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1.
PLoS One ; 15(2): e0228932, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32040532

RESUMO

Although the beneficial effects of probiotics in the prevention or treatment of metabolic disorders have been extensively researched, the precise mechanisms by which probiotics improve metabolic homeostasis are still not clear. Given that probiotics usually exert a comprehensive effect on multiple metabolic disorders, defining a concurrent mechanism underlying the multiple effects is critical to understand the function of probiotics. In this study, we identified the SIRT1-dependent or independent PGC-1α pathways in multiple organs that mediate the protective effects of a strain of Lactobacillus plantarum against high-fat diet-induced adiposity, glucose intolerance, and dyslipidemia. L. plantarum treatment significantly enhanced the expression of SIRT1, PPARα, and PGC-1α in the liver and adipose tissues under HFD-fed condition. L. plantarum treated mice also exhibited significantly increased expressions of genes involved in bile acid synthesis and reverse cholesterol transport in the liver, browning and thermogenesis of adipose tissue, and fatty acid oxidation in the liver and adipose tissue. Additionally, L. plantarum treatment significantly upregulated the expressions of adiponectin in adipose tissue, irisin in skeletal muscle and subcutaneous adipose tissue (SAT), and FGF21 in SAT. These beneficial changes were associated with a significantly improved HFD-induced alteration of gut microbiota. Our findings suggest that the PGC-1α-mediated pathway could be regarded as a potential target in the development of probiotics-based therapies for the prevention and treatment of metabolic disorders.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Doenças Metabólicas/prevenção & controle , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Probióticos/uso terapêutico , Tecido Adiposo/metabolismo , Adiposidade , Animais , Ácidos e Sais Biliares/biossíntese , Colesterol/metabolismo , Dislipidemias/metabolismo , Dislipidemias/prevenção & controle , Dislipidemias/terapia , Microbioma Gastrointestinal , Intolerância à Glucose/metabolismo , Intolerância à Glucose/prevenção & controle , Intolerância à Glucose/terapia , Lactobacillus plantarum/fisiologia , Metabolismo dos Lipídeos , Fígado/metabolismo , Masculino , Doenças Metabólicas/metabolismo , Doenças Metabólicas/terapia , Camundongos , Camundongos Endogâmicos C57BL , Transdução de Sinais , Sirtuína 1/metabolismo
2.
Life Sci ; 244: 117305, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31953161

RESUMO

Diabetes mellitus (DM) is a complex metabolic disorder involving multiple deleterious molecular pathways and cellular defects leading to disturbance in the biologic milieu. It is currently a global health concern with growing incidence, especially among younger adults. There is an unmet need to find new therapeutic targets for the management of diabetes. Vitamin D is a promising target in the pathophysiology of DM, especially since vitamin D deficiency is common in patients with diabetes compared to people without diabetes. Evidence suggests that it can play significant roles in improving peripheral insulin sensitivity and glucose metabolism, however, the exact pathophysiological mechanism is not clarified yet. In this current study, we have reviewed the evidence on the effect of vitamin D in improving insulin resistance via distinct molecular pathways.


Assuntos
Intolerância à Glucose/prevenção & controle , Homeostase , Deficiência de Vitamina D/complicações , Vitamina D/administração & dosagem , Vitaminas/administração & dosagem , Animais , Intolerância à Glucose/etiologia , Humanos
3.
Nutrients ; 11(9)2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31443365

RESUMO

Development of obesity-associated comorbidities is related to chronic inflammation, which has been linked to gut microbiota dysbiosis. Thus, modulating gut microbiota composition could have positive effects for metabolic disorders, supporting the use of probiotics as potential therapeutics in vivo, which may be enhanced by a microencapsulation technique. Here we investigated the effects of non-encapsulated or pectin-encapsulated probiotic supplementation (Lactobacillus paracasei subsp. paracasei L. casei W8®; L. casei W8) on gut microbiota composition and metabolic profile in high-fat (HF) diet-fed rats. Four male Wistar rat groups (n = 8/group) were fed 10% low-fat, 45% HF, or HF with non-encapsulated or encapsulated L. casei W8 (4 × 107 CFU/g diet) diet for seven weeks. Microbiota composition, intestinal integrity, inflammatory profiles, and glucose tolerance were assessed. Non-encapsulated and pectin-encapsulated probiotic supplementation positively modulated gut microbiota composition in HF-fed male rats. These changes were associated with improvements in gut barrier functions and local and systemic inflammation by non-encapsulated probiotics and improvement in glucose tolerance by encapsulated probiotic treatment. Thus, these findings suggest the potential of using oral non-encapsulated or encapsulated probiotic supplementation to ameliorate obesity-associated metabolic abnormalities.


