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1.
Semina cienc. biol. saude ; 45(2)jul./dez. 2024. tab
Article in Portuguese | LILACS | ID: biblio-1567949

ABSTRACT

Hábitos alimentares inadequados, sedentarismo e a maior expectativa de vida da população contribuem significativamente para a prevalência da síndrome metabólica. Essa doença predispõe uma pessoa a desenvolver diabetes mellitus tipo 2 e doenças cardiovasculares, as quais têm um amplo impacto na saúde pública, induzindo sobrecarga no sistema de saúde e reduzindo a qualidade de vida dos indivíduos afetados. A síndrome metabólica é uma doença multifatorial e está relacionada ao processo de envelhecimento, contudo, ainda há uma lacuna significativa, em termos de estudos, sobre a prevalência da condição em populações idosas. Nesse contexto, o presente estudo objetivou rastrear a prevalência da síndrome metabólica em participantes da Universidade Aberta da Terceira Idade (UNATI), localizada em Francisco Beltrão, Paraná. Os critérios diagnósticos de síndrome metabólica abordados nesta pesquisa incluem: circunferência abdominal ≥ 90 cm para homens e ≥ 80 cm para mulheres, triglicerídeos ≥ 150 mg/dL, HDL ≤ 40 mg/dL para homens e ≤ 50 mg/dL para mulheres, pressão arterial sistólica ≥ 130 mmHg e/ou pressão arterial diastólica ≥ 85 mmHg ou estar em farmacoterapia para hipertensão, além de glicemia de jejum ≥ 100 mg/dL ou estar em tratamento farmacológico para diabetes. Um total de 44 idosos foram avaliados, apresentando uma média de idade de 66,9 ± 7,1 anos, com uma predominância de mulheres (88%). Os resultados revelaram uma prevalência alarmante de síndrome metabólica, atingindo 36,4% da amostra estudada. Além disso, observou-se uma alta prevalência de condições associadas, como hipertensão arterial (67,2%), sobrepeso (58,6%) e obesidade visceral (31%). Esses achados ressaltam a importância da implementação de medidas preventivas direcionadas à promoção da qualidade de vida saudável e ao controle dos fatores de risco metabólicos.


Inadequate dietary habits, sedentary lifestyle, and increased life expectancy significantly contribute to the prevalence of metabolic syndrome. This condition predisposes an individual to develop type 2 diabetes mellitus and cardiovascular diseases, which have a broad impact on public health, inducing a burden on the healthcare system and reducing the quality of life of affected individuals. Metabolic syndrome is a multifactorial disease and is related to the aging process; however, there is still a significant gap in terms of studies on the prevalence of the condition in elderly populations. In this context, this study aimed to screen the prevalence of metabolic syndrome in participants of the Open University for the Third Age (UNATI), located in Francisco Beltrão, Paraná. The diagnostic criteria for metabolic syndrome addressed in this research include: abdominal circumference ≥ 90 cm for men and ≥ 80 cm for women, triglycerides ≥ 150 mg/dL, HDL ≤ 40 mg/dL for men and ≤ 50 mg/dL for women, systolic blood pressure ≥ 130 mmHg and/or diastolic blood pressure ≥ 85 mmHg or being on pharmacotherapy for hypertension, in addition to fasting glucose ≥ 100 mg/dL or being on pharmacological treatment for diabetes. A total of 44 elderly individuals were evaluated, with a mean age of 66.9 ± 7.1 years, predominantly women (88%). The results revealed an alarming prevalence of metabolic syndrome, affecting 36.4% of the studied sample. Furthermore, a high prevalence of associated conditions was observed, such as arterial hypertension (67.2%), overweight (58.6%), and visceral obesity (31%). These findings underscore the importance of implementing preventive measures aimed at promoting healthy lifestyles and controlling metabolic risk factors.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged
2.
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1569587

