Metabólica/complicações , Síndrome Metabólica/fisiopatologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/complicações , Obesidade/fisiopatologia , Ganho de Peso/efeitos dos fármacos
11.
Biomed Pharmacother ; 137: 111370, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33761597

RESUMO

Diabetic gastroparesis (DG) exhibits delayed gastric emptying (GE) due to impaired gastric non-adrenergic, non-cholinergic (NANC) relaxation. These defects are due to loss or reduction of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) that causes reduced expression and/or dimerization of neuronal nitric oxide synthase alpha (nNOSα) gene expression and function. We investigated the effect of potent Nrf2 activators (cinnamaldehyde [CNM] & curcumin [CUR]) on GE in obesity-induced diabetic female mice. We fed adult female homozygous Nfe2l2-/- (Nrf2 KO) and wild-type (WT) female mice with either a high-fat diet (HFD) or a normal diet (ND) for a period of 16 weeks. Groups of HFD mice were fed with CUR or CNM either at 6th or 10th week respectively. Our results demonstrate that supplementation of CNM or CUR restored impaired nitrergic relaxation and attenuated delayed GE in HFD fed mice. Supplementation of CNM or CUR normalized altered gastric antrum protein expression of (1) p-ERK/p-JNK/MAPK/p-GSK-3ß, (2) BH4 (Cofactor of nNOS) biosynthesis enzyme GCH-1 and the GSH/GSSG ratio, (3) nNOSα protein & dimerization and soluble guanylate cyclase (sGC), (4) AhR and ER expression, (5) inflammatory cytokines (TNF α, IL-1ß, IL-6), (6)TLR-4, as well as (7) reduced oxidative stress markers in WT but not in Nrf2 KO obesity-induced chronic diabetic female mice. Immunoprecipitation experiments revealed an interaction between nNOS and Nrf2 proteins. Our results conclude that Nrf2 activation restores nitrergic-mediated gastric motility and GE by normalizing inflammation and oxidative stress induced by obesity-induced chronic diabetes.


Assuntos
Antioxidantes/farmacologia , Diabetes Mellitus Experimental/fisiopatologia , Dieta Hiperlipídica , Esvaziamento Gástrico/efeitos dos fármacos , Acroleína/análogos & derivados , Acroleína/farmacologia , Animais , Curcumina/farmacologia , Diabetes Mellitus Experimental/genética , Feminino , Expressão Gênica/efeitos dos fármacos , Camundongos , Camundongos Knockout , Fator 2 Relacionado a NF-E2/genética , Óxido Nítrico/fisiologia , Óxido Nítrico Sintase Tipo I/biossíntese , Estresse Oxidativo/efeitos dos fármacos , Antro Pilórico/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Ganho de Peso/efeitos dos fármacos
12.
Nutrients ; 13(2)2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33669347

RESUMO

7,8-Dihydroxyflavone (DHF) is a naturally occurring flavonoid that has been reported to protect against a variety of pathologies. Chronic administration of DHF prevents high-fat diet (HFD)-induced obesity in female, but not male, mice. However, the mechanisms underlying this sexual dimorphism have not been elucidated. We have discovered that oral DHF supplementation significantly attenuates fat mass, hepatic lipid accumulation, and adipose tissue inflammation in female mice. In contrast, male mice were not protected from adiposity, and had a paradoxical worsening of hepatic lipid accumulation and adipose tissue inflammation upon DHF supplementation. Consistent with these sexually dimorphic effects on body weight and metabolic health, 7,8-DHF induced early and stable remodeling of the female intestinal microbiome. DHF supplementation significantly increased gut microbial diversity, and suppressed potentially detrimental bacteria, particularly Desulfovibrionaceae, which are pro-inflammatory and positively associated with obesity and inflammation. Changes in the female gut microbiome preceded alterations in body weights, and in silico analyses indicated that these early microbial changes were highly predictive of subsequent weight gain in female mice. While some alterations in the intestinal microbiome were also observed in male DHF-supplemented mice, these changes were distinct from those in females and, importantly, were not predictive of subsequent body weight changes in male animals. The temporality of microbial changes preceding alterations in body weight in female mice suggests a role for the gut microbiome in mediating the sexually dimorphic effects of DHF on body weight. Given the significant clinical interest in this flavonoid across a wide range of pathologies, further elucidation of these sexually dimorphic effects will aid the development of effective clinical therapies.


Assuntos
Flavonas/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Adipocinas/metabolismo , Tecido Adiposo/efeitos dos fármacos , Animais , Dieta Hiperlipídica/efeitos adversos , Fezes/microbiologia , Feminino , Inflamação/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/química , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/induzido quimicamente , Fatores Sexuais , Ganho de Peso/efeitos dos fármacos
13.
Clin Drug Investig ; 41(4): 303-319, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33686614

RESUMO

BACKGROUND AND OBJECTIVES: Second-generation antipsychotics (SGAs) for schizophrenia show different risk profiles, whose evidence has been evaluated through comparative reviews on randomized controlled trials (RCTs) and observational studies. METHODS: We performed a systematic review and meta-analysis of weight gains, metabolic and cardiovascular side effects of SGAs, relying on both RCTs and observational studies, by comparing variations between the start of treatment and the end of follow-up. The systematic review refers to papers published from June 2009 to November 2020. PRISMA criteria were followed. No restrictions on heterogeneity level have been considered for meta-analysis. A test for the summary effect measure and heterogeneity (I2 metric) was used. RESULTS: Seventy-nine papers were selected from 3076 studies (61% RCTs, 39% observational studies). Olanzapine and risperidone reported the greatest weight gain and olanzapine the largest BMI increase. Paliperidone showed the highest increase in total cholesterol, but is the only drug reporting an increase in the HDL cholesterol. Quetiapine XR showed the highest decrease in fasting glucose. Lurasidone showed the lowest increase in body weight and a reduction in BMI and was also the only treatment reporting a decrease in total cholesterol and triglycerides. The highest increase in systolic and diastolic blood pressure was reported by quetiapine XR. CONCLUSIONS: Despite some limitations (differences in the mean dosages per patient and other side effects not included) this paper provides the first complete meta-analysis on SGAs in variations on metabolic risk profile between start of treatment and end of follow-up, with useful results for clinical practice and possibly for future economic evaluation studies.


Assuntos
Antipsicóticos/administração & dosagem , Esquizofrenia/tratamento farmacológico , Antipsicóticos/efeitos adversos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Ganho de Peso/efeitos dos fármacos
14.
Pharmacology ; 106(5-6): 305-315, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33756489

RESUMO

BACKGROUND: Piperidines are biogenic amines studied mainly in toxicology because they were initially found as alkaloids from peppers and insect venoms. Piperidines are also produced in the human body, and their actions seem to be related to wakefulness/sleep and other cognitive phenomena. Piperidines have been minimally characterized for therapeutic applications. In this context, 1-Boc-piperidine-4-carboxaldehyde (1-Boc-piperidine) is a piperidine-derivative molecule with no mechanism of action reported, although its uses include the synthesis of GPR119 selective agonists that have been patented as anti-obesity drugs. OBJECTIVES: The aim of this work was to study the effects of 1-Boc-piperidine on binge-eating behaviour and anxiety in Wistar rats. METHODS: In experimental protocol 1, binge-eating behaviour was induced in animals that received pre-treatment (i.p.) with (i) vehicle (methanol 10%; 1 mL/kg), (ii) 1-Boc-piperidine (1 µmol kg-1), or (iii) 1-Boc-piperidine (10 µmol kg-1). In experimental protocol 2, mildly stressed animals were evaluated in the elevated plus maze under the acute effects of the pre-treatments applied in experimental protocol 1. RESULTS AND CONCLUSIONS: 1-Boc-piperidine decreased, in a dose-dependent manner, the intake of calories from a succulent hyper-caloric food in a binge-eating protocol in female rats, whereas the acute exposition to this piperidine exerted an anxiolytic effect in the male rat. In both effects, the mechanism of action remains to be characterized.


Assuntos
Ansiedade/tratamento farmacológico , Transtorno da Compulsão Alimentar/tratamento farmacológico , Animais , Ansiedade/etiologia , Comportamento Animal/efeitos dos fármacos , Transtorno da Compulsão Alimentar/etiologia , Relação Dose-Resposta a Droga , Ingestão de Energia/efeitos dos fármacos , Comportamento Alimentar/efeitos dos fármacos , Injeções Intraperitoneais , Ligantes , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Dor/complicações , Ligação Proteica , Ratos Wistar , Receptores Acoplados a Proteínas G/química , Receptores Acoplados a Proteínas G/metabolismo , Receptores de Serotonina/química , Receptores de Serotonina/metabolismo , Estresse Psicológico/complicações , Ganho de Peso/efeitos dos fármacos
15.
Int J Biol Macromol ; 176: 404-412, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33571595

RESUMO

Here, we compared the effects of different physical forms of arabinoxylan (AX) - a microsphere of cross-linked arabinoxylan (CAX) in a Ca2+-alginate matrix (MC) and physical mixture of AX and alginate (PM) on gut microbiota and development of obesity in C57BL/6J mice. Supplementation of MC in high fat (HF) diet to mice for 10 weeks significantly reversed the body weight gain induced by the HF diet, along with less fat accumulation in both livers and the epididymal adipose than the PM group. Microbiome analysis showed that MC significantly altered the gut microbiota composition with a noticeable increase of butyrogenic bacteria of Lachnospiraceae. The butyrate produced by MC fermentation and the increased abundance of Lachnospiraceae might be the underlying mechanism of the anti-obesity effect of MC. The results indicated that the physical forms of dietary fiber are closely associated with its health benefits, and MC might be served as a new functional food ingredient to prevent obesity.


Assuntos
Alginatos , Cálcio , Dieta Hiperlipídica/efeitos adversos , Microbioma Gastrointestinal/efeitos dos fármacos , Obesidade , Xilanos , Alginatos/química , Alginatos/farmacologia , Animais , Cálcio/química , Cálcio/farmacologia , Clostridiales/classificação , Clostridiales/crescimento & desenvolvimento , Masculino , Camundongos , Obesidade/induzido quimicamente , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Obesidade/microbiologia , Ganho de Peso/efeitos dos fármacos , Xilanos/química , Xilanos/farmacologia
16.
Toxicol Appl Pharmacol ; 417: 115464, 2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33636197

RESUMO

In this work, the acute and subchronic toxicities of desaminotyrosine (DAT) by oral administration in SD rats and its effects on the intestinal microflora were investigated. The acute toxicity test showed that DAT is a low-toxic substance with a LD50 of 3129 mg/kg. The subchronic toxicity test showed that DAT has no toxicity at a low dose (125 mg/kg/day). However, DAT exhibited obvious toxicities to food intake, liver, kidney, and lung at higher dose (250 mg/kg/day and 500 mg/kg/day). DAT inhibited the food intake of rats in a dose-dependent manner. Serum biochemical analysis showed that DAT can increase the serum glucose level of rats. Fecal microbiota analysis showed that DAT treatment can significantly change the intestinal microflora of rats, the dose of 125 mg/kg/day has the most significant effect on the diversity of intestinal microbiota. In daily application, the side effects caused by DAT might be gastrointestinal irritation, weight loss, liver or kidney injury, and blood sugar elevation. Based on our study, the no-observed-adverse-effect level (NOAEL) of DAT is 125 mg/kg BW/day for rats.


Assuntos
Bactérias/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Fenilpropionatos/toxicidade , Administração Oral , Animais , Bactérias/crescimento & desenvolvimento , Biomarcadores/sangue , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Relação Dose-Resposta a Droga , Disbiose , Ingestão de Alimentos/efeitos dos fármacos , Feminino , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Dose Letal Mediana , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Masculino , Nível de Efeito Adverso não Observado , Fenilpropionatos/administração & dosagem , Ratos Sprague-Dawley , Medição de Risco , Testes de Toxicidade Subcrônica , Ganho de Peso/efeitos dos fármacos
17.
Molecules ; 26(4)2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33546367

RESUMO

In Asia, Amomum tsao-ko has long been used as a spice or seasoning in food to stimulate digestion. In the present study, we evaluated the effects of ethanol extract of Amomum tsao-ko (EEAT) on menopausal osteoporosis and obesity. After the administration of EEAT in ovariectomy (OVX) mice models for five weeks, microcomputed tomography and a histological analysis were performed to assess, respectively, the trabecular structure and the fat accumulation in adipose, liver, and bone tissues. We also examined the effects of EEAT on a bone marrow macrophage model of osteoclastogenesis by in vitro stimulation from the receptor activator of nuclear factor-kappa Β ligand (RANKL) through real-time PCR and Western blot analysis. In addition, ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) with authentic standards was applied to characterize the phytochemical profiling of EEAT. We found that EEAT significantly decreased OVX-induced body weight gain and fat accumulation, significantly prevented OVX-induced deterioration of bone mineral density and microstructure of trabecular tissues, and significantly inhibited osteoclast differentiation by downregulating NF-κB/Fos/NFATc1 signaling in osteoclasts. Furthermore, UHPLC-MS/MS identified eight beneficial phytochemicals in EEAT. Collectively, these results suggest that EEAT might be an effective nutraceutical candidate to attenuate menopausal osteoporosis by inhibiting osteoclastogenesis and to prevent obesity by suppressing fat accumulation.


Assuntos
Amomum/química , Osso Esponjoso/metabolismo , Etanol/química , Lipogênese/efeitos dos fármacos , Osteoporose/tratamento farmacológico , Extratos Vegetais/farmacologia , Animais , Osso Esponjoso/patologia , Feminino , Camundongos , Osteoclastos/metabolismo , Osteoclastos/patologia , Osteoporose/etiologia , Osteoporose/metabolismo , Osteoporose/patologia , Ovariectomia , Extratos Vegetais/química , Transdução de Sinais/efeitos dos fármacos , Ganho de Peso/efeitos dos fármacos
18.
Acta Diabetol ; 58(5): 615-621, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33459895

RESUMO

AIM: Metformin use in gestational diabetes (GDM) is a common practice. Although its use in combination with insulin might be advantageous, it was never formally tested. We studied whether combined treatment was associated with better obstetric or neonatal outcomes compared to insulin alone. METHODS: This is a retrospective study, using the Portuguese National Registry of GDM (2012-2017), of women treated with insulin ± metformin. Primary endpoints were obstetric and neonatal complications. Secondary endpoints were gestational weight gain (GWG) and insulin dose. A propensity score-matched analysis was performed to balance the distribution of age, BMI, insulin treatment duration, HbA1c, first trimester diagnosis of GDM and previous GDM or macrosomia. Women treated with metformin plus insulin and insulin only were then compared. RESULTS: A total of 4034 women were treated with insulin or insulin plus metformin (10.2%). After propensity score matching, we studied two groups of 386 patients. Obstetric and neonatal complications were similar. Women treated with metformin plus insulin had 201 (52.1%) obstetric complications versus 184 (47.7%) in insulin-only group, p = 0.22; and 112 (29.0%) neonatal complications versus 96 (24.9%), p = 0.19. Patients treated with metformin plus insulin had similar GWG, excessive weight gain and insulin dose compared to the insulin-only group. CONCLUSIONS: Women with GDM treated with insulin plus metformin had similar obstetric and neonatal complications, weight gained and insulin dose compared to those only treated with insulin.


Assuntos
Diabetes Gestacional/tratamento farmacológico , Insulina/administração & dosagem , Metformina/administração & dosagem , Adulto , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Diabetes Gestacional/epidemiologia , Quimioterapia Combinada , Feminino , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Insulina/efeitos adversos , Metformina/efeitos adversos , Gravidez , Pontuação de Propensão , Estudos Retrospectivos , Ganho de Peso/efeitos dos fármacos
19.
Obesity (Silver Spring) ; 29(2): 265-273, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33491309

RESUMO

Obesity is a chronic, multifactorial disease associated with a large number of comorbidities. The clinical management of obesity involves a stepwise integrated approach, beginning with behavioral and lifestyle modification, followed by antiobesity medications, endobariatric procedures, and bariatric surgery. Weight gain and subsequent obesity are common side effects of medications, such as prednisone or antipsychotics. In this era of precision medicine, it is essential to identify patients at the highest risk of weight gain as a result of medication use. Pharmacogenomics could play an important role in obesity management by optimizing use of antiobesity medications as well as minimizing adverse weight gain. This review aims to provide a comprehensive analysis of the current literature on the role of pharmacogenomics in obesity and medication-induced weight gain. In summary, there are more robust studies of medication associated with weight gain and pharmacogenomics, and more studies are needed to understand the role of pharmacogenomics in antiobesity medications.


Assuntos
Fármacos Antiobesidade , Obesidade , Farmacogenética , Ganho de Peso/efeitos dos fármacos , Fármacos Antiobesidade/farmacologia , Fármacos Antiobesidade/uso terapêutico , Humanos , Obesidade/induzido quimicamente , Obesidade/tratamento farmacológico , Obesidade/genética
20.
Obesity (Silver Spring) ; 29(2): 337-349, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33491319

RESUMO

OBJECTIVE: The aryl hydrocarbon receptor (AHR) plays a key role in obesity. In vitro studies revealed that the tryptophan metabolite kynurenine (Kyn) activates AHR signaling in cultured hepatocytes. The objective of this study was to determine whether Kyn activated the AHR in mice to induce obesity. METHODS: Mice were fed a low-fat diet and the same diet supplemented with Kyn. Body mass, liver status, and the expression of identified relevant genes were determined. RESULTS: Kyn caused mice to gain significant body mass, develop fatty liver and hyperglycemia, and increase expression levels of cytochrome P450 1B1 and stearoyl-CoA desaturase 1. The hyperglycemia was accompanied with decreased insulin levels, which may have been due to the repression of genes involved in insulin secretion. Kyn plasma concentrations and BMI were measured in female patients, and a significant association was observed between Kyn and age in patients with obesity but not in patients who were lean. CONCLUSIONS: Results show that (1) Kyn or a metabolite thereof is a ligand responsible for inducing AHR-based obesity, fatty liver, and hyperglycemia in mice; (2) plasma Kyn levels increase with age in women with obesity but not in lean women; and (3) an activated AHR is necessary but not sufficient to attain obesity, a status that also requires fat in the diet.


Assuntos
Fígado Gorduroso/metabolismo , Hiperglicemia/induzido quimicamente , Cinurenina/farmacologia , Receptores de Hidrocarboneto Arílico/metabolismo , Ganho de Peso/efeitos dos fármacos , Animais , Fígado/efeitos dos fármacos , Camundongos , Transdução de Sinais/efeitos dos fármacos
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