Assuntos
Glicemia/metabolismo , Dieta Hiperlipídica , Microbioma Gastrointestinal , Intolerância à Glucose/prevenção & controle , Inflamação/prevenção & controle , Intestinos/microbiologia , Lactobacillus/crescimento & desenvolvimento , Probióticos/administração & dosagem , Animais , Modelos Animais de Doenças , Disbiose , Metabolismo Energético , Intolerância à Glucose/sangue , Intolerância à Glucose/etiologia , Intolerância à Glucose/microbiologia , Inflamação/sangue , Inflamação/etiologia , Inflamação/microbiologia , Mediadores da Inflamação/sangue , Insulina/sangue , Masculino , Permeabilidade , Ratos Wistar
4.
Am J Physiol Endocrinol Metab ; 317(2): E362-E373, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31237447

RESUMO

Skeletal muscle insulin resistance manifests shortly after high-fat feeding, yet mechanisms are not known. Here we set out to determine whether excess skeletal muscle membrane cholesterol and cytoskeletal derangement known to compromise glucose transporter (GLUT)4 regulation occurs early after high-fat feeding. We fed 6-wk-old male C57BL/6NJ mice either a low-fat (LF, 10% kcal) or a high-fat (HF, 45% kcal) diet for 1 wk. This HF feeding challenge was associated with an increase, albeit slight, in body mass, glucose intolerance, and hyperinsulinemia. Liver analyses did not reveal signs of hepatic insulin resistance; however, skeletal muscle immunoblots of triad-enriched regions containing transverse tubule membrane showed a marked loss of stimulated GLUT4 recruitment. An increase in cholesterol was also found in these fractions from HF-fed mice. These derangements were associated with a marked loss of cortical filamentous actin (F-actin) that is essential for GLUT4 regulation and known to be compromised by increases in membrane cholesterol. Both the withdrawal of the HF diet and two subcutaneous injections of the cholesterol-lowering agent methyl-ß-cyclodextrin at 3 and 6 days during the 1-wk HF feeding intervention completely mitigated cholesterol accumulation, cortical F-actin loss, and GLUT4 dysregulation. Moreover, these beneficial membrane/cytoskeletal changes occurred concomitant with a full restoration of metabolic responses. These results identify skeletal muscle membrane cholesterol accumulation as an early, reversible, feature of insulin resistance and suggest cortical F-actin loss as an early derangement of skeletal muscle insulin resistance.


Assuntos
Membrana Celular/metabolismo , Colesterol/metabolismo , Dieta Hiperlipídica/efeitos adversos , Intolerância à Glucose/etiologia , Resistência à Insulina , Músculo Esquelético/metabolismo , Animais , Membrana Celular/efeitos dos fármacos , Colesterol/farmacologia , Dieta Ocidental/efeitos adversos , Gorduras na Dieta/farmacologia , Intolerância à Glucose/metabolismo , Intolerância à Glucose/prevenção & controle , Hiperinsulinismo/etiologia , Hiperinsulinismo/metabolismo , Hiperinsulinismo/prevenção & controle , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Músculo Esquelético/efeitos dos fármacos , beta-Ciclodextrinas/farmacologia , beta-Ciclodextrinas/uso terapêutico
5.
Zhonghua Nei Ke Za Zhi ; 58(5): 372-376, 2019 May 01.
Artigo em Chinês | MEDLINE | ID: mdl-31060146

RESUMO

Objective: To explore the influence of lifestyle intervention on long-term diabetes in subjects with impaired glucose tolerance (IGT) returned to normal glucose tolerance (NGT) within 6 years. Methods: A total of 577 subjects (aged 25-74 years old) with IGT in Daqing were enrolled and randomly assigned to control, and diet, exercise and diet plus exercise groups in a six-year intervention trial in 1986. Subjects who were non-diabetic at the end of the intervention were followed up for additional 14 years. Results: Among all the subjects, 41.38% of them who had returned to NGT from IGT within 6 years maintained NGT status after 20 years, and had a lower incidence of diabetes than subjects maintained IGT status (46.55% vs. 75.25%). Of note, in the intervention group, the percentage of participants developed diabetes in the NGT subjects was significantly lower than that in the IGT group (43.71% vs. 76.25%) after 20 years. There was high long-term risk for diabetes in the IGT subjects after the adjustment of age, sex and baseline glucose (HR=1.81, 95%CI 1.27-2.58, P=0.001), whereas in the non-intervention group, no significant difference could be viewed in long-term diabetic risk between subjects maintained IGT status and those returned to NGT (71.43% vs. 65.22%) after adjusting of the same confounders (HR=1.03, 95%CI 0.45-2.35, P=0.94). Conclusions: IGT subjects who had returned to NGT in early years had lower risk for future diabetes than those who remained IGT. However, this beneficial effect could only be viewed in the intervention group, but not in the non-intervention group.


Assuntos
Diabetes Mellitus Tipo 2/prevenção & controle , Intolerância à Glucose/prevenção & controle , Insulina/metabolismo , Adulto , Idoso , Glicemia/análise , Diabetes Mellitus Tipo 2/diagnóstico , Exercício Físico , Seguimentos , Intolerância à Glucose/complicações , Teste de Tolerância a Glucose , Hemoglobina A Glicada/análise , Humanos , Hiperglicemia/complicações , Hiperglicemia/diagnóstico , Pessoa de Meia-Idade , Comportamento de Redução do Risco
6.
Int J Mol Sci ; 20(10)2019 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-31100973

RESUMO

It is known that green tea helps prevent obesity and diabetes mellitus. In this study, we aimed to determine whether green tea ameliorates hyperglycemia and the mechanism involved in diabetic rodents. Green tea consumption reduced blood glucose and ameliorated glucose intolerance, which was assessed using an oral glucose tolerance test in both streptozotocin-induced type 1 diabetic rats and type 2 diabetic KK-Ay mice. Green tea also reduced the plasma fructosamine and glycated hemoglobin concentrations in both models. Furthermore, it increased glucose uptake into the skeletal muscle of both model animals, which was accompanied by greater translocation of glucose transporter 4 (GLUT4). Moreover, epigallocatechin gallate (EGCG), the principal catechin in green tea, also ameliorated glucose intolerance in high-fat diet-induced obese and diabetic mice. These results suggest that green tea can ameliorate hyperglycemia in diabetic rodents by stimulating GLUT4-mediated glucose uptake in skeletal muscle, and that EGCG is one of the effective compounds that mediate this effect.