ABSTRACT

Introducción: La enfermedad por hígado graso no alcohólico es una de las principales causas de afección hepática. La citoqueratina 18 surge como marcador no invasivo para la valoración de fibrosis hepática. El objetivo del trabajo fue validar el uso de la citoqueratina 18 en sangre periférica en el diagnóstico y evolución de los pacientes con enfermedad por hígado graso no alcohólico. Metodología: Para validar la citoqueratina 18 en el diagnóstico se realizó un estudio de tipo caso-control. El grupo caso fueron los pacientes mayores de 18 años, de ambos sexos, con diagnóstico de enfermedad por hígado graso no alcohólico vinculado al síndrome metabólico, captados entre 2/2/2019 al 2/2/2020. El grupo control fueron personas donantes de sangre. Se parearon 1-1 por edad y sexo. Se cuantificó la citoqueratina 18 en sangre periférica de ambos grupos. Para validar la citoqueratina 18 en la evolución de los pacientes con enfermedad de hígado graso no alcohólico se realizó un trabajo prospectivo, longitudinal. El grupo de pacientes captados fueron seguidos durante un año bajo tratamiento estándar, finalizando el mismo se realizó la cuantificación de citoqueratina 18 en sangre periférica. Las variables continuas se expresan con la media y desvío estándar. Se analizó con test de t Student, error α < 5% Resultados: 13 pacientes integran el grupo caso (12 mujeres), de 53 ± 11 años, con IMC 35.01 ± 8.9 kg/m2. El valor de citoqueratina 18 pre-tratamiento fue de 1410 ± 120 UI, y el valor post-tratamiento fue de 117 ± 56, p < 0,005.El grupo control fueron 13 personas (12 mujeres), de 43,4 ± 8,1 años e IMC 28,10 ± 5,4 kg/m2 El valor de citoqueratina 18 fue de 193 ± 7.2 UI, p < 0.005 vs grupo caso pretratamiento. Conclusiones: La citoqueratina 18 es más elevada en los pacientes con enfermedad hígado graso no alcohólico, siendo estadísticamente significativa y disminuye con el tratamiento con significación estadística, pudiendo constituirse en un marcador útil en este grupo de pacientes.


Introduction: Nonalcoholic fatty liver disease is one of the main causes of liver disease. Cytokeratin 18 emerges as a non-invasive marker for the assessment of liver fibrosis. The objective of the work was to validate the use of cytokeratin 18 in peripheral blood in the diagnosis and evolution of patients with non-alcoholic fatty liver disease. Methodology: To validate cytokeratin 18 in the diagnosis, a case-control study was carried out. The case group was patients over 18 years of age, of both sexes, with a diagnosis of non-alcoholic fatty liver disease linked to metabolic syndrome, recruited between 2/2/2019 to 2/2/2020. The control group were blood donors. They were matched 1-1 for age and sex. Cytokeratin 18 was quantified in peripheral blood of both groups. To validate cytokeratin 18 in the evolution of patients with non-alcoholic fatty liver disease, a prospective, longitudinal study was carried out. The group of patients recruited were followed for one year under standard treatment, at the end of which cytokeratin 18 was quantified in peripheral blood. Continuous variables are expressed with the mean and standard deviation. It was analyzed with Student's t test, α error < 5%. Results: 13 patients make up the case group (12 women), 53 ± 11 years old, with BMI 35.01 ± 8.9 kg/m2. The pre-treatment cytokeratin 18 value was 1410 ± 120 IU, and the post-treatment value was 117 ± 56, p < 0.005. The control group was 13 people (12 women), 43.4 ± 8.1 years and BMI 28.10 ± 5.4 kg/m2 The cytokeratin 18 value was 193 ± 7.2 IU, p < 0.005 vs. pretreatment case group. Conclusions: Cytokeratin 18 is higher in patients with non-alcoholic fatty liver disease, being statistically significant, and decreases with treatment with statistical significance, and may become a useful marker in this group of patients.


Introdução: A doença hepática gordurosa não alcoólica é uma das principais causas de doença hepática. A citoqueratina 18 surge como um marcador não invasivo para avaliação de fibrose hepática. O objetivo do trabalho foi validar o uso da citoqueratina 18 no sangue periférico no diagnóstico e evolução de pacientes com doença hepática gordurosa não alcoólica. Metodologia: Para validar a citoqueratina 18 no diagnóstico, foi realizado um estudo caso-controle. O grupo caso foi composto por pacientes maiores de 18 anos, de ambos os sexos, com diagnóstico de doença hepática gordurosa não alcoólica ligada à síndrome metabólica, recrutados entre 02/02/2019 a 02/02/2020. O grupo controle eram doadores de sangue. Eles foram comparados em 1 a 1 por idade e sexo. A citoqueratina 18 foi quantificada no sangue periférico de ambos os grupos. Para validar a citoqueratina 18 na evolução de pacientes com doença hepática gordurosa não alcoólica, foi realizado um estudo prospectivo e longitudinal. O grupo de pacientes recrutados foi acompanhado durante um ano sob tratamento padrão, ao final do qual a citoqueratina 18 foi quantificada no sangue periférico. As variáveis ​​contínuas são expressas com média e desvio padrão. Foi analisado com teste t de Student, erro α < 5%. Resultados: Compõem o grupo caso 13 pacientes (12 mulheres), 53 ± 11 anos, com IMC 35,01 ± 8,9 kg/m2. O valor de citoqueratina 18 pré-tratamento foi de 1410 ± 120 UI e o valor pós-tratamento foi de 117 ± 56, p < 0,005. O grupo controle foi de 13 pessoas (12 mulheres), 43,4 ± 8,1 anos e IMC 28,10 ± 5,4 kg/m2 O valor da citoqueratina 18 foi de 193 ± 7,2 UI, p < 0,005 vs. grupo de casos pré-tratamento. Conclusões: A citoqueratina 18 é maior em pacientes com doença hepática gordurosa não alcoólica, sendo estatisticamente significativa, e diminui com o tratamento com significância estatística, podendo se tornar um marcador útil neste grupo de pacientes.

