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1.
Nat Commun ; 12(1): 5249, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34475397

RESUMO

The wake-active orexin system plays a central role in the dynamic regulation of glucose homeostasis. Here we show orexin receptor type 1 and 2 are predominantly expressed in dorsal raphe nucleus-dorsal and -ventral, respectively. Serotonergic neurons in ventral median raphe nucleus and raphe pallidus selectively express orexin receptor type 1. Inactivation of orexin receptor type 1 in serotonin transporter-expressing cells of mice reduced insulin sensitivity in diet-induced obesity, mainly by decreasing glucose utilization in brown adipose tissue and skeletal muscle. Selective inactivation of orexin receptor type 2 improved glucose tolerance and insulin sensitivity in obese mice, mainly through a decrease in hepatic gluconeogenesis. Optogenetic activation of orexin neurons in lateral hypothalamus or orexinergic fibers innervating raphe pallidus impaired or improved glucose tolerance, respectively. Collectively, the present study assigns orexin signaling in serotonergic neurons critical, yet differential orexin receptor type 1- and 2-dependent functions in the regulation of systemic glucose homeostasis.


Assuntos
Glucose/metabolismo , Obesidade/metabolismo , Receptores de Orexina/metabolismo , Neurônios Serotoninérgicos/metabolismo , Tecido Adiposo Marrom/metabolismo , Animais , Dieta Hiperlipídica/efeitos adversos , Homeostase , Região Hipotalâmica Lateral/citologia , Região Hipotalâmica Lateral/metabolismo , Resistência à Insulina , Fígado/metabolismo , Camundongos , Fibras Nervosas/metabolismo , Obesidade/etiologia , Receptores de Orexina/genética , Orexinas/metabolismo , Núcleos da Rafe/metabolismo , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo , Transdução de Sinais
2.
JAMA Netw Open ; 4(8): e2121675, 2021 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-34436611

RESUMO

Importance: Previous studies have shown reductions in self-reported physical activity levels in children associated with implementation of COVID-19 mitigation measures, and data on objectively assessed health parameters are limited. Objective: To examine the association of COVID-19 mitigation measures with changes in cardiorespiratory fitness (CRF) measures and body mass index (BMI) among primary schoolchildren. Design, Setting, and Participants: This cohort study included children aged 7 to 10 years from 12 randomly selected primary schools in urban and rural districts of Klagenfurt, Austria. Baseline CRF and BMI measurements were obtained in September 2019 before COVID-19 mitigation measures were implemented, and follow-up measurements were obtained in June and September 2020. Exposures: COVID-19 mitigation measures. Main Outcomes and Measures: Cardiorespiratory fitness was measured with a 6-minute endurance run test. Height and weight were objectively measured. Standard deviation scores were calculated for CRF and BMI. Changes over time were analyzed using analyses of variance. Secondary analyses were performed for subgroups stratified by sex. Results: A total of 764 children (383 girls [50.1%]) aged 7 to 10 years had all measurements completed. From September 2019 to September 2020, CRF SD scores changed by -1.06 (95% CI, -1.13 to -1.00), with a similar decrease in both boys and girls. Body mass index SD scores had increased by 0.12 (95% CI, 0.06-0.16) in June 2020 and by 0.16 (95% CI, 0.12-0.20) in September 2020 compared with September 2019. The increase in BMI SD scores (from September 2019 to September 2020) was greater among boys (0.23; 95% CI, 0.18-0.29) than among girls (0.09; 95% CI, 0.04-0.15). During the 1-year period, the percentage of children with overweight or obesity increased from 20.3% (155 children) to 24.1% (184 children) (difference, 3.8% [29 children]). Conclusions and Relevance: In this cohort study of children in Austria, COVID-19 mitigation measures were associated with decreases in CRF measures and increases in BMI. The findings suggest that collaborative efforts are needed to reverse these changes in children's health to prevent long-term negative health outcomes.


Assuntos
Índice de Massa Corporal , COVID-19 , Aptidão Cardiorrespiratória , Exercício Físico , Obesidade/etiologia , Pandemias , Distanciamento Físico , Áustria , COVID-19/prevenção & controle , Criança , Saúde da Criança , Estudos de Coortes , Feminino , Humanos , Masculino , Sobrepeso , SARS-CoV-2 , Instituições Acadêmicas , Esportes
3.
Nutrients ; 13(8)2021 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-34444957