Assuntos
Diabetes Mellitus Experimental/prevenção & controle , Transportador de Glucose Tipo 4/metabolismo , Hiperglicemia/prevenção & controle , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Extratos Vegetais/farmacologia , Chá/química , Animais , Catequina/análogos & derivados , Catequina/farmacologia , Dieta Hiperlipídica , Frutosamina/sangue , Glucose/metabolismo , Intolerância à Glucose/metabolismo , Intolerância à Glucose/prevenção & controle , Teste de Tolerância a Glucose , Hemoglobina A Glicada , Hiperglicemia/metabolismo , Lipídeos/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/prevenção & controle , Ratos , Ratos Wistar , Roedores , Estreptozocina/farmacologia
7.
Diabetes Metab Res Rev ; 35(4): e3127, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30635961

RESUMO

AIM: To investigate whether high-intensity breastfeeding (HIB) reduces insulin resistance during early post-partum period in women with gestational diabetes (GDM), independent of post-partum weight change (PWC). MATERIALS AND METHODS: In this multicentre prospective study, we included Japanese women with GDM who underwent a 75-g oral glucose tolerance test (OGTT) during early post-partum. We measured plasma insulin during OGTT to obtain a homeostasis model of assessment of insulin resistance (HOMA-IR). We defined the condition in which infants were fed by breastfeeding alone or greater than or equal to 80% of the volume as HIB, and other statuses, including partial and nonbreastfeeding, as non-HIB. We investigated the association between post-partum HOMA-IR and the breastfeeding status after adjusting for confounders including PWC. RESULTS: Among 222 women with GDM who underwent the OGTT at 7.9 ± 2.3 weeks post-partum with a PWC of -7.8 ± 3.4 kg, although the rate of abnormal glucose tolerance (prediabetes and diabetes) did not differ between the groups (33% vs 32%), the HOMA-IR in the HIB women (n = 166) was significantly lower than that in the non-HIB women (n = 56) (1.12 ± 0.85 vs 1.72 ± 1.43, P = 0.0002). The effect of the HIB was independently associated with lower HOMA-IR after adjusting for confounders including PMC. However, the subgroup analysis according to their pre-pregnancy obesity states showed that the effect was seen only in the obese subjects (BMI ≥ 25). CONCLUSIONS: In obese Japanese women with GDM, HIB has a significant effect in reducing insulin resistance during early post-partum, independent of the post-partum weight loss.


Assuntos
Aleitamento Materno/estatística & dados numéricos , Diabetes Mellitus Tipo 2/prevenção & controle , Diabetes Gestacional/reabilitação , Intolerância à Glucose/prevenção & controle , Resistência à Insulina , Adulto , Biomarcadores/análise , Glicemia/análise , Feminino , Seguimentos , Teste de Tolerância a Glucose , Homeostase , Humanos , Masculino , Obesidade/fisiopatologia , Período Pós-Parto , Gravidez , Prognóstico , Estudos Prospectivos , Perda de Peso
8.
Biochim Biophys Acta Mol Basis Dis ; 1865(3): 678-687, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30543855

RESUMO

Hexokinase domain containing 1, a recently discovered putative fifth hexokinase, is hypothesized to play key roles in glucose metabolism. Specifically, during pregnancy in a recent genome wide association study (GWAS), a strong correlation between HKDC1 and 2-h plasma glucose in pregnant women from different ethnic backgrounds was shown. Our earlier work also reported diminished glucose tolerance during pregnancy in our whole body HKDC1 heterozygous mice. Therefore, we hypothesized that HKDC1 plays important roles in gestational metabolism, and designed this study to assess the role of hepatic HKDC1 in whole body glucose utilization and insulin action during pregnancy. We overexpressed human HKDC1 in mouse liver by injecting a human HKDC1 adenoviral construct; whereas, for the liver-specific HKDC1 knockout model, we used AAV-Cre constructs in our HKDC1fl/fl mice. Both groups of mice were subjected to metabolic testing before and during pregnancy on gestation day 17-18. Our results indicate that hepatic HKDC1 overexpression during pregnancy leads to improved whole-body glucose tolerance and enhanced hepatic and peripheral insulin sensitivity while hepatic HKDC1 knockout results in diminished glucose tolerance. Further, we observed reduced gluconeogenesis with hepatic HKDC1 overexpression while HKDC1 knockout led to increased gluconeogenesis. These changes were associated with significantly enhanced ketone body production in HKDC1 overexpressing mice, indicating that these mice shift their metabolic needs from glucose reliance to greater fat oxidation and ketone utilization during fasting. Taken together, our results indicate that hepatic HKDC1 contributes to whole body glucose disposal, insulin sensitivity, and aspects of nutrient balance during pregnancy.


