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1.
Front Endocrinol (Lausanne) ; 13: 918467, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35774143

RESUMO

Irisin is a myokine involved in the browning of white adipose tissue and regulation of energy expenditure, glucose homeostasis and insulin sensitivity. Debated evidence exists on the metabolic role played by irisin in children with overweight or obesity, while few information exist in children with Prader Willi Syndrome (PWS), a condition genetically prone to obesity. Here we assessed serum irisin in relation to the metabolic profile and body composition in children and adolescents with and without PWS. In 25 PWS subjects [age 6.6-17.8y; body mass index standard deviation score (BMI SDS) 2.5 ± 0.3] and 25 age, and BMI-matched controls (age 6.8-18.0y; BMI SDS, 2.8 ± 0.1) we assessed irisin levels and metabolic profile inclusive of oral glucose tolerance test (OGTT), and body composition by dual-energy X-ray absorptiometry (DXA). In PWS, we recorded lower levels of fat-free mass (FFM) (p <0.05), fasting (p<0.0001) and 2h post-OGTT insulin (p<0.05) and lower insulin resistance as expressed by homeostatic model of insulin resistance (HOMA-IR) (p<0.0001). Irisin levels were significantly lower in PWS group than in controls with common obesity (p<0.05). In univariate correlation analysis, positive associations linked irisin to insulin OGTT0 (p<0.05), insulin OGTT120 (p<0.005), HOMA-IR (p<0.05) and fasting C-peptide (p<0.05). In stepwise multivariable regression analysis, irisin levels were independently predicted by insulin OGTT120. These results suggest a link between irisin levels and insulin sensitivity in two divergent models of obesity.


Assuntos
Fibronectinas , Glucose , Obesidade , Síndrome de Prader-Willi , Adolescente , Glicemia/metabolismo , Criança , Fibronectinas/sangue , Fibronectinas/metabolismo , Glucose/metabolismo , Humanos , Insulina/sangue , Resistência à Insulina/fisiologia , Obesidade/sangue , Síndrome de Prader-Willi/sangue , Síndrome de Prader-Willi/metabolismo
2.
Iran J Immunol ; 19(2): 193-200, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35767893

RESUMO

BACKGROUND: Obesity and diabetes are related to chronic low-grade inflammation. As a pro-inflammatory cytokine, IL-18 stimulates various cell types and has pleiotropic functions. OBJECTIVE: To assess the levels of IL-18 in subjects from the entire spectrum of glycemic disorders. METHODS: This study included 387 Caucasians divided into four groups: healthy controls, obese subjects without carbohydrate issues, prediabetic patients, and recently discovered type 2 diabetics. RESULTS: Subject with body mass index ≥30kg/m2 and glycemic disorders showed significantly high levels of IL-18 (249.77 ± 89.96 pg/ml; 259.01 ± 95.70 pg/ml; and 340.98 ± 127.65 pg/ml) compared with that of the control group (219.47 ± 110.53 pg/ml, p < 0.05). IL-18 also had significant positive associations with some anthropometric parameters, liver enzymes, fasting, post-load glucose, insulin, uric acid, and triglycerides while negative with HDL. The circulating IL-18 levels for differentiating subjects with carbohydrate disturbances and those with metabolic syndrome were determined by ROC analysis. The AUC for the disturbances of the carbohydrate metabolism was 0.597 (p = 0.001; 95% CI = 0.539 - 0.654) and for MS AUC was 0.581 (p = 0.021; 95 % CI = 0.516 - 0.647). CONCLUSION: Our data indicate that as the levels of IL-18 are increased the carbohydrate tolerance is deteriorated. However, the significance of IL-18 in the progression of diabetes mellitus and subsequent consequences requires further exploration.


Assuntos
Diabetes Mellitus Tipo 2 , Interleucina-18 , Obesidade , Estado Pré-Diabético , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Humanos , Interleucina-18/sangue , Obesidade/sangue , Obesidade/diagnóstico , Estado Pré-Diabético/sangue , Estado Pré-Diabético/diagnóstico
3.
Nutrients ; 14(11)2022 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-35684004

RESUMO

Our study evaluated the association between the increase in body mass index (BMI) in men and women (menstruating and non-menstruating) (n = 1340) with different dietary groups (omnivores, semi-vegetarians, lacto-ovo-vegetarian, and vegans) and the measurement of the biochemical markers high-sensitive C-reactive protein (hs-CRP), ferritin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), glycated hemoglobin (HbA1C), and insulin resistance index (HOMA-IR). Increasing BMI values in all groups and dietary profiles were related to a significant increase in hs-CRP (p < 0.0001), ALT (p = 0.02), ferritin (p = 0.009), and HbA1C (p < 0.0001), with no difference between dietary groups (p < 0.05). The increase in BMI increases the levels of HOMA-IR (p < 0.0001) and GGT (p < 0.05), with higher values found in men when compared to women (p < 0.0001 for HOMA- IR and p = 0.0048 for GGT). The association between ALT and BMI was different between dietary groups, as it showed a decrease in vegan women who do not menstruate compared to other dietary groups (p = 0.0099). When including only obese individuals (BMI ≥ 30 kg/m2, n = 153) in the analysis, we observed lower concentrations of GGT and ferritin in vegetarians than in omnivores, regardless of gender and menstrual blood loss (p = 0.0395). Our data showed that for both vegetarians and omnivores, the higher the BMI, the worse the metabolic parameters. However, regarding obesity, vegetarians showed better antioxidant status (lower GGT elevation) and lower inflammatory status (lower ferritin elevation), which may provide them with potential protection in the development of morbidities associated with overweight.


