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1.
Nutrients ; 13(7)2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34371987

RESUMO

It was previously observed that in a population of a high-income country, dietary multiple micronutrient supplementation in pregnancy was associated with an increased risk of gestational diabetes (GDM) and increased offspring size at birth. In this follow-up study, we investigated whether similar changes are observed with dietary iron supplementation. For this we used the prospective Cambridge Baby Growth Study with records of maternal GDM status, nutrient supplementation, and extensive offspring birth size measurements. Maternal iron supplementation in pregnancy was associated with GDM development (risk ratio 1.67 (1.01-2.77), p = 0.048, n = 677) as well as offspring size and adiposity (n = 844-868) at birth in terms of weight (ß' = 0.078 (0.024-0.133); p = 0.005), head circumference (ß' = 0.060 (0.012-0.107); p = 0.02), body mass index (ß' = 0.067 (0.014-0.119); p = 0.01), and various skinfold thicknesses (ß' = 0.067-0.094; p = 0.03-0.003). In a subset of participants for whom GDM statuses were available, all these associations were attenuated by adjusting for GDM. Iron supplementation also attenuated the associations between multiple micronutrient supplementation and these same measures. These results suggest that iron supplementation may mediate the effects associated with multiple micronutrient supplementation in pregnancy in a high-income country, possibly through the increased risk of developing GDM.


Assuntos
Peso ao Nascer/efeitos dos fármacos , Suplementos Nutricionais , Ferro na Dieta/efeitos adversos , Fenômenos Fisiológicos da Nutrição Materna/efeitos dos fármacos , Micronutrientes/efeitos adversos , Adiposidade/efeitos dos fármacos , Adulto , Índice de Massa Corporal , Diabetes Gestacional/induzido quimicamente , Diabetes Gestacional/fisiopatologia , Feminino , Seguimentos , Humanos , Recém-Nascido , Ferro na Dieta/administração & dosagem , Masculino , Micronutrientes/administração & dosagem , Gravidez , Estudos Prospectivos , Pregas Cutâneas
2.
Nutrients ; 13(6)2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34208508

RESUMO

Obesity and ageing are current issues of global concern. Adaptive homeostasis is compromised in the elderly, who are more likely to suffer age-related health issues, such as obesity, metabolic syndrome, and cardiovascular disease. The current worldwide prevalence of obesity and higher life expectancy call for new strategies for treating metabolic disorders. Grape-seed proanthocyanidin extract (GSPE) is reported to be effective in ameliorating these pathologies, especially in young animal models. In this study, we aimed to test the effectiveness of GSPE in modulating obesity-related pathologies in aged rats fed an obesogenic diet. To do so, 21-month-old rats were fed a high-fat/high-sucrose diet (cafeteria diet) for 11 weeks. Two time points for GSPE administration (500 mg/kg body weight), i.e., a 10-day preventive GSPE treatment prior to cafeteria diet intervention and a simultaneous GSPE treatment with the cafeteria diet, were assayed. Body weight, metabolic parameters, liver steatosis, and systemic inflammation were analysed. GSPE administered simultaneously with the cafeteria diet was effective in reducing body weight, total adiposity, and liver steatosis. However, the preventive treatment was effective in reducing only mesenteric adiposity in these obese, aged rats. Our results confirm that the simultaneous administration of GSPE improves metabolic disruptions caused by the cafeteria diet also in aged rats.


Assuntos
Extrato de Sementes de Uva/uso terapêutico , Obesidade/tratamento farmacológico , Proantocianidinas/uso terapêutico , Adiposidade/efeitos dos fármacos , Animais , Glicemia/efeitos dos fármacos , Modelos Animais de Doenças , Fígado Gorduroso/tratamento farmacológico , Feminino , Glucagon/sangue , Insulina/sangue , Obesidade/metabolismo , Ratos , Ratos Wistar , Perda de Peso/efeitos dos fármacos
3.
Biomed Pharmacother ; 139: 111687, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34243611

RESUMO

Obesity is one of the world's largest health problems, and 3-N-butylphthalide (NBP), a bioactive compound in celery, has been used in dieting and weight management programs. In this study, NBP prevented high-fat-diet-induced weight gain, reduced the food efficiency ratio, altered the blood biochemical profile, and reduced the obesity-related index. NBP reduced adiposity, white fat depots, liver weight, and hepatic steatosis in obese mice. NBP ameliorated the diabetic state by decreasing glucose levels and improving glucose and insulin tolerance. NBP increased uncoupling protein-1 expression in white adipose tissue and upregulated thermogenesis by enhancing mitochondrial respiration. NBP inhibited white adipocyte development by prohibiting lipid accumulation in human adipose-derived stem cells. NBP increased free fatty acid uptake and the oxygen consumption rate in beige adipocytes. Our results suggest that NBP could be used as functional natural supplement against obesity and its associated disorders.