Assuntos
Intolerância à Glucose/genética , Glucose/metabolismo , Hexoquinase/fisiologia , Resistência à Insulina/genética , Complicações na Gravidez/genética , Animais , Metabolismo dos Carboidratos/genética , Modelos Animais de Doenças , Metabolismo Energético/genética , Feminino , Intolerância à Glucose/metabolismo , Intolerância à Glucose/prevenção & controle , Células HEK293 , Hexoquinase/genética , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Gravidez , Complicações na Gravidez/metabolismo , Complicações na Gravidez/prevenção & controle
9.
FASEB J ; 33(2): 2343-2358, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30277821

RESUMO

Calorie restriction (CR) exerts remarkable, beneficial effects on glucose homeostasis by mechanisms that are not fully understood. Given the relevance of white adipose tissue (WAT) in glucose homeostasis, we aimed at identifying the main cellular processes regulated in WAT in response to CR in a pathologic context of obesity. For this, a gene-expression profiling study was first conducted in mice fed ad libitum or subjected to 40% CR. We found that the gene network related to mitochondria was the most highly upregulated in WAT by CR. To study the role that increased mitochondrial biogenesis plays on glucose homeostasis following CR, we generated a mouse model devoid of the coactivators peroxisome proliferator-activated receptor γ coactivator 1 (PGC-1)α and PGC-1ß specifically in adipocytes. Our results show that mice lacking PGC-1s in adipocytes are unable to increase mitochondrial biogenesis in WAT upon CR. Despite a blunted induction of mitochondrial biogenesis in response to calorie deprivation, mice lacking adipose PGC-1s still respond to CR by improving their glucose homeostasis. Our study demonstrates that PGC-1 coactivators are major regulators of CR-induced mitochondrial biogenesis in WAT and that increased mitochondrial biogenesis and oxidative function in adipose tissue are not required for the improvement of glucose homeostasis mediated by CR.-Pardo, R., Vilà, M., Cervela, L., de Marco, M., Gama-Pérez, P., González-Franquesa, A., Statuto, L., Vilallonga, R., Simó, R., Garcia-Roves, P. M., Villena, J. A. Calorie restriction prevents diet-induced insulin resistance independently of PGC-1-driven mitochondrial biogenesis in white adipose tissue.


Assuntos
Tecido Adiposo Branco/fisiopatologia , Restrição Calórica , Dieta/efeitos adversos , Intolerância à Glucose/prevenção & controle , Resistência à Insulina , Biogênese de Organelas , Fatores de Transcrição/fisiologia , Animais , Perfilação da Expressão Gênica , Intolerância à Glucose/etiologia , Intolerância à Glucose/metabolismo , Homeostase , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout
10.
J Diabetes Investig ; 10(4): 909-914, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30451382

RESUMO

Given the established roles of glucose-dependent insulinotropic polypeptide (GIP) in promoting fat storage and bone formation, we assessed the contribution of GIP to obesity and osteopenia in ovariectomized mice with a gene encoding green fluorescent protein (GFP) inserted into the GIP locus, in which GIP was either reduced (GIPgfp/+ ) or absent (GIPgfp/gfp ). In GIPgfp/gfp mice, weight gain, subcutaneous and visceral fat mass were reduced, and glucose intolerance was improved compared with wild-type mice with the same magnitude of insulin responses. Cancellous bone mineral density and bone cortical thickness were reduced in GIPgfp/gfp mice compared with wild-type mice. In GIPgfp/+ mice, weight gain, glucose intolerance and cancellous bone mineral density were not different from that of wild-type mice. These results indicate that the total elimination of GIP ameliorates weight gain and adiposity in ovariectomized mice, but it enhances osteopenia, particularly in cancellous bone by partly suppressing bone formation.


Assuntos
Doenças Ósseas Metabólicas/etiologia , Reabsorção Óssea/etiologia , Polipeptídeo Inibidor Gástrico/deficiência , Intolerância à Glucose/prevenção & controle , Resistência à Insulina , Gordura Intra-Abdominal , Ovariectomia/efeitos adversos , Animais , Distribuição da Gordura Corporal , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Ganho de Peso
11.
J Matern Fetal Neonatal Med ; 32(2): 225-228, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28877616

RESUMO

BACKGROUND: Some studies have already investigated about the short-term favorable metabolic effects of breastfeeding in women with previous gestational diabetes mellitus (GDM). AIM: The aim of our study is to confirm whether the positive effects reported are maintained in the larger cohorts of patients with mild form of gestational diabetes mellitus (GDM) because recently diagnosed according to IADPSG criteria. MATERIALS AND METHODS: This retrospective study includes 97 evaluable consecutive women with prior GDM who have the follow-up oral glucose tolerance test at least 3 months after delivery. Fasting and 2-h plasma glucose values, homeostasis model assessment (HOMA-IR), total cholesterol, and triglycerides were obtained in pregnancy and during the post-partum control. RESULTS: These patients were divided in 81 (83.5%) who lactate until 3 months and 16 (16.5%) who did not lactate. During pregnancy, there are no significant differences between the two groups for age, BMI, fasting and 2-h plasma glucose values, HOMA-IR, total cholesterol and triglycerides. At the postpartum control, we have at univariate analysis significant differences for all these parameters except total cholesterol. After adjustment for confounders we still have, in the breastfeeding group, HOMA-IR reduction (OR 0.370; 95% CI 0.170-0.805; p < .01) as significant independent variable, whose improvement is the most acknowledged important factor for the prevention of abnormal glucose tolerance later in life. CONCLUSION: These encouraging results confirm our determination to warmly advice the women affected by GDM to breastfeeding at least for 3 months.


