RESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Persian medicine (TPM), people often use herbal infusions as a dosage form to treat diseases related to hyperglycemia, known as 'dam-kardeh'. Traditionally, herbal preparations of Eryngium bungei Boiss. (E. b), Tragopogon buphthalmoides (DC.) Boiss. (T. b), Salvia hydrangea DC. ex Benth. (S. h), and Juniperus polycarpos K. Koch. (J. p) are used to manage diabetes in Iran. However, there is no evidence of their effectiveness in controlling glucose levels and their mechanisms remain unclear. AIM OF THE STUDY: This study aimed to investigate whether traditional doses of plant infusions can have hypoglycemic and/or anti-hyperglycemic effects during fasting and/or postprandial states and establish the basis for future research on their potential mechanisms of action. MATERIALS AND METHODS: The effects of traditional doses of herbal extracts on blood glucose levels in STZ-NA-induced hyperglycemic rats were investigated in 2-h acute tests during fasting and postprandial states (with a glucose load). In addition, the potential inhibitory effect in vitro of enzymes involved in relevant pathways, such as gluconeogenesis (fructose-1,6-bisphosphatase, FBPase and glucose-6-phosphatase, G6Pase), carbohydrate breakdown (intestinal α-glucosidases), and insulin sensitivity (protein tyrosine phosphatase 1B, PTP-1B) was evaluated. Acute toxicity tests were carried out and HPLC-SQ-TOF was used to analyze the chemical profiles of the plant extracts. RESULTS: In the fasting state, T. b, S. h, and E. b were as effective as glibenclamide in lowering blood glucose levels in hyperglycemic rats. Moreover, all three suppressed G6Pase and FBPase enzymatic activity by 90-97% and 80-91%, respectively. On the other hand, significant postprandial hypoglycemic efficacy was observed for E. b, S. h, and T. b. Based on the AUC values, T. b caused a reduction comparable to the therapeutic efficacy of repaglinide. When investigating the possible mechanisms of action involved in this activity, E. b, S. h, and T. b showed significant inhibition of PTP-1B in vitro (>70%). Finally, all plant extracts showed no signs of acute toxicity. Several compounds that may contribute to biological activities were identified, including phenolic acids and flavonoid glycosides. CONCLUSIONS: The present study supports the traditional use of T. b, E. b and S. h for the control of diabetes in the fasting and postprandial state. Moreover, these plants were found to be rich in bioactive compounds with hypoglycemic and antihyperglycemic activities. On the other hand, J. p, showed a modest effect only in the fasting state and after 90 min. Further studies are needed to expand these results by analyzing the chemical composition and using complementary experimental models.
Assuntos
Glicemia , Diabetes Mellitus Experimental , Jejum , Hipoglicemiantes , Extratos Vegetais , Período Pós-Prandial , Animais , Hipoglicemiantes/farmacologia , Extratos Vegetais/farmacologia , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/sangue , Masculino , Irã (Geográfico) , Ratos , Medicina Persa , Ratos Wistar , Hiperglicemia/tratamento farmacológico , Plantas Medicinais/química , Estreptozocina , Juniperus/químicaRESUMO
Pinus koraiensis (PK) leaf extract, derived from Korean pine byproducts, holds promise for alleviating postprandial hyperlipidemia. In this study, we investigated the potential of PK leaf extract for modulating postprandial hyperlipidemia in adults with normal or borderline fasting triglyceride levels. In a randomized, double-blind, parallel design, 70 subjects were randomly assigned to either the placebo or PK group for 4 weeks. After 4 weeks of consuming PK leaf extract, the results indicated a trend toward decreased serum apolipoprotein B-100 (ApoB100) levels 2 h after a high-fat challenge. Furthermore, significant improvements were observed in the incremental area under the curve (iAUC) at 0-4 h and 2-4 h compared to baseline, particularly among individuals with a higher body weight (>61.35 kg) and daily caloric intake (>1276.5 kcal). Based on these findings, PK leaf extract may have beneficial effects on postprandial lipoprotein metabolism, especially among individuals with a relatively high body weight and caloric intake.