Assuntos
Dieta Vegetariana , Obesidade/metabolismo , Proteína C-Reativa/análise , Feminino , Ferritinas/sangue , Hemoglobina A Glicada/análise , Humanos , Masculino , Obesidade/sangue , Vegetarianos
4.
J Med Food ; 25(6): 675-682, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35708634

RESUMO

Since low serum l-arginine (Arg) and high asymmetric dimethylarginine (ADMA) can predict microvascular complications in type 2 diabetes mellitus (T2DM), we tested whether Arg and ADMA are affected by diet and physical activity in overweight/obese and T2DM subjects. We tested the effects on serum Arg and ADMA of single loads of dextrose, protein, fat, or alcohol (∼300 calories each); one episode of physical exercise; and 12 weeks of standard lifestyle modification (dietary and physical activity counseling). Alcohol drink was followed by ∼30% lowering in Arg. Arg and ADMA increased after a protein load but remained stable after glucose or fat load or 30 min of treadmill walk. Following 12 weeks of lifestyle modification, ADMA declined only in subjects achieving weight loss >5%. In conclusion, alcohol is a previously unrecognized acute suppressor of serum Arg. Lifestyle modification lowers ADMA in subjects who achieve weight loss >5%. Clinical Trial Registration Number: NCT04406402.


Assuntos
Consumo de Bebidas Alcoólicas , Arginina , Diabetes Mellitus Tipo 2 , Arginina/sangue , Humanos , Obesidade/sangue , Sobrepeso , Redução de Peso
5.
Metabolism ; 133: 155237, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35700837

RESUMO

BACKGROUND: Growth differentiation factor 15 (GDF-15) is a stress-response cytokine proposed to be associated with body weight regulation. AIMS: The primary aim was to investigate changes of circulating intact GDF-15 (wildtype, non-carrier of the rs1058587 polymorphism coding for the H2O2D mutation) and total GDF-15 (measured irrespective of the mutation) in response to liraglutide (GLP-1 receptor agonist) and lorcaserin (5-HT2C receptor agonist), two pharmacologic agents that induce food intake and weight reduction. In addition, we perform exploratory correlations of total and intact GDF-15 with clinical, hormonal and metabolo-lipidomic parameters in humans with obesity. MATERIALS AND METHODS: We utilized two studies: 1) Study 1, a randomized, double-blinded, cross-over trial of liraglutide and placebo administration for 5 weeks in subjects with obesity (n = 20; BMI = 35.6 ± 5.9 kg/m2), in escalating doses starting at 0.6 mg/day on week 1 and increased every week, up to the highest dose of 3.0 mg/day during week 5. b) Study 2, a randomized, double-blinded trial of lorcaserin 10 mg twice daily, or placebo for 12-weeks in humans with obesity (n = 34 BMI = 37.4 ± 6.1 kg/m2). Total and intact GDF-15 levels were measured with novel enzyme-linked immunosorbent assays and the metabolomics and lipidomics analysis was performed with nuclear magnetic resonance spectroscopy. RESULTS: Total and intact GDF-15 were positively correlated with diabetes risk index and trimethylamine N-oxide and negatively with eGFR. Despite significant changes in body weight, total and intact GDF-15 were not altered in response to liraglutide or lorcaserin treatment in subjects with obesity. CONCLUSIONS: Total and intact GDF-15 levels are not altered in response to liraglutide or lorcaserin therapy and are thus not directly involved in the metabolic feedback loop pathways downstream of GLP1 or 5-HT2C receptor agonists. Since neither total nor intact GDF-15 levels were altered in response to weight loss, future studies are needed to elucidate the pathways activated by GDF-15 in humans and its role, if any, in body weight regulation and energy homeostasis.


Assuntos
Benzazepinas , Fator 15 de Diferenciação de Crescimento , Liraglutida , Obesidade , Benzazepinas/administração & dosagem , Peso Corporal , Método Duplo-Cego , Fator 15 de Diferenciação de Crescimento/sangue , Humanos , Liraglutida/administração & dosagem , Obesidade/sangue , Obesidade/tratamento farmacológico , Receptor 5-HT2C de Serotonina/metabolismo , Agonistas do Receptor 5-HT2 de Serotonina/administração & dosagem , Redução de Peso
6.
PLoS One ; 17(6): e0263658, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35700181

RESUMO

Polycystic ovarian syndrome (PCOS) is a common poignant endocrine disorder affecting women, posing a close association with metabolic syndrome and obesity. Existing literature characterizes PCOS with deranged levels of several adipokines and myokines. CTRP15 is a paralogue of adiponectin, mainly expressed by skeletal muscles, and plays a key role in insulin, glucose, and lipid metabolism. In the current study, we aim to determine the circulating levels of CTRP15 and evaluate its association with cardiometabolic and inflammatory parameters in PCOS women. This case-control study included 120 PCOS patients (60 Recurrent pregnancy loss (RPL) and 60 infertile (inf) PCOS) and 60 healthy non-PCOS controls. Serum levels of hs-CRP were measured by commercial kits, while serum levels of adiponectin and CTRP15 were determined using the ELISA technique. Serum levels of CTRP15 were significantly elevated in PCOS-RPL and PCOS-inf subgroups when compared to controls (94.80 ± 27.08 and 87.77 ± 25.48 vs. 54.78 ± 15.45, both P < 0.001). Moreover, serum adiponectin was considerably lower in the PCOS group and subgroups (P < 0.001), while serum hs-CRP, fasting insulin, HOMA-IR, and free testosterone were significantly higher when compared to the non-PCOS group (P < 0.05). Furthermore, CTRP15 closely associated with FSH, HOMA-IR, hs-CRP, and BMI. These results highlight a possible involvement of CTRP15 in the pathogenesis of PCOS. The elevated levels of CTRP15 might be a compensatory mechanism for the metabolic dysregulations (excess adiposity, insulin resistance, metaflammation) associated with the syndrome. Nevertheless, future studies are necessary to unravel the underlying mechanism.