Assuntos
Aleitamento Materno , Diabetes Gestacional , Lactação/metabolismo , Diagnóstico Pré-Natal , Adulto , Glicemia/metabolismo , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/metabolismo , Diabetes Gestacional/reabilitação , Feminino , Intolerância à Glucose/metabolismo , Intolerância à Glucose/prevenção & controle , Teste de Tolerância a Glucose , Humanos , Período Pós-Parto , Gravidez , Diagnóstico Pré-Natal/métodos , Estudos Retrospectivos
12.
FASEB J ; 33(2): 2553-2562, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30285581

RESUMO

The implication of αß and γδ T cells in obesity-associated inflammation and insulin resistance (IR) remains uncertain. Mice lacking γδ T cells show either no difference or a decrease in high-fat diet (HFD)-induced IR, whereas partial depletion in γδ T cells does not protect from HFD-induced IR. αß T-cell deficiency leads to a decrease in white adipose tissue (WAT) inflammation and IR without weight change, but partial depletion of these cells has not been studied. We previously described a mouse model overexpressing peroxisome proliferator-activated receptor ß (PPAR-ß) specifically in T cells [transgenic (Tg) T-PPAR-ß] that exhibits a partial depletion in αß T cells and no change in γδ T-cell number. This results in a decreased αß/γδ T-cell ratio in lymphoid organs. We now show that Tg T-PPAR-ß mice are partially protected against HFD-induced weight gain and exhibit decreased IR and liver steatosis independently of animal weight. These mice display an alteration of WAT-depots distribution with an increased epididymal-WAT mass and a decreased subcutaneous WAT mass. Immune cell number is decreased in both WAT-depots, except for γδ T cells, which are increased in epididymal-WAT. Overall, we show that decreasing αß/γδ T-cell ratio in WAT-depots alters their inflammatory state and mass repartition, which might be involved in improvement of insulin sensitivity.-Le Menn, G., Sibille, B., Murdaca, J., Rousseau, A.-S., Squillace, R., Vergoni, B., Cormont, M., Niot, I., Grimaldi, P. A., Mothe-Satney, I., Neels, J. G. Decrease in αß/γδ T-cell ratio is accompanied by a reduction in high-fat diet-induced weight gain, insulin resistance, and inflammation.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Inflamação/prevenção & controle , Resistência à Insulina , Obesidade/prevenção & controle , Receptores de Antígenos de Linfócitos T alfa-beta/metabolismo , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Linfócitos T/metabolismo , Ganho de Peso , Animais , Peso Corporal , Intolerância à Glucose/etiologia , Intolerância à Glucose/metabolismo , Intolerância à Glucose/patologia , Intolerância à Glucose/prevenção & controle , Inflamação/etiologia , Inflamação/metabolismo , Inflamação/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/etiologia , Obesidade/metabolismo , Obesidade/patologia , Linfócitos T/imunologia
13.
Life Sci ; 218: 185-196, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30594666

RESUMO

Glucocorticoids increase appetite and body weight gain in rats and ovariectomy (OVX) induces obesity, while estrogen (E) replacement attenuates OVX-induced changes. It is known that animals with obesity are more responsive to glucocorticoids anabolic effects than lean ones. This study aimed to evaluate the effects of ovariectomy and the protective role of estradiol on the responses induced by prolonged treatment with corticosterone or dexamethasone on energy homeostasis. For this, female Wistar rats subjected to SHAM or OVX surgery, composing the SHAM, OVX, and OVX + E groups, received water/ETOH or corticosterone (15 mg/l) and water or dexamethasone (0.5 µg/l) as drinking fluid for 28 days. The OVX + E group, since the first day, was daily treated with estradiol (10 µg/0.2 ml/rat SC). OVX induced enhancement of body weight gain, food intake, area of the adipocytes and weight of retroperitoneal adipose tissue, plasma cholesterol and glucose intolerance, with reduction on uterus weight. In OVX animals, treatment with glucocorticoids induced increases on body weight gain, food intake, weight of retroperitoneal adipose tissue, area of adipocytes of retroperitoneal and perigonadal + perirenal fat depots, plasma triglycerides (corticosterone), and glycemic response after GTT (dexamethasone), with minor effects on SHAM group. Estradiol treatment to OVX rats prevented these effects induced by glucocorticoids, in addition to decrease body weight gain, fat accumulation and glucose intolerance, and to increase weight of uterus, triglycerides and free fatty acids plasma levels. These data demonstrate that protection against glucocorticoids-induced anabolic responses in females is eliminated by ovariectomy and estradiol can prevent these responses.


Assuntos
Anabolizantes/toxicidade , Estrogênios/farmacologia , Glucocorticoides/toxicidade , Intolerância à Glucose/prevenção & controle , Obesidade/prevenção & controle , Ovariectomia/efeitos adversos , Substâncias Protetoras/farmacologia , Animais , Peso Corporal , Feminino , Intolerância à Glucose/etiologia , Intolerância à Glucose/patologia , Obesidade/etiologia , Obesidade/patologia , Ratos , Ratos Wistar , Ganho de Peso/efeitos dos fármacos
14.
FASEB J ; 33(2): 2899-2909, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30346829

RESUMO

Infants of obese mothers have an increased risk of developing obesity, insulin resistance, and type 2 diabetes. The underlying mechanisms remain elusive, and no effective interventions to limit the transmission of metabolic disease from the obese mother to her infant are currently available. Obese pregnant women have decreased circulating levels of adiponectin, which is associated with increased placental nutrient transport and fetal overgrowth. We have reported that normalization of adiponectin levels during late gestation reversed placental dysfunction and fetal overgrowth in a mouse model of maternal obesity in pregnancy. In the current study, we hypothesized that adiponectin supplementation during pregnancy in obese mice attenuates the adverse metabolic outcomes in adult offspring. Adult male offspring of obese mice developed obesity, fatty liver, and insulin resistance, with adult female offspring of obese mice having a less pronounced metabolic phenotype. These metabolic abnormalities in offspring born to obese mice were largely prevented by normalization of maternal adiponectin levels in late pregnancy. We provide evidence that low circulating maternal adiponectin is a critical mechanistic link between maternal obesity and the development of metabolic disease in offspring. Strategies aimed at improving maternal adiponectin levels may prevent long-term metabolic dysfunction in offspring of obese mothers.-Paulsen, M. E., Rosario, F. J., Wesolowski, S. R., Powell, T. L., Jansson, T. Normalizing adiponectin levels in obese pregnant mice prevents adverse metabolic outcomes in offspring.