3.
Hepatol Int ; 18(5): 1396-1415, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39117942

ABSTRACT

BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) is present in lean people. However, the magnitude of the prognostic hepatic and cardiovascular risk in these patients compared to non-lean counterparts remains unclear. We aimed to investigate this topic, and to explore whether these risks change based on factors related to NAFLD severity. METHODS: PubMed and Embase databases were searched for cohort studies (published through April 2024) that evaluated liver and cardiovascular (CV) outcomes in lean and non-lean individuals with NAFLD and reported unadjusted or adjusted data. We pooled risk ratios (RRs) or hazard ratios (HRs) using a random-effects modeling and performed subgroup and meta-regressions analyses. RESULTS: We identified 22 studies with over 1 million NAFLD patients (13.0% were lean). Lean NAFLD showed a similar risk of liver-related events in unadjusted analysis (RR 1.08, 95% CI 0.79-1.49, I2 = 31%), but a higher risk in adjusted analysis (HR 1.66, 95% CI 1.17-2.36, I2 = 83%) compared to non-lean NAFLD. Lean NAFLD had a higher risk of liver-related mortality (RR 2.22, 95% CI 1.57-3.15, I2 = 0%; HR 2.26, 95% CI 1.14-4.51, I2 = 0%). For CV outcomes, lean NAFLD had a lower risk of any cardiovascular disease in unadjusted analysis (RR = 0.82, 95% CI 0.70-0.95, I2 = 88%), but similar risk in adjusted analysis (HR 0.89, 95% CI 0.77-1.02, I2 = 78%), and similar risk of cardiovascular mortality (RR 1.09, 95% CI 0.71-1.66, I2 = 85%; HR 1.26, 95% CI 0.89-1.78, I2 = 46%) compared to non-lean NAFLD. CONCLUSIONS: Lean NAFLD patients have worse liver outcomes, but similar CV outcomes compared to non-lean NAFLD patients, highlighting the importance of monitoring both groups closely.


Subject(s)
Cardiovascular Diseases , Non-alcoholic Fatty Liver Disease , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/epidemiology , Humans , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/mortality , Thinness/complications , Thinness/epidemiology , Risk Factors
4.
Nutrients ; 16(15)2024 Jul 30.
Article in English | MEDLINE | ID: mdl-39125348

ABSTRACT

BACKGROUND: The most frequent body composition alterations in post-COVID-19 syndrome include low muscle mass, dynapenia, sarcopenia, and obesity. These conditions share interconnected pathophysiological mechanisms that exacerbate each other. The relationship between body composition phenotypes and metabolic abnormalities in post-COVID-19 syndrome remains unclear. OBJECTIVE: To evaluate the association between body composition phenotypes and insulin resistance (IR) and metabolic abnormalities in non-diabetic individuals with post-COVID-19 syndrome. METHODS: A cross-sectional, single-center study involving 483 subjects with post-COVID-19 syndrome following moderate to severe acute COVID-19 requiring hospitalization. Individuals with diabetes, those who declined to participate, or those who could not be contacted were excluded. Body composition phenotypes were classified as normal weight, dynapenia, sarcopenia, dynapenic obesity, and sarcopenic obesity (SO). RESULTS: The average age was 52.69 ± 14.75 years; of note, 67.08% were male. The prevalence of body composition phenotypes was as follows: 13.25% were of normal weight, 9.52% had dynapenia, 9.94% had sarcopenia, 43.69% had obesity, 18.84% had dynapenic obesity, and 4.76% had SO. Additionally, 58.18% had IR. Obesity (OR: 2.98, CI95%; 1.64-5.41) and dynapenic obesity (OR: 4.98, CI95%; 1.46-6.88) were associated with IR. CONCLUSION: The most common body composition phenotypes were obesity, dynapenic obesity, and dynapenia. Furthermore, obesity and dynapenic obesity were associated with IR in post-COVID-19 syndrome.