Assuntos
Complemento C1q , Resistência à Insulina , Hormônios Peptídicos , Síndrome do Ovário Policístico , Adiponectina/sangue , Índice de Massa Corporal , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Complemento C1q/metabolismo , Feminino , Humanos , Insulina , Resistência à Insulina/fisiologia , Obesidade/sangue , Hormônios Peptídicos/sangue , Síndrome do Ovário Policístico/sangue
7.
Sci Rep ; 12(1): 8331, 2022 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-35585213

RESUMO

To establish whether obesity involves activation of endogenous ciliary neurotrophic factor (CNTF) signalling, we evaluated its plasma levels in patients with obesity and correlated its values with the major clinical and haematological indices of obesity, insulin resistance and systemic inflammation. This study involved 118 subjects: 39 healthy controls (19 men), 39 subjects with obesity (19 men) and 40 subjects with obesity and diabetes (20 men). Plasma CNTF and CNTF receptor α (CNTFRα) were measured using commercial ELISA kits. The results showed that plasma CNTF was significantly higher in males and females with obesity with and without diabetes than in healthy subjects. Women consistently exhibited higher levels of circulating CNTF. In both genders, CNTF levels correlated significantly and positively with obesity (BMI, WHR, leptin), diabetes (fasting insulin, HOMA index and HbA1c) and inflammation (IL-6 and hsCRP) indices. Circulating CNTFRα and the CNTF/CNTFRα molar ratio tended to be higher in the patient groups than in controls. In conclusion, endogenous CNTF signalling is activated in human obesity and may help counteract some adverse effects of obesity. Studies involving a higher number of selected patients may reveal circulating CNTF and/or CNTFRα as potential novel diagnostic and/or prognostic markers of obesity, diabetes and associated diseases.


Assuntos
Subunidade alfa do Receptor do Fator Neutrófico Ciliar , Diabetes Mellitus , Obesidade , Estudos de Casos e Controles , Subunidade alfa do Receptor do Fator Neutrófico Ciliar/sangue , Diabetes Mellitus/sangue , Feminino , Humanos , Inflamação/sangue , Masculino , Obesidade/sangue
8.
J Endocrinol Invest ; 45(9): 1741-1748, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35585295

RESUMO

PURPOSE: Impaired activity of the peptidylprolyl cis/trans isomerase NIMA-interacting 1 (PIN1) isomerase might contribute to link disturbed glucose metabolism and risk of glucose related neurotoxicity, neurodegeneration and cognitive decline. The isomerase modulates also pathways of peripheral insulin sensitivity and secretion. We aimed at investigating the levels of circulating PIN1 in adolescents with obesity and any association with their glucose metabolism. METHODS: We enrolled 145 adolescents (age 12-17.8 years); 67 lean controls (46.2%) and 78 (53.8%) with overweight or obesity (males n = 62, 46%). We estimated glucose and insulin in fasting condition and after a standard oral glucose tolerance test; fasting serum levels of PIN1, amyloid ß-protein 42 (Aß42), presenilin 1 (PSEN1), glucagon-like peptide 1 (GLP1) and Non Esterified Fatty Acids (NEFA). We calculated the homeostasis model assessment of insulin resistance (HOMA-IR), the ß cell function (HOMA-ß) and the Adipo-IR. RESULTS: There was no difference in PIN1 serum levels between normal weight individuals and patients with obesity. However, there was an inverse correlation between serum fasting PIN1 and glucose (r - 0.183 and p = 0.027). We confirmed levels of Aß42 and PSEN1 were higher in teens with obesity than in lean controls and their correlation with the body mass index (Aß42: r = 0.302, p = 0.0001, PSEN1 r = 0.231, p = 0.005) and the HOMA-IR (Aß42: r = 0.219, p = 0.009, r = 0.170, p < 0.042). CONCLUSIONS: There was no significant rise of circulating PIN1 levels in young individuals with obesity. Increased levels reported in the literature in adult patients are likely to occur late in the natural history of the disease with the onset of an overt impairment of glucose homeostasis.