Assuntos
Adiponectina/metabolismo , Glicemia/análise , Intolerância à Glucose/prevenção & controle , Doenças Metabólicas/prevenção & controle , Obesidade/complicações , Complicações na Gravidez/prevenção & controle , Animais , Animais Recém-Nascidos , Feminino , Intolerância à Glucose/etiologia , Intolerância à Glucose/metabolismo , Resistência à Insulina , Masculino , Doenças Metabólicas/etiologia , Doenças Metabólicas/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Gravidez , Complicações na Gravidez/etiologia , Complicações na Gravidez/metabolismo
15.
Eur J Nutr ; 58(2): 689-696, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29569007

RESUMO

PURPOSE: Women with prior gestational diabetes mellitus (GDM) are at higher risk of type 2 diabetes (T2D). The aim of this study was to investigate the association between fruit and vegetables (FV) intake and abnormal glucose tolerance (AGT) among women with prior GDM. METHODS: A total of 281 women with prior GDM have been recruited a mean of 6 years after their pregnancy in this cohort study. FV intake was obtained with a validated food frequency questionnaire (FFQ). Anthropometric and glycemic components were measured during their clinical visit and women were stratified according to normal glucose tolerance (NGT) or AGT. RESULTS: A cross-sectional analysis showed that a total of 155 women had NGT and 126 AGT. Women with AGT had significantly lower FV (6.5 ± 0.2) and vegetables servings (3.9 ± 0.2) and tended to have lower fruit servings (2.6 ± 0.2) than women with NGT (7.4 ± 0.2, 4.5 ± 0.2 and 3.0 ± 0.1, respectively) (p = 0.001, p = 0.04 and p = 0.10, respectively, adjusted for age and BMI). FV intake, per one serving increase, was associated with a reduced likelihood of having AGT [OR = 0.88 (0.81-0.97) after adjustment for age and BMI]. Vegetables or fruit intake tended to be associated with a reduced likelihood of having AGT [OR = 0.88 (0.78-1.00) and OR = 0.88 (0.76-1.02), respectively, after adjustment for age and BMI]. CONCLUSIONS: Higher intake of FV may be associated with a lower likelihood of AGT among women with prior GDM. Further studies are needed to confirm these results in this high-risk population.


Assuntos
Diabetes Gestacional/epidemiologia , Dieta/métodos , Frutas , Intolerância à Glucose/epidemiologia , Verduras , Adulto , Canadá/epidemiologia , Estudos de Coortes , Estudos Transversais , Feminino , Intolerância à Glucose/prevenção & controle , Humanos , Gravidez , Fatores de Risco
16.
J Diabetes ; 11(1): 32-45, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29845722

RESUMO

BACKGROUND: N-Acetylcysteine (NAC), an antioxidative reagent for clinical diseases, shows potential in the treatment of diabetes and other metabolic diseases. However, it is unknown how NAC modulates the gut microbiota of mice with metabolic syndrome. The aim of the present study was to demonstrate the preventive effect of NAC on intestinal dysbiosis and glucose metabolic disorder. METHODS: Mice (C57BL/6J strain) were fed either a normal chow diet (NCD), NCD plus NAC, a high-fat diet (HFD), or HFD plus NAC for 5 months, after which glucose levels, circulating endotoxins and key metabolism-related proteins were determined. Fecal samples were analyzed by 16S rRNA sequencing. A novel analysis was performed to predict functional changes in gut microbiota. In addition, Spearman's correlation analysis was performed between metabolic biomarkers and bacterial abundance. RESULTS: Treatment with NAC significantly reversed the glucose intolerance, fasting glucose concentrations, and gains in body weight and plasma endotoxin in HFD-fed mice. Further, NAC upregulated occludin and mucin glycoprotein levels in the proximal colon of HFD-treated mice. Noticeably, NAC promoted the growth of beneficial bacteria (i.e. Akkermansia, Bifidobacterium, Lactobacillus and Allobaculum) and decreased populations of diabetes-related genera, including Desulfovibrio and Blautia. In addition, NAC may affect the metabolic pathways of intestinal bacteria, including lipopolysaccharide biosynthesis, oxidative stress, and bacterial motility. Finally, the modified gut microbiota was closely associated with the metabolic changes in NAC-treated HFD-fed mice. CONCLUSIONS: N-Acetylcysteine may be a potential drug to prevent glucose metabolic disturbances by reshaping the structure of the gut microbiota.