Subject(s)
Body Composition , COVID-19 , Insulin Resistance , Obesity , Phenotype , Sarcopenia , Humans , Male , COVID-19/complications , Cross-Sectional Studies , Middle Aged , Female , Adult , Obesity/complications , Sarcopenia/epidemiology , Aged , SARS-CoV-2 , Post-Acute COVID-19 Syndrome
5.
Diabetes Metab Syndr ; 18(7): 103095, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39098208

ABSTRACT

BACKGROUND & AIMS: Asprosin is a promising candidate for novel treatments for metabolic-endocrine disorders. The objective of this systematic review and meta-analysis was to consolidate the existing evidence regarding asprosin levels in patients diagnosed with type 2 diabetes (T2D), metabolic syndrome (MetS), and obesity. METHODS: Scopus, Embase, PubMed, Ovid/Medline, and Web of Science were systematically searched without restrictions. We only used the standardized mean differences (SMD) with their 95 % confidence intervals (95 % CI) as the effect measure. A random-effects model (DerSimonian and Laird method) was used for the meta-analysis. Risk of bias was assessed with the Newcastle-Ottawa Scale and Newcastle-Ottawa Scale for Cross-Sectional Studies. RESULTS: Twenty-six studies (n = 3,787) were included in the meta-analysis. Participants with T2D had higher asprosin values than those without T2D (SMD: 1.64; 95 % CI: 1.08-2.21; I2 = 97 %). Patients with MetS had higher asprosin levels compared to those without MetS (SMD: 0.99; 95 % CI: 0.34-1.64; I2 = 96 %). Patients with obesity had higher asprosin levels than participants without obesity (SMD: 1.49; 95 % CI: 0.23-2.76; I2 = 98 %). CONCLUSIONS: Asprosin is significantly higher in patients with either T2D, MetS, or obesity, compared with controls.


Subject(s)
Diabetes Mellitus, Type 2 , Fibrillin-1 , Metabolic Syndrome , Obesity , Humans , Metabolic Syndrome/blood , Diabetes Mellitus, Type 2/blood , Obesity/complications , Obesity/blood , Biomarkers/analysis , Biomarkers/blood , Prognosis , Adipokines
6.
Pediatr Nephrol ; 2024 Aug 02.
Article in English | MEDLINE | ID: mdl-39093454

ABSTRACT

Metabolic effects of high diet acid load (DAL) have been studied for years in adults, although only recently in children. Contemporary diets, especially those of Western societies, owe their acidogenic effect to high animal-origin protein content and low contribution of base-forming elements, such as fruits and vegetables. This imbalance, where dietary acid precursors exceed the body's buffering capacity, results in an acid-retaining state known by terms such as "eubicarbonatemic metabolic acidosis," "low-grade metabolic acidosis," "subclinical acidosis," or "acid stress". Its consequences have been linked to chronic systemic inflammation, contributing to various noncommunicable diseases traditionally considered more common in adulthood, but now have been recognized to originate at much earlier ages. In children, effects of high DAL are not limited to growth impairment caused by alterations of bone and muscle metabolism, but also represent a risk factor for conditions such as obesity, insulin resistance, diabetes, hypertension, urolithiasis, and chronic kidney disease (CKD). The possibility that high DAL may be a cause of chronic acid-retaining states in children with growth impairment should alert pediatricians and pediatric nephrologists, since its causes have been attributed traditionally to inborn errors of metabolism and renal pathologies such as CKD and renal tubular acidosis. The interplay between DAL, overall diet quality, and its cascading effects on children's health necessitates comprehensive nutritional assessments and interventions. This narrative review explores the clinical relevance of diet-induced acid retention in children and highlights the potential for prevention through dietary modifications, particularly by increasing fruit and vegetable intake alongside appropriate protein consumption.

7.
J Hazard Mater ; 477: 135316, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-39098202

ABSTRACT

We use the sentinel mangrove crab, Minuca rapax, as a model to investigate the effects of metallic settleable particulate matter (SePM) on wetland. Multiple levels of energetic responses, including (i) metabolic rate and energy budget, (ii) oxidative stress, and (iii) behavioral response by righting time, were assessed as well as the metal and metalloid content in crabs exposed to 0, 0.1 and 1 g.L-1 of SePM, under emerged and submerged conditions over five days, simulating the rigors of the intertidal habitat. Al, Fe, Mn, Cr, and Y exhibited a concentration-dependent increase. Metal concentrations were higher in submerged crabs due to the continuous ingestion of SePM and direct exposure through gills. Exposure concentration up to 1 g.L-1 decreased metabolic rate and enzymatic activities, reduced assimilation efficiency and energy for maintenance, and induces a slower response to righting time, probably by metal effects on nervous system and energy deficits. In conclusion, SePM exposure affects the redox status and physiology of M. rapax depending on he submersion regime and SePM concentration. The disruption to the energy budget and the lethargic behavior in M. rapax exposed to SePM implies potential ecological alterations in the mangrove ecosystem with unknown consequences for the local population.