Assuntos
Peptídeos beta-Amiloides , Resistência à Insulina , Peptidilprolil Isomerase de Interação com NIMA/sangue , Obesidade/sangue , Adolescente , Adulto , Glicemia , Criança , Feminino , Glucose , Teste de Tolerância a Glucose , Humanos , Insulina , Masculino , Peptidilprolil Isomerase de Interação com NIMA/metabolismo
9.
Eur Rev Med Pharmacol Sci ; 26(8): 2818-2831, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35503626

RESUMO

OBJECTIVE: Obesity is a serious public health problem associated with excessive food intake. Regulation of food intake in highly organized organisms is under the control of a large number of orexigenic and anorexigenic molecules. Therefore, the main purpose of this study has been to determine the relationship between obesity and some of the circulating orexigenic and anorexigenic peptides that have a role in appetite control and to determine whether the concentrations of these molecules differ according to blood groups. PATIENTS AND METHODS: The study included 400 individuals of whom 100 were obese women, 100 obese men, 100 healthy men and 100 healthy women. Obese women and men were divided into 4 groups, according to their blood groups. In the control group, healthy women and healthy men were similarly divided into 4 blood groups. Each blood group within the groups, therefore, had 25 participants. RESULTS: When leptin, nesfatin-1, obestatin and neuropeptide-Y, ghrelin and galanin levels of the control group and obese participants were compared, regardless of blood groups, leptin, nesfatin-1, obestatin and neuropeptide-Y were significantly higher, whereas only the ghrelin levels were significantly lower in obese patients. When the amounts of these hormones were measured according to gender, the situation was similar. When leptin, nesfatin-1, obestatin and neuropeptide-Y values of the control and obese participants' blood groups were compared with each other; these hormones were high in all blood groups; however, leptin levels in A blood group, nesfatin-1 levels in AB and O blood group, obestatin levels in AB blood group, neuropeptide-Y levels in A, B, AB blood groups were significantly higher. When the ghrelin levels of the blood groups in the control group and obese participants were compared, it was only significantly lower in the AB blood group. The ghrelin levels in the other blood groups of the obese individuals were again low, but not significantly so. When the distribution of hormones according to gender was evaluated, a situation parallel to the above results was recorded. CONCLUSIONS: Leptin, nesfatin-1, obestatin and neuropeptide-Y and galanin levels of obese individuals were significantly higher than the control values, whereas the ghrelin values were significantly lower regardless of blood groups. Also, these hormones in blood partly varied with ABO blood groups. These different concentrations of hormones in ABO blood groups might be related with stimulation or suppression of appetite in human. However, further studies in other ethnic groups are needed to confirm these results.


Assuntos
Sistema ABO de Grupos Sanguíneos , Obesidade/sangue , Orexinas/sangue , Feminino , Galanina/sangue , Grelina/sangue , Humanos , Leptina/sangue , Masculino , Neuropeptídeo Y/sangue
10.
Endokrynol Pol ; 73(2): 353-360, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35593684

RESUMO

INTRODUCTION: The study was designed to evaluate the effect of thyroid function on serum levels of different adipokines in obesity. We investigated relationships between the thyroid axis and serum levels of leptin, adiponectin, and chemerin, and we assessed the influence of autoimmune thyroiditis (AIT) on those relations. MATERIAL AND METHODS: The participants of this study included 181 euthyroid patients (147 women and 34 men) with obesity [body mass index (BMI) 30-39.9 kg/m²] and severe (morbid) obesity (BMI ≥ 40 kg/m²), aged 18 to 65 years. We divided all obese patients by thyrotropic hormone (TSH) tertiles, and we compared all participants according to BMI. Patients were further divided into the following subgroups: with chronic autoimmune thyroiditis and without autoimmune thyroiditis. RESULTS: Comparison of obese patients according to TSH tertile showed significantly higher serum concentrations of leptin, chemerin, and thyroid antibodies and an increased leptin/adiponectin ratio in the group with high normal TSH. We observed statistically significant correlations between serum TSH and BMI, leptin, chemerin, thyroid peroxidase antibodies, and the leptin/adiponectin ratio. In patients diagnosed with autoimmune thyroiditis, higher levels of antibodies and TSH were found, but there were no differences in homeostatic model assessment index (HOMA-I), the leptin/adiponectin ratio, and adipokine levels. In obese patients the relationships between serum leptin, chemerin, the leptin/adiponectin ratio, and BMI were dependent on each other. CONCLUSION: Serum leptin, chemerin, the leptin/adiponectin ratio, and BMI are significantly higher in patients with high normal TSH; however, selected adipokines are not related to the presence of autoimmune thyroiditis. There are interplays between TSH, adipokines, and obesity, but how these relationships are related remains unknown.


Assuntos
Adipocinas , Doença de Hashimoto , Obesidade , Tireoidite Autoimune , Adipocinas/sangue , Adiponectina , Adolescente , Adulto , Idoso , Índice de Massa Corporal , Feminino , Humanos , Leptina , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/complicações , Tireotropina , Adulto Jovem
11.
BMC Gastroenterol ; 22(1): 184, 2022 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-35413837