Assuntos
Benzofuranos/farmacologia , Dieta Hiperlipídica/efeitos adversos , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipídeos/fisiologia , Obesidade/metabolismo , Substâncias Protetoras/farmacologia , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Tecido Adiposo Branco/efeitos dos fármacos , Tecido Adiposo Branco/metabolismo , Adiposidade/efeitos dos fármacos , Animais , Glicemia/efeitos dos fármacos , Células Cultivadas , Fígado Gorduroso/metabolismo , Humanos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Termogênese/efeitos dos fármacos
4.
J Endocrinol ; 251(1): 15-25, 2021 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-34156346

RESUMO

Women usually experience body weight gain with aging, which can put them at risk for many chronic diseases. Previous studies indicated that melatonin treatment attenuates body weight gain and abdominal fat deposition in several male animals. However, it is unclear whether melatonin affects female animals in the same way. This study investigated whether long-term melatonin treatment can attenuate body weight gain with aging and, if it does, what the mechanism is. Ten-week-old female ICR mice were given melatonin-containing water (100 µg/mL) or only water until 43 weeks. Melatonin treatment significantly attenuated body weight gain at 23 weeks (control; 57.2 ± 2.0 g vs melatonin; 44.4 ± 3.1 g), 33 weeks (control; 65.4 ± 2.6 g vs melatonin; 52.2 ± 4.2 g) and 43 weeks (control; 66.1 ± 3.2 g vs melatonin; 54.4 ± 2.5 g) without decreasing the amount of food intake. Micro-CT analyses showed that melatonin significantly decreased the deposition of visceral and s.c. fat. These results suggested that melatonin attenuates body weight gain by inhibiting abdominal fat deposition. Metabolome analysis of the liver revealed that melatonin treatment induced a drastic change in the metabolome with the downregulation of 149 metabolites, including the metabolites of glucose and amino acids. Citrate, which serves as a source of de novo lipogenesis, was one of the downregulated metabolites. These results show that long-term melatonin treatment induces drastic changes in metabolism and attenuates body weight gain and fat deposition with aging in female mice.


Assuntos
Envelhecimento/fisiologia , Antioxidantes/farmacologia , Melatonina/farmacologia , Ganho de Peso/efeitos dos fármacos , Adiposidade/efeitos dos fármacos , Animais , Feminino , Camundongos , Camundongos Endogâmicos ICR
5.
J Endocrinol ; 250(2): 37-48, 2021 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-34060474

RESUMO

Chronic exposure to high circulating glucocorticoid or ghrelin concentrations increases food intake, weight gain and adiposity, suggesting that ghrelin could contribute to the metabolic effects of chronic glucocorticoids. In male mice, however, blocking ghrelin receptor (GHSR) signaling increased the weight gain and adiposity induced by chronic corticosterone (CORT), rather than attenuating them. In the current study, we investigated the role of GHSR signaling in the metabolic effects of chronic exposure to high circulating CORT in female mice. To do this, female WT and GHSR KO mice were treated with either CORT in a 1% ethanol (EtOH) solution or 1% EtOH alone in their drinking water for 32 days (n = 5-8/group). Body weight, food, and water intake as well as vaginal cyclicity were assessed daily. As expected, CORT treatment-induced significant increases in body weight, food intake, adiposity and also impaired glucose tolerance. In contrast to results observed in male mice, WT and GHSR KO female mice did not differ on any of these parameters. Neither plasma levels of ghrelin, LEAP-2, the endogenous GHSR antagonist produced by the liver, nor their ratio were altered by chronic glucocorticoid exposure. In addition, CORT treatment disrupted vaginal cyclicity, produced a reduction in sucrose consumption and increased locomotor activity regardless of genotype. Chronic CORT also decreased exploration in WT but not GHSR KO mice. Collectively, these data suggest that most metabolic, endocrine, reproductive and behavioral effects of chronic CORT exposure are independent of GHSR signaling in female mice.


Assuntos
Corticosterona/administração & dosagem , Obesidade/etiologia , Receptores de Grelina/fisiologia , Transdução de Sinais/fisiologia , Adiposidade/efeitos dos fármacos , Animais , Peptídeos Catiônicos Antimicrobianos/sangue , Comportamento Animal/efeitos dos fármacos , Corticosterona/sangue , Ingestão de Alimentos/efeitos dos fármacos , Feminino , Grelina/sangue , Camundongos , Camundongos Knockout , Receptores de Grelina/deficiência , Receptores de Grelina/genética , Ganho de Peso/efeitos dos fármacos
6.
Life Sci ; 278: 119550, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-33932442

RESUMO

AIMS: Vitamin (Vit) D regulates various organic processes, including adipose tissue morphofunction and lipid metabolism. Studies indicate that Vit D bioavailability is reduced in obesity, which could contribute to obesity development; however, the effects of Vit D supplementation on increased adiposity in western diet (WD)-obese rats (an experimental model that better resembles the obesogenic human obesity condition) have not been studied, to date. Thus, we hypothesized that Vit D supplementation following the induction of obesity in WD rats might reduce their body weight (BW) and adiposity. MAIN METHODS: Male Wistar rats were fed on a standard chow [control (CTL) group] or a WD to induce obesity (WD group), from 21 to 59 days of age. Subsequently, from 60 to 90-days, half of the CTL and of the WD rats were randomly submitted, or not, to oral Vit D supplementation (CTL-VD and WD-VD groups, respectively). KEY FINDINGS: At 91 days of age, WD rats were obese, displaying higher abdominal circumference and white fat stores, dyslipidemia, hyperleptinemia and greater plasma levels of tumor necrosis factor (TNF)-α. Vit D supplementation decreased BW gain, abdominal fat deposition and ameliorated the plasma lipid profile in WD-VD rats. These effects were accompanied by reductions in leptinemia and in circulating TNF-α levels in these rodents. SIGNIFICANCE: Vit D supplementation, following the induction of obesity, may represent a good strategy to attenuate BW gain and abdominal adiposity, and ameliorate the plasma lipid profile in WD rats. These effects may be mediated, at least in part, by reductions in circulating levels of leptin and TNF-α.


Assuntos
Adiposidade/efeitos dos fármacos , Dieta Ocidental/efeitos adversos , Obesidade/tratamento farmacológico , Fator de Necrose Tumoral alfa/sangue , Vitamina D/uso terapêutico , Vitaminas/uso terapêutico , Animais , Peso Corporal/efeitos dos fármacos , Lipídeos/sangue , Masculino , Obesidade/sangue , Obesidade/etiologia , Obesidade/fisiopatologia , Ratos Wistar
7.
Nutrients ; 13(4)2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33918334

RESUMO

Dry extracts from the Eurasian plants, Ajuga turkestanica, Eurycoma longifolia, and Urtica dioica have been used as anabolic supplements, despite the limited scientific data on these effects. To assess their actions on early sarcopenia signs, male and female castrated mice were supplemented with lyophilized extracts of the three plants, isolated or in association (named TLU), and submitted to resistance exercise. Ovariectomy (OVX) led to body weight increase and non-high-density cholesterol (HDL) cholesterol elevation, which had been restored by exercise plus U. dioica extract, or by exercise and TLU, respectively. Orchiectomy (ORX) caused skeletal muscle weight loss, accompanied by increased adiposity, being the latter parameter reduced by exercise plus E. longifolia or U. dioica extracts. General physical activity was improved by exercise plus herbal extracts in either OVX or ORX animals. Exercise combined with TLU improved resistance to fatigue in OVX animals, though A. turkestanica enhanced the grip strength in ORX mice. E. longifolia or TLU also reduced the ladder climbing time in ORX mice. Resistance exercise plus herbal extracts partly altered gastrocnemius fiber size frequencies in OVX or ORX mice. We provide novel data that tested ergogenic extracts, when combined with resistance exercise, improved early sarcopenia alterations in castrated male and female mice.


Assuntos
Anabolizantes/farmacologia , Suplementos Nutricionais , Magnoliopsida/química , Condicionamento Físico Animal/fisiologia , Extratos Vegetais/farmacologia , Adiposidade/efeitos dos fármacos , Ajuga/química , Animais , Modelos Animais de Doenças , Eurycoma/química , Feminino , Masculino , Camundongos , Músculo Esquelético/efeitos dos fármacos , Orquiectomia , Ovariectomia , Sarcopenia/etiologia , Sarcopenia/prevenção & controle , Urtica dioica/química
8.
Molecules ; 26(9)2021 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-33922045

RESUMO

Nonalcoholic fatty liver disease is the most common chronic disease affecting a wide range of the world's population and associated with obesity-induced metabolic syndrome. It is possibly emerging as a leading cause of life-threatening liver diseases for which a drug with a specific therapeutic target has not been developed yet. Previously, there have been reports on the benefits of Cudrania tricuspidata (CT) for treating obesity and diabetes via regulation of metabolic processes, such as lipogenesis, lipolysis, and inflammation. In this study, we investigated the ameliorative effect of orally administered 0.25% and 0.5% (w/w) CT mixed with high-fat diet (HFD) to C57BL/6J mice for 7 weeks. It was found that body weight, fat mass, hepatic mass, serum glucose level, and liver cholesterol levels were significantly reduced after CT treatment. In CT-treated HFD-fed mice, the mRNA expression levels of hepatic lipogenic and inflammatory cytokine-related genes were markedly reduced, whereas the expression level of epididymal lipogenic genes was increased. The mRNA expression level of beta-oxidation and Nrf-2/HO-1 genes significantly increased in CT-treated obese mice livers. We propose that CT alleviates hepatic steatosis by reducing oxidative stress and inflammation.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Heme Oxigenase-1/metabolismo , Proteínas de Membrana/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Extratos Vegetais/farmacologia , Transdução de Sinais/efeitos dos fármacos , Adiposidade/efeitos dos fármacos , Animais , Biomarcadores , Glicemia , Modelos Animais de Doenças , Regulação da Expressão Gênica , Teste de Tolerância a Glucose , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Lipogênese/efeitos dos fármacos , Camundongos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/patologia , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/genética , Extratos Vegetais/química , Espécies Reativas de Oxigênio/metabolismo
9.
J Nutr Biochem ; 93: 108628, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33705952

RESUMO

Early-life nutrition plays an important role in regulating adult metabolism. This study evaluated the effects of early nutrition during the suckling and postweaning periods on expression of the adipocytokine Neuregulin 4 (Nrg4) and its relationship with nonalcoholic fatty liver disease (NAFLD) in adulthood. In vivo, male rats were adjusted to litter sizes of three (small litter, SL) or ten (normal litter, NL) on postnatal day 3. Pups were fed control chow (NL and SL groups) or a high-fat diet (NL-HF and SL-HF groups), and SL pups specifically were fed a fish oil diet rich in n-3 polyunsaturated fatty acids (n-3 PUFAs) (SL-FO group), from postnatal weeks 3 to 13. The results demonstrated that postnatal overnutrition increased weight, hepatic de novo lipogenesis (DNL) gene expression and NAFLD and decreased body temperature and Nrg4, Ucp1 and Pgc1a mRNA expression in adipose tissues in SL, SL-HF and NL-HF rats compared to NL rats in adulthood. The opposite trends were observed in SL-FO rats. Moreover, in vitro, recombinant NRG4 protein reduced lipid accumulation by inhibiting DNL gene expression in fatty HepG2 cells stimulated with sodium oleate. In HPAs, eicosapentaenoic acid (EPA) treatment elevated NRG4 production and caused adipocyte browning, and these effects were abrogated by PPARG antagonism. In conclusion, a postweaning n-3 PUFA diet enhanced Nrg4 expression in adipose tissues, associated with attenuation of NAFLD induced by SL rearing. Additionally, external NRG4 reduced lipogenesis in steatotic hepatocytes. Thus, white adipose tissue browning induced by n-3 PUFAs may promote NRG4 production through the PPARG pathway.


