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1.
Int J Mol Sci ; 25(9)2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38732183

RESUMO

The impact of microplastics (MPs) on the metabolic functions of the liver is currently unclear and not completely understood. To investigate the effects of the administration of MPs on the hepatic metabolism of normal and obese mice, alterations in the lipid, glucose (Glu), and amino acid regulation pathways were analyzed in the liver and adipose tissues of C57BL/6Korl (wild type, WT) or C57BL/6-Lepem1hwl/Korl mice (leptin knockout, Lep KO) orally administered polystyrene (PS) MPs for 9 weeks. Significant alterations in the lipid accumulation, adipogenesis, lipogenesis, and lipolysis pathways were detected in the liver tissue of MP-treated WT and Lep KO mice compared to the vehicle-treated group. These alterations in their liver tissues were accompanied by an upregulation of the serum lipid profile, as well as alterations in the adipogenesis, lipogenesis, and lipolysis pathways in the adipose tissues of MP-treated WT and Lep KO mice. Specifically, the level of leptin was increased in the adipose tissues of MP-treated WT mice without any change in their food intake. Also, MP-induced disruptions in the glycogenolysis, Glu transporter type 4 (GLUT4)-5' AMP-activated protein kinase (AMPK) signaling pathway, levels of lipid intermediates, and the insulin resistance of the liver tissues of WT and Lep KO mice were observed. Furthermore, the levels of seven endogenous metabolites were remarkably changed in the serum of WT and Lep KO mice after MP administrations. Finally, the impact of the MP administration observed in both types of mice was further verified in differentiated 3T3-L1 adipocytes and HepG2 cells. Thus, these results suggest that the oral administration of MPs for 9 weeks may be associated with the disruption of lipid, Glu, and amino acid metabolism in the liver tissue of obese WT and Lep KO mice.


Assuntos
Aminoácidos , Glucose , Metabolismo dos Lipídeos , Fígado , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microplásticos , Poliestirenos , Animais , Fígado/metabolismo , Fígado/efeitos dos fármacos , Camundongos , Glucose/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Aminoácidos/metabolismo , Administração Oral , Leptina/metabolismo , Tecido Adiposo/metabolismo , Tecido Adiposo/efeitos dos fármacos , Adipogenia/efeitos dos fármacos , Masculino , Lipogênese/efeitos dos fármacos , Obesidade/metabolismo , Obesidade/etiologia , Obesidade/genética , Humanos , Lipólise/efeitos dos fármacos
2.
FASEB J ; 38(9): e23643, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38703030

RESUMO

Secreted phospholipase A2s are involved in the development of obesity, type 2 diabetes mellitus (T2DM) and cardiovascular disease, which have become serious and growing health concerns worldwide. Integration of genome-wide association study and gene co-expression networks analysis showed that the secreted phospholipase A2 group XIIA (PLA2G12A) may participate in hepatic lipids metabolism. Nevertheless, the role of PLA2G12A in lipid metabolism and its potential mechanism remain elusive. Here, we used AAV9 vector carrying human PLA2G12A gene to exogenously express hPLA2G12A in the liver of mice. We demonstrated that the overexpression of hPLA2G12A resulted in a significant decrease in serum lipid levels in wild-type mice fed with chow diet or high-fat diet (HFD). Moreover, hPLA2G12A treatment protected against diet-induced obesity and insulin resistance in mice fed a HFD. Notably, we found that hPLA2G12A treatment confers protection against obesity and hyperlipidemia independent of its enzymatic activity, but rather by increasing physical activity and energy expenditure. Furthermore, we demonstrated that hPLA2G12A treatment induced upregulation of ApoC2 and Cd36 and downregulation of Angptl8, which contributed to the increase in clearance of circulating triglycerides and hepatic uptake of fatty acids without affecting hepatic de novo lipogenesis, very low-density lipoprotein secretion, or intestinal lipid absorption. Our study highlights the potential of PLA2G12A gene therapy as a promising approach for treating obesity, insulin resistance and T2DM.