Assuntos
Acetilcisteína/farmacologia , Dieta Hiperlipídica/efeitos adversos , Disbiose/prevenção & controle , Microbioma Gastrointestinal/efeitos dos fármacos , Transtornos do Metabolismo de Glucose/prevenção & controle , Acetilcisteína/administração & dosagem , Animais , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/genética , Glicemia/análise , Disbiose/metabolismo , Disbiose/microbiologia , Fezes/microbiologia , Depuradores de Radicais Livres/administração & dosagem , Depuradores de Radicais Livres/farmacologia , Microbioma Gastrointestinal/genética , Intolerância à Glucose/sangue , Intolerância à Glucose/prevenção & controle , Transtornos do Metabolismo de Glucose/etiologia , Transtornos do Metabolismo de Glucose/microbiologia , Hiperglicemia/sangue , Hiperglicemia/prevenção & controle , Lipopolissacarídeos/sangue , Camundongos Endogâmicos C57BL , RNA Ribossômico 16S/genética , Análise de Sequência de DNA
17.
Biochim Biophys Acta Mol Basis Dis ; 1865(2): 494-501, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30448542

RESUMO

OBJECTIVE: Proteoglycan 4 (Prg4) has emerged from human association studies as a possible factor contributing to weight gain, dyslipidemia and insulin resistance. In the current study, we investigated the causal role of Prg4 in controlling lipid and glucose metabolism in mice. METHODS: Prg4 knockout (KO) mice and wild-type (WT) littermates were challenged with an obesogenic high-fat diet (45% of total calories as fat) for 16 weeks. To further stimulate the development of metabolic alterations, 10% fructose water was provided starting from week 13. RESULTS: Prg4 deficiency only tended to reduce diet-induced body weight gain, but significantly improved glucose handling (AUC: -29%; p < 0.05), which was also reflected by a tendency towards a reduced HOMA-IR score (-49%; p = 0.06 as compared to WT mice). This coincided with lower hepatic expression of glycolysis (Gck: -30%; p < 0.05) and lipogenesis (Acc: -21%; p < 0.05 and Scd1: -38%; p < 0.001) genes, which translated in significantly lower hepatic triglyceride levels (-56%; p < 0.001) in Prg4 KO mice as compared to WT mice. Prg4 KO mice likely had lower glucose utilization by skeletal muscle as compared to WT mice, judged by a significant reduction in the genes Glut4 (-29%; p < 0.01), Pfkm (-21%; p < 0.05) and Hk2 (-39%; p < 0.001). Moreover, Prg4 KO mice showed a favorable white adipose tissue phenotype with lower uptake of triglyceride-derived fatty acids (-46%; p < 0.05) and lower gene expression of inflammatory markers Cd68, Mcp1 and Tnfα (-65%, -81% and -63%, respectively; p < 0.01) than WT mice. CONCLUSION: Prg4 KO mice are protected from high-fat diet-induced glucose intolerance and fatty liver disease.


Assuntos
Fígado Gorduroso/complicações , Fígado Gorduroso/prevenção & controle , Intolerância à Glucose/complicações , Intolerância à Glucose/prevenção & controle , Proteoglicanas/deficiência , Tecido Adiposo Branco/metabolismo , Animais , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Dieta Hiperlipídica , Fígado Gorduroso/patologia , Feminino , Glucose/metabolismo , Intolerância à Glucose/patologia , Humanos , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Obesos , Músculos/metabolismo , Proteoglicanas/metabolismo , Gordura Subcutânea/metabolismo
18.
Sci Rep ; 8(1): 17814, 2018 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-30546031

RESUMO

Type 2 diabetes is an age-and-obesity associated disease driven by impairments in glucose homeostasis that ultimately result in defective insulin secretion from pancreatic ß-cells. To deconvolve the effects of age and obesity in an experimental model of prediabetes, we fed young and aged mice either chow or a short-term high-fat/high-sucrose Western diet (WD) and examined how weight, glucose tolerance, and ß-cell function were affected. Although WD induced a similar degree of weight gain in young and aged mice, a high degree of heterogeneity was found exclusively in aged mice. Weight gain in WD-fed aged mice was well-correlated with glucose intolerance, fasting insulin, and in vivo glucose-stimulated insulin secretion, relationships that were not observed in young animals. Although ß-cell mass expansion in the WD-fed aged mice was only three-quarters of that observed in young mice, the islets from aged mice were resistant to the sharp WD-induced decline in ex vivo insulin secretion observed in young mice. Our findings demonstrate that age is associated with the protection of islet function in diet-induced obese mice, and furthermore, that WD challenge exposes variability in the resilience of the insulin secretory pathway in aged mice.


Assuntos
Envelhecimento/metabolismo , Dieta Ocidental/efeitos adversos , Intolerância à Glucose/metabolismo , Secreção de Insulina , Células Secretoras de Insulina/metabolismo , Insulina/metabolismo , Obesidade/metabolismo , Envelhecimento/patologia , Animais , Intolerância à Glucose/etiologia , Intolerância à Glucose/patologia , Intolerância à Glucose/prevenção & controle , Células Secretoras de Insulina/patologia , Masculino , Camundongos , Obesidade/etiologia , Obesidade/patologia , Obesidade/prevenção & controle
19.
J Physiol Biochem ; 74(4): 647-654, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30232707