Assuntos
Tecido Adiposo Branco/fisiologia , Adiposidade/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Ácidos Graxos Ômega-3/farmacologia , Neurregulinas/metabolismo , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Adipócitos/fisiologia , Animais , Ingestão de Energia , Regulação da Expressão Gênica , Células Hep G2 , Humanos , Masculino , Neurregulinas/genética , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Ratos
10.
J Nutr ; 151(5): 1139-1149, 2021 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-33693900

RESUMO

BACKGROUND: Fructose consumption has been linked to nonalcoholic fatty liver disease (NAFLD) in children. However, the effect of high-fructose corn syrup (HFCS) compared with sucrose in pediatric NAFLD has not been investigated. OBJECTIVES: We tested whether the isocaloric substitution of dietary sucrose by HFCS would increase the severity of NAFLD in juvenile pigs, and whether this effect would be associated with changes in gut histology, SCFA production, and microbial diversity. METHODS: Iberian pigs, 53-d-old and pair-housed in pens balanced for weight and sex, were randomly assigned to receive a mash diet top-dressed with increasing amounts of sucrose (SUC; n = 3 pens; 281.6-486.8 g/kg diet) or HFCS (n = 4; 444.3-724.8 g/kg diet) during 16 wk. Diets exceeded the animal's energy requirements by providing sugars in excess, but met the requirements for all other nutrients. Animals were killed at 165 d of age after blood sampling, and liver, muscle, and gut were collected for histology, metabolome, and microbiome analyses. Data were analyzed by multivariate and univariate statistics. RESULTS: Compared with SUC, HFCS increased subcutaneous fat, triacylglycerides in plasma, and butyrate in colon (P ≤ 0.05). In addition, HFCS decreased UMP and short-chain acyl carnitines in liver, and urea nitrogen and creatinine in serum (P ≤ 0.05). Microbiome analysis showed a 24.8% average dissimilarity between HFCS and SUC associated with changes in SCFA-producing bacteria. Body weight gain, intramuscular fat, histological and serum markers of liver injury, and circulating hormones, glucose, and proinflammatory cytokines did not differ between diets. CONCLUSIONS: Fructose consumption derived from HFCS promoted butyrate synthesis, triglyceridemia, and subcutaneous lipid deposition in juvenile Iberian pigs, but did not increase serum and histological markers of NAFLD compared with a sucrose-enriched diet. Longer studies could be needed to observe differences in liver injury among sugar types.


Assuntos
Adiposidade/efeitos dos fármacos , Sacarose na Dieta/efeitos adversos , Xarope de Milho Rico em Frutose/efeitos adversos , Hepatopatia Gordurosa não Alcoólica/etiologia , Triglicerídeos/sangue , Animais , Sacarose na Dieta/administração & dosagem , Ácidos Graxos Voláteis/metabolismo , Feminino , Microbioma Gastrointestinal , Trato Gastrointestinal/anatomia & histologia , Trato Gastrointestinal/efeitos dos fármacos , Xarope de Milho Rico em Frutose/administração & dosagem , Masculino , Distribuição Aleatória , Suínos
11.
Nutrients ; 13(2)2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33671850

RESUMO

The increasing impact of obesity on global human health intensifies the importance of studies focusing on agents interfering with the metabolism and remodeling not only of the white adipose tissue (WAT) but also of the liver. In the present study, we have addressed the impact of n-3 PUFA in adipose cells' proliferation and adipogenesis, as well as in the hepatic lipid profile and morphology. Mice were induced to obesity by the consumption of a high-fat diet (HFD) for 16 weeks. At the 9th week, the treatment with fish oil (FO) was initiated and maintained until the end of the period. The FO treatment reduced the animals' body mass, plasma lipids, glucose, plasma transaminases, liver mass, triacylglycerol, and cholesterol liver content when compared to animals consuming only HFD. FO also decreased the inguinal (ing) WAT mass, reduced adipocyte volume, increased adipose cellularity (hyperplasia), and increased the proliferation of adipose-derived stromal cells (AdSCs) which corroborates the increment in the proliferation of 3T3-L1 pre-adipocytes or AdSCs treated in vitro with n-3 PUFA. After submitting the in vitro treated (n-3 PUFA) cells, 3T3-L1 and AdSCs, to an adipogenic cocktail, there was an increase in the mRNA expression of adipogenic transcriptional factors and other late adipocyte markers, as well as an increase in lipid accumulation when compared to not treated cells. Finally, the expression of browning-related genes was also higher in the n-3 PUFA treated group. We conclude that n-3 PUFA exerts an attenuating effect on body mass, dyslipidemia, and hepatic steatosis induced by HFD. FO treatment led to decreasing adiposity and adipocyte hypertrophy in ingWAT while increasing hyperplasia. Data suggest that FO treatment might induce recruitment (by increased proliferation and differentiation) of new adipocytes (white and/or beige) to the ingWAT, which is fundamental for the healthy expansion of WAT.


Assuntos
Adipogenia/efeitos dos fármacos , Ácidos Graxos Ômega-3/farmacologia , Óleos de Peixe/farmacologia , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Obesidade/terapia , Células 3T3-L1 , Adipócitos/efeitos dos fármacos , Tecido Adiposo Branco/efeitos dos fármacos , Adiposidade/efeitos dos fármacos , Animais , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Dieta Hiperlipídica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/etiologia , Obesidade/complicações
12.
Nutrients ; 13(2)2021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33572368

RESUMO

Maternal obesity, a state of chronic low-grade metabolic inflammation, is a growing health burden associated with offspring adiposity, abnormal fetal growth and prematurity, which are all linked to adverse offspring cardiometabolic health. Higher intake of anti-inflammatory omega-3 (n-3) polyunsaturated fatty acids (PUFA) in pregnancy has been associated with lower adiposity, higher birthweight and longer gestation. However, the effects of n-3 supplementation specifically in pregnant women with overweight and obesity (OWOB) have not been explored. We conducted a pilot double-blind randomized controlled trial of 72 pregnant women with first trimester body mass index (BMI) ≥ 25 kg/m2 to explore preliminary efficacy of n-3 supplementation. Participants were randomized to daily DHA plus EPA (2 g/d) or placebo (wheat germ oil) from 10-16 weeks gestation to delivery. Neonatal body composition, fetal growth and length of gestation were assessed. For the 48 dyads with outcome data, median (IQR) maternal BMI was 30.2 (28.2, 35.4) kg/m2. In sex-adjusted analyses, n-3 supplementation was associated with higher neonatal fat-free mass (ß: 218 g; 95% CI 49, 387) but not with % body fat or fat mass. Birthweight for gestational age z-score (-0.17 ± 0.67 vs. -0.61 ± 0.61 SD unit, p = 0.02) was higher, and gestation longer (40 (38.5, 40.1) vs. 39 (38, 39.4) weeks, p = 0.02), in the treatment vs. placebo group. Supplementation with n-3 PUFA in women with OWOB led to higher lean mass accrual at birth as well as improved fetal growth and longer gestation. Larger well-powered trials of n-3 PUFA supplementation specifically in pregnant women with OWOB should be conducted to confirm these findings and explore the long-term impact on offspring obesity and cardiometabolic health.


Assuntos
Composição Corporal/efeitos dos fármacos , Ácidos Graxos Ômega-3/administração & dosagem , Desenvolvimento Fetal/efeitos dos fármacos , Idade Gestacional , Obesidade/complicações , Complicações na Gravidez/tratamento farmacológico , Adiposidade/efeitos dos fármacos , Adulto , Anti-Inflamatórios/administração & dosagem , Peso ao Nascer , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Humanos , Recém-Nascido , Masculino , Obesidade/tratamento farmacológico , Projetos Piloto , Gravidez
13.
Nutrients ; 13(2)2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33572881

RESUMO

Human milk oligosaccharides (HMOs) are bioactive molecules playing a critical role in infant health. We aimed to quantify the composition of HMOs of women with normal weight (18.5-24.9 kg/m2), overweight (25.0-29.9 kg/m2), or obesity (30.0-60.0 kg/m2) and determine the effect of HMO intake on infant growth. Human milk (HM) samples collected at 2 months (2 M; n = 194) postpartum were analyzed for HMO concentrations via high-performance liquid chromatography. Infant HM intake, anthropometrics and body composition were assessed at 2 M and 6 M postpartum. Linear regressions and linear mixed-effects models were conducted examining the relationships between maternal BMI and HMO composition and HMO intake and infant growth over the first 6 M, respectively. Maternal obesity was associated with lower concentrations of several fucosylated and sialylated HMOs and infants born to women with obesity had lower intakes of these HMOs. Maternal BMI was positively associated with lacto-N-neotetraose, 3-fucosyllactose, 3-sialyllactose and 6-sialyllactose and negatively associated with disialyllacto-N-tetraose, disialyllacto-N-hexaose, fucodisialyllacto-N-hexaose and total acidic HMOs concentrations at 2 M. Infant intakes of 3-fucosyllactose, 3-sialyllactose, 6-sialyllactose, disialyllacto-N-tetraose, disialyllacto-N-hexaose, and total acidic HMOs were positively associated with infant growth over the first 6 M of life. Maternal obesity is associated with changes in HMO concentrations that are associated with infant adiposity.


Assuntos
Desenvolvimento Infantil/efeitos dos fármacos , Fenômenos Fisiológicos da Nutrição Materna/fisiologia , Leite Humano/química , Oligossacarídeos/análise , Sobrepeso/metabolismo , Adiposidade/efeitos dos fármacos , Adulto , Antropometria , Composição Corporal , Índice de Massa Corporal , Ingestão de Alimentos/fisiologia , Feminino , Humanos , Lactente , Modelos Lineares , Masculino , Obesidade/metabolismo , Período Pós-Parto/metabolismo
14.
Metabolism ; 117: 154724, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33548253

RESUMO

AIMS: Mitochondrial uncouplers decrease caloric efficiency and have potential therapeutic benefits for the treatment of obesity and related metabolic disorders. Herein we investigate the metabolic and physiologic effects of a recently identified small molecule mitochondrial uncoupler named SHC517 in a mouse model of diet-induced obesity. METHODS: SHC517 was administered as an admixture in food. The effect of SHC517 on in vivo energy expenditure and respiratory quotient was determined by indirect calorimetry. A dose-finding obesity prevention study was performed by starting SHC517 treatment concomitant with high fat diet for a period of 12 days. An obesity reversal study was performed by feeding mice western diet for 4 weeks prior to SHC517 treatment for 7 weeks. Biochemical assays were used to determine changes in glucose, insulin, triglycerides, and cholesterol. SHC517 concentrations were determined by mass spectrometry. RESULTS: SHC517 increased lipid oxidation without affecting body temperature. SHC517 prevented diet-induced obesity when administered at 0.05% and 0.1% w/w in high fat diet and reversed established obesity when tested at the 0.05% dose. In the obesity reversal model, SHC517 restored adiposity to levels similar to chow-fed control mice without affecting food intake or lean body mass. SHC517 improved glucose tolerance and fasting glucose levels when administered in both the obesity prevention and obesity reversal modes. CONCLUSIONS: SHC517 is a mitochondrial uncoupler with potent anti-obesity and insulin sensitizing effects in mice. SHC517 reversed obesity without altering food intake or compromising lean mass, effects that are highly sought-after in anti-obesity therapeutics.


Assuntos
Ingestão de Alimentos/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Obesidade/tratamento farmacológico , Bibliotecas de Moléculas Pequenas/farmacologia , Adiposidade/efeitos dos fármacos , Animais , Peso Corporal/efeitos dos fármacos , Calorimetria Indireta/métodos , Dieta Hiperlipídica/efeitos adversos , Dieta Ocidental/efeitos adversos , Metabolismo Energético/efeitos dos fármacos , Glucose/metabolismo , Insulina/metabolismo , Resistência à Insulina/fisiologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Doenças Metabólicas/tratamento farmacológico , Doenças Metabólicas/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo , Obesidade/metabolismo
15.
J Int Soc Sports Nutr ; 18(1): 13, 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33557850

RESUMO

Supplementing with creatine is very popular amongst athletes and exercising individuals for improving muscle mass, performance and recovery. Accumulating evidence also suggests that creatine supplementation produces a variety of beneficial effects in older and patient populations. Furthermore, evidence-based research shows that creatine supplementation is relatively well tolerated, especially at recommended dosages (i.e. 3-5 g/day or 0.1 g/kg of body mass/day). Although there are over 500 peer-refereed publications involving creatine supplementation, it is somewhat surprising that questions regarding the efficacy and safety of creatine still remain. These include, but are not limited to: 1. Does creatine lead to water retention? 2. Is creatine an anabolic steroid? 3. Does creatine cause kidney damage/renal dysfunction? 4. Does creatine cause hair loss / baldness? 5. Does creatine lead to dehydration and muscle cramping? 6. Is creatine harmful for children and adolescents? 7. Does creatine increase fat mass? 8. Is a creatine 'loading-phase' required? 9. Is creatine beneficial for older adults? 10. Is creatine only useful for resistance / power type activities? 11. Is creatine only effective for males? 12. Are other forms of creatine similar or superior to monohydrate and is creatine stable in solutions/beverages? To answer these questions, an internationally renowned team of research experts was formed to perform an evidence-based scientific evaluation of the literature regarding creatine supplementation.


Assuntos
Creatina/efeitos adversos , Suplementos Nutricionais/efeitos adversos , Adiposidade/efeitos dos fármacos , Adolescente , Adulto , Alopecia/induzido quimicamente , Água Corporal/efeitos dos fármacos , Criança , Creatina/administração & dosagem , Creatina/química , Creatina/metabolismo , Desidratação/induzido quimicamente , Feminino , Humanos , Rim/efeitos dos fármacos , Nefropatias/induzido quimicamente , Masculino , Cãibra Muscular/induzido quimicamente , Músculo Esquelético/efeitos dos fármacos , Fatores Sexuais , Fenômenos Fisiológicos da Nutrição Esportiva , Testosterona/metabolismo , Congêneres da Testosterona/farmacologia
16.
Food Funct ; 12(3): 1008-1019, 2021 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-33502407

RESUMO

High-protein diets are known to reduce weight and fat deposition. However, there have been only a few studies on the efficacy of different types of high-protein diets in preventing obesity. Therefore, the emphasis of this study lies in comparing the efficacy of two high-protein diets (milk protein and whey protein) in preventing obesity and exploring specific mechanisms. Eighty Sprague Dawley rats were divided into two groups and fed with milk protein concentrate (MPC) and whey protein concentrate (WPC) for 12 weeks. Each group was divided into four levels: two low-fat regimens with either low or high protein content (L-14%, L-40%) and two high-fat regimens with either low or high protein content (H-14%, H-40%). The studies we have performed showed that rats treated with MPC at the 40% protein level had significantly reduced body weight, fat weight and fat ratio gain induced by a high-fat diet, while the protein level in the WPC group had no effect on body weight or body fat in rats fed with a high-fat diet. What is more, rats fed with MPC at the H-40% energy level showed a significant decrease in plasma triglyceride, total cholesterol and low-density lipoprotein cholesterol levels and a significant increase in plasma high-density lipoprotein cholesterol levels compared with the H-14% energy level group. In contrast, in the WPC groups, increasing the protein content in high-fat diets had no significant influence on plasma lipid levels. The results of the amino acid composition of the two proteins and plasma showed that the MPC diet of 40% protein level increased the transsulfuration pathway in rats, thereby increasing the level of H2S. This research work has shown that not all types of high-protein diets can effectively prevent obesity induced by high-fat diets, as effectiveness depends on the amino acid composition of the protein.


Assuntos
Adiposidade/efeitos dos fármacos , Dieta Rica em Proteínas , Proteínas do Leite/farmacologia , Proteínas do Soro do Leite/farmacologia , Fator 4 Ativador da Transcrição , Tecido Adiposo , Animais , Antioxidantes , Peso Corporal/efeitos dos fármacos , Dieta com Restrição de Gorduras , Dieta Hiperlipídica , Modelos Animais de Doenças , Expressão Gênica , Sulfeto de Hidrogênio , Metabolismo dos Lipídeos/genética , Masculino , Obesidade/prevenção & controle , Ratos , Ratos Sprague-Dawley , Triglicerídeos
17.
J Nutr ; 151(4): 892-901, 2021 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-33484149

RESUMO

BACKGROUND: There are few evidence-based strategies to attenuate the risk of metabolic syndrome in offspring exposed to gestational diabetes mellitus (GDM). Berberine (BBR) is an isoquinoline alkaloid extracted from Chinese herbs and exhibits glucose lowering properties. OBJECTIVES: We hypothesized that dietary BBR would improve health outcomes in the mouse offspring of GDM dams. METHODS: Wild-type C57BL/6 female mice were fed either a Lean-inducing low-fat diet (L-LF,10% kcal fat, 35% kcal sucrose) or a GDM-inducing high-fat diet (GDM-HF, 45% kcal fat, 17.5% sucrose) for 6 wk prior to breeding with wild-type C57BL/6 male mice throughout pregnancy and the suckling period. The resulting Lean and GDM-exposed male and female offspring were randomly assigned an LF (10% kcal fat, 35% kcal sucrose), HF (45% kcal fat, 17.5% sucrose), or high-fat berberine (HFB) (45% kcal fat, 17.5% sucrose diet) containing BBR (160 mg/kg/d, HFB) at weaning for 12 wk. The main outcome was to evaluate the effects of BBR on obesity, pancreatic islet function, and cardiac contractility in GDM-exposed HF-fed offspring. Significance between measurements was determined using a 2 (gestational exposure) × 3 (diet) factorial design by a 2- way ANOVA using Tukey post-hoc analysis. RESULTS: In the GDM-HF group, body weights were significantly increased (16%) compared with those in baseline (L-LF) animals (P < 0.05). Compared with the L-LF animals, the GDM-HF group had a reduction in pancreatic insulin glucose-stimulated insulin secretion (74%) and increased cardiac isovolumetric contraction time (IVCT; ∼150%) (P < 0.05). Compared with GDM-HF animals, the GDM-HFB group with the dietary addition of BBR had significantly reduced body weight (16%), increased glucose-stimulated insulin secretion from pancreatic islets (254%), and reduced systolic heart function (46% IVCT) (P < 0.05). CONCLUSIONS: In a mouse model of GDM, dietary BBR treatment provided protection from obesity and the development of pancreatic islet and cardiac dysfunction.


Assuntos
Berberina/administração & dosagem , Diabetes Gestacional/dietoterapia , Dieta Hiperlipídica/efeitos adversos , Suplementos Nutricionais , Adiposidade/efeitos dos fármacos , Animais , Peso Corporal/efeitos dos fármacos , Feminino , Glucose/metabolismo , Cardiopatias/prevenção & controle , Insulina/sangue , Insulina/metabolismo , Ilhotas Pancreáticas/efeitos dos fármacos , Ilhotas Pancreáticas/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias Cardíacas/efeitos dos fármacos , Mitocôndrias Cardíacas/metabolismo , Obesidade/prevenção & controle , Gravidez , Efeitos Tardios da Exposição Pré-Natal/dietoterapia
18.
Am J Physiol Regul Integr Comp Physiol ; 320(4): R471-R487, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33470901

RESUMO

Previous studies indicate that oxytocin (OT) administration reduces body weight in high-fat diet (HFD)-induced obese (DIO) rodents through both reductions in food intake and increases in energy expenditure. We recently demonstrated that chronic hindbrain [fourth ventricular (4V)] infusions of OT evoke weight loss in DIO rats. Based on these findings, we hypothesized that chronic 4V OT would elicit weight loss in DIO mice. We assessed the effects of 4V infusions of OT (16 nmol/day) or vehicle over 28 days on body weight, food intake, and body composition. OT reduced body weight by approximately 4.5% ± 1.4% in DIO mice relative to OT pretreatment body weight (P < 0.05). These effects were associated with reduced adiposity and adipocyte size [inguinal white adipose tissue (IWAT)] (P < 0.05) and attributed, in part, to reduced energy intake (P < 0.05) at a dose that did not increase kaolin intake (P = NS). OT tended to increase uncoupling protein-1 expression in IWAT (0.05 < P < 0.1) suggesting that OT stimulates browning of WAT. To assess OT-elicited changes in brown adipose tissue (BAT) thermogenesis, we examined the effects of 4V OT on interscapular BAT temperature (TIBAT). 4V OT (1 µg) elevated TIBAT at 0.75 (P = 0.08), 1, and 1.25 h (P < 0.05) postinjection; a higher dose (5 µg) elevated TIBAT at 0.75-, 1-, 1.25-, 1.5-, 1.75- (P < 0.05), and 2-h (0.05 < P < 0.1) postinjection. Together, these findings support the hypothesis that chronic hindbrain OT treatment evokes sustained weight loss in DIO mice by reducing energy intake and increasing BAT thermogenesis at a dose that is not associated with evidence of visceral illness.


Assuntos
Fármacos Antiobesidade/administração & dosagem , Dieta Hiperlipídica , Obesidade/tratamento farmacológico , Ocitocina/administração & dosagem , Rombencéfalo/efeitos dos fármacos , Perda de Peso/efeitos dos fármacos , Adipócitos Marrons/efeitos dos fármacos , Adipócitos Marrons/metabolismo , Adipócitos Marrons/patologia , Adipócitos Brancos/efeitos dos fármacos , Adipócitos Brancos/metabolismo , Adipócitos Brancos/patologia , Adiposidade/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Ingestão de Alimentos/efeitos dos fármacos , Ingestão de Energia/efeitos dos fármacos , Infusões Intraventriculares , Leptina/sangue , Masculino , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Obesidade/patologia , Obesidade/fisiopatologia , Rombencéfalo/fisiopatologia , Termogênese/efeitos dos fármacos , Proteína Desacopladora 1/metabolismo
19.
J Med Chem ; 64(2): 1037-1053, 2021 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-33417443

RESUMO

Tryptophan hydroxylase 1 (TPH1) has been recently suggested as a promising therapeutic target for treating obesity and fatty liver disease. A new series of 1,2,4-oxadiazolylphenyl alanine derivatives were identified as TPH1 inhibitors. Among them, compound 23a was the most active in vitro, with an IC50 (half-maximal inhibitory concentration) value of 42 nM, showed good liver microsomal stability, and showed no significant inhibition of CYP and hERG. Compound 23a inhibited TPH1 in the peripheral tissue with limited BBB penetration. In high-fat diet-fed mice, 23a reduced body weight gain, body fat, and hepatic lipid accumulation. Also, 23a improved glucose intolerance and energy expenditure. Taken together, compound 23a shows promise as a therapeutic agent for the treatment of obesity and fatty liver diseases.


Assuntos
Alanina/síntese química , Alanina/farmacologia , Fármacos Antiobesidade/síntese química , Fármacos Antiobesidade/farmacologia , Fígado Gorduroso/tratamento farmacológico , Triptofano Hidroxilase/antagonistas & inibidores , Adiposidade/efeitos dos fármacos , Alanina/análogos & derivados , Animais , Fármacos Antiobesidade/uso terapêutico , Dieta Hiperlipídica , Metabolismo Energético/efeitos dos fármacos , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/farmacologia , Intolerância à Glucose/tratamento farmacológico , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Microssomos Hepáticos/metabolismo , Modelos Moleculares , Ganho de Peso/efeitos dos fármacos
20.
J Nutr Biochem ; 90: 108572, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33388348

RESUMO

We investigated whether combined long-term fructose and prednisolone intake would be more detrimental to the glucose homeostasis than if ingested separately. We also evaluated whether fish oil administration or interruption of treatments has any positive impact. For this, male adult Wistar rats ingested fructose (20%) (F) or prednisolone (12.5 µg/mL) (P) or both (FP) through drinking water for 12 weeks. A separate group of fructose and prednisolone-treated rats received fish oil treatment (1 g/kg) in the last 6 weeks. In another group, the treatment with fructose and prednisolone was interrupted after 12 weeks, and the animals were followed for more 12 weeks. Control groups ran in parallel (C). The F group had higher plasma TG (+42%) and visceral adiposity (+63%), whereas the P group had lower insulin sensitivity (-33%) and higher insulinemia (+200%). Only the the FP group developed these alterations combined with higher circulating uric acid (+126%), hepatic triacylglycerol content (+16.2-fold), lipid peroxidation (+173%) and lower catalase activity (-32%) that were associated with lower protein kinase B content and AMP-activated protein kinase (AMPK) phosphorylation in the liver, lower AMPK phosphorylation in the adipose tissue and higher beta-cell mass. Fish oil ingestion attenuated the elevation in circulating triacylglycerol and uric acid values, while the interruption of sugar and glucocorticoid intake reverted almost all modified parameters. In conclusion, long-term intake of fructose and prednisolone by male rats are more detrimental to glucose and lipid homeostasis than if ingested separately and the benefits of treatment interruption are broader than fish oil treatment.


Assuntos
Óleos de Peixe/farmacologia , Frutose/farmacologia , Glucocorticoides/farmacologia , Glucose/metabolismo , Metabolismo dos Lipídeos , Prednisolona/farmacologia , Tecido Adiposo/metabolismo , Adiposidade/efeitos dos fármacos , Animais , Óleos de Peixe/administração & dosagem , Frutose/administração & dosagem , Glucocorticoides/administração & dosagem , Homeostase , Humanos , Insulina/metabolismo , Resistência à Insulina , Peroxidação de Lipídeos , Fígado/metabolismo , Masculino , Prednisolona/administração & dosagem , Ratos , Ratos Wistar , Bebidas Adoçadas com Açúcar , Triglicerídeos/sangue , Ácido Úrico/metabolismo
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