Assuntos
Dieta Hiperlipídica , Metabolismo Energético , Resistência à Insulina , Camundongos Endogâmicos C57BL , Obesidade , Triglicerídeos , Animais , Obesidade/metabolismo , Obesidade/etiologia , Camundongos , Triglicerídeos/metabolismo , Triglicerídeos/sangue , Masculino , Dieta Hiperlipídica/efeitos adversos , Humanos , Fígado/metabolismo , Metabolismo dos Lipídeos
3.
Adipocyte ; 13(1): 2339418, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38706095

RESUMO

A Disintegrin And Metalloproteinase domain-containing protein 10 (ADAM10), is involved in several metabolic and inflammatory pathways. We speculated that ADAM10 plays a modulatory role in adipose tissue inflammation and metabolism. To this end, we studied adipose tissue-specific ADAM10 knock-out mice (aKO). While young, regular chow diet-fed aKO mice showed increased insulin sensitivity, following prolonged (33 weeks) high-fat diet (HFD) exposure, aKO mice developed obesity and insulin resistance. Compared to controls, aKO mice showed less inflammatory adipokine profile despite the significant increase in adiposity. In brown adipose tissue, aKO mice on HFD had changes in CD8+ T cell populations indicating a lesser inflammatory pattern. Following HFD, both aKO and control littermates demonstrated decreased adipose tissue pro-inflammatory macrophages, and increased anti-inflammatory accumulation, without differences between the genotypes. Collectively, our observations indicate that selective deletion of ADAM10 in adipocytes results in a mitigated inflammatory response, leading to increased insulin sensitivity in young mice fed with regular diet. This state of insulin sensitivity, following prolonged HFD, facilitates energy storage resulting in increased fat accumulation which ultimately leads to the development of a phenotype of obesity and insulin resistance. In conclusion, the data indicate that ADAM10 has a modulatory effect of inflammation and whole-body energy metabolism.


Assuntos
Proteína ADAM10 , Tecido Adiposo , Dieta Hiperlipídica , Camundongos Knockout , Animais , Masculino , Camundongos , Proteína ADAM10/metabolismo , Proteína ADAM10/genética , Adipócitos/metabolismo , Tecido Adiposo/metabolismo , Secretases da Proteína Precursora do Amiloide/metabolismo , Dieta Hiperlipídica/efeitos adversos , Inflamação/metabolismo , Resistência à Insulina , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Obesidade/metabolismo , Obesidade/etiologia , Fenótipo
4.
FASEB J ; 38(10): e23664, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38775797

RESUMO

Adipogenesis, a pivotal cellular process involving the differentiation of mesenchymal stem cells (MSCs) to mature adipocytes, plays a significant role in various physiological functions. Dysregulation of adipogenesis is implicated in conditions such as obesity. However, the complete molecular understanding of adipogenesis remains elusive. This study aimed to uncover the novel role of lamina-associated polypeptide 2 alpha (LAP2α) in human adipose-derived stem cells (hASCs) adipogenesis and its impact on high-fat diet (HFD)-induced obesity and associated metabolic disturbances. LAP2α expression was assessed during the adipogenic differentiation of hASCs using RT-qPCR and western blotting. The functional role of LAP2α in adipogenesis was explored both in vitro and in vivo through loss- and gain-of-function studies. Moreover, mice with HFD-induced obesity received lentivirus injection to assess the effect of LAP2α knockdown on fat accumulation. Molecular mechanisms underlying LAP2α in adipogenic differentiation were investigated using RT-qPCR, Western blotting, immunofluorescence staining, and Oil Red O staining. LAP2α expression was upregulated during hASCs adipogenic differentiation. LAP2α knockdown hindered adipogenesis, while LAP2α overexpression promoted adipogenic differentiation. Notably, LAP2α deficiency resisted HFD-induced obesity, improved glucose intolerance, mitigated insulin resistance, and prevented fatty liver development. Mechanistically, LAP2α knockdown attenuated signal transducer and activator of transcription 3 (STAT3) activation by reducing the protein level of phosphorylated STAT3. A STAT3 activator (Colivelin) counteracted the negative impact of LAP2α deficiency on hASCs adipogenic differentiation. Taken together, our current study established LAP2α as a crucial regulator of hASCs adipogenic differentiation, unveiling a new therapeutic target for obesity prevention.


Assuntos
Adipogenia , Dieta Hiperlipídica , Células-Tronco Mesenquimais , Obesidade , Humanos , Dieta Hiperlipídica/efeitos adversos , Obesidade/metabolismo , Obesidade/genética , Obesidade/etiologia , Animais , Camundongos , Células-Tronco Mesenquimais/metabolismo , Masculino , Diferenciação Celular , Camundongos Endogâmicos C57BL , Tecido Adiposo/metabolismo , Tecido Adiposo/citologia , Adipócitos/metabolismo , Células Cultivadas , Técnicas de Silenciamento de Genes , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/genética , Proteínas de Ligação a DNA , Proteínas de Membrana
5.
Sci Rep ; 14(1): 11366, 2024 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-38762543

RESUMO

Placental leptin may impact foetal development. Maternal overnutrition has been linked to increased plasma leptin levels and adverse effects on offspring, whereas choline, an essential nutrient for foetal development, has shown promise in mitigating some negative impacts of maternal obesity. Here, we investigate whether a maternal obesogenic diet alters foetal growth and leptin levels in the foetal stomach, amniotic fluid (AF), and placenta in late gestation and explore the potential modulating effects of maternal choline supplementation. Female rats were fed a control (CD) or a western diet (WD) four weeks before mating and during gestation, half of them supplemented with choline (pregnancy days 11-17). Leptin levels (in foetal stomach, AF, and placenta) and leptin gene expression (in placenta) were assessed on gestation days 20 and 21. At day 20, maternal WD feeding resulted in greater leptin levels in foetal stomach, placenta, and AF. The increased AF leptin levels were associated with a premature increase in foetal weight in both sexes. Maternal choline supplementation partially prevented these alterations, but effects differed in CD dams, causing increased AF leptin levels and greater weight in male foetuses at day 20. Maternal choline supplementation effectively mitigates premature foetal overgrowth induced by an obesogenic diet, potentially linked to increased AF leptin levels. Further research is needed to explore the sex-specific effects.


Assuntos
Líquido Amniótico , Colina , Suplementos Nutricionais , Leptina , Animais , Feminino , Leptina/sangue , Leptina/metabolismo , Gravidez , Colina/administração & dosagem , Líquido Amniótico/metabolismo , Ratos , Masculino , Placenta/metabolismo , Placenta/efeitos dos fármacos , Desenvolvimento Fetal/efeitos dos fármacos , Obesidade/metabolismo , Obesidade/etiologia , Peso Fetal/efeitos dos fármacos , Ratos Sprague-Dawley , Dieta Ocidental/efeitos adversos
6.
Am J Clin Nutr ; 119(4): 990-1006, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38569789

RESUMO

BACKGROUND: Consumption of sugar-sweetened beverages (SSBs) has been linked to several adverse health outcomes, thus many countries introduced taxation to reduce it. OBJECTIVES: To summarize national SSB taxation laws and to assess their association with obesity, overweight and diabetes. METHODS: We conducted a systematic scoping review up to January 2022 on PubMed, Web of Science, Embase, and Google Search to identify taxes on SSBs. An interrupted time series analysis (ITSA) was conducted on 17 countries with taxation implemented in 2013 or before to evaluate the level and slope modifications in the rate of change of standardized prevalence rates of overweight, obesity, and diabetes. Random-effects meta-regression was used to assess whether year of entry into force of the law, national income, and tax design affected observed results. RESULTS: We included 76 tax laws issued between 1940 and 2020 by 43 countries, which were heterogeneous in terms of tax design, amount, and taxed products. Among children and adolescents, ITSA showed level or slope reduction for prevalence of overweight and obesity in 5 (Brazil, Samoa, Palau, Panama, Tonga) and 6 (El Salvador, Uruguay, Nauru, Norway, Palau, Tonga) countries out of 17, respectively. No clear pattern of modification of results according to investigated factors emerged from the meta-regression analysis. CONCLUSIONS: Taxation is highly heterogeneous across countries in terms of products and design, which might influence its effectiveness. Our findings provide some evidence regarding a deceleration of the increasing prevalence rates of overweight and obesity among children occurring in some countries following introduction of taxation. PROSPERO registration number: CRD42021233309.


Assuntos
Diabetes Mellitus , Bebidas Adoçadas com Açúcar , Adolescente , Criança , Humanos , Sobrepeso/epidemiologia , Bebidas Adoçadas com Açúcar/efeitos adversos , Obesidade/epidemiologia , Obesidade/etiologia , Impostos , Bebidas/efeitos adversos
7.
Front Endocrinol (Lausanne) ; 15: 1359772, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38586455

RESUMO

Meal timing emerges as a crucial factor influencing metabolic health that can be explained by the tight interaction between the endogenous circadian clock and metabolic homeostasis. Mistimed food intake, such as delayed or nighttime consumption, leads to desynchronization of the internal circadian clock and is associated with an increased risk for obesity and associated metabolic disturbances such as type 2 diabetes and cardiovascular diseases. Conversely, meal timing aligned with cellular rhythms can optimize the performance of tissues and organs. In this review, we provide an overview of the metabolic effects of meal timing and discuss the underlying mechanisms. Additionally, we explore factors influencing meal timing, including internal determinants such as chronotype and genetics, as well as external influences like social factors, cultural aspects, and work schedules. This review could contribute to defining meal-timing-based recommendations for public health initiatives and developing guidelines for effective lifestyle modifications targeting the prevention and treatment of obesity and associated metabolic diseases. Furthermore, it sheds light on crucial factors that must be considered in the design of future food timing intervention trials.


Assuntos
Relógios Circadianos , Diabetes Mellitus Tipo 2 , Humanos , Ritmo Circadiano , Diabetes Mellitus Tipo 2/complicações , Obesidade/etiologia , Refeições
8.
Agri ; 36(2): 106-112, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38558400

RESUMO

OBJECTIVES: The aim of this study was to investigate the effect of epidural steroid injections on the menstrual cycle of women and to identify risk factors in those with changes. METHODS: A total of 78 women who had epidural steroid injections between the ages of 18 and 55 years were retrospectively analyzed. The patients were called by phone and asked whether there was any change in their menstrual cycles after the epidural injections. Data including demographic and clinical characteristics, body height and weight, education status, alcohol and smoking habits, comorbidities, number of children, birth control method, history of cesarean section, miscarriage, and abortion were recorded. RESULTS: Changes in the menstrual cycle were seen in five of 12 patients who underwent cervical interlaminar epidural steroid injection, in 27 of 56 patients who underwent lumbar transforaminal epidural steroid injection, in one of two patients who underwent lumbar interlaminar epidural steroid injection, and in three of eight patients who underwent caudal epidural steroid injection. The number of patients with obesity was higher in the patients with changes than those without, indicating a statistically significant difference (41.7% vs. 14.3%, respectively; p=0.007). CONCLUSION: Our study suggests that epidural steroid injections are associated with changes in the menstrual cycle. Obesity is a risk factor for menstrual cycle changes after epidural steroid injections.


Assuntos
Ciclo Menstrual , Esteroides , Adolescente , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Adulto Jovem , Injeções Epidurais/efeitos adversos , Injeções Epidurais/métodos , Obesidade/etiologia , Estudos Retrospectivos , Resultado do Tratamento
9.
Nutrients ; 16(7)2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38612978

RESUMO

Safe water is a global public health concern amid increasing scarcity and pollution. Bottled water production and consumption contribute to these problems. This study examines tap water consumption in Italy, assessing associated sociodemographic factors and related health outcomes such as obesity and self-perceived health status. Data from the Italian National Statistics Institute's "Aspects of daily life" survey (N = 45,597) were analyzed. Covariates included education, age, gender, economic status, region, concerns about waste and climate change, consumption of carbonated drinks excluding water, alcohol consumption, consumption of vegetables, consumption of snacks, body mass index, and self-perceived health status. Bivariate analyses and mixed-effect logistic regression models explored the associations. People who drink tap water made up 19,674, with a higher prevalence in people aged 45 to 59 old, people with a graduate/post-graduate degree diploma, with optimal economic resources, people concerned about waste production and climate change, and those coming from the north-east regions of Italy. Underweight people showed a higher prevalence of TW consumption as well as those who less than occasionally drank carbonated drinks, drank alcohol, consumed vegetables more than once a day and snacks less than once a week, dairy products more than once a day, sweet less than once a week, cured meat less than once a week, and chicken meat less than once a week, those with no consumption of sheep meat, consumption of beef meat less than once a week and consumption of pork meat less than once a week, and those with a satisfactory level of perceived health status. Regressions showed that all other age classes are less likely to drink tap water than people younger than 20 years old. The category with "inadequate" economic resources is more likely to consume tap water. Low educational classes show a low likelihood of consuming tap water as well as islands. A concern about waste production and climate change is associated with an increased likelihood of consuming tap water. Tap water consumption was negatively associated with obesity but not with a satisfactory self-perceived health status. Insights from this study can inform public health strategies.


Assuntos
Obesidade , Água , Bovinos , Humanos , Animais , Ovinos , Adulto Jovem , Adulto , Estudos Transversais , Fatores Socioeconômicos , Escolaridade , Obesidade/epidemiologia , Obesidade/etiologia
10.
Appetite ; 197: 107329, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561064

RESUMO

Consumption of sugar-sweetened beverages (SSB) is considered as an important risk factor for the development of overweight and obesity in populations worldwide, with a particular focus on the risks in the younger parts of the population - children and adolescents. Together with fiscal measures and information tools, innovation-based approaches such as the development of sugar-free or sugar-reduced versions of established beverages and development of new beverage products have been used to reduce this challenge, but the effects of product innovation on sugar intake are not well understood from the literature, as previous studies have largely ignored substitution effects of product innovation in the beverage domain. The objective of the present study was to investigate the potential effectiveness of product innovation as a strategy to affect consumers' intake of energy from sweetened non-alcoholic beverages. Using household panel shopping data from approximately 3000 Danish households over the years 2006-2014, we developed a hedonic pricing approach to estimate the influence of product attributes on consumers' utility, based on observed data for Danish households' purchases of sweet drinks. Overall, the study found that beverages' degree of sweetness positively affected the satiation effect of beverage consumption and in turn made the demand for these beverages less sensitive to e.g. price changes or introduction of competing products, whereas the energy density of the beverages positively affected the demand sensitivity to market changes. Findings like these can be useful for assessing market effects as well as environmental and public health impacts of changes to the market environment.


Assuntos
Comportamento do Consumidor , Bebidas Adoçadas com Açúcar , Criança , Adolescente , Humanos , Bebidas , Obesidade/etiologia , Obesidade/prevenção & controle , Sobrepeso , Comércio
11.
PLoS One ; 19(4): e0300705, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38603672

RESUMO

Obesity is a major independent risk factor for chronic kidney disease and can activate renal oxidative stress injury. Ascorbate and aldarate metabolism is an important carbohydrate metabolic pathway that protects cells from oxidative damage. However the effect of oxidative stress on this pathway is still unclear. Therefore, the primary objective of this study was to investigate the ascorbate and aldarate metabolism pathway in the kidneys of high-fat diet-fed obese mice and determine the effects of oxidative stress. Male C57BL/6J mice were fed on a high-fat diet for 12 weeks to induce obesity. Subsequently, non-targeted metabolomics profiling was used to identify metabolites in the kidney tissues of the obese mice, followed by RNA sequencing using transcriptomic methods. The integrated analysis of metabolomics and transcriptomics revealed the alterations in the ascorbate and aldarate metabolic pathway in the kidneys of these high-fat diet-fed obese mice. The high-fat diet-induced obesity resulted in notable changes, including thinning of the glomerular basement membrane, alterations in podocyte morphology, and an increase in oxidative stress. Metabolomics analysis revealed 649 metabolites in the positive-ion mode, and 470 metabolites in the negative-ion mode. Additionally, 659 differentially expressed genes (DEGs) were identified in the obese mice, of which 34 were upregulated and 625 downregulated. Integrated metabolomics and transcriptomics analyses revealed two DEGs and 13 differential metabolites in the ascorbate and aldarate metabolic pathway. The expression levels of ugt1a9 and ugt2b1 were downregulated, and the ascorbate level in kidney tissue of obese mice was reduced. Thus, renal oxidative stress injury induced by high-fat diet affects metabolic regulation of ascorbate and aldarate metabolism in obese mice. Ascorbate emerged as a potential marker for predicting kidney damage due to high-fat diet-induced obesity.


Assuntos
Dieta Hiperlipídica , Rim , Animais , Camundongos , Masculino , Dieta Hiperlipídica/efeitos adversos , Camundongos Obesos , Camundongos Endogâmicos C57BL , Rim/metabolismo , Obesidade/etiologia , Obesidade/metabolismo , Metabolômica , Perfilação da Expressão Gênica
12.
Int J Mol Sci ; 25(7)2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38612776

RESUMO

This study examines the impact of insulin-like growth factor 1 (IGF-1) and insulin-like growth factor 2 (IGF-2) on various aspects of children's health-from the realms of growth and puberty to the nuanced characteristics of metabolic syndrome, diabetes, liver pathology, carcinogenic potential, and cardiovascular disorders. A comprehensive literature review was conducted using PubMed, with a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method employing specific keywords related to child health, obesity, and insulin-like growth factors. This study reveals associations between insulin-like growth factor 1 and birth weight, early growth, and adiposity. Moreover, insulin-like growth factors play a pivotal role in regulating bone development and height during childhood, with potential implications for puberty onset. This research uncovers insulin-like growth factor 1 and insulin-like growth factor 2 as potential biomarkers and therapeutic targets for metabolic dysfunction-associated liver disease and hepatocellular carcinoma, and it also highlights the association between insulin-like growth factors (IGFs) and cancer. Additionally, this research explores the impact of insulin-like growth factors on cardiovascular health, noting their role in cardiomyocyte hypertrophy. Insulin-like growth factors play vital roles in human physiology, influencing growth and development from fetal stages to adulthood. The impact of maternal obesity on children's IGF levels is complex, influencing growth and carrying potential metabolic consequences. Imbalances in IGF levels are linked to a range of health conditions (e.g., insulin resistance, glucose intolerance, metabolic syndrome, and diabetes), prompting researchers to seek novel therapies and preventive strategies, offering challenges and opportunities in healthcare.


Assuntos
Diabetes Mellitus , Síndrome Metabólica , Gravidez , Criança , Feminino , Humanos , Fator de Crescimento Insulin-Like I , Fator de Crescimento Insulin-Like II , Síndrome Metabólica/etiologia , Obesidade/etiologia , Peptídeos Semelhantes à Insulina
13.
Appetite ; 198: 107355, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38621593

RESUMO

Associative learning can drive many different types of behaviors, including food consumption. Previous studies have shown that cues paired with food delivery while mice are hungry will lead to increased consumption in the presence of those cues at later times. We previously showed that overconsumption can be driven in male mice by contextual cues, using chow pellets. Here we extended our findings by examining other parameters that may influence the outcome of context-conditioned overconsumption training. We found that the task worked equally well in males and females, and that palatable substances such as high-fat diet and Ensure chocolate milkshake supported learning and induced overconsumption. Surprisingly, mice did not overconsume when sucrose was used as the reinforcer during training, suggesting that nutritional content is a critical factor. Interestingly, we also observed that diet-induced obese mice did not learn the task. Overall, we find that context-conditioned overconsumption can be studied in lean male and female mice, and with multiple reinforcer types.


Assuntos
Sinais (Psicologia) , Dieta Hiperlipídica , Camundongos Endogâmicos C57BL , Obesidade , Animais , Masculino , Feminino , Obesidade/etiologia , Obesidade/psicologia , Camundongos , Reforço Psicológico , Camundongos Obesos , Hiperfagia/psicologia , Comportamento Alimentar/psicologia , Sacarose/administração & dosagem , Magreza/psicologia
14.
PLoS One ; 19(4): e0301496, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38635745

RESUMO

Obesity leads to insulin resistance (IR) and type 2 diabetes. In humans, low levels of the hormone prolactin (PRL) correlate with IR, adipose tissue (AT) dysfunction, and increased prevalence of T2D. In obese rats, PRL treatment promotes insulin sensitivity and reduces visceral AT adipocyte hypertrophy. Here, we tested whether elevating PRL levels with the prokinetic and antipsychotic drug sulpiride, an antagonist of dopamine D2 receptors, improves metabolism in high fat diet (HFD)-induced obese male mice. Sulpiride treatment (30 days) reduced hyperglycemia, IR, and the serum and pancreatic levels of triglycerides in obese mice, reduced visceral and subcutaneous AT adipocyte hypertrophy, normalized markers of visceral AT function (PRL receptor, Glut4, insulin receptor and Hif-1α), and increased glycogen stores in skeletal muscle. However, the effects of sulpiride reducing hyperglycemia were also observed in obese prolactin receptor null mice. We conclude that sulpiride reduces obesity-induced hyperglycemia by mechanisms that are independent of prolactin/prolactin receptor activity. These findings support the therapeutic potential of sulpiride against metabolic dysfunction in obesity.


Assuntos
Diabetes Mellitus Tipo 2 , Hiperglicemia , Resistência à Insulina , Humanos , Camundongos , Masculino , Ratos , Animais , Camundongos Obesos , Antagonistas dos Receptores de Dopamina D2 , Prolactina , Receptores da Prolactina , Diabetes Mellitus Tipo 2/tratamento farmacológico , Sulpirida/farmacologia , Sulpirida/uso terapêutico , Obesidade/tratamento farmacológico , Obesidade/etiologia , Dieta Hiperlipídica/efeitos adversos , Hiperglicemia/tratamento farmacológico , Hipertrofia , Insulina/metabolismo
15.
Zebrafish ; 21(2): 223-230, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38621217

RESUMO

Obesity is a public health concern resulting in a variety of health complications, including heart disease and insulin resistance. Estrogens have been associated with a reduced risk of obesity, but this relationship remains incompletely understood. We assessed the role of 17ß-estradiol (E2) in mitigating complications associated with obesity by supplementing E2 in the diets of overfed zebrafish. We report that dietary E2 supplementation protects against weight gain and modulates de novo cholesterol synthesis in a sex-specific manner. Our studies lead us to propose a model in which E2 regulates hmgcr expression independently of unsaturated fat consumption. These data can be used to develop sex-specific treatments for obesity-related health conditions.


Assuntos
Gorduras Insaturadas , Peixe-Zebra , Masculino , Feminino , Animais , Peixe-Zebra/metabolismo , Gorduras Insaturadas/metabolismo , Estradiol/farmacologia , Estradiol/metabolismo , Estrogênios/metabolismo , Obesidade/etiologia , Colesterol/metabolismo , Suplementos Nutricionais
16.
Nat Commun ; 15(1): 2835, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38565540

RESUMO

Obesity is a well-established risk factor for human cancer, yet the underlying mechanisms remain elusive. Immune dysfunction is commonly associated with obesity but whether compromised immune surveillance contributes to cancer susceptibility in individuals with obesity is unclear. Here we use a mouse model of diet-induced obesity to investigate tumor-infiltrating CD8 + T cell responses in lean, obese, and previously obese hosts that lost weight through either dietary restriction or treatment with semaglutide. While both strategies reduce body mass, only dietary intervention restores T cell function and improves responses to immunotherapy. In mice exposed to a chemical carcinogen, obesity-related immune dysfunction leads to higher incidence of sarcoma development. However, impaired immunoediting in the obese environment enhances tumor immunogenicity, making the malignancies highly sensitive to immunotherapy. These findings offer insight into the complex interplay between obesity, immunity and cancer, and provide explanation for the obesity paradox observed in clinical immunotherapy settings.


Assuntos
Neoplasias , Obesidade , Humanos , Animais , Camundongos , Monitorização Imunológica , Obesidade/etiologia , Dieta , Fatores de Risco
17.
In Vivo ; 38(3): 1152-1161, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38688615

RESUMO

BACKGROUND/AIM: The global prevalence of type 2 diabetes (T2D) continues to increase, necessitating the need for understanding the causes of its development. The widespread use of high-fructose corn syrup (HFCS) in drinks and diets is suspected to play a role in metabolic disorders. Although many studies have reported on the effects of excessive HFCS and excessive energy intakes in middle-aged individuals, few have focused on energy restriction. This study aimed to investigate the effects of excessive HFCS drink intake under energy restriction on developing T2D in early middle-aged mice. MATERIALS AND METHODS: Early middle-aged mice were divided in HFCS and control groups; they were provided either 10% HFCS water or deionized water ad libitum for 12 weeks, respectively. Total energy intake was controlled using a standard rodent diet. Oral glucose tolerance test (OGTT), insulin tolerance test (ITT), tissue weight measurements, serum parameter analyses, and mRNA expression assessments were performed. RESULTS: No increase in body and adipose tissue weight was observed with excessive HFCS intake under energy restriction. Moreover, serum lipid parameters did not differ from those of controls. However, in the OGTT and ITT, the HFCS group showed higher blood glucose levels than the control group. Moreover, the pancreatic weight and insulin II mRNA expression were reduced. CONCLUSION: The excessive HFCS drink intake under energy restriction did not induce obesity; however, it induced impaired glucose tolerance, indicating its negative effects on the pancreas in early middle-aged mice. When translated in human physiology, our results show that even if one does not become obese, excessive HFCS may affect the overall metabolic mechanism; these effects may vary depending on age.


Assuntos
Glicemia , Teste de Tolerância a Glucose , Xarope de Milho Rico em Frutose , Animais , Xarope de Milho Rico em Frutose/efeitos adversos , Xarope de Milho Rico em Frutose/administração & dosagem , Camundongos , Masculino , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/metabolismo , Ingestão de Energia , Modelos Animais de Doenças , Insulina/sangue , Peso Corporal/efeitos dos fármacos , Resistência à Insulina , Obesidade/etiologia , Obesidade/metabolismo , Obesidade/induzido quimicamente
18.
Int J Mol Sci ; 25(8)2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38674060

RESUMO

Mandarin peel, a main by-product from the processing of citrus juice, has been highlighted for its various bioactivities and functional ingredients. Our previous study proved the inhibitory effects of Celluclast extract from mandarin peel (MPCE) on lipid accumulation and differentiation in 3T3-L1 adipocytes. Therefore, the current study aimed to evaluate the anti-obesity effect of MPCE in high-fat diet (HFD)-induced obese mice. The high-performance liquid chromatography (HPLC) analysis exhibited that narirutin and hesperidin are the main active components of MPCE. Our current results showed that MPCE supplementation decreased adiposity by reducing body and organ weights in HFD-induced obese mice. MPCE also reduced triglyceride (TG), alanine transaminase (ALT), aspartate transaminase (AST), and leptin contents in the serum of HFD-fed mice. Moreover, MPCE significantly inhibited hepatic lipid accumulation by regulating the expression levels of proteins associated with lipid metabolism, including sterol regulatory element-binding protein (SREBP1c), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC). Furthermore, MPCE administration significantly inhibited both adipogenesis and lipogenesis, with modulation of energy metabolism by activating 5' adenosine monophosphate-activated protein kinase (AMPK) and lipolytic enzymes such as hormone-sensitive lipase (HSL) in the white adipose tissue (WAT). Altogether, our findings indicate that MPCE improves HFD-induced obesity and can be used as a curative agent in pharmaceuticals and nutraceuticals to alleviate obesity and related disorders.


Assuntos
Adipogenia , Citrus , Dieta Hiperlipídica , Dissacarídeos , Metabolismo Energético , Flavanonas , Camundongos Endogâmicos C57BL , Obesidade , Extratos Vegetais , Animais , Dieta Hiperlipídica/efeitos adversos , Obesidade/metabolismo , Obesidade/tratamento farmacológico , Obesidade/etiologia , Citrus/química , Camundongos , Metabolismo Energético/efeitos dos fármacos , Extratos Vegetais/farmacologia , Masculino , Adipogenia/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Células 3T3-L1 , Fármacos Antiobesidade/farmacologia , Fígado/metabolismo , Fígado/efeitos dos fármacos , Lipogênese/efeitos dos fármacos , Triglicerídeos/metabolismo , Triglicerídeos/sangue
19.
Nutrients ; 16(8)2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38674875

RESUMO

The prolonged consumption of a high-fat diet (HFD) leads to abnormal growth of the visceral adipose tissue (VAT), increased macrophage infiltration, and altered secretion of biologically active molecules. This is considered as a precondition for the development of obesity, inflammation, and obesity-related disorders. Therefore, we studied HFD-induced changes in the tissue levels of the inflammatory markers C-reactive protein, serum amyloid-A, and interleukin-4 in healthy male Wistar rats. The animals were first divided at random into two groups subjected to either a standard or a high-fat diet. The initial effect of the diet was evaluated after fourteen weeks. In order to study the diet duration effect, the standard diet was given to twelve animals from the HFD group, while the remaining continued with the HFD for an additional four weeks. Our results showed that the HFD barely affected body mass index, conicity, relative fat mass, and Lee indices, whereas it provoked adipocyte hypertrophy and gradually increased the levels of both the pro- and anti-inflammatory markers. The switch from the high-fat to the standard diet resulted in the comparatively fast restoration of the baseline levels of the studied molecules. Although, the prolonged consumption of an HFD causes adipocyte hypertrophy in healthy male animals, the inflammatory process in VAT is well-coordinated, time-dependent, and reversible.


Assuntos
Proteína C-Reativa , Dieta Hiperlipídica , Inflamação , Gordura Intra-Abdominal , Ratos Wistar , Animais , Masculino , Gordura Intra-Abdominal/metabolismo , Dieta Hiperlipídica/efeitos adversos , Proteína C-Reativa/metabolismo , Ratos , Proteína Amiloide A Sérica/metabolismo , Interleucina-4/metabolismo , Biomarcadores/sangue , Adipócitos , Obesidade/metabolismo , Obesidade/etiologia
20.
Nutrients ; 16(8)2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38674900

RESUMO

We aimed to investigate the associations between maternal intake of folate, vitamin B12, B6, B2, methionine, choline, phosphatidylcholine and betaine during the period surrounding pregnancy and offspring weight outcomes from birth to early adulthood. These associations were examined among 2454 mother-child pairs from the Nurses' Health Study II and Growing Up Today Study. Maternal energy-adjusted nutrient intakes were derived from food frequency questionnaires. Birth weight, body size at age 5 and repeated BMI measurements were considered. Overweight/obesity was defined according to the International Obesity Task Force (<18 years) and World Health Organization guidelines (18+ years). Among other estimands, we report relative risks (RRs) for offspring ever being overweight with corresponding 95% confidence intervals across quintiles of dietary factors, with the lowest quintile as the reference. In multivariate-adjusted models, higher maternal intakes of phosphatidylcholine were associated with a higher risk of offspring ever being overweight (RRQ5vsQ1 = 1.16 [1.01-1.33] p-trend: 0.003). The association was stronger among offspring born to mothers with high red meat intake (high red meat RRQ5vsQ1 = 1.50 [1.14-1.98], p-trend: 0.001; low red meat RRQ5vsQ1 = 1.05 [0.87-1.27], p-trend: 0.46; p-interaction = 0.13). Future studies confirming the association between a higher maternal phosphatidylcholine intake during pregnancy and offspring risk of being overweight or obese are needed.


Assuntos
Fenômenos Fisiológicos da Nutrição Materna , Sobrepeso , Humanos , Feminino , Gravidez , Estudos Prospectivos , Adulto , Sobrepeso/epidemiologia , Dieta/efeitos adversos , Fatores de Risco , Masculino , Obesidade/epidemiologia , Obesidade/etiologia , Pré-Escolar , Índice de Massa Corporal , Colina/administração & dosagem , Fosfatidilcolinas , Efeitos Tardios da Exposição Pré-Natal , Peso ao Nascer
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