Assuntos
Apolipoproteína B-100 , Metabolismo dos Lipídeos , Pinus , Extratos Vegetais , Folhas de Planta , Período Pós-Prandial , Humanos , Método Duplo-Cego , Pinus/química , Masculino , Extratos Vegetais/farmacologia , Folhas de Planta/química , Feminino , Adulto , Apolipoproteína B-100/sangue , Metabolismo dos Lipídeos/efeitos dos fármacos , Pessoa de Meia-Idade , Dieta Hiperlipídica , Triglicerídeos/sangue , Adulto Jovem , Voluntários Saudáveis , Hiperlipidemias/tratamento farmacológico , Hiperlipidemias/sangueAssuntos
Hipóxia , Período Pós-Prandial , Triglicerídeos , Humanos , Masculino , Triglicerídeos/sangue , Hipóxia/sangue , Adulto Jovem , AdultoRESUMO
AIMS: Extended fasting-postprandial switch intermitting time has been shown to affect Alzheimer's disease (AD). Few studies have investigated the cerebral perfusion response to fasting-postprandial metabolic switching (FMS) in AD patients. We aimed to evaluate the cerebral perfusion response to FMS in AD patients. METHODS: In total, 30 AD patients, 32 mild cognitive impairment (MCI) patients, and 30 healthy control individuals (HCs) were included in the quantification of cerebral perfusion via cerebral blood flow (CBF). The cerebral perfusion response to FMS was defined as the difference (ΔCBF) between fasting and postprandial CBF. RESULTS: Patients with AD had a regional negative ΔCBF in the anterior temporal lobe, part of the occipital lobe and the parietal lobe under FMS stimulation, whereas HCs had no significant ΔCBF. The AD patients had lower ΔCBF values in the right anterior temporal lobe than the MCI patients and HCs. ΔCBF in the anterior temporal lobe was negatively correlated with cognitive severity and cognitive reserve factors in AD patients. CONCLUSIONS: AD patients exhibited a poor ability to maintain cerebral perfusion homeostasis under FMS stimulation. The anterior temporal lobe is a distinct area that responds to FMS in AD patients and negatively correlates with cognitive function.
Assuntos
Doença de Alzheimer , Circulação Cerebrovascular , Disfunção Cognitiva , Jejum , Período Pós-Prandial , Humanos , Masculino , Feminino , Doença de Alzheimer/metabolismo , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/fisiopatologia , Idoso , Circulação Cerebrovascular/fisiologia , Período Pós-Prandial/fisiologia , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/diagnóstico por imagem , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Neuroimagem/métodos , Encéfalo/metabolismo , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Encéfalo/irrigação sanguínea , Imageamento por Ressonância MagnéticaRESUMO
Molecular effects of lifestyle interventions are typically studied in a single tissue. Here, we perform a secondary analysis on the sex-specific effects of the Growing Old TOgether trial (GOTO, trial registration number GOT NL3301 ( https://onderzoekmetmensen.nl/nl/trial/27183 ), NL-OMON27183 , primary outcomes have been previously reported in ref. 1), a moderate 13-week combined lifestyle intervention on the transcriptomes of postprandial blood, subcutaneous adipose tissue (SAT) and muscle tissue in healthy older adults, the overlap in effect between tissues and their relation to whole-body parameters of metabolic health. The GOTO intervention has virtually no effect on the postprandial blood transcriptome, while the SAT and muscle transcriptomes respond significantly. In SAT, pathways involved in HDL remodeling, O2/CO2 exchange and signaling are overrepresented, while in muscle, collagen and extracellular matrix pathways are significantly overexpressed. Additionally, we find that the effects of the SAT transcriptome closest associates with gains in metabolic health. Lastly, in males, we identify a shared variation between the transcriptomes of the three tissues. We conclude that the GOTO intervention has a significant effect on metabolic and muscle fibre pathways in the SAT and muscle transcriptome, respectively. Aligning the response in the three tissues revealed a blood transcriptome component which may act as an integrated health marker for metabolic intervention effects across tissues.
Assuntos
Estilo de Vida , Gordura Subcutânea , Transcriptoma , Humanos , Masculino , Feminino , Idoso , Gordura Subcutânea/metabolismo , Músculo Esquelético/metabolismo , Período Pós-Prandial , Pessoa de Meia-IdadeRESUMO
Background: The functional changes in alpha cells in patients with type 1 diabetes (T1D) with different residual beta cell functions remain poorly elucidated. The study aimed to investigate the relationship between glucagon secretion and C-peptide levels and to explore the relationship between glucagon response and glucose increment in respond to a secretagogue in a steamed bread meal tolerance test (BMTT) in T1D. Methods: The study enrolled 43 adult patients with T1D and 24 healthy control subjects. Patients with T1D who underwent BMTT were divided into two groups based on peak C-peptide levels: C peptide low (CPL; C-peptide < 200 pmol/L; n=14) and high (CPH; C peptide ≥ 200 pmol/L; n=29). Plasma glucose, C-peptide, glucagon levels at 0, 30, 60, 120, and 180 min were measured. The glucagon response to the BMTT was defined by areas under the curve (AUC) as early (AUC0-30), late (AUC30-180), or total (AUC0-180) glucagon. Results: Compared to healthy individuals, fasting plasma glucagon was lower and postprandial plasma glucagon level was increased in patients with T1D. Glucagon levels after BMTT between the CPL and CPH group showed significant group by time interaction. Peak glucagon and glucagon at 60-180 min, total and late glucagon response were higher in CPL than CPH group, while fasting glucagon and early glucagon response adjusted for glucose were comparable between CPL and CPH group. The higher late glucagon response and late glucagon response adjusted for glucose were associated with lower peak C-peptide in T1D. The higher late glucagon response and lower peak C-peptide were associated with the higher value of âµglucose at 180 min. Conclusion: Stimulated C-peptide levels affect the paradoxical increase in postprandial glucagon secretion in patients with T1D, especially late glucagon response. The exaggerated postprandial glucagon secretion further stimulates the elevation of postprandial glucose in patients with T1D.