Subject(s)
Behavior, Animal , Brachyura , Energy Metabolism , Particulate Matter , Animals , Energy Metabolism/drug effects , Brachyura/drug effects , Brachyura/metabolism , Particulate Matter/toxicity , Behavior, Animal/drug effects , Oxidative Stress/drug effects , Water Pollutants, Chemical/toxicity , Wetlands , Metals/toxicity , Air Pollutants/toxicity
8.
Cell Mol Life Sci ; 81(1): 348, 2024 Aug 13.
Article in English | MEDLINE | ID: mdl-39136766

ABSTRACT

The biological clock in eukaryotes controls daily rhythms in physiology and behavior. It displays a complex organization that involves the molecular transcriptional clock and the redox oscillator which may coordinately work to control cellular rhythms. The redox oscillator has emerged very early in evolution in adaptation to the environmental changes in O2 levels and has been shown to regulate daily rhythms in glycerolipid (GL) metabolism in different eukaryotic cells. GLs are key components of lipid droplets (LDs), intracellular storage organelles, present in all living organisms, and essential for energy and lipid homeostasis regulation and survival; however, the cell bioenergetics status is not constant across time and depends on energy demands. Thus, the formation and degradation of LDs may reflect a time-dependent process following energy requirements. This work investigated the presence of metabolic rhythms in LD content along evolution by studying prokaryotic and eukaryotic cells and organisms. We found sustained temporal oscillations in LD content in Pseudomonas aeruginosa bacteria and Caenorhabditis elegans synchronized by temperature cycles, in serum-shock synchronized human embryonic kidney cells (HEK 293 cells) and brain tumor cells (T98G and GL26) after a dexamethasone pulse. Moreover, in synchronized T98G cells, LD oscillations were altered by glycogen synthase kinase-3 (GSK-3) inhibition that affects the cytosolic activity of the metabolic oscillator or by knocking down LIPIN-1, a key GL synthesizing enzyme. Overall, our findings reveal the existence of metabolic oscillations in terms of LD content highly conserved across evolutionary scales notwithstanding variations in complexity, regulation, and cell organization.


Subject(s)
Caenorhabditis elegans , Lipid Droplets , Pseudomonas aeruginosa , Humans , Lipid Droplets/metabolism , Animals , Caenorhabditis elegans/metabolism , Caenorhabditis elegans/genetics , HEK293 Cells , Pseudomonas aeruginosa/metabolism , Pseudomonas aeruginosa/genetics , Biological Clocks/genetics , Biological Evolution , Lipid Metabolism/genetics , Circadian Rhythm/genetics , Circadian Rhythm/physiology
9.
J Physiol ; 2024 Aug 08.
Article in English | MEDLINE | ID: mdl-39116002

ABSTRACT

The placenta plays an essential role in pregnancy, leading to proper fetal development and growth. As an organ with multiple physiological functions for both mother and fetus, it is a highly energetic and metabolically demanding tissue. Mitochondrial physiology plays a crucial role in the metabolism of this organ and thus any alteration leading to mitochondrial dysfunction has a severe outcome in the development of the fetus. Pregnancy-related pathological states with a mitochondrial dysfunction outcome include preeclampsia and gestational diabetes mellitus. In this review, we address the role of mitochondrial morphology, metabolism and physiology of the placenta during pregnancy, highlighting the roles of the cytotrophoblast and syncytiotrophoblast. We also describe the relationship between preeclampsia, gestational diabetes, gestational diabesity and pre-pregnancy maternal obesity with mitochondrial dysfunction.

10.
Article in English | MEDLINE | ID: mdl-39102641

ABSTRACT

Introduction: This report aimed to analyze the outcomes of patients with obesity who were on a bariatric program during the SARS-Cov-2 pandemic outbreak and compare those who received surgery with the ones who were not operated on. Methods: This was a retrospective study between 2020 and 2021. Patients were divided into two groups: those who underwent surgery (O) and those who were not operated (NO). The evolution of the risk factors identified for severe COVID infection and death was studied (ASMBS criteria). For this study, a follow-up period of 12 months was initiated. Results: In the O group, 83 patients were included and 99 were in the NO group. In the O group, patients with body mass index (BMI) > 35 Kg/m2 before surgery resolved the condition in 73.5% (61) cases, and this was done in the first 30 days by 38 (45.7%). Type 2 diabetes mellitus remission was documented in 18 patients (85.7%) of the O group, and the mean time elapsed for remission was 102.2 days (P < .01). Hypertension remitted in 66.7% (20) of the patients in group O in 82.4 days (P < .01). The subgroup of patients with obesity and one high-risk associated condition (30.2%, 25) resolved both in 44% (11) cases and one in 48% (12) cases. In the group of patients with obesity and two high-risk associated conditions (15.6%, 13), 47% (6) patients resolved the three conditions, 38% (5) resolved two conditions, and 15% (2) resolved one condition. Among the NO group, no comorbidity resolutions were recorded (P < .01). Admission because of COVID infection was necessary for 7.1% of NO and 1.2% of O (P = .04). Conclusion: Bariatric metabolic surgery would not increase the risk of COVID infection or of suffering serious complications resulting from it. Patients undergoing bariatric metabolic surgery rapidly resolved high-risk comorbidities and had less need for hospitalization because of SARS-CoV-2 infection.

11.
J Neuroinflammation ; 21(1): 191, 2024 Aug 02.
Article in English | MEDLINE | ID: mdl-39095788

ABSTRACT

OBJECTIVE: Obesity represents a significant global health challenge characterized by chronic low-grade inflammation and metabolic dysregulation. The hypothalamus, a key regulator of energy homeostasis, is particularly susceptible to obesity's deleterious effects. This study investigated the role of the immunoproteasome, a specialized proteasomal complex implicated in inflammation and cellular homeostasis, during metabolic diseases. METHODS: The levels of the immunoproteasome ß5i subunit were analyzed by immunostaining, western blotting, and proteasome activity assay in mice fed with either a high-fat diet (HFD) or a regular diet (CHOW). We also characterized the impact of autophagy inhibition on the levels of the immunoproteasome ß5i subunit and the activation of the AKT pathway. Finally, through confocal microscopy, we analyzed the contribution of ß5i subunit inhibition on mitochondrial function by flow cytometry and mitophagy assay. RESULTS: Using an HFD-fed obese mouse model, we found increased immunoproteasome levels in hypothalamic POMC neurons. Furthermore, we observed that palmitic acid (PA), a major component of saturated fats found in HFD, increased the levels of the ß5i subunit of the immunoproteasome in hypothalamic neuronal cells. Notably, the increase in immunoproteasome expression was associated with decreased autophagy, a critical cellular process in maintaining homeostasis and suppressing inflammation. Functionally, PA disrupted the insulin-glucose axis, leading to reduced AKT phosphorylation and increased intracellular glucose levels in response to insulin due to the upregulation of the immunoproteasome. Mechanistically, we identified that the protein PTEN, a key regulator of insulin signaling, was reduced in an immunoproteasome-dependent manner. To further investigate the potential therapeutic implications of these findings, we used ONX-0914, a specific immunoproteasome inhibitor. We demonstrated that this inhibitor prevents PA-induced insulin-glucose axis imbalance. Given the interplay between mitochondrial dysfunction and metabolic disturbances, we explored the impact of ONX-0914 on mitochondrial function. Notably, ONX-0914 preserved mitochondrial membrane potential and attenuated mitochondrial ROS production in the presence of PA. Moreover, we found that ONX-0914 reduced mitophagy in the presence of PA. CONCLUSIONS: Our findings strongly support the pathogenic involvement of the immunoproteasome in hypothalamic neurons in the context of HFD-induced obesity and metabolic disturbances. Targeting the immunoproteasome highlights a promising therapeutic strategy to mitigate the detrimental effects of obesity on the insulin-glucose axis and cellular homeostasis. This study provides valuable insights into the mechanisms driving obesity-related metabolic diseases and offers potential avenues for developing novel therapeutic interventions.


Subject(s)
Diet, High-Fat , Hypothalamus , Mice, Inbred C57BL , Neurons , Obesity , Proteasome Endopeptidase Complex , Animals , Diet, High-Fat/adverse effects , Mice , Hypothalamus/metabolism , Obesity/metabolism , Neurons/metabolism , Neurons/drug effects , Proteasome Endopeptidase Complex/metabolism , Male , Metabolic Diseases/metabolism , Metabolic Diseases/etiology , Oligopeptides
12.
Article in English | MEDLINE | ID: mdl-39133224

ABSTRACT

Background: Metabolic syndrome (MetS) in children is a rising health issue that is strongly associated with cardiovascular diseases and type 2 diabetes mellitus development. Low-affinity antibodies reactive to leptin and ghrelin are suggested to regulate hormone stability and function; nevertheless, the role of the leptin/ghrelin axis and antibodies reactive to both hormones in relation to MetS or its components in the pediatric population remains unknown. Methods: Fifty-eight children (7-12 years) were included and categorized according to the presence of one or more criteria for the diagnosis of MetS or according to body mass index. Body composition, biochemical variables, and metabolic risk indexes were determined. Antibodies reactive to leptin and ghrelin were quantified by an in-house enzyme-linked immunosorbent assay test. Ratios of leptin/ghrelin hormones and anti-leptin/anti-ghrelin immune complexes were obtained. Results: The biochemical variables glucose (P = 0.0009), insulin (P = 0.0001), leptin (P = 0.0036), HOMA-IR (homeostatic model assessment for insulin resistance) (P < 0.0001), and plasma atherogenic index (P < 0.0001) were significantly higher in children with two or three components of MetS (MetS 2-3) in comparison to children with none or one component (MetS 0-1). Ratios of leptin/ghrelin (P = 0.0307) and anti-leptin/anti-ghrelin immune complexes (P = 0.0338) were higher in MetS 2-3 group versus MetS 0-1 group. In MetS 2-3 group, both insulin (r = 0.4361, P = 0.0293) and HOMA-IR (r = 0.4761, P = 0.0161) were positively correlated with the leptin/ghrelin hormone ratio. Conclusions: The higher leptin/ghrelin hormone ratio scores observed in MetS 2-3 group, along with their correlation with insulin levels and HOMA-IR, highlight the role of leptin and ghrelin on insulin sensitivity and metabolic regulation. An increased ratio of anti-leptin/anti-ghrelin immune complexes suggests affinity changes in these antibodies that may lead to alterations in hormone function.

13.
Food Chem ; 460(Pt 2): 140653, 2024 Dec 01.
Article in English | MEDLINE | ID: mdl-39089038

ABSTRACT

Multifunctional peptides derived from various food sources, including ancestral grains, hold significant promise for managing metabolic syndrome. These bioactive peptides exhibit diverse properties that collectively contribute to improving the components of metabolic syndrome. In this study, we investigated the in vitro multifunctionality of six peptides (PW, PM, SW, PPG, PW, and IW) identified through in silico analysis and chemically synthesized. These peptides were evaluated for their potential to address metabolic syndrome-related activities such as antidiabetic, antiobesity, antihypertensive, and antioxidative properties. Assessment included their capacity to inhibit key enzymes associated with these activities, as well as their free radical scavenging and cellular antioxidative activities. Principal component analysis was employed to cluster the peptides according to their multifunctionality. Our results revealed that peptides containing tryptophan (SW, PW, and IW) exhibited the most promising multifunctional attributes, with SW showing particularly high potential. This multifunctional peptide represents a promising avenue for addressing metabolic syndrome.


Subject(s)
Metabolic Syndrome , Peptides , Metabolic Syndrome/drug therapy , Metabolic Syndrome/metabolism , Peptides/chemistry , Peptides/pharmacology , Humans , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/pharmacology , Antioxidants/chemistry , Antioxidants/pharmacology , Animals , Antihypertensive Agents/chemistry , Antihypertensive Agents/pharmacology , Anti-Obesity Agents/chemistry , Anti-Obesity Agents/pharmacology
14.
Clin Genet ; 2024 Aug 05.
Article in English | MEDLINE | ID: mdl-39099467

ABSTRACT

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.

15.
PeerJ ; 12: e17815, 2024.
Article in English | MEDLINE | ID: mdl-39131616

ABSTRACT

Nutrient foramina are small openings in the periosteal surface of the mid-shaft region of long bones that traverse the cortical layer and reach the medullary cavity. They are important for the delivery of nutrients and oxygen to bone tissue and are crucial for the repair and remodeling of bones over time. The nutrient foramina in the femur's diaphysis are related to the energetic needs of the femur and have been shown to be related to the maximum metabolic rate (MMR) of taxa. Here, we investigate the relationship between nutrient foramen size and body mass as a proxy to the aerobic capacity of taxa in living and extinct xenarthrans, including living sloths, anteaters, and armadillos, as well as extinct xenarthrans such as glyptodonts, pampatheres, and ground sloths. Seventy femora were sampled, including 20 from extant taxa and 50 from extinct taxa. We obtained the blood flow rate (Q̇) based on foramina area and performed PGLS and phylogenetic ANCOVA in order to explore differences among mammalian groups. Our results show that, among mammals, taxa commonly associated with lower metabolism like living xenarthrans showed relatively smaller foramina, while the foramina of giant extinct xenarthrans like ground sloths and glyptodonts overlapped with non-xenarthran placentals. Consequently, Q̇ estimations indicated aerobic capacities comparable to other placental giant taxa like elephants or some ungulates. Furthermore, the estimation of the MMR for fossil giant taxa showed similar results, with almost all taxa showing high values except for those for which strong semi-arboreal or fossorial habits have been proposed. Moreover, the results are compatible with the diets predicted for extinct taxa, which indicate a strong consumption of grass similar to ungulates and in contrast to the folivorous or insectivorous diets of extant xenarthrans. The ancestral reconstruction of the MMR values indicated a lack of a common pattern for all xenarthrans, strongly supporting the occurrence of low metabolic rates in extant forms due to their particular dietary preferences and arboreal or fossorial habits. Our results highlight the importance of considering different evidence beyond the phylogenetic position of extinct taxa, especially when extinct forms are exceptionally different from their extant relatives. Future studies evaluating the energetic needs of giant extinct xenarthrans should not assume lower metabolic rates for these extinct animals based solely on their phylogenetic position and the observations on their extant relatives.


Subject(s)
Femur , Fossils , Xenarthra , Animals , Femur/anatomy & histology , Femur/physiology , Xenarthra/anatomy & histology , Xenarthra/physiology , Extinction, Biological , Phylogeny , Sloths/physiology , Sloths/anatomy & histology
16.
Vive (El Alto) ; 7(20): 497-504, ago. 2024.
Article in Spanish | LILACS | ID: biblio-1568527

ABSTRACT

El síndrome metabólico (SM) se previene controlando sus factores de riesgo, el programa de reforma de vida (PRV) busca el control y regulación de estos. Objetivo: evaluar el impacto del PRV. Materiales y métodos: Investigación aplicativo, longitudinal, prospectivo, diseño longitudinal, inductivo y deductivo, en una población inicial de 104 trabajadores de una universidad del Perú, la población final fue 31 quienes completaron el programa, los factores de riesgo fueron evaluados por un laboratorista clínico, se utilizó fichas de recolección y se procesó con el programa SPSS V.26, prueba de Wilcoxon y T de Student según el criterio de normalidad. Resultados: el PRV disminuye los niveles de triglicéridos, promedio antes 235,6 mg/dl y después 196,1 mg/dl, no se evidencio efectos positivos en el resto de los factores de riesgo. En personas con algún factor de riesgo el PRV impacto positivamente; antes del PRV 2 personas tenían la glucosa >= a 100 mg/dl y después del PRV 1, en cuanto al perímetro abdominal ≥ 90cm M, ≥ 80cm F antes (30), después (19), presión arterial ≥130/85 mmHg antes (06), después (0), triglicéridos ≥ 150 mg/dl antes (30), después (17), C-HDL < 40 M < 50 F antes (29), después (24). Con un p valor de 0,004 el PRV disminuye los niveles de triglicéridos. Conclusión: En la población en general el PRV disminuye el nivel de triglicéridos; en personas con algún factor de riesgo el PRV controla y regula todos los factores SM


Metabolic syndrome (MS) is prevented by controlling its risk factors; the lifestyle reform program (LRP) seeks to control and regulate them. Objective: to evaluate the impact of the LRP. Materials and methods: Applied, longitudinal, prospective, longitudinal, inductive and deductive design, in an initial population of 104 workers of a Peruvian university, the final population was 31 who completed the program, the risk factors were evaluated by a clinical laboratorist, collection cards were used and processed with the SPSS V.26 program, Wilcoxon and Student's t-test according to the normality criterion. Results: the PRV decreases triglyceride levels, average before 235,6 mg/dl and after 196,1 mg/dl; no positive effects were evidenced in the rest of the risk factors. In people with some risk factor the PRV had a positive impact; before the PRV 2 people had glucose >= 100mg/dl and after the PRV 1, regarding abdominal perimeter ≥ 90cm M, ≥ 80cm F before (30), after (19), blood pressure ≥ 130/85 mmHg before (06), after (0), triglycerides ≥ 150mg/dl before (30), after (17), C-HDL < 40 M < 50 F before (29), after (24). With a p value of 0,004 the PRV decreases triglyceride levels. Conclusion: In the general population the PRV decreases the triglyceride level; in people with some risk factor the PRV controls and regulates all the SM factors


A síndrome metabólica (SM) é prevenida através do controlo dos seus factores de risco, o programa de reforma do estilo de vida (PRV) visa o seu controlo e regulação. Objetivo: Avaliar o impacto do PRV. Materiais e métodos: Investigação aplicada, longitudinal, prospetiva, longitudinal, desenho indutivo e dedutivo, numa população inicial de 104 trabalhadores de uma universidade do Peru, a população final foi de 31 que completaram o programa, os factores de risco foram avaliados por um laboratorista clínico, foram utilizadas fichas de recolha e processadas com o programa SPSS V.26, teste de Wilcoxon e teste t de Student de acordo com o critério de normalidade. Resultados: O PRV reduz os níveis de triglicéridos, em média antes 235,6 mg/dl e depois 196,1 mg/dl, não se evidenciando efeitos positivos nos restantes factores de risco. Em pessoas com algum fator de risco o PRV teve um impacto positivo; antes do PRV 2 pessoas tinham glicose >= 100 mg/dl e depois do PRV 1, quanto ao perímetro abdominal ≥90cm M, ