RESUMEN

This study aimed to assess the impact of roasting degree on antioxidant and metabolic parameters in vitro and in vivo. In vitro, we evaluated radical scavenging, lipid peroxidation, and the activity of digestive enzymes (α-glucosidase, α-amylase, and lipase). In vivo, we first examined coffee's effect on carbohydrate and lipid absorption in healthy rats, followed by a chronic evaluation of metabolic disorders and antioxidant markers using a diet-induced obesity model. In vitro results revealed that increased roasting degree reduced the antioxidant capacity of coffee brews. All brews showed lower inhibition of α-glucosidase and α-amylase, and lipase inhibition compared to the positive control (acarbose or orlistat). In vivo, all roasting degrees consistently reduced postprandial glucose levels by 20%. Notably, coffee with a high roasting degree (HRD) decreased serum triglycerides (TG) by ∼44% after a lipid load, while other roasts did not. Chronic administration of unroasted (UN) or HRD coffee significantly reduced weight gain compared to the obese control (∼15% and ∼10%, respectively). Notably, all coffee samples improved lipid metabolism parameters. UN and HRD coffee significantly decreased adipocyte volume by 58% and 48%, respectively, compared to the obese control. Additionally, all groups exhibited less than 30% hepatic lipid droplets independent of roasting degree. HRD treatment notably increased liver catalase (CAT) activity and reduced lipid peroxidation in serum (∼90%), liver (∼59%), and adipose tissue (∼37%) compared to the obese control group. These findings suggest that HRD in coffee may confer certain biological advantages.

RESUMEN

Inherited metabolic disorders (IMDs) are genetic disorders often characterized by the accumulation of toxic metabolites in patient tissues and bodily fluids. Although the pathophysiologic effect of these metabolites and their direct effect on cellular function is not yet established for many of these disorders, animal and cellular studies have shown that mitochondrial bioenergetic dysfunction with impairment of citric acid cycle activity and respiratory chain, along with secondary damage induced by oxidative stress are prominent in some. Mitochondrial quality control, requiring the coordination of multiple mechanisms such as mitochondrial biogenesis, dynamics, and mitophagy, is responsible for the correction of such defects. For inborn errors of enzymes located in the mitochondria, secondary abnormalities in quality control this organelle could play a role in their pathophysiology. This review summarizes preclinical data (animal models and patient-derived cells) on mitochondrial quality control disturbances in selected IMDs.

RESUMEN

As obesity rates continue to rise, the prevalence of metabolic dysfunction and alcohol-associated steatotic liver disease (MetALD), a new term for Nonalcoholic Fatty Liver Disease (NAFLD), also increases. In an aging population, it is crucial to understand the interplay between metabolic disorders, such as MetALD, and bone health. This understanding becomes particularly significant in the context of implant osseointegration. This study introduces an in vitro model simulating high lipogenesis through the use of human Mesenchymal Stroma Cells-derived adipocytes, 3D intrahepatic cholangiocyte organoids (ICO), and Huh7 hepatocytes, to evaluate the endocrine influence on osteoblasts interacting with titanium. We observed a significant increase in intracellular fat accumulation in all three cell types, along with a corresponding elevation in metabolic gene expression compared to the control groups. Notably, osteoblasts undergoing mineralization in this high-lipogenesis environment also displayed lipid vesicle accumulation. The study further revealed that titanium surfaces modulate osteogenic gene expression and impact cell cycle progression, cell survival, and extracellular matrix remodeling under lipogenic conditions. These findings provide new insights into the challenges of implant integration in patients with obesity and MetALD, offering a deeper understanding of the metabolic influences on bone regeneration and implant success.

Asunto(s)

Lipogénesis , Osteogénesis , Titanio , Humanos , Titanio/farmacología , Osteogénesis/efectos de los fármacos , Lipogénesis/efectos de los fármacos , Adipocitos/metabolismo , Células Madre Mesenquimatosas/metabolismo , Osteoblastos/metabolismo , Osteoblastos/efectos de los fármacos , Organoides/metabolismo , Hepatocitos/metabolismo

RESUMEN

There are few cerebrotendineous xanthomatosis (CTX) case series and observational studies including a significant number of Latin American patients. We describe a multicenter Brazilian cohort of patients with CTX highlighting their clinical phenotype, recurrent variants and assessing possible genotype-phenotype correlations. We analyzed data from all patients with clinical and molecular or biochemical diagnosis of CTX regularly followed at six genetics reference centers in Brazil between March 2020 and August 2023. We evaluated 38 CTX patients from 26 families, originating from 4 different geographical regions in Brazil. Genetic analysis identified 13 variants in the CYP27A1 gene within our population, including 3 variants that had not been previously described. The most frequent initial symptom of CTX in Brazil was cataract (27%), followed by xanthomas (24%), chronic diarrhea (13.5%), and developmental delay (13.5%). We observed that the median age at loss of ambulation correlates with the age of onset of neurological symptoms, with an average interval of 10 years (interquartile range 6.9 to 11 years). This study represents the largest CTX case series ever reported in South America. We describe phenotypic characteristics and report three new pathogenic or likely pathogenic variants.

Asunto(s)

Colestanotriol 26-Monooxigenasa , Estudios de Asociación Genética , Xantomatosis Cerebrotendinosa , Humanos , Xantomatosis Cerebrotendinosa/genética , Xantomatosis Cerebrotendinosa/diagnóstico , Xantomatosis Cerebrotendinosa/epidemiología , Brasil/epidemiología , Masculino , Femenino , Colestanotriol 26-Monooxigenasa/genética , Niño , Preescolar , Fenotipo , Adolescente , Adulto , Mutación , Predisposición Genética a la Enfermedad , Adulto Joven , Catarata/genética , Catarata/epidemiología

RESUMEN

Variations in parathyroid gland positions often cause failure in initial parathyroid adenoma surgery, especially when imaging fails to localise the adenoma. This report describes a female patient with primary hyperparathyroidism for which preoperative localisation studies did not determine the position of the hyperfunctioning gland. The initial approach with bilateral cervical exploration and intraoperative parathyroid hormone monitoring was performed unsuccessfully. A mediastinal adenoma was suspected due to meticulous negative neck exploration and repeated negative images for a neck adenoma. Subsequently, a second approach involving mediastinal exploration was performed. After the removal of remnant thymic tissue in the mediastinal space, a significant drop in intraoperative parathyroid hormone levels was achieved. The pathological result confirmed the presence of a tiny pathological parathyroid adenoma within the thymus. At 6 months follow-up, postoperative biochemical assessment was consistent with normal calcium and parathyroid hormone levels.

Asunto(s)

Adenoma , Hiperparatiroidismo Primario , Neoplasias de las Paratiroides , Humanos , Neoplasias de las Paratiroides/complicaciones , Neoplasias de las Paratiroides/cirugía , Neoplasias de las Paratiroides/diagnóstico por imagen , Femenino , Hiperparatiroidismo Primario/cirugía , Hiperparatiroidismo Primario/etiología , Hiperparatiroidismo Primario/complicaciones , Hiperparatiroidismo Primario/diagnóstico , Hiperparatiroidismo Primario/diagnóstico por imagen , Adenoma/complicaciones , Adenoma/cirugía , Adenoma/diagnóstico por imagen , Neoplasias del Mediastino/complicaciones , Neoplasias del Mediastino/diagnóstico por imagen , Neoplasias del Mediastino/cirugía , Hormona Paratiroidea/sangre , Persona de Mediana Edad , Glándulas Paratiroides/diagnóstico por imagen , Paratiroidectomía

RESUMEN

Glycolipid metabolic disorders (GLMDs) are various metabolic disorders resulting from dysregulation in glycolipid levels, consequently leading to an increased risk of obesity, diabetes, liver dysfunction, neuromuscular complications, and cardiorenal vascular diseases (CRVDs). In patients with GLMDs, excess caloric intake and a lack of physical activity may contribute to oxidative stress (OxS) and systemic inflammation. This study aimed to review the connection between GLMD, OxS, metainflammation, and the onset of CRVD. GLMD is due to various metabolic disorders causing dysfunction in the synthesis, breakdown, and absorption of glucose and lipids in the body, resulting in excessive ectopic accumulation of these molecules. This is mainly due to neuroendocrine dysregulation, insulin resistance, OxS, and metainflammation. In GLMD, many inflammatory markers and defense cells play a vital role in related tissues and organs, such as blood vessels, pancreatic islets, the liver, muscle, the kidneys, and adipocytes, promoting inflammatory lesions that affect various interconnected organs through their signaling pathways. Advanced glycation end products, ATP-binding cassette transporter 1, Glucagon-like peptide-1, Toll-like receptor-4, and sphingosine-1-phosphate (S1P) play a crucial role in GLMD since they are related to glucolipid metabolism. The consequences of this is system organ damage and increased morbidity and mortality.

RESUMEN

Carotenoids constitute compounds of significant biological interest due to their multiple biological activities, such as antimicrobial, anticancer, antiadipogenic, antidiabetic, and antioxidant properties. Metabolic syndrome (MetS) comprehends a series of metabolic abnormalities (e.g., hypertension, obesity, and atherogenic dyslipidemia) that can affect children, adolescents, and the elderly. The treatment of MetS involves numerous medications, which, despite their efficacy, pose challenges due to prolonged use, high costs, and various side effects. Carotenoids and their derivatives have been proposed as alternative treatments to MetS because they reduce serum triglyceride concentrations, promote insulin response, inhibit adipogenesis, and downregulate angiotensin-converting enzyme activity. However, carotenoids are notably sensitive to pH, light exposure, and temperature. This review addresses the activity of carotenoids such as lycopene, lutein, fucoxanthin, astaxanthin, crocin, and ß-carotene towards MetS. It includes a discussion of sources, extraction methods, and characterization techniques for analyzing carotenoids. Encapsulation approaches are critically reviewed as alternatives to prevent degradation and improve the biological performance of carotenoids. A brief overview of the physiopathology and epidemiology of the diseases, including MetS, is also provided.

RESUMEN

Background: Acute hepatic porphyrias (AHP) represent a rare group of inherited metabolic disorders of heme biosynthesis pathway. This study aims to determine the diagnostic and prognostic value of serum neurofilament light chain (NfL) as potential biomarker for AHP. Methods: We conducted a cross-sectional observational study to evaluate NfL levels in patients with AHP. They were divided in different groups: normal health individuals; patients with definitive diagnosis of AHP during acute episodes; patients with AHP and infrequent attacks; patients with AHP and recurrent attacks; asymptomatic individuals with positive genetic testing and urinary delta-aminolevulinic acid (ALA) and porphobilinogen (PBG) levels elevated 4 or more times ("high excretors"); asymptomatic individuals with exclusive positive genetic test; control group with Hereditary Amyloidosis related to Transthyretin with Polyneuropathy (ATTRv-PN). Results: During acute attacks, serum NfL levels were 68 times higher compared to normal controls and disclosed a strong correlation with ALA and PBG levels; also exhibited elevated levels in patients with chronic symptoms regardless of the number of disease attacks compared to healthy controls, and at similar levels to patients with ATTRv-PN, which is a model of progressive neuropathy. Conclusion: This study represents the first to establish NfL as a biomarker for AHP, disclosing NfL as a sensitive biomarker for axonal damage and chronic symptom occurrence. This study not only underscores that neurological damage associated with the disease in any patient, irrespective of the number of attacks, but also reinforces the progressive and profoundly debilitating nature of acute and chronic symptoms observed in individuals with AHP.

Asunto(s)

Menopausia , Trastornos del Humor , Obesidad , Humanos , Obesidad/metabolismo , Obesidad/psicología , Trastornos del Humor/etiología , Menopausia/fisiología , Femenino

RESUMEN

LOX-1, ORL-1, or lectin-like oxidized low-density lipoprotein receptor 1 is a transmembrane glycoprotein that binds and internalizes ox-LDL in foam cells. LOX-1 is the main receptor for oxidized low-density lipoproteins (ox-LDL). The LDL comes from food intake and circulates through the bloodstream. LOX-1 belongs to scavenger receptors (SR), which are associated with various cardiovascular diseases. The most important and severe of these is the formation of atherosclerotic plaques in the intimal layer of the endothelium. These plaques can evolve into complicated thrombi with the participation of fibroblasts, activated platelets, apoptotic muscle cells, and macrophages transformed into foam cells. This process causes changes in vascular endothelial homeostasis, leading to partial or total obstruction in the lumen of blood vessels. This obstruction can result in oxygen deprivation to the heart. Recently, LOX-1 has been involved in other pathologies, such as obesity and diabetes mellitus. However, the development of atherosclerosis has been the most relevant due to its relationship with cerebrovascular accidents and heart attacks. In this review, we will summarize findings related to the physiologic and pathophysiological processes of LOX-1 to support the detection, diagnosis, and prevention of those diseases.

Asunto(s)

Enfermedades Cardiovasculares , Receptores Depuradores de Clase E , Humanos , Receptores Depuradores de Clase E/metabolismo , Receptores Depuradores de Clase E/genética , Enfermedades Cardiovasculares/metabolismo , Enfermedades Cardiovasculares/etiología , Animales , Lipoproteínas LDL/metabolismo , Aterosclerosis/metabolismo , Aterosclerosis/patología

RESUMEN

Type 2 diabetes (T2D) is a common forerunner of neurodegeneration and dementia, including Alzheimer's Disease (AD), yet the underlying mechanisms remain unresolved. Individuals of Mexican descent living in South Texas have increased prevalence of comorbid T2D and early onset AD, despite low incidence of the predisposing APOE-e4 variant and an absence of the phenotype among relatives residing in Mexico - suggesting a role for environmental factors in coincident T2D and AD susceptibility. Here, in a small clinical trial, we show dysbiosis of the human gut microbiome could contribute to neuroinflammation and risk for AD in this population. Divergent Gastrointestinal Symptom Rating Scale (GSRS) responses, despite no differences in expressed dietary preferences, provided the first evidence for altered gut microbial ecology among T2D subjects (sT2D) versus population-matched healthy controls (HC). Metataxonomic 16S rRNA sequencing of participant stool revealed a decrease in alpha diversity of sT2D versus HC gut communities and identified BMI as a driver of gut community structure. Linear discriminant analysis effect size (LEfSe) identified a significant decrease in the relative abundance of the short-chain fatty acid-producing taxa Lachnospiraceae, Faecalibacterium, and Alistipes and an increase in pathobionts Escherichia-Shigella, Enterobacter, and Clostridia innocuum among sT2D gut microbiota, as well as differentially abundant gene and metabolic pathways. These results suggest characterization of the gut microbiome of individuals with T2D could identify key actors among "disease state" microbiota which may increase risk for or accelerate the onset of neurodegeneration. Furthermore, they identify candidate microbiome-targeted approaches for prevention and treatment of neuroinflammation in AD.

RESUMEN

Polycystic ovary syndrome (PCOS) is often accompanied with metabolic disturbances attributed to androgen excess and obesity, but the contribution of each has not been defined, and the occurrence of metabolic disturbances is usually not investigated. Ninety-nine women with PCOS and forty-one without PCOS were evaluated. The clinical biomarkers of alterations related to glucose (glucose, insulin, and clamp-derived glucose disposal - M), liver (aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transferase), and endothelium (arginine, asymmetric dymethylarginine, carotid intima-media thickness, and flow-mediated dilation) metabolism were measured; participants were categorized into four groups according to their obesity (OB) and hyperandrogenemia (HA) status as follows: Healthy (no-HA, lean), HA (HA, lean), OB (no-HA, OB), and HAOB (HA, OB). Metabolic disturbances were very frequent in women with PCOS (≈70%). BMI correlated with all biomarkers, whereas free testosterone (FT) correlated with only glucose- and liver-related indicators. Although insulin sensitivity and liver enzymes were associated with FT, women with obesity showed lower M (coef = 8.56 - 0.080(FT) - 3.71(Ob); p < 0.001) and higher aspartate aminotransferase (coef = 26.27 + 0.532 (FT) + 8.08 (Ob); p = 0.015) than lean women with the same level of FT. Women with obesity showed a higher risk of metabolic disorders than lean women, independent of hyperandrogenemia. Clinicians are compelled to look for metabolic alterations in women with PCOS. Obesity should be treated in all cases, but hyperandrogenemia should also be monitored in those with glucose-or liver-related disturbances.

RESUMEN

Significance: Sirtuins are NAD+-dependent histone deacetylases regulating important processes in cellular biology such as inflammation, metabolism, oxidative stress, and apoptosis. Recent Advances: Despite initially being discovered to regulate transcription and life span via histone deacetylase activities, emerging data continually uncover new targets and propose additional roles. Due to the outstanding importance of the sirtuins in the control of the inflammatory response, their roles in the pathogenesis of several inflammatory-based diseases have become an area of intense research. Although sirtuins have been traditionally regarded as anti-inflammatory players, several recent findings suggest that their role in inflammation is complex and that in some cases sirtuins can indeed promote inflammation. Critical Issues: In this article, we provide an update on the latest findings concerning the new mechanisms of action and concepts about the role of sirtuins during inflammation. We focus on the impact that inflammatory-based processes exert on the liver, adipose tissue, and nervous system as well as on macrophage function and activation. Also, we discuss available data pointing to the dual role that, in particular contexts, sirtuins may have on inflammation control. Future Directions: Since the knowledge of sirtuin impact on metabolism is continually expanding, new venues of research arise. Besides become being regarded as candidates of therapeutic targets, posttranscriptional control of sirtuin expression by means of microRNAs challenges our traditional concepts of sirtuin regulation; importantly, the emerging role of NAD+ metabolism in aging and longevity has added a new dimension to the interest in sirtuin function. Antioxid. Redox Signal. 39, 1185-1208.

Asunto(s)

Sirtuinas , Humanos , Sirtuinas/metabolismo , NAD/metabolismo , Estrés Oxidativo , Envejecimiento/fisiología , Inflamación

RESUMEN

This study aimed to evaluate the effects of parity, body condition score (BCS) at calving, and milk yield on the metabolic profile of Gyr (Zebu) cows. Healthy cows in late pregnancy were grouped according to parity (primiparous, biparous, and multiparous); to BCS scale at calving (high-HBCS and normal-NBCS); and to milk yield (high-HP and moderate-MP production). BCS was assessed, and blood samples were collected on -21, -7, 0, 7, 21, and 42 days relative to parturition. The concentrations of non-esterified fatty acids (NEFA), beta-hydroxybutyrate (BHB), cholesterol, glucose, total protein (TP), albumin, total calcium (Ca), phosphorus (P), and magnesium (Mg); and activities of aspartate aminotransferase and gamma-glutamyltransferase were measured. Data were analyzed by two-way repeated measures ANOVA. The frequencies of high lipomobilization, subclinical ketosis, subclinical hypocalcemia (SCH), and the occurrence of diseases during early lactation were established. Regardless of grouping, NEFA, BHB, and cholesterol increased during early lactation; glucose showed higher values at calving; TP and albumin were higher at 21 and 42 DIM; and Ca, P, and Mg were lower at calving. Parity had little effect on the metabolic profile, HBCS did not differ from NBCS cows, and HP did not differ from MP cows in most metabolites. High lipomobilization in early lactation and SCH at calving were the most common imbalances but were not related to postpartum diseases. High-yielding Gyr cows have a balanced metabolic profile during the transition period, with few biologically relevant effects of parity, BCS at parturition, or milk yielded.

RESUMEN

Butyrylcholinesterase (BChE), an enzyme primarily found in the liver, plasma, and brain, has been recognized for its role in the hydrolysis of choline esters. Recent studies have shed light on its involvement in lipid metabolism, revealing its potential as a crucial player in maintaining lipid homeostasis. However, the interactions between external factors and BChE activity in lipid metabolic pathways remain a complex subject of study. This review summarizes the current knowledge regarding BChE activity and lipid metabolism and seeks to clarify the nature of this relationship as causal or consequential. Evidence supports the role of BChE in energy homeostasis disruption, such as obesity and related metabolic disorders, where it exhibits lipolytic activity and mediates fatty acid use and storage. The unexpected functions of BChE in lipoprotein synthesis and the impact of polymorphic variants of the BCHE gene suggest a central role in lipid metabolism; however, further investigation is needed to confirm and describe these functions, especially considering the metabolic context. Furthermore, exploring therapeutic interventions in lipid metabolism disorders contributes to elucidating their implications on BChE activity, but attention to the metabolic status and genotypes as possible factors in this interaction is needed. In summary, further research in this field holds promise for improving our understanding of the complex interplay between BChE and lipid metabolism, and its potential clinical applications. However, the available data corroborate the dual role of BChE activity, both as a critical responsive element to metabolic challenges and as a predisposition factor to metabolic diseases.

Asunto(s)

Butirilcolinesterasa , Enfermedades Metabólicas , Humanos , Butirilcolinesterasa/genética , Metabolismo de los Lípidos , Genotipo , Ácidos Grasos

RESUMEN

BACKGROUND AND AIMS: Hyperinsulinemia and hyperuricemia are known to increase the risk of mortality due to certain complications, such as Type 2 Diabetes and cardiovascular disease. However, despite their common comorbidities, their combined effect has not been evaluated. The study's aim was to evaluate the combine effect of hyperinsulinemia and hyperuricemia on all-cause mortality. METHODS AND RESULTS: NHANES datasets (cycles 2003-2018) were examined. Differences between groups were evaluated using Rao-Scott Chi-square and General Linear Model for categorical and continuous data, respectively. Hazard Ratios (HR) were calculated using Cox regression with 95% confidence intervals (95%CI). There was significant difference (p < 0.05) in the mortality rate between the control group (2.3 ± 0.2%), the hyperinsulinemia only group (3.1 ± 0.3%), the hyperuricemia only group (4.0 ± 0.8%), and both conditions (5.1 ± 0.8%). Individually, when compared to the control group, there was a significant increase in mortality risk for hyperinsulinemia (HR: 1.50, 95%CI: 1.12-2.01, p = 0.007) and hyperuricemia (HR: 1.80, 95%CI:1.18-2.75, p = 0.006). However, when both conditions were present, there appeared an additive effect in the mortality risk (HR: 2.32, 95%CI: 1.66-3.25, p < 0.001). When stratified by BMI class, only normal weight participants presented with a significant risk (HR: 7.00, 95%CI: 2.50-20.30, p < 0.001). Also, when stratified by age, only participants older than 40 years presented a risk (HR: 2.22, 95%CI: 1.56-3.16, p < 0.001). CONCLUSION: Alone, hyperuricemia and hyperinsulinemia significantly increased the mortality rate; however, the combined presence of both pathologies was associated with a significantly augmented mortality rate. Normal weight participant or that were >40 years old had a greater risk for mortality.

Asunto(s)

Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Hiperinsulinismo , Hiperuricemia , Humanos , Adulto , Hiperuricemia/diagnóstico , Hiperuricemia/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Encuestas Nutricionales , Hiperinsulinismo/diagnóstico , Factores de Riesgo

RESUMEN

Metabolic disorders, such as obesity, type 2 diabetes mellitus (T2DM), and metabolic syndrome (MS) are related to chronic pro-inflammatory conditions. Evidence suggests that heat shock proteins are linked to metabolic disorders. Intracellular HSP70 (iHSP70) is mandatory for normal insulin signalling, and proteostasis, and exerts a powerful anti-inflammatory role. On the other hand, the extracellular (eHSP72) is linked with a pro-inflammatory state and induces insulin resistance in humans. Then, we conducted a systematic review with meta-analysis to summarize the data of HSP70 in people with and without metabolic disorders. PubMed, Embase, Scopus, and Web of Science databases were used. Eligibility criteria included observational and baseline data of experimental studies that assessed iHSP70 and/or eHSP72 in adults with metabolic disorders and healthy people. The risk of bias was assessed by the Newcastle-Ottawa scale. Meta-analysis was performed using a random-effect model and the mean difference was estimated for eHSP72 and the standardized mean difference for iHSP70. A total of 11,255 articles were retrieved, 31 articles were assessed for eligibility and 15 were included for data extraction. There was no difference in eHSP72 between metabolic disorders and healthy controls (mean difference (MD) = 0.11; 95% confidence interval (CIs) = -0.05 to 0.27; I2 = 95%). Subgroup analysis showed higher levels of eHSP72 in T2DM people than healthy ones (MD = 0.32; 95% CIs = 0.17 to 0.47; I2 = 92%). For iHSP70 no difference was found (standardized mean difference (SMD) =-0.24; 95% CIs =-1.62 to 1.15; I2 = 86%). Our results suggest that eHSP72 levels may be dependent on metabolic condition and no difference in iHSP70 levels are attributed to high heterogeneity level between studies (PROSPERO REGISTRATION: CRD42022323514).

Asunto(s)

Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Adulto , Humanos , Diabetes Mellitus Tipo 2/metabolismo , Proteínas HSP70 de Choque Térmico/metabolismo , Obesidad/metabolismo , Insulina

RESUMEN

Over the last decades, the increased incidence of metabolic disorders, such as type two diabetes and obesity, has motivated researchers to investigate new enzyme inhibitors. In this study, the inhibitory effects of synthetic amino acid derivatives (PPC80, PPC82, PPC84, PPC89, and PPC101) on the activity of digestive enzymes were assessed using in vitro assays. The inhibitory effect was determined by the inhibition percentage and the 50% inhibitory concentration (IC50), and the mechanism of action was investigated using kinetic parameters and Lineweaver-Burk plots. PPC80, PPC82, and PPC84 inhibited pancreatic lipase (IC50 of 167-1023 µM) via competitive or mixed mechanisms. The activity of pancreatic α-amylase was suppressed by PPC80, PPC82, PPC84, PPC89, and PPC101 (IC50 of 162-519 µM), which acted as competitive or mixed inhibitors. Finally, PPC84, PPC89, and PPC101 also showed potent inhibitory effects on α-glucosidase (IC50 of 51-353 µM) as competitive inhibitors. The results suggest that these synthetic amino acid derivatives have inhibitory potential against digestive enzymes and may be used as therapeutic agents to control metabolic disorders.

Asunto(s)

Fármacos Antiobesidad , Hipoglucemiantes , Hipoglucemiantes/farmacología , Hipoglucemiantes/química , Fármacos Antiobesidad/farmacología , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , alfa-Glucosidasas/metabolismo , Aminoácidos

RESUMEN

Obesity is defined as abnormal and excessive fat accumulation, and it is a risk factor for developing metabolic and neurodegenerative diseases and cognitive deficits. Obesity is caused by an imbalance in energy homeostasis resulting from increased caloric intake associated with a sedentary lifestyle. However, the entire physiopathology linking obesity with neurodegeneration and cognitive decline has not yet been elucidated. During the progression of obesity, adipose tissue undergoes immune, metabolic, and functional changes that induce chronic low-grade inflammation. It has been proposed that inflammatory processes may participate in both the peripheral disorders and brain disorders associated with obesity, including the development of cognitive deficits. In addition, mitochondrial dysfunction is related to inflammation and oxidative stress, causing cellular oxidative damage. Preclinical and clinical studies of obesity and metabolic disorders have demonstrated mitochondrial brain dysfunction. Since neuronal cells have a high energy demand and mitochondria play an important role in maintaining a constant energy supply, impairments in mitochondrial activity lead to neuronal damage and dysfunction and, consequently, to neurotoxicity. In this review, we highlight the effect of obesity and high-fat diet consumption on brain neuroinflammation and mitochondrial changes as a link between metabolic dysfunction and cognitive decline.