Assuntos
Glicemia , Peptídeo C , Diabetes Mellitus Tipo 1 , Glucagon , Período Pós-Prandial , Humanos , Glucagon/sangue , Peptídeo C/sangue , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/metabolismo , Masculino , Feminino , Período Pós-Prandial/fisiologia , Adulto , Glicemia/metabolismo , Pessoa de Meia-Idade , Estudos de Casos e Controles , Adulto JovemRESUMO
OBJECTIVE: We aimed to evaluate the heterogeneity of gestational diabetes mellitus (GDM) patients diagnosed with various screening criteria. METHODS: We stratified pregnant women using consecutive fasting plasma glucose (FPG) and 2-hour postprandial plasma glucose (2hPPG) intervals of 0.2 mmol/L. The incidence of abnormal neonatal birthweight and birth-related adverse outcomes was compared with that of pregnant women without GDM. RESULTS: The study included 39,988 pregnant women (18-45 years, mean [SD], 31.5 [4.7] years) in Ningbo, China. The means (SDs) of FPG and 2hPPG within 24-28 weeks of gestation were 4.5 (0.5) and 6.8 (1.3) mmol/L, respectively. A total of 3025 (7.6%) women had 5.1-6.9 mmol/L FPG and 4560 (11.4%) had 8.5-11.0 mmol/L 2hPPG. The incidence of GDM according to the two combination criteria was 17.3% (6908 cases). The relative risk (RR) for < 10th percentile birthweight (< 10th WT) was 0.82 (95% CI, 0.74-0.91, p < 0.001) by 5.1 mmol/L FPG criterion and 1.14 (95% CI, 1.06-1.23, p < 0.001) by 8.5 mmol/L 2hPPG criterion, while the RRs for > 90th percentile birthweight (> 90th WT) were 1.48 (95% CI, 1.35-1.63, p < 0.001) and 0.95 (95% CI, 0.86-1.04, p = 0.29) according to the corresponding criteria. The FPG criterion was more strongly associated with maternal hypertension than the 2hPPG criterion. Both criteria did not show a distinct association with other composite adverse outcomes. CONCLUSION: High FPG is significantly associated with high birth weight, whereas high 2hPPG is slightly associated with low birth weight. Our findings highlight the heterogeneity of patients with GDM diagnosed by different criteria.
Assuntos
Peso ao Nascer , Glicemia , Diabetes Gestacional , Jejum , Período Pós-Prandial , Humanos , Feminino , Diabetes Gestacional/sangue , Diabetes Gestacional/epidemiologia , Diabetes Gestacional/diagnóstico , Gravidez , Adulto , Jejum/sangue , Glicemia/análise , China/epidemiologia , Adulto Jovem , Adolescente , Resultado da Gravidez/epidemiologia , Recém-Nascido , Teste de Tolerância a Glucose , Pessoa de Meia-Idade , IncidênciaRESUMO
BACKGROUND: In recent years, numerous methods have been introduced to predict glucose levels using machine-learning techniques on patients' daily behavioral and continuous glucose data. Nevertheless, a definitive consensus remains elusive regarding modeling the combined effects of diet and exercise for optimal glucose prediction. A notable challenge is the propensity for observational patient datasets from uncontrolled environments to overfit due to skewed feature distributions of target behaviors; for instance, diabetic patients seldom engage in high-intensity exercise post-meal. METHODS: In this study, we introduce a unique application of Bayesian transfer learning for postprandial glucose prediction using randomized controlled trial (RCT) data. The data comprises a time series of three key variables: continuous glucose levels, exercise expenditure, and carbohydrate intake. For building the optimal model to predict postprandial glucose levels we initially gathered balanced training data from RCTs on healthy participants by randomizing behavioral conditions. Subsequently, we pretrained the model's parameter distribution using RCT data from the healthy cohort. This pretrained distribution was then adjusted, transferred, and utilized to determine the model parameters for each patient. RESULTS: The efficacy of the proposed method was appraised using data from 68 gestational diabetes mellitus (GDM) patients in uncontrolled settings. The evaluation underscored the enhanced performance attained through our method. Furthermore, when modeling the joint impact of diet and exercise, the synergetic model proved more precise than its additive counterpart. CONCLUSION: An innovative application of the transfer-learning utilizing randomized controlled trial data can improve the challenging modeling task of postprandial glucose prediction for GDM patients, integrating both dietary and exercise behaviors. For more accurate prediction, future research should focus on incorporating the long-term effects of exercise and other glycemic-related factors such as stress, sleep.