RESUMO

The association between the consumption of ultra-processed food (UPF) with overweight/obesity in Chinese adults has not been investigated. This study included a cohort of 12,451 adults aged >20 years who participated at least twice in the China Nutrition and Health Survey (CNHS) during 1997-2011. Food intake at each survey was assessed using a 3-day 24-h dietary recall. Body weight (kg), height (m), and waist circumference (WC) were measured during the survey. UPF was defined by the NOVA classification. Mixed effect logistic regression analyses were used. The mean UPF consumption of the study population (baseline mean age 43.7 years) increased from 12.0 g in 1997 to 41.5 g in 2011 with the corresponding proportion of UPF in daily diet from 1.0% to 3.6%. The adjusted odds ratios (95% CI) for BMI ≥ 25 kg/m2 for those with mean UPF consumption of 1-19 g/d, 20-49 g/d, and ≥50 g/d were 1.45 (1.26-1.65), 1.34 (1.15-1.57), and 1.45 (1.21-1.74), respectively (p-trend = 0.015), compared with the non-consumers. Similarly, the corresponding adjusted ORs (95% CI) for central obesity were 1.54 (1.38-1.72), 1.35 (1.19-1.54), and 1.50 (1.29-1.74). Higher long-term UPF consumption was associated with increased risk of overweight/obesity among Chinese adults.


Assuntos
Dieta/estatística & dados numéricos , Fast Foods/estatística & dados numéricos , Obesidade/epidemiologia , Sobrepeso/epidemiologia , Adulto , China/epidemiologia , Dieta/efeitos adversos , Ingestão de Alimentos , Fast Foods/efeitos adversos , Feminino , Manipulação de Alimentos , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Obesidade/etiologia , Razão de Chances , Sobrepeso/etiologia , Adulto Jovem
4.
Int J Mol Sci ; 22(16)2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34445634

RESUMO

Cannabinoids have been reported as orexigenic, i.e., as promoting food intake that, among others, is controlled by the so-called "hunger" hormone, ghrelin. The aim of this paper was to look for functional and/or molecular interactions between ghrelin GHSR1a and cannabinoid CB2 receptors at the central nervous system (CNS) level. In a heterologous system we identified CB2-GHSR1a receptor complexes with a particular heteromer print consisting of impairment of CB2 receptor/Gi-mediated signaling. The blockade was due to allosteric interactions within the heteromeric complex as it was reverted by antagonists of the GHSR1a receptor. Cannabinoids acting on the CB2 receptor did not affect cytosolic increases of calcium ions induced by ghrelin acting on the GHSR1a receptor. In situ proximity ligation imaging assays confirmed the expression of CB2-GHSR1a receptor complexes in both heterologous cells and primary striatal neurons. We tested heteromer expression in neurons from offspring of high-fat-diet mouse mothers as they have more risk to be obese. Interestingly, there was a marked upregulation of those complexes in striatal neurons from siblings of pregnant female mice under a high-fat diet.


Assuntos
Corpo Estriado/patologia , Dieta Hiperlipídica/efeitos adversos , Grelina/metabolismo , Neurônios/patologia , Obesidade/patologia , Receptor CB2 de Canabinoide/metabolismo , Receptores de Grelina/metabolismo , Animais , Canabinoides/farmacologia , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Feminino , Grelina/genética , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Obesidade/etiologia , Obesidade/metabolismo , Receptor CB2 de Canabinoide/genética , Receptores de Grelina/genética , Transdução de Sinais , Regulação para Cima
5.
Nat Commun ; 12(1): 4878, 2021 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-34385447

RESUMO

A postprandial increase of translation mediated by eukaryotic Initiation Factor 6 (eIF6) occurs in the liver. Its contribution to steatosis and disease is unknown. In this study we address whether eIF6-driven translation contributes to disease progression. eIF6 levels increase throughout the progression from Non-Alcoholic Fatty Liver Disease (NAFLD) to hepatocellular carcinoma. Reduction of eIF6 levels protects the liver from disease progression. eIF6 depletion blunts lipid accumulation, increases fatty acid oxidation (FAO) and reduces oncogenic transformation in vitro. In addition, eIF6 depletion delays the progression from NAFLD to hepatocellular carcinoma, in vivo. Mechanistically, eIF6 depletion reduces the translation of transcription factor C/EBPß, leading to a drop in biomarkers associated with NAFLD progression to hepatocellular carcinoma and preserves mitochondrial respiration due to the maintenance of an alternative mTORC1-eIF4F translational branch that increases the expression of transcription factor YY1. We provide proof-of-concept that in vitro pharmacological inhibition of eIF6 activity recapitulates the protective effects of eIF6 depletion. We hypothesize the existence of a targetable, evolutionarily conserved translation circuit optimized for lipid accumulation and tumor progression.


Assuntos
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Hepatopatia Gordurosa não Alcoólica/genética , Fatores de Iniciação de Peptídeos/genética , Biossíntese de Proteínas/genética , Animais , Proteína beta Intensificadora de Ligação a CCAAT/genética , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Carcinoma Hepatocelular/metabolismo , Linhagem Celular , Transformação Celular Neoplásica/efeitos dos fármacos , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Clofazimina/farmacologia , Dieta Hiperlipídica/efeitos adversos , Progressão da Doença , Inativação Gênica , Humanos , Lipogênese/efeitos dos fármacos , Lipogênese/genética , Neoplasias Hepáticas/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Hepatopatia Gordurosa não Alcoólica/metabolismo , Obesidade/etiologia , Obesidade/genética , Obesidade/metabolismo , Fatores de Iniciação de Peptídeos/antagonistas & inibidores , Fatores de Iniciação de Peptídeos/metabolismo
6.
Nutrients ; 13(7)2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34371968

RESUMO

In recent decades, the prevalence of obesity has risen dramatically worldwide among all age groups. Obesity is characterized by excess fat accumulation and chronic low-grade inflammation. The adipose tissue functions as a metabolically active endocrine organ secreting adipokines. A novel duo of adipokines, the anti-inflammatory secreted frizzled-related protein 5 (Sfrp5) and the proinflammatory wingless type mouse mammary tumor virus (MMTV) integration site family member 5A (Wnt5a), signal via the non-canonical Wnt pathway. Recent evidence suggests that Sfpr5 and Wnt5a play a key role in the pathogenesis of obesity and its metabolic complications. This review summarizes the current knowledge on the novel regulatory system of anti-inflammatory Sfrp5 and pro-inflammatory Wnt5a, and their relation to obesity and obesity-related complications. Future studies are required to investigate the potential role of Sfrp5 and Wnt5a as biomarkers for monitoring the response to lifestyle interventions and for predicting the development of cardiometabolic risk factors. These adipokines may also serve as novel therapeutic targets for obesity-related disorders.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/fisiologia , Obesidade/etiologia , Proteína Wnt-5a/fisiologia , Tecido Adiposo/fisiopatologia , Adolescente , Adulto , Animais , Fatores de Risco Cardiometabólico , Criança , Dieta Saudável , Humanos , Inflamação/fisiopatologia , Resistência à Insulina , Estilo de Vida , Hepatopatia Gordurosa não Alcoólica , Obesidade/fisiopatologia , Obesidade/terapia
7.
Nat Commun ; 12(1): 4829, 2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34376643

RESUMO

Plasma hyaluronan (HA) increases systemically in type 2 diabetes (T2D) and the HA synthesis inhibitor, 4-Methylumbelliferone, has been proposed to treat the disease. However, HA is also implicated in normal physiology. Therefore, we generated a Hyaluronan Synthase 2 transgenic mouse line, driven by a tet-response element promoter to understand the role of HA in systemic metabolism. To our surprise, adipocyte-specific overproduction of HA leads to smaller adipocytes and protects mice from high-fat-high-sucrose-diet-induced obesity and glucose intolerance. Adipocytes also have more free glycerol that can be released upon beta3 adrenergic stimulation. Improvements in glucose tolerance were not linked to increased plasma HA. Instead, an HA-driven systemic substrate redistribution and adipose tissue-liver crosstalk contributes to the systemic glucose improvements. In summary, we demonstrate an unexpected improvement in glucose metabolism as a consequence of HA overproduction in adipose tissue, which argues against the use of systemic HA synthesis inhibitors to treat obesity and T2D.


Assuntos
Adipócitos/metabolismo , Tecido Adiposo/metabolismo , Dioxóis/farmacologia , Glucose/metabolismo , Ácido Hialurônico/metabolismo , Lipólise/efeitos dos fármacos , Adipócitos/citologia , Tecido Adiposo/citologia , Animais , Células Cultivadas , Diabetes Mellitus Tipo 2/metabolismo , Dieta Hiperlipídica/efeitos adversos , Feminino , Intolerância à Glucose/metabolismo , Homeostase , Humanos , Hipoglicemiantes/farmacologia , Masculino , Camundongos , Camundongos Transgênicos , Obesidade/etiologia , Obesidade/metabolismo
8.
Int J Mol Sci ; 22(15)2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34361032

RESUMO

17,18-Epoxyeicosatetraenoic acid (17,18-EEQ) and 19,20-epoxydocosapentaenoic acid (19,20-EDP) are bioactive epoxides produced from n-3 polyunsaturated fatty acid eicosapentaenoic acid and docosahexaenoic acid, respectively. However, these epoxides are quickly metabolized into less active diols by soluble epoxide hydrolase (sEH). We have previously demonstrated that an sEH inhibitor, t-TUCB, decreased serum triglycerides (TG) and increased lipid metabolic protein expression in the brown adipose tissue (BAT) of diet-induced obese mice. This study investigates the preventive effects of t-TUCB (T) alone or combined with 19,20-EDP (T + EDP) or 17,18-EEQ (T + EEQ) on BAT activation in the development of diet-induced obesity and metabolic disorders via osmotic minipump delivery in mice. Both T + EDP and T + EEQ groups showed significant improvement in fasting glucose, serum triglycerides, and higher core body temperature, whereas heat production was only significantly increased in the T + EEQ group. Moreover, both the T + EDP and T + EEQ groups showed less lipid accumulation in the BAT. Although UCP1 expression was not changed, PGC1α expression was increased in all three treated groups. In contrast, the expression of CPT1A and CPT1B, which are responsible for the rate-limiting step for fatty acid oxidation, was only increased in the T + EDP and T + EEQ groups. Interestingly, as a fatty acid transporter, CD36 expression was only increased in the T + EEQ group. Furthermore, both the T + EDP and T + EEQ groups showed decreased inflammatory NFκB signaling in the BAT. Our results suggest that 17,18-EEQ or 19,20-EDP combined with t-TUCB may prevent high-fat diet-induced metabolic disorders, in part through increased thermogenesis, upregulating lipid metabolic protein expression, and decreasing inflammation in the BAT.


Assuntos
Fármacos Antiobesidade/uso terapêutico , Ácidos Araquidônicos/uso terapêutico , Benzoatos/uso terapêutico , Obesidade/tratamento farmacológico , Compostos de Fenilureia/uso terapêutico , Adipogenia , Tecido Adiposo Marrom/citologia , Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Marrom/metabolismo , Animais , Fármacos Antiobesidade/administração & dosagem , Fármacos Antiobesidade/farmacologia , Ácidos Araquidônicos/administração & dosagem , Ácidos Araquidônicos/farmacologia , Benzoatos/administração & dosagem , Benzoatos/farmacologia , Glicemia/metabolismo , Carnitina O-Palmitoiltransferase/metabolismo , Dieta Hiperlipídica , Epóxido Hidrolases/antagonistas & inibidores , Ácidos Graxos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Obesidade/etiologia , Obesidade/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Compostos de Fenilureia/administração & dosagem , Compostos de Fenilureia/farmacologia
9.
Nutrients ; 13(7)2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34371851

RESUMO

Diet-induced obesity reduces dopaminergic neurotransmission in the nucleus accumbens (NAc), and stressful weight loss interventions could promote cravings for palatable foods high in fat and sugar that stimulate dopamine. Activation of κ-opioid receptors (KORs) reduces synaptic dopamine, but contribution of KORs to lower dopamine tone after dietary changes is unknown. Therefore, the purpose of this study was to determine the function of KORs in C57BL/6 mice that consumed a 60% high-fat diet (HFD) for six weeks followed by replacement of HFD with a control 10% fat diet for one day or one week. HFD replacement induced voluntary caloric restriction and weight loss. However, fast-scan cyclic voltammetry revealed no differences in baseline dopamine parameters, whereas sex effects were revealed during KOR stimulation. NAc core dopamine release was reduced by KOR agonism after one day of HFD replacement in females but after one week of HFD replacement in males. Further, elevated plus-maze testing revealed no diet effects during HFD replacement on overt anxiety. These results suggest that KORs reduce NAc dopamine tone and increase food-related anxiety during dietary weight loss interventions that could subsequently promote palatable food cravings and inhibit weight loss.


Assuntos
Dieta com Restrição de Gorduras/métodos , Dopamina/metabolismo , Núcleo Accumbens/metabolismo , Obesidade/metabolismo , Receptores Opioides kappa/efeitos dos fármacos , Animais , Dieta Hiperlipídica/efeitos adversos , Gorduras na Dieta/farmacologia , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/etiologia , Transmissão Sináptica/efeitos dos fármacos
10.
Nutrients ; 13(7)2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34371839

RESUMO

The obesity pandemic is associated with increased consumption of restaurant food. Labeling of menus is an intervention used to provide consumers with kilocalorie (calorie) information in hopes of them making healthier food choices. This study evaluated the relationship between young adults' calorie choices on restaurant menus and menu design, dietary behaviors, and demographic characteristics. A 3 (fast-casual restaurants) × 4 (menu-designs based on menu engineering theories) between-subjects (n = 480, 18-24-year olds) experimental design was used. The relationship between the participants' calorie choices (high versus low) and menu design, stage of change, gender, race, educational level and weight status was evaluated using logistic regression. All independent variables had at least one category that had greater odds (CI 95% ± 5%) of subjects choosing a lower calorie entree, except education level and race/ethnic group. Normal weight and overweight subjects had greater odds of choosing lower calorie entrees than those that were obese. In addition, subjects that had started to control their calorie intake for less than six months or had sustained this change for at least six months, had greater odds of choosing lower calorie entrees compared to others. Including a green symbol and calories on fast casual restaurant menus may influence some young adults to choose lower calorie entrees.


Assuntos
Comportamento de Escolha , Dieta Saudável/psicologia , Fast Foods/análise , Rotulagem de Alimentos/métodos , Preferências Alimentares/psicologia , Adolescente , Comportamento do Consumidor , Ingestão de Energia , Fast Foods/efeitos adversos , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Masculino , Valor Nutritivo , Obesidade/etiologia , Obesidade/psicologia , Restaurantes , Adulto Jovem
11.
Przegl Epidemiol ; 75(1): 45-50, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34338337

RESUMO

Currently, the issue of lifestyle combined with lack of physical activity in quarantine conditions during the COVID-19 pandemic has become a major health problem in many countries around the world. Increased inactivity is associated with increased obesity as well as decreased physical activity and general health. Kidney stones are the third most common urinary tract disease. Prevention of non-communicable diseases depends on controlling risk factors such as low levels of physical activity. Kidney stones are also among the noncommunicable diseases that can be prevented by changing behavioral habits. Physical activity is a behavior that has many proven health benefits and is one of the most effective ways to prevent chronic diseases. The aim of this study was to investigate sedentary lifestyle and its relationship with oxidative stress and kidney stone formation, and finally to provide medical solutions and recommendations.


Assuntos
COVID-19/prevenção & controle , Exercício Físico/fisiologia , Cálculos Renais/etiologia , Obesidade/etiologia , Pandemias/prevenção & controle , Quarentena , Comportamento Sedentário , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polônia , Medição de Risco , Fatores de Risco , SARS-CoV-2
12.
Int J Health Geogr ; 20(1): 34, 2021 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-34320996

RESUMO

BACKGROUND: Obesity remains one of the most challenging public health issues of our modern time. Despite the face validity of claims for influence, studies on the causes of obesity have reported the influence of the food environment to be inconsistent. This inconsistency has been attributed to the variability of measures used by researchers to represent the food environments-Researcher-Defined Food Environments (RDFE) like circular, street-network buffers, and others. This study (i.) determined an individual's Activity Space (AS) (ii.) explored the accuracy of the RDFE in representing the AS, (iii.) investigated the accuracy of the RDFE in representing actual exposure, and (iv.) explored whether exposure to food outlet reflects the use of food outlets. METHODS: Data were collected between June and December 2018. A total of 65 participants collected Global Positioning System (GPS) data, kept receipt of all their food purchases, completed a questionnaire about their personal information and had their weight and height measured. A buffer was created around the GPS points and merged to form an AS (GPS-based AS). RESULTS: Statistical and geospatial analyses found that the AS size of participants working away from home was positively related to the Euclidean distance from home to workplace; the orientation (shape) of AS was also influenced by the direction of workplace from home and individual characteristics were not predictive of the size of AS. Consistent with some previous studies, all types and sizes of RDFE variably misrepresented individual exposure in the food environments. Importantly, the accuracy of the RDFE was significantly improved by including both the home and workplace domains. The study also found no correlation between exposure and use of food outlets. CONCLUSIONS: Home and workplace are key activity nodes in modelling AS or food environments and the relationship between exposure and use is more complex than is currently suggested in both empirical and policy literature.


Assuntos
Abastecimento de Alimentos , Sistemas de Informação Geográfica , Humanos , Obesidade/diagnóstico , Obesidade/epidemiologia , Obesidade/etiologia , Características de Residência , Inquéritos e Questionários , Local de Trabalho
13.
Nat Genet ; 53(8): 1233-1242, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34326545

RESUMO

The agouti viable yellow (Avy) allele is an insertional mutation in the mouse genome caused by a variably methylated intracisternal A particle (VM-IAP) retrotransposon. Avy expressivity is sensitive to a range of early-life chemical exposures and nutritional interventions, suggesting that environmental perturbations can have long-lasting effects on the methylome. However, the extent to which VM-IAP elements are environmentally labile with phenotypic implications is unknown. Using a recently identified repertoire of VM-IAPs, we assessed the epigenetic effects of different environmental contexts. A longitudinal aging analysis indicated that VM-IAPs are stable across the murine lifespan, with only small increases in DNA methylation detected for a subset of loci. No significant effects were observed after maternal exposure to the endocrine disruptor bisphenol A, an obesogenic diet or methyl donor supplementation. A genetic mouse model of abnormal folate metabolism exhibited shifted VM-IAP methylation levels and altered VM-IAP-associated gene expression, yet these effects are likely largely driven by differential targeting by polymorphic KRAB zinc finger proteins. We conclude that epigenetic variability at retrotransposons is not predictive of environmental susceptibility.


Assuntos
Metilação de DNA , Disruptores Endócrinos/toxicidade , Obesidade/genética , Retroelementos , Animais , Compostos Benzidrílicos/toxicidade , Metilação de DNA/efeitos dos fármacos , Dieta/efeitos adversos , Epigênese Genética , Feminino , Ferredoxina-NADP Redutase/genética , Ácido Fólico/genética , Ácido Fólico/metabolismo , Deficiência de Ácido Fólico/genética , Regulação da Expressão Gênica , Masculino , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Mutação , Obesidade/etiologia , Fenóis/toxicidade , Gravidez , Efeitos Tardios da Exposição Pré-Natal
14.
J Endocrinol ; 251(1): 27-39, 2021 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-34265741

RESUMO

High-fat diet (HFD) consumption induces prediabetes and left ventricular dysfunction through many pathways including cell death pathway like necroptosis. Although the benefit of necroptosis inhibitor (necrostatin-1 or Nec-1) in the brain of prediabetic rats was shown, the effects of Nec-1 on cardiac autonomic function, blood pressure, cardiac function, along with its mechanistic insight have not been investigated. Male Wistar rats were fed with either a normal diet (n = 8) or HFD (n = 24) for 12 weeks to induce prediabetes. Prediabetic rats were randomly assigned into three interventional groups (n = 8/group): (1) vehicle, (2) Nec-1 (1.65 mg/kg, sc injection), and (3) metformin (300 mg/kg, oral gavage feeding). Treatments lasted for 8 weeks. Normal saline was given to normal diet-fed rats and vehicle group. Metabolic parameters, cardiac function and biochemical parameters were assessed. Prediabetic rats exhibited peripheral metabolic impairment as indicated by increased body weight, hyperinsulinemia with euglycemia, and dyslipidemia. Prediabetic rats also had cardiac autonomic imbalance, high blood pressure, and cardiac dysfunction, together with cardiac mitochondrial dysfunction, mitochondrial dynamic imbalance, and increased necroptosis and apoptosis. Treatment with Nec-1 did not affect peripheral metabolic parameters, however, it effectively reduced cardiac autonomic imbalance, blood pressure, and cardiac dysfunction via reducing cardiac inflammation, necroptosis, mitochondrial dysfunction, and increased mitochondrial fusion. Treatment with metformin reduced peripheral metabolic impairment and cardiac dysfunction via decreased cardiac mitochondrial dysfunction, mitochondrial dynamic imbalance, and apoptosis. In summary, Nec-1 directly suppressed necroptosis, cardiac mitochondrial dysfunction, and increased mitochondrial fusion independent of peripheral metabolic function, leading to an improved cardiac function in prediabetic rats.


Assuntos
Imidazóis/farmacologia , Indóis/farmacologia , Mitocôndrias Cardíacas/efeitos dos fármacos , Estado Pré-Diabético/induzido quimicamente , Estado Pré-Diabético/complicações , Disfunção Ventricular Esquerda/tratamento farmacológico , Disfunção Ventricular Esquerda/etiologia , Animais , Dieta Hiperlipídica/efeitos adversos , Imidazóis/uso terapêutico , Indóis/uso terapêutico , Resistência à Insulina , Masculino , Metformina/farmacologia , Obesidade/etiologia , Distribuição Aleatória , Ratos , Ratos Wistar
15.
Pain Res Manag ; 2021: 5563959, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34257764

RESUMO

Obese animals and humans demonstrate higher sensitivity to pain stimuli. Among the endogenous factors prompting obesity, the intestinal microbiota has been proposed to influence responsiveness to pain. The beneficial effects of probiotics on obesity are well documented, whereas data on their analgesic efficacy is minimal. The protective effect of probiotics on nociception in diet-induced obese male mice has been previously demonstrated, but the sex differences in pain sensitivity and analgesic response do not allow for the generalization of these findings to the female gender. Hence, this study aimed at investigating the potential effects of oral probiotic supplementation on mechanical pain thresholds in female diet-induced obese mice compared with controls. Thirty-two adult female mice (N=32) were randomly divided into two groups receiving standard (normal-weight group; NW) or high-fat diet (diet-induced obesity; DIO). All rats received a single daily dose (1 × 109 CFU) of probiotics (Lactobacillus rhamnosus PB01, DSM14870) for four weeks by gavage. Mechanical pain thresholds were recorded by an electronic von Frey device at baseline, at the end of weeks 2, 4, 6, and 8 in both DIO and NW groups with and without consumption of probiotics. Blood samples were obtained for the measurement of lipid profile and reproductive hormone levels. Bodyweight was considerably lower (P < 0.001) in groups supplied with probiotics than groups without probiotics. Pressure pain threshold values showed a significant (P < 0.001) increase (reduced pain sensitivity) following probiotic supplementation, proposing a modulatory effect of probiotics on mechanical sensory circuits and mechanical sensitivity, which might be a direct consequence of weight loss or an indirect result of the probiotics' anti-inflammatory properties. Understanding the precise underlying mechanism for the effect of probiotics on weight loss and mechanical pain sensitivity seen in this study warrants further investigation.


Assuntos
Lactobacillus rhamnosus/química , Obesidade/dietoterapia , Probióticos/farmacologia , Animais , Dieta Hiperlipídica/efeitos adversos , Feminino , Camundongos , Obesidade/etiologia
16.
Nutrients ; 13(6)2021 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-34203025

RESUMO

Clinical decision support systems (CDSS) are data aggregation tools based on computer technology that assist clinicians to promote healthy weight management and prevention of cardiovascular diseases. We carried out a randomised controlled 3-month trial to implement lifestyle modifications in breast cancer (BC) patients by means of CDSS during the COVID-19 pandemic. In total, 55 BC women at stages I-IIIA were enrolled. They were randomly assigned either to Control group, receiving general lifestyle advice (n = 28) or the CDSS group (n = 27), to whom the CDSS provided personalised dietary plans based on the Mediterranean diet (MD) together with physical activity guidelines. Food data, anthropometry, blood markers and quality of life were evaluated. At 3 months, higher adherence to MD was recorded in the CDSS group, accompanied by lower body weight (kg) and body fat mass percentage compared to control (p < 0.001). In the CDSS arm, global health/quality of life was significantly improved at the trial endpoint (p < 0.05). Fasting blood glucose and lipid levels (i.e., cholesterol, LDL, triacylglycerols) of the CDSS arm remained unchanged (p > 0.05) but were elevated in the control arm at 3 months (p < 0.05). In conclusion, CDSS could be a promising tool to assist BC patients with lifestyle modifications during the COVID-19 pandemic.


Assuntos
Neoplasias da Mama , COVID-19 , Sistemas de Apoio a Decisões Clínicas , Dieta Mediterrânea , Estilo de Vida , Obesidade/prevenção & controle , Pandemias , Tecido Adiposo/metabolismo , Adulto , Terapia Comportamental , Glicemia/metabolismo , Índice de Massa Corporal , Peso Corporal , LDL-Colesterol/sangue , Feminino , Nível de Saúde , Humanos , Pessoa de Meia-Idade , Obesidade/etiologia , Cooperação do Paciente , Qualidade de Vida , SARS-CoV-2 , Triglicerídeos/sangue
17.
Nutrients ; 13(6)2021 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-34205138

RESUMO

The pandemic of Coronavirus Disease 2019 (COVID-19) has shocked world health authorities generating a global health crisis. The present study discusses the main finding in nutrition sciences associated with COVID-19 in the literature. We conducted a consensus critical review using primary sources, scientific articles, and secondary bibliographic indexes, databases, and web pages. The method was a narrative literature review of the available literature regarding nutrition interventions and nutrition-related factors during the COVID-19 pandemic. The main search engines used in the present research were PubMed, SciELO, and Google Scholar. We found how the COVID-19 lockdown promoted unhealthy dietary changes and increases in body weight of the population, showing obesity and low physical activity levels as increased risk factors of COVID-19 affection and physiopathology. In addition, hospitalized COVID-19 patients presented malnutrition and deficiencies in vitamin C, D, B12 selenium, iron, omega-3, and medium and long-chain fatty acids highlighting the potential health effect of vitamin C and D interventions. Further investigations are needed to show the complete role and implications of nutrition both in the prevention and in the treatment of patients with COVID-19.


Assuntos
COVID-19 , Controle de Doenças Transmissíveis , Dieta , Comportamento Alimentar , Estilo de Vida , Estado Nutricional , Pandemias , Exercício Físico , Feminino , Comportamentos Relacionados com a Saúde , Hospitalização , Humanos , Masculino , Nutrientes/deficiência , Obesidade/etiologia , SARS-CoV-2
18.
Nat Commun ; 12(1): 4623, 2021 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-34330904

RESUMO

Visceral obesity increases risk of cognitive decline in humans, but subcutaneous adiposity does not. Here, we report that beige adipocytes are indispensable for the neuroprotective and anti-inflammatory effects of subcutaneous fat. Mice lacking functional beige fat exhibit accelerated cognitive dysfunction and microglial activation with dietary obesity. Subcutaneous fat transplantation also protects against chronic obesity in wildtype mice via beige fat-dependent mechanisms. Beige adipocytes restore hippocampal synaptic plasticity following transplantation, and these effects require the anti-inflammatory cytokine interleukin-4 (IL4). After observing beige fat-mediated induction of IL4 in meningeal T-cells, we investigated the contributions of peripheral lymphocytes in donor fat. There was no sign of donor-derived lymphocyte trafficking between fat and brain, but recipient-derived lymphocytes were required for the effects of transplantation on cognition and microglial morphology. These findings indicate that beige adipocytes oppose obesity-induced cognitive impairment, with a potential role for IL4 in the relationship between beige fat and brain function.


Assuntos
Adipócitos Bege/metabolismo , Tecido Adiposo Bege/metabolismo , Adiposidade , Obesidade/metabolismo , Gordura Subcutânea/metabolismo , Adipócitos Bege/citologia , Animais , Anti-Inflamatórios/metabolismo , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/fisiopatologia , Dieta Hiperlipídica/efeitos adversos , Humanos , Interleucina-4/metabolismo , Camundongos Obesos , Plasticidade Neuronal/fisiologia , Fármacos Neuroprotetores/metabolismo , Obesidade/etiologia , Obesidade/fisiopatologia , Gordura Subcutânea/transplante , Linfócitos T/metabolismo
19.
Commun Biol ; 4(1): 826, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34211098

RESUMO

Genome-wide association studies have identified SLC16A13 as a novel susceptibility gene for type 2 diabetes. The SLC16A13 gene encodes SLC16A13/MCT13, a member of the solute carrier 16 family of monocarboxylate transporters. Despite its potential importance to diabetes development, the physiological function of SLC16A13 is unknown. Here, we validate Slc16a13 as a lactate transporter expressed at the plasma membrane and report on the effect of Slc16a13 deletion in a mouse model. We show that Slc16a13 increases mitochondrial respiration in the liver, leading to reduced hepatic lipid accumulation and increased hepatic insulin sensitivity in high-fat diet fed Slc16a13 knockout mice. We propose a mechanism for improved hepatic insulin sensitivity in the context of Slc16a13 deficiency in which reduced intrahepatocellular lactate availability drives increased AMPK activation and increased mitochondrial respiration, while reducing hepatic lipid content. Slc16a13 deficiency thereby attenuates hepatic diacylglycerol-PKCε mediated insulin resistance in obese mice. Together, these data suggest that SLC16A13 is a potential target for the treatment of type 2 diabetes and non-alcoholic fatty liver disease.


Assuntos
Diabetes Mellitus Tipo 2/genética , Predisposição Genética para Doença/genética , Resistência à Insulina/genética , Metabolismo dos Lipídeos/genética , Transportadores de Ácidos Monocarboxílicos/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Diabetes Mellitus Tipo 2/metabolismo , Dieta Hiperlipídica/efeitos adversos , Expressão Gênica , Humanos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mitocôndrias/metabolismo , Transportadores de Ácidos Monocarboxílicos/deficiência , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Obesidade/etiologia , Obesidade/genética , Obesidade/metabolismo , Consumo de Oxigênio/genética
20.
Int J Mol Sci ; 22(12)2021 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-34201257

RESUMO

Despite the substantial role played by the hypothalamus in the regulation of energy balance and glucose homeostasis, the exact mechanisms and neuronal circuits underlying this regulation remain poorly understood. In the last 15 years, investigations using transgenic models, optogenetic, and chemogenetic approaches have revealed that SF1 neurons in the ventromedial hypothalamus are a specific lead in the brain's ability to sense glucose levels and conduct insulin and leptin signaling in energy expenditure and glucose homeostasis, with minor feeding control. Deletion of hormonal receptors, nutritional sensors, or synaptic receptors in SF1 neurons triggers metabolic alterations mostly appreciated under high-fat feeding, indicating that SF1 neurons are particularly important for metabolic adaptation in the early stages of obesity. Although these studies have provided exciting insight into the implications of hypothalamic SF1 neurons on whole-body energy homeostasis, new questions have arisen from these results. Particularly, the existence of neuronal sub-populations of SF1 neurons and the intricate neurocircuitry linking these neurons with other nuclei and with the periphery. In this review, we address the most relevant studies carried out in SF1 neurons to date, to provide a global view of the central role played by these neurons in the pathogenesis of obesity and diabetes.


Assuntos
Diabetes Mellitus/patologia , Hipotálamo/patologia , Neurônios/patologia , Obesidade/patologia , Fator Esteroidogênico 1/metabolismo , Animais , Diabetes Mellitus/etiologia , Diabetes Mellitus/metabolismo , Humanos , Hipotálamo/metabolismo , Neurônios/metabolismo , Obesidade/etiologia , Obesidade/metabolismo
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