RESUMO

BACKGROUND: Zonulin is observed in animal models to regulate intestinal permeability and influenced by dietary intake, gut microbiota, and inflammation. We conducted a secondary analysis of a randomized controlled crossover trial (NCT03582306) in individuals with a BMI greater than 30 kg/m2 and high habitual red meat intake and low habitual green leafy vegetable (GLV) intake. METHODS: Participants were provided with frozen GLV during the first or last four weeks (immediate or delayed intervention) of the twelve-week trial. Biological and anthropometric measures were taken at the beginning and at each four-week interval. A subset of 20 participants was selected for this secondary analysis of the intestinal permeability and inflammation-related biomarkers: serum and fecal zonulin; serum lipopolysaccharide binding protein (LBP), Alpha-1-acid glycoprotein 1 (ORM-1), tumor necrosis factor α (TNFα), interleukin-6 (IL-6), and C-reactive protein; 8-hydroxy-2'-deoxyguanosine (8OHdG) and plasma Vitamin K1 as a marker of protocol adherence. Nutrient and food group intake from two-24-h dietary recalls collected at each time point were assessed. Fecal microbiota was measured by 16 s rRNA PCR sequencing. Changes in biological markers, dietary factors, and microbial taxa were assessed with Wilcoxon Sign Ranks Tests. Exploratory analyses of the relationship between changes in outcome variables were conducted with Spearman correlations. RESULTS: No changes in serum and fecal zonulin and serum LBP were observed. Plasma Vitamin K (p = 0.005) increased, while plasma 8OHdG (p = 0.023) decreased during the intervention compared to the control. The only dietary factors that changed significantly were increases during intervention in Vitamin K and Dark GLV (p < 0.001 for both) compared to control. Fecal microbiota did not change significantly across all times points; however, change in serum zonulin was associated with change in Proteobacteria (ρ = - 0.867, p = 0.001) in females and Bifidobacterium (ρ = - 0.838, p = 0.009) and Bacteroidaceae (ρ = 0.871, p = 0.005) in men. CONCLUSIONS: A high GLV dietary intervention increased serum zonulin levels and had no effect on fecal zonulin. Lack of concordance between several inflammation-associated biomarkers and zonulin corroborate recent reports of limited utility of zonulin in obese adults free of lower gastrointestinal disease. Trial Registration information: https://clinicaltrials.gov/ct2/show/NCT03582306 (NCT03582306) registered on 07/11/2018.


Assuntos
Haptoglobinas , Inflamação , Obesidade , Precursores de Proteínas , Verduras , 8-Hidroxi-2'-Desoxiguanosina/sangue , 8-Hidroxi-2'-Desoxiguanosina/metabolismo , Biomarcadores/sangue , Biomarcadores/metabolismo , Estudos Cross-Over , Fezes , Feminino , Haptoglobinas/metabolismo , Humanos , Obesidade/sangue , Obesidade/dietoterapia , Obesidade/metabolismo , Precursores de Proteínas/sangue , Precursores de Proteínas/metabolismo , Ensaios Clínicos Controlados Aleatórios como Assunto , Vitamina K
12.
Atherosclerosis ; 350: 1-8, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35461093

RESUMO

BACKGROUND AND AIMS: The Apolipoprotein A5 (APOA5) rs662799 was significantly associated with blood lipid level at genome-wide significance level. Whether dynamic changes of adiposity influence the effect of lipid loci on long-term blood lipid profile remains unclear. We assessed interactions of 5-year body mass index (BMI) change and rs662799 genotypes with risk of incident dyslipidemia and longitudinal changes in serum lipids in a prospective cohort. METHODS: We included 4329 non-dyslipidemia participants aged ≥ 40 years at baseline from a well-defined community-based cohort and followed up for an average of 5 years. BMI and blood lipids were measured at baseline and follow-up. RESULTS: The association of each rs662799 A-allele with risk of incident dyslipidemia was stronger along with the increase in BMI change level, with the odds ratios (OR) increasing from 1.03 in the lowest tertile of BMI change (< 0.02 kg/m2) to 1.17 in the second (0.02-1.29), and 1.46 in the highest tertile (> 1.29) (pfor interaction< 0.001). Associations of each 1-unit of BMI (kg/m2) increase with incident dyslipidemia were more prominent in the AA carriers (OR = 1.50, 95%CI [1.26-1.80], p < 0.001), while much weaker in the GA (OR = 1.10) or GG carriers (OR = 1.09) (pfor interaction = 0.002). Similar results were found for the risk of incident higher triglycerides (TG) and lower high-density lipoprotein cholesterol (HDL-c), or the longitudinal changes in log10-TG (all pfor interaction ≤ 0.02). CONCLUSIONS: BMI changes significantly modulate rs662799 genetic contribution to dyslipidemia and long-term lipid profile, which provide new evidence for personalized clinical management of lipids according to individual genetic background.


Assuntos
Adiposidade , Apolipoproteína A-V , Dislipidemias , Lipídeos , Adiposidade/genética , Adulto , Apolipoproteína A-V/genética , Estudos de Coortes , Dislipidemias/diagnóstico , Dislipidemias/epidemiologia , Dislipidemias/genética , Humanos , Lipídeos/sangue , Estudos Longitudinais , Obesidade/sangue , Obesidade/diagnóstico , Obesidade/genética , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , Triglicerídeos/sangue
13.
Dis Markers ; 2022: 6777283, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35295321

RESUMO

Background: The effects of weight loss therapies on omentin-1 levels have been unclear, showing both elevations and decreases in circulating levels. The role of dietary fat might have an important role. The aim of our investigation was to evaluate the influence of weight decrease on omentin-1 levels after two different high-fat hypocaloric diets. Methods: 319 Caucasian obese subjects were randomly allocated during 12 weeks (Diet M (high monounsaturated fat diet) vs. Diet P (high polyunsaturated fat diet)). The mean age was 47.2 ± 5.0 years (range: 26-64), and the mean body mass index (BMI) was 37.9 ± 4.1 kg/m2 (range: 30.6-39.8). Sex distribution was 237 females (74.7%) and 72 males (25.3%). Anthropometric and biochemical parameters were evaluated at basal and after both diets. SPSS 23.0 has been used to realize univariant and multivariant statistical analysis. Results: After both diets, BMI, weight, fat mass, waist circumference, systolic blood, LDL-cholesterol, insulin levels, and HOMA-IR decreased in a statistical way from basal values. These improvements were similar in both diets. After Diet P, omentin-1 levels increase (21.2 ± 9.1 ng/ml: P = 0.02), and after Diet M, this adipokine increases (47.1 ± 11.2 ng/ml: P = 0.02), too. The increase of omentin-1 with Diet M was statistically significantly higher than that after Diet P (P = 0.01). A multiple regression analyses adjusted by age and sex reported a statistical relation between BMI (kg/m2) and insulin (UI/L) with omentin-1 levels. Conclusions: Our study demonstrated a significant improvement on serum omentin-1 levels after weight loss secondary to both diets; in contrast, omentin-1 improvement was higher with Diet M than with Diet P.


Assuntos
Dieta Hiperlipídica , Dieta Redutora , Obesidade/sangue , Obesidade/dietoterapia , Redução de Peso , Adipocinas/metabolismo , Índice de Massa Corporal , Citocinas/sangue , Feminino , Proteínas Ligadas por GPI/sangue , Humanos , Insulina/sangue , Lectinas/sangue , Masculino , Pessoa de Meia-Idade , Obesidade/genética
14.
Acta Med Okayama ; 76(1): 51-56, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35236998

RESUMO

Polycystic ovary syndrome (PCOS) is a common endocrine metabolic disorder that is associated with high insulin resistance and obesity. However, ~70% of women with PCOS in Japan are non-obese. We retrospectively analyzed the cases of 163 Japanese women with PCOS who visited our Ob/Gyn department in 2006-2018 to determine which has a greater effect on insulin resistance: PCOS or obesity. We reviewed the women's medical records and calculated their insulin resistance and insulin secretion. The women's mean age and pre-pregnancy body mass index (BMI) were 30±5.8 years and 24.8±5.6 kg/m2, respectively; their mean ± SD fasting plasma glucose, 94.1±13.7 mg/dL; HOMA-IR, 2.1±2.0; QUICKI, 0.4±0.0; and HOMA-ß, 108.9±88.0%. Sixtyeight women were pregnant, and 37% (n=25) were obese (BMI ≥ 25 kg/m2). Obesity had a greater effect on insulin resistance: fasting plasma glucose F(1, 53)=6.134, p<0.05; fasting insulin F(1, 53)=31.606, p<0.01; HOMA-IR F(1, 53)=31.670, p<0.01; QUICKI F(1, 53)=16.156, p<0.01. There was no significant difference in values other than QUICKI and testosterone between the women with and without PCOS. Obesity thus had a greater effect on increased insulin resistance in pregnant women with PCOS. Further studies of the insulin resistance of non-obese women with PCOS is needed, as non-obese women with PCOS are common in Asia.


Assuntos
Resistência à Insulina/fisiologia , Obesidade/sangue , Síndrome do Ovário Policístico/sangue , Adulto , Glicemia , Índice de Massa Corporal , Jejum , Feminino , Humanos , Insulina/sangue , Japão , Gravidez , Estudos Retrospectivos , Testosterona/sangue , Adulto Jovem
15.
Molecules ; 27(4)2022 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-35209038

RESUMO

Obesity is becoming increasingly common all over the world and global strategies are accordingly being developed to prevent it. In order to support the strategies, the effects of green apple (Golden Delicious) and the consumption of its three major flavonols (quercetin-3-glucoside, quercetin-3-D-galactoside, and quercetin-3-rhamnoside) on body weight; the weight of liver, kidney, and spleen; some lipid parameters in serum; and total lipid ratios of liver and kidney and oxidative stress parameters of obese rats were studied. This study was conducted on two experimental groups: one of which was given an apple, and the other was given flavonols, in addition to their high-energy diet; along with a sham and a control rat group, for 4 weeks. According to results, there was no difference in body and organ weights between groups. The liver and kidney weights increased in obese rats, but there was no difference between the total lipid ratios in these organs. The addition of green apple and selected flavonols to the high-energy diet of rats was not sufficient to prevent the increase in body and organ weights, but it supported the reduction in some lipid fractions and in oxidative stress parameters of obese rats. Moreover, this study supported the argument that obesity causes most of the lipid fractions increase in serum and induces oxidative stress.


Assuntos
Flavonóis , Frutas/química , Metabolismo dos Lipídeos/efeitos dos fármacos , Malus/química , Obesidade , Estresse Oxidativo/efeitos dos fármacos , Animais , Flavonóis/química , Flavonóis/farmacologia , Masculino , Obesidade/sangue , Obesidade/tratamento farmacológico , Ratos , Ratos Wistar
16.
Physiol Rep ; 10(4): e15148, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35179822

RESUMO

AIM: To reexamine the associations of NK cell number and function in the peripheral blood with overweight/obesity and the metabolic syndrome in a large, well-phenotyped human cohort. METHODS: Cross-sectional analysis of 273 women in the PPSDiab Study; measurement of absolute and relative number of NK cells in peripheral blood, and of functional parameters CD69 positivity and cytotoxicity against K562 cells; group comparison of NK cell characteristics between lean, overweight, and obese participants, as well as metabolic syndrome scores of 0, 1, 2, and ≥3; Spearman correlation analyses to clinical parameters related to the metabolic syndrome. RESULTS: We found no differences in NK cell number and function between lean, overweight, and obese women (relative NK cell number (median (Q1-Q3), [%]) 5.1(2.6-9.4) vs. 4.8 (2.9-8.4) vs. 3.8 (1.7-7.8), p = 0.187; absolute NK cell number [106 /L]: 86.9 (44.6-188.8) vs. 92.6 (52.5-154.6) vs. 85.9 (44-153.8), p = 0.632; CD69+ [%]: 27.2 (12.9-44.3) vs. 37.6 (13.2-52.8) vs. 33.6 (16.3-45), p = 0.136; cytotoxicity [%]: 11.0 (7.1-14.5) vs. 8.5 (6.4-13.2) vs. 11.3 (8.7-14.2), p = 0.094), as well as between different metabolic syndrome scores. Nonesterified fatty acids correlated with absolute and relative NK cell number and cytotoxicity (ρ [p-value]: 0.142 [0.021], 0.119 [0.049], and 0.131 [0.035], respectively). Relative NK cell number further correlated with high-density lipoprotein cholesterol (0.144 [0.018]) and cytotoxicity with 2 h glucose in oral glucose tolerance testing (0.132 [0.034]). CD69 positivity correlated with body fat (0.141 [0.021]), triglycerides (0.129 [0.033]), and plasma leptin (0.155 [0.010]). After correction for multiple testing, none of the associations remained significant. CONCLUSION: In the present study, we observed no associations of NK cell number and function in the peripheral blood with overweight/obesity and the metabolic syndrome. Extreme phenotypes of obesity and the metabolic syndrome might have caused differing results in previous studies. Further analyses with a focus on compartments other than peripheral blood may help to clarify the relation between NK cells and metabolic diseases.


Assuntos
Células Matadoras Naturais/imunologia , Síndrome Metabólica/sangue , Obesidade/sangue , Adulto , Antígenos CD/metabolismo , Antígenos de Diferenciação de Linfócitos T/metabolismo , Citotoxicidade Imunológica , Feminino , Humanos , Lectinas Tipo C/metabolismo , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/imunologia , Pessoa de Meia-Idade , Obesidade/epidemiologia , Obesidade/imunologia
17.
Dis Markers ; 2022: 7058389, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35126789

RESUMO

BACKGROUND AND AIMS: rs822393 (-4522C/T) genetic variant is associated with hypoadiponectinemia and other metabolic parameters. The aim of our investigation was to analyze the effects of a hypocaloric diet with Mediterranean dietary pattern during 9 months according to genetic variant rs822393 of ADIPOQ gene. METHODS AND RESULTS: A sample of 269 obese patients was enrolled. Anthropometric and serum parameters (lipid profile, insulin, homeostasis model assessment (HOMA-IR), glucose, C reactive protein, and adipokines) were determined, at basal time and after 3 and 9 months. All patients were genotyped in the rs822393. The genotype distribution was as follow; 176 patients (65.4%) CC, 83 patients CT (30.9%), and 10 patients TT (3.7%). After dietary intervention, the following parameters improved in non-T allele carriers; BMI, weight, fat mass, waist circumference, systolic blood pressure, insulin levels, HOMA-IR, leptin, total cholesterol, and LDL-cholesterol improved significantly. HDL-cholesterol (delta: 5.7 ± 1.1 mg/dl vs. 1.0 ± 0.8 mg/dl; p = 0.01), serum adiponectin (delta: 14.4 ± 2.0 ng/dl vs. 7.1 ± 3.1 ng/dl; p = 0.02), and adiponectin/leptin ratio (delta: 0.54 ± 0.1 vs. 0.22 ± 0.09 ng/dl; p = 0.03). Basal and postintervention HDL cholesterol, adiponectin levels, and adiponectin/leptin levels were lower in T-allele carriers than non-T Allele carriers. CONCLUSION: T allele carriers showed lower levels of HDL-cholesterol, adiponectin, and adiponectin/leptin ratio than non-T allele carriers. A medium-term hypocaloric diet with a Mediterranean partner increased adiponectin levels, ratio adiponectin/leptin, and HDL-cholesterol in non-T allele carriers.


Assuntos
Adiponectina/genética , Restrição Calórica , Dieta Mediterrânea , Obesidade/sangue , Obesidade/dietoterapia , Obesidade/genética , Avaliação de Resultados em Cuidados de Saúde , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
18.
Eur J Endocrinol ; 186(4): 457-467, 2022 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-35118996

RESUMO

BACKGROUND: Obstructive sleep apnea (OSA) is prevalent in people with obesity and is a major risk factor for type 2 diabetes (T2D). The effect of OSA on metabolic function and the precise mechanisms (insulin resistance, ß-cell dysfunction, or both) responsible for the increased T2D risk in people with OSA are unknown. DESIGN AND METHODS: We used a two-stage hyperinsulinemic-euglycemic clamp procedure in conjunction with stable isotopically labeled glucose and palmitate tracer infusions and 18F-fluorodeoxyglucose injection and positron emission tomography to quantify multi-organ insulin action and oral and intravenous tolerance tests to evaluate glucose-stimulated insulin secretion in fifteen people with obesity and OSA and thirteen people with obesity without OSA. RESULTS: OSA was associated with marked insulin resistance of adipose tissue triglyceride lipolysis and glucose uptake into both skeletal muscles and adipose tissue, whereas there was no significant difference between the OSA and control groups in insulin action on endogenous glucose production, basal insulin secretion, and glucose-stimulated insulin secretion during both intravenous and oral glucose tolerance tests. CONCLUSIONS: These data demonstrate that OSA is a key determinant of insulin sensitivity in people with obesity and underscore the importance of taking OSA status into account when evaluating metabolic function in people with obesity. These findings may also have important clinical implications because disease progression and the risk of diabetes-related complications vary by T2D subtype (i.e. severe insulin resistance vs insulin deficiency). People with OSA may benefit most from the targeted treatment of peripheral insulin resistance and early screening for complications associated with peripheral insulin resistance.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Técnica Clamp de Glucose/métodos , Resistência à Insulina/fisiologia , Obesidade/sangue , Apneia Obstrutiva do Sono/sangue , Adulto , Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Glucose/administração & dosagem , Teste de Tolerância a Glucose/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/diagnóstico , Obesidade/epidemiologia , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/epidemiologia
19.
Oxid Med Cell Longev ; 2022: 9171684, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35132354

RESUMO

Mitochondrial DNA copy number (mtDNAcn) has been proposed for use as a surrogate biomarker of mitochondrial health, and evidence suggests that mtDNA might be methylated. Intermediates of the one-carbon cycle (1CC), which is duplicated in the cytoplasm and mitochondria, have a major role in modulating the impact of diet on the epigenome. Moreover, epigenetic pathways and the redox system are linked by the metabolism of glutathione (GSH). In a cohort of 101 normal-weight and 97 overweight/obese subjects, we evaluated mtDNAcn and methylation levels in both mitochondrial and nuclear areas to test the association of these marks with body weight, metabolic profile, and availability of 1CC intermediates associated with diet. Body composition was associated with 1CC intermediate availability. Reduced levels of GSH were measured in the overweight/obese group (p = 1.3∗10-5). A high BMI was associated with lower LINE-1 (p = 0.004) and nominally lower methylenetetrahydrofolate reductase (MTHFR) gene methylation (p = 0.047). mtDNAcn was lower in overweight/obese subjects (p = 0.004) and independently correlated with MTHFR methylation levels (p = 0.005) but not to LINE-1 methylation levels (p = 0.086). DNA methylation has been detected in the light strand but not in the heavy strand of the mtDNA. Although mtDNA methylation in the light strand did not differ between overweight/obese and normal-weight subjects, it was nominally correlated with homocysteine levels (p = 0.035) and MTHFR methylation (p = 0.033). This evidence suggests that increased body weight might perturb mitochondrial-nuclear homeostasis affecting the availability of nutrients acting as intermediates of the one-carbon cycle.


Assuntos
Carbono/metabolismo , DNA Mitocondrial/sangue , DNA Mitocondrial/genética , Epigênese Genética , Obesidade/sangue , Obesidade/genética , Transdução de Sinais/genética , Adulto , Biomarcadores/sangue , Composição Corporal , Índice de Massa Corporal , Estudos de Casos e Controles , Estudos de Coortes , Variações do Número de Cópias de DNA , Metilação de DNA , Feminino , Glutationa/sangue , Humanos , Masculino , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/metabolismo , Mitocôndrias/metabolismo , Obesidade/epidemiologia , Polônia/epidemiologia , Adulto Jovem
20.
PLoS One ; 17(2): e0263312, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35213570

RESUMO

BACKGROUND: It remains unclear as to whether polycystic ovary syndrome (PCOS) is an additional risk factor in the development of left ventricular (LV) hypertrophy in obese women. In the current study, we provide clarity on this issue by rigorously analysing patient LV geometry beyond the basic clinical measures currently used. Importantly, the cohort contained only normotensive patients that would normally be deemed low risk with no further intervention required. METHODS: The study comprised 24 obese women with PCOS and 29 obese Control women. Transthoracic echocardiography was used to evaluate LV structure/function. Basic clinical and metabolic data were collected for each participant consisting of age, BMI, blood pressure, fasting glucose, LDL-C, HLD-C, cholesterol and triglyceride levels. Exclusion criteria; BMI < 30 g/m2, type 2 diabetes, hypertension. RESULTS: Both groups exhibited concentric remodelling of the LV posterior wall at a prevalence of ~20%, this associated with grade 1 diastolic dysfunction. Estimated LV mass/height2.7 was increased patients with PCOS (45 ± 2.2 vs 37 ± 1.6) with 33% exhibiting LV mass/height2.7 above ASE guidelines, compared to 7% in Controls. Furthermore, 25% of patients with PCOS were characterised with concentric hypertrophy, an alteration in LV geometry that was not observed in the Control group. CONCLUSIONS: To our knowledge, this is the first study to assess LV geometric patterns in obese women with PCOS. The results suggest that obese women with PCOS are at greater risk of concentric hypertrophy than obese only women and provide justification for additional cardiovascular risk assessment in normotensive obese/PCOS women.


Assuntos
Ecocardiografia , Hipertrofia Ventricular Esquerda/diagnóstico , Obesidade/diagnóstico por imagem , Síndrome do Ovário Policístico/diagnóstico por imagem , Adulto , Glicemia , Pressão Sanguínea , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Insuficiência Cardíaca Diastólica/complicações , Insuficiência Cardíaca Diastólica/diagnóstico por imagem , Insuficiência Cardíaca Diastólica/patologia , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/patologia , Humanos , Hipertrofia Ventricular Esquerda/sangue , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/etiologia , Obesidade/sangue , Obesidade/complicações , Obesidade/patologia , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/patologia , Triglicerídeos/sangue , Função Ventricular Esquerda/fisiologia
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