Assuntos
Teorema de Bayes , Glicemia , Exercício Físico , Aprendizado de Máquina , Período Pós-Prandial , Humanos , Glicemia/metabolismo , Glicemia/análise , Feminino , Período Pós-Prandial/fisiologia , Exercício Físico/fisiologia , Dieta , Gravidez , Diabetes Gestacional/sangue , Diabetes Gestacional/metabolismo , AdultoRESUMO
In type 1 diabetes, high-fat meals require more insulin to prevent hyperglycemia while meals followed by aerobic exercises require less insulin to prevent hypoglycemia, but the adjustments needed vary between individuals. We propose a decision support system with reinforcement learning to personalize insulin doses for high-fat meals and postprandial aerobic exercises. We test this system in a single-arm 16-week study in 15 adults on multiple daily injections therapy (NCT05041621). The primary objective of this study is to assess the feasibility of the novel learning algorithm. This study looks at glucose outcomes and patient reported outcomes. The postprandial incremental area under the glucose curve is improved from the baseline to the evaluation period for high-fat meals (378 ± 222 vs 38 ± 223 mmol/L/min, p = 0.03) and meals followed by exercises (-395 ± 192 vs 132 ± 181 mmol/L/min, p = 0.007). The postprandial time spent below 3.9 mmol/L is reduced after high-fat meals (5.3 ± 1.6 vs 1.8 ± 1.5%, p = 0.003) and meals followed by exercises (5.3 ± 1.2 vs 1.4 ± 1.1%, p = 0.003). Our study shows the feasibility of automatically personalizing insulin doses for high-fat meals and postprandial exercises. Randomized controlled trials are warranted.
Assuntos
Glicemia , Diabetes Mellitus Tipo 1 , Exercício Físico , Insulina , Refeições , Período Pós-Prandial , Humanos , Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/sangue , Insulina/administração & dosagem , Masculino , Feminino , Adulto , Exercício Físico/fisiologia , Glicemia/metabolismo , Estudo de Prova de Conceito , Pessoa de Meia-Idade , Hipoglicemiantes/administração & dosagem , Dieta Hiperlipídica/efeitos adversos , Reforço Psicológico , Medicina de Precisão/métodos , Hipoglicemia/prevenção & controle , Algoritmos , Adulto JovemRESUMO
BACKGROUND: Insulin resistance is a frequent precursor of typical obesity and metabolic syndrome complications. However, accurate diagnosis remains elusive because of its pathophysiological complexity and heterogeneity. Herein, we have explored the utility of insulin secretion dynamics in response to an oral glucose tolerance test as a surrogate marker to identify distinct metabotypes of disease severity. METHODS: The study population consisted of children with obesity and insulin resistance, stratified according to the post-challenge insulin peak timing (i.e., early, middle, and late peak), from whom fasting and postprandial plasma and erythrocytes were collected for metabolomics analysis. RESULTS: Children with late insulin peak manifested worse cardiometabolic health (i.e., higher blood pressure, glycemia, and HOMA-IR scores) than early responders. These subjects also showed more pronounced changes in metabolites mirroring failures in energy homeostasis, oxidative stress, metabolism of cholesterol and phospholipids, and adherence to unhealthy dietary habits. Furthermore, delayed insulin peak was associated with impaired metabolic flexibility, as reflected in compromised capacity to regulate mitochondrial energy pathways and the antioxidant defense in response to glucose overload. CONCLUSIONS: Altogether, these findings suggest that insulin resistance could encompass several phenotypic subtypes characterized by graded disturbances in distinctive metabolic derangements occurring in childhood obesity, which serve as severity predictive markers.
Assuntos
Biomarcadores , Glicemia , Teste de Tolerância a Glucose , Resistência à Insulina , Insulina , Síndrome Metabólica , Metabolômica , Obesidade Infantil , Índice de Gravidade de Doença , Humanos , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/sangue , Síndrome Metabólica/fisiopatologia , Síndrome Metabólica/epidemiologia , Criança , Masculino , Feminino , Obesidade Infantil/diagnóstico , Obesidade Infantil/sangue , Obesidade Infantil/fisiopatologia , Obesidade Infantil/epidemiologia , Adolescente , Insulina/sangue , Glicemia/metabolismo , Biomarcadores/sangue , Fenótipo , Fatores Etários , Fatores de Tempo , Valor Preditivo dos Testes , Secreção de Insulina , Período Pós-Prandial , Metabolismo EnergéticoRESUMO
OBJECTIVES: To explore parameters that may determine the improvement in C-peptide levels in patients with type 2 diabetes (T2D) receiving continuous subcutaneous insulin infusion (CSII) therapy. METHODS: The trial included a lead-in period for collecting baseline parameters and correcting hyperglycemia, a 4-day CGM period, and a 2-3 weeks treatment period. After screening, patients were hospitalized and randomized to the metformin add-on NovoRapid group or the Prandilin group. Once the glycemic target was reached, all patients underwent a 4-day CGM, with treatments maintained for 2-3 weeks. OGTTs were performed at baseline and endpoint. The primary endpoint was identifying factors contributing to better ß-cell function recovery after CSII therapy. RESULTS: A total of 99 recruited patients were admitted as inpatients and achieved glycemic control within 3.8 ± 1.1 days. Of these, 83 (84 %) patients showed improvement in C-peptide levels, while 16 (16 %) did not show any change in C-peptide levels at the endpoint. Pearson analysis showed a negative correlation between the incremental AUC of glucose concentration (from 0700 to 1000) and the increase in incremental AUC of C-peptide levels (r = -0.199, P < 0.05). CONCLUSIONS: Drug-naïve T2D patients with lower postprandial glucose concentration during CSII therapy exhibit better ß-cell function recovery.
Assuntos
Glicemia , Peptídeo C , Diabetes Mellitus Tipo 2 , Hipoglicemiantes , Células Secretoras de Insulina , Insulina , Período Pós-Prandial , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Células Secretoras de Insulina/fisiologia , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Glicemia/metabolismo , Glicemia/análise , Insulina/administração & dosagem , Insulina/uso terapêutico , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/administração & dosagem , Período Pós-Prandial/fisiologia , Peptídeo C/sangue , Idoso , Sistemas de Infusão de Insulina , Metformina/uso terapêuticoRESUMO
OBJECTIVE: The objective of this study was to explore how dietary macronutrient composition influences postprandial appetite hormone responses and subsequent energy intake. METHODS: A total of 20 adults (mean [SEM], age 30 [1] years, BMI 27.8 [1.3] kg/m2, n = 8 with normal weight, n = 6 with overweight, n = 6 with obesity) consumed a low-fat (LF) diet (10% fat, 75% carbohydrate) and a low-carbohydrate (LC) diet (10% carbohydrate, 75% fat) for 2 weeks each in an inpatient randomized crossover design. At the end of each diet, participants consumed isocaloric macronutrient-representative breakfast test meals, and 6-h postprandial responses were measured. Ad libitum energy intake was measured for the rest of the day. RESULTS: The LC meal resulted in greater mean postprandial plasma active glucagon-like peptide-1 (GLP-1; LC: 6.44 [0.78] pg/mL, LF: 2.46 [0.26] pg/mL; p < 0.0001), total glucose-dependent insulinotropic polypeptide (GIP; LC: 578 [60] pg/mL, LF: 319 [37] pg/mL; p = 0.0004), and peptide YY (PYY; LC: 65.6 [5.6] pg/mL, LF: 50.7 [3.8] pg/mL; p = 0.02), whereas total ghrelin (LC: 184 [25] pg/mL, LF: 261 [47] pg/mL; p = 0.0009), active ghrelin (LC: 91 [9] pg/mL, LF: 232 [28] pg/mL; p < 0.0001), and leptin (LC: 26.9 [6.5] ng/mL, LF: 35.2 [7.5] ng/mL; p = 0.01) were lower compared with LF. Participants ate more during LC at lunch (244 [85] kcal; p = 0.01) and dinner (193 [86] kcal; p = 0.04), increasing total subsequent energy intake for the day compared with LF (551 [103] kcal; p < 0.0001). CONCLUSIONS: In the short term, endogenous gut-derived appetite hormones do not necessarily determine ad libitum energy intake.
Assuntos
Apetite , Estudos Cross-Over , Dieta com Restrição de Carboidratos , Dieta com Restrição de Gorduras , Ingestão de Energia , Polipeptídeo Inibidor Gástrico , Grelina , Peptídeo 1 Semelhante ao Glucagon , Peptídeo YY , Período Pós-Prandial , Humanos , Adulto , Masculino , Feminino , Peptídeo 1 Semelhante ao Glucagon/sangue , Grelina/sangue , Peptídeo YY/sangue , Polipeptídeo Inibidor Gástrico/sangue , Dieta com Restrição de Gorduras/métodos , Obesidade/sangue , Hormônios Gastrointestinais/sangue , Sobrepeso/sangue , Glicemia/metabolismo , Insulina/sangueRESUMO
Constricting pythons, known for their ability to consume infrequent, massive meals, exhibit rapid and reversible cardiac hypertrophy following feeding. Our primary goal was to investigate how python hearts achieve this adaptive response after feeding. Isolated myofibrils increased force after feeding without changes in sarcomere ultrastructure and without increasing energy cost. Ca2+ transients were prolonged after feeding with no changes in myofibril Ca2+ sensitivity. Feeding reduced titin-based tension, resulting in decreased cardiac tissue stiffness. Feeding also reduced the activity of sirtuins, a metabolically linked class of histone deacetylases, and increased chromatin accessibility. Transcription factor enrichment analysis on transposase-accessible chromatin with sequencing revealed the prominent role of transcription factors Yin Yang1 and NRF1 in postfeeding cardiac adaptation. Gene expression also changed with the enrichment of translation and metabolism. Finally, metabolomics analysis and adenosine triphosphate production demonstrated that cardiac adaptation after feeding not only increased energy demand but also energy production. These findings have broad implications for our understanding of cardiac adaptation across species and hold promise for the development of innovative approaches to address cardiovascular diseases.
Assuntos
Boidae , Cardiomegalia , Epigênese Genética , Animais , Cardiomegalia/metabolismo , Cardiomegalia/genética , Cardiomegalia/fisiopatologia , Boidae/fisiologia , Boidae/genética , Período Pós-Prandial/fisiologia , Metabolismo Energético , Miofibrilas/metabolismo , Cálcio/metabolismo , Adaptação Fisiológica , Miocárdio/metabolismo , Reprogramação MetabólicaRESUMO
BACKGROUND: Bariatric surgery is an effective treatment option for obesity and provides long-term weight loss and positive effects on metabolism, but the underlying mechanisms are poorly understood. Alterations in bile acid metabolism have been suggested as a potential contributing factor, but comprehensive studies in humans are lacking. METHODS: In this study, we analysed the postprandial responses of bile acids, C4 and FGF19 in plasma, and excretion of bile acids in faeces, before and after bariatric surgery in patients (n = 38; 74% females) with obesity with or without type 2 diabetes from the BARIA cohort. FINDINGS: We observed that total fasting plasma bile acid levels increased, and faecal excretion of bile acids decreased after surgery suggesting increased reabsorption of bile acids. Consistent with increased bile acid levels after surgery we observed increased postprandial levels of FGF19 and suppression of the bile acid synthesis marker C4, suggesting increased FXR activation in the gut. We also noted that a subset of bile acids had altered postprandial responses before and after surgery. Finally, fasting plasma levels of 6α-hydroxylated bile acids, which are TGR5 agonists and associated with improved glucose metabolism, were increased after surgery and one of them, HDCA, covaried with diabetes remission in an independent cohort. INTERPRETATION: Our findings provide new insights regarding bile acid kinetics and suggest that bariatric surgery in humans alters bile acid profiles leading to activation of FXR and TGR5, which may contribute to weight loss, improvements in glucose metabolism, and diabetes remission. FUNDING: Novo Nordisk Fonden, Leducq Foundation, Swedish Heart-Lung Foundation, Knut and Alice Wallenberg Foundation, the ALF-agreement, ZonMw.
Assuntos
Cirurgia Bariátrica , Ácidos e Sais Biliares , Diabetes Mellitus Tipo 2 , Fatores de Crescimento de Fibroblastos , Obesidade , Humanos , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/cirurgia , Diabetes Mellitus Tipo 2/sangue , Ácidos e Sais Biliares/metabolismo , Ácidos e Sais Biliares/sangue , Cirurgia Bariátrica/métodos , Feminino , Masculino , Obesidade/cirurgia , Obesidade/metabolismo , Obesidade/sangue , Pessoa de Meia-Idade , Adulto , Fatores de Crescimento de Fibroblastos/sangue , Fatores de Crescimento de Fibroblastos/metabolismo , Período Pós-Prandial , Biomarcadores , Fezes/química , Cinética , JejumRESUMO
Fuel substrate switching between carbohydrates and fat is essential for maintaining metabolic homeostasis. During aerobic exercise, the predominant energy source gradually shifts from carbohydrates to fat. While it is well known that exercise mobilizes fat storage from adipose tissues, it remains largely obscure how circulating lipids are distributed tissue-specifically according to distinct energy requirements. Here, we demonstrate that aerobic exercise is linked to nutrient availability to regulate tissue-specific activities of lipoprotein lipase (LPL), the key enzyme catabolizing circulating triglyceride (TG) for tissue uptake, through the differential actions of angiopoietin-like (ANGPTL) proteins. Exercise reduced the tissue binding of ANGPTL3 protein, increasing LPL activity and TG uptake in the heart and skeletal muscle in the postprandial state specifically. Mechanistically, exercise suppressed insulin secretion, attenuating hepatic Angptl8 transcription through the PI3K/mTOR/CEBPα pathway, which is imperative for the tissue binding of its partner ANGPTL3. Constitutive expression of ANGPTL8 hampered lipid utilization and resulted in cardiac dysfunction in response to exercise. Conversely, exercise promoted the expression of ANGPTL4 in white adipose tissues, overriding the regulatory actions of ANGPTL8/ANGPTL3 in suppressing adipose LPL activity, thereby diverting circulating TG away from storage. Collectively, our findings show an overlooked bifurcated ANGPTL-LPL network that orchestrates fuel switching in response to aerobic exercise.