RESUMO

To fight against metabolic disorders such as insulin resistance, new alimentary behaviors are developed. For instance, hyperproteined, gluten-free, or collagen-enriched diets could be preconized in order to reduce the consequences of obesity. In this aim, this study evaluates the potential effects of warm sea fish collagen peptides (Naticol®) on representative metabolic and inflammatory parameters. For that, male C57Bl6/J mice fed with either a chow- (CD) or high-fat diet (HFD) were submitted or not to specific collagen peptides in drinking water (4 g/kg bw/d) for 20 weeks. Weight, body composition, glucose tolerance, and insulin sensitivity were followed up. Effects of fish collagen peptides on various blood parameters reflecting the metabolism status were also measured (free fatty acids, triglycerides, cholesterol, hormones) together with adipocyte inflammation. Results showed that HFD-fed mice supplemented by fish collagen peptides exhibited a significant lower increase in body weight as soon as the twelfth week of treatment whereas no effect of the peptide was observed in CD fed mice. In line with this result, a weaker increase in fat mass in HFD-fed mice supplemented with Naticol® at both 9 and 18 weeks of treatment was also observed. In spite of this resistance to obesity promoted by fish collagen peptides treatment, no difference in glucose tolerance was found between groups whereas mice treated with Naticol® exhibited a lower basal glycemia. Also, even if no effect of the treatment on adipocyte lipolysis was found, a decrease of inflammatory cytokines was retrieved in collagen-supplemented group arguing for a potential better insulin sensitivity. Altogether, these results need to be completed but are the first describing a benefic role of warm sea fish collagen peptides in a context of metabolic disease paving the route for a potential utilization in human obesity-associated disorders.


Assuntos
Fármacos Antiobesidade/uso terapêutico , Colágeno/uso terapêutico , Suplementos Nutricionais , Proteínas de Peixes da Dieta/uso terapêutico , Resistência à Insulina , Obesidade/terapia , Fragmentos de Peptídeos/uso terapêutico , Tecido Adiposo/imunologia , Tecido Adiposo/metabolismo , Animais , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/metabolismo , Anti-Inflamatórios não Esteroides/uso terapêutico , Fármacos Antiobesidade/efeitos adversos , Fármacos Antiobesidade/química , Fármacos Antiobesidade/metabolismo , Apelina/agonistas , Apelina/genética , Apelina/metabolismo , Colágeno/efeitos adversos , Colágeno/química , Colágeno/metabolismo , Citocinas/antagonistas & inibidores , Citocinas/genética , Citocinas/metabolismo , Dieta Hiperlipídica/efeitos adversos , Suplementos Nutricionais/efeitos adversos , Proteínas de Peixes da Dieta/efeitos adversos , Proteínas de Peixes da Dieta/química , Proteínas de Peixes da Dieta/metabolismo , Regulação da Expressão Gênica , Intolerância à Glucose/etiologia , Intolerância à Glucose/imunologia , Intolerância à Glucose/prevenção & controle , Lipólise , Masculino , Camundongos Endogâmicos C57BL , Obesidade/etiologia , Obesidade/metabolismo , Obesidade/fisiopatologia , Paniculite/etiologia , Paniculite/imunologia , Paniculite/prevenção & controle , Fragmentos de Peptídeos/efeitos adversos , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/metabolismo , Ganho de Peso
20.
Life Sci ; 211: 147-156, 2018 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-30227131

RESUMO

AIMS: Obesity is associated with comorbidities such as diabetes and hepatic steatosis. ß-Glucans have been described as effective in treating conditions including dyslipidaemia and diabetes. Thus, the objective of this study was to evaluate the effects of botryosphaeran [(1 → 3)(1 → 6)-ß-D-glucan] on obesity and its comorbidities, and understand its mechanism of action. MAIN METHODS: Obesity was induced in adult male Wistar rats by ingestion of a high-fat diet and water with sucrose (300 g/L) for 8 weeks. Control rats received standard diet. After six weeks, treatment commenced with botryosphaeran (12 mg/kg.b.w., via gavage, 15 days), respective controls received water. Rats were divided into 3 groups: control (C), obese (O), and obese + botryosphaeran (OB). In the 8th week, obesity was characterized. Feed-intake, glucose and lipid profiles, glucose tolerance, and concentrations of glycogen and lipids in liver were analyzed. Protein expression was determined by Western blotting. KEY FINDINGS: Obese rats showed significant increases in weight gain and adipose tissue, presented glucose intolerance, dyslipidaemia, and hepatic steatosis. Botryosphaeran significantly reduced feed intake, weight gain, periepididymal and mesenteric fat, and improved glucose tolerance. Botryosphaeran also reduced triglyceride and VLDL, and increased HDL levels. Furthermore, botryosphaeran increased glycogen and reduced total lipids, triglycerides and cholesterol in liver, and increased AMP-activated protein kinase(AMPK) activity and Forkhead transcription factor 3a(FOXO3a) protein expression in adipose tissue. SIGNIFICANCE: This study demonstrated that botryosphaeran was effective in reducing obesity, hepatic steatosis, dyslipidaemia insulin resistance and glucose intolerance in diet-induced obese rats, and these effects were, at least in part, associated with reduced feed intake, and AMPK and FOXO3a activities.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Dislipidemias/prevenção & controle , Fígado Gorduroso/prevenção & controle , Glucanos/farmacologia , Intolerância à Glucose/prevenção & controle , Resistência à Insulina , Obesidade/prevenção & controle , Animais , Glicemia/análise , Dislipidemias/etiologia , Dislipidemias/patologia , Fígado Gorduroso/etiologia , Fígado Gorduroso/patologia , Intolerância à Glucose/etiologia , Intolerância à Glucose/patologia , Masculino , Obesidade/etiologia , Obesidade/patologia , Ratos , Ratos Wistar
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