Assuntos
Proteína 3 Semelhante a Angiopoietina , Proteína 8 Semelhante a Angiopoietina , Proteínas Semelhantes a Angiopoietina , Lipase Lipoproteica , Músculo Esquelético , Período Pós-Prandial , Triglicerídeos , Proteínas Semelhantes a Angiopoietina/metabolismo , Proteínas Semelhantes a Angiopoietina/genética , Triglicerídeos/metabolismo , Animais , Camundongos , Lipase Lipoproteica/metabolismo , Músculo Esquelético/metabolismo , Proteína 3 Semelhante a Angiopoietina/metabolismo , Masculino , Humanos , Condicionamento Físico Animal/fisiologia , Proteína 4 Semelhante a Angiopoietina/metabolismo , Proteína 4 Semelhante a Angiopoietina/genética , Hormônios Peptídicos/metabolismo , Miocárdio/metabolismo , Exercício Físico/fisiologia , Fígado/metabolismo , Camundongos Endogâmicos C57BL , Metabolismo dos LipídeosRESUMO
Hypoxemia occurs during exposure to high altitude (continuous hypoxemia) or in the context of breathing disorders such as obstructive sleep apnea (OSA; intermittent hypoxemia). Growing evidence demonstrates that hypoxemia induces an anorexigenic effect on appetite; however, few studies have assessed hypoxemia-related reductions in appetite during acute passive exposures and during intermittent hypoxemia. This study thus pooled together four same-single-site randomized crossover trials using simulated models of high altitude (fraction of inspired oxygen = 0.1200, â¼5000 m) and moderate OSA (â¼15 hypoxemic cycles per hour, â¼85 oxyhemoglobin saturation). Changes in appetite were evaluated during 6 h of passive normoxia and intermittent or continuous hypoxemia in postprandial or fasting states among healthy young adults (n = 40) and middle-aged individuals living with OSA (n = 7). Our results demonstrate that (1) acute passive intermittent hypoxemia leads to statistically significant, but likely not clinically significant reductions in appetite in the postprandial state, (2) the anorexigenic effect of acute passive hypoxemia on appetite is not consistent across hypoxemic methods and nutritional states, and (3) variations in individual factors may influence appetite responses during normoxia and hypoxemia. These findings indicate that the effect of acute passive hypoxemia on appetite is heterogeneous, particularly across different hypoxemic methods and nutritional states.
Assuntos
Apetite , Estudos Cross-Over , Jejum , Hipóxia , Período Pós-Prandial , Apneia Obstrutiva do Sono , Humanos , Masculino , Adulto , Feminino , Adulto Jovem , Pessoa de Meia-Idade , Apneia Obstrutiva do Sono/terapia , Apneia Obstrutiva do Sono/fisiopatologia , AltitudeRESUMO
OBJECTIVES: This study aimed to assess postprandial blood glucose response (PBGR), relative glycemic response (RGR) and insulin response when 25 g available carbohydrates (AC) is replaced with cooked lentils in the formulation of muffins, chilies and soups. METHODS: In randomized, crossover studies, healthy adults consumed foods containing 25 g AC from green lentils, red lentils or a control (wheat muffin, n = 24; rice chili, n = 24; potato soup, n = 20). Blood collected at fasting and at 15, 30, 45, 60, 90 and 120 min was analyzed to derive the incremental area under the response curve (iAUC) for glucose, insulin, RGR and maximum concentration (CMAX). Treatment effects were assessed with repeated measures ANOVA. RESULTS: A replacement of 25 g AC with green lentils significantly decreased glucose iAUC compared to chili and soup (p < 0.0001), but not muffin (p = 0.07) controls, while also eliciting a significantly lower insulin iAUC for all three foods (muffin p = 0.03; chili p = 0.0002; soup p < 0.0001). Red lentil foods significantly decreased glucose iAUC (muffin p = 0.02; chili p < 0.0001; soup p < 0.0001) compared to controls, with a significantly lower insulin iAUC for chili and soup (p < 0.0001) but not muffins (p = 0.09). The RGR for muffins, chilies and soups was 88, 58 and 61%, respectively, for green lentils, and 84, 48 and 49%, respectively, for red lentils. CONCLUSIONS: PBGR, insulin and RGR are decreased when lentils are incorporated into food products, providing credible evidence to promote carbohydrate replacement with lentil-based foods.
Assuntos
Glicemia , Estudos Cross-Over , Índice Glicêmico , Insulina , Lens (Planta) , Período Pós-Prandial , Humanos , Glicemia/metabolismo , Lens (Planta)/química , Adulto , Insulina/sangue , Masculino , Feminino , Adulto Jovem , Carboidratos da Dieta/administração & dosagem , Ingredientes de Alimentos/análise , Pessoa de Meia-Idade , Voluntários Saudáveis , Oryza/químicaRESUMO
The rising incidence of type 2 diabetes underscores the need for technological innovations aimed at enhancing diabetes management by aiding individuals in monitoring their dietary intake. This has resulted in the development of technologies capable of tracking the timing and content of an individual's meals. However, the ability to use non-invasive wearables to estimate or classify the carbohydrate content of the food an individual has just consumed remains a relatively unexplored area. This study investigates carbohydrate content classification using postprandial heart rate responses from non-invasive wearables. We designed and developed timeStampr, an iOS application for collecting timestamps essential for data labeling and establishing ground truth. We then conducted a pilot study in controlled, yet naturalistic settings. Data were collected from 23 participants using an Empatica E4 device worn on the upper arm, while each participant consumed either low-carbohydrate or carbohydrate-rich foods. Due to sensor irregularities with dark skin tones and non-compliance with the study's health criteria, we excluded data from three participants. Finally, we configured and trained a Light Gradient Boosting Machine (LGBM) model for carbohydrate content classification. Our classifiers demonstrated robust performance, with the carbohydrate content classification model consistently achieving at least 84% in accuracy, precision, recall, and AUCROC within a 60 s window. The results of this study demonstrate the potential of postprandial heart rate responses from non-invasive wearables in carbohydrate content classification.
Assuntos
Frequência Cardíaca , Período Pós-Prandial , Dispositivos Eletrônicos Vestíveis , Humanos , Frequência Cardíaca/fisiologia , Período Pós-Prandial/fisiologia , Masculino , Feminino , Adulto , Carboidratos da Dieta/análise , Pessoa de Meia-Idade , Projetos Piloto , Diabetes Mellitus Tipo 2/fisiopatologiaRESUMO
Roux-en-Y Gastric Bypass may be associated with an alteration of protein bioavailability in relation to intestinal remodeling. Our study aimed to test this hypothesis by Roux-en-Y Gastric Bypass. Diet-induced obese rats underwent Roux-en-Y Gastric Bypass surgery (RYGB rats) while a Sham-operated control group was used. All rats received a 15N-labeled protein meal 1 or 3 months after surgery and were euthanized 6h later. Protein digestibility, 15N recovered in organs and urea pool, fractional protein synthesis rate, and intestinal morphometry were assessed. Protein digestibility was similar in all groups (94.2±0.3%). The small intestine was hypertrophied in RYGB rats 1 month after surgery, weighing 9.1±0.2g vs. 7.0±0.3g in Sham rats (P = 0.003). Villus height and crypt depth were increased in the alimentary limb and ileum of RYGB rats. However, Roux-en-Y Gastric Bypass had no impact on the fractional synthesis rate. In the gastrointestinal tract, 15N retention only differed in the ileal mucosa and was higher in RYGB rats at 1 month (0.48±0.2% vs. 0.3±0.09%, P = 0.03). 15N recovery from the liver, muscle, and skin was lower in RYGB rats at 1 month. 15N recovery from urinary and plasma urea was higher in RYGB rats at both times, resulting in increased total deamination (13.2±0.9% vs. 10.1±0.5%, P<0.01). This study showed that Roux-en-Y Gastric Bypass did not affect protein digestibility. Dietary nitrogen sequestration was transitorily and moderately diminished in several organs. This was associated with a sustained elevation of postprandial deamination after Roux-en-Y Gastric Bypass, whose mechanisms merit further studies.
Assuntos
Proteínas Alimentares , Derivação Gástrica , Isótopos de Nitrogênio , Período Pós-Prandial , Animais , Ratos , Masculino , Proteínas Alimentares/metabolismo , Proteínas Alimentares/administração & dosagem , Digestão , Obesidade/metabolismo , Obesidade/cirurgiaRESUMO
INTRODUCTION: Longitudinal metabolomics data from a meal challenge test contains both fasting and dynamic signals, that may be related to metabolic health and diseases. Recent work has explored the multiway structure of time-resolved metabolomics data by arranging it as a three-way array with modes: subjects, metabolites, and time. The analysis of such dynamic data (where the fasting data is subtracted from postprandial states) reveals dynamic markers of various phenotypes, and differences between fasting and dynamic states. However, there is still limited success in terms of extracting static and dynamic biomarkers for the same subject stratifications. OBJECTIVES: Through joint analysis of fasting and dynamic metabolomics data, our goal is to capture static and dynamic biomarkers of a phenotype for the same subject stratifications providing a complete picture, that will be more effective for precision health. METHODS: We jointly analyze fasting and dynamic metabolomics data collected during a meal challenge test from the COPSAC 2000 cohort using coupled matrix and tensor factorizations (CMTF), where the dynamic data (subjects by metabolites by time) is coupled with the fasting data (subjects by metabolites) in the subjects mode. RESULTS: The proposed data fusion approach extracts shared subject stratifications in terms of BMI (body mass index) from fasting and dynamic signals as well as the static and dynamic metabolic biomarker patterns corresponding to those stratifications. Specifically, we observe a subject stratification showing the positive association with all fasting VLDLs and higher BMI. For the same subject stratification, a subset of dynamic VLDLs (mainly the smaller sizes) correlates negatively with higher BMI. Higher correlations of the subject quantifications with the phenotype of interest are observed using such a data fusion approach compared to individual analyses of the fasting and postprandial state. CONCLUSION: The CMTF-based approach provides a complete picture of static and dynamic biomarkers for the same subject stratifications-when markers are present in both fasting and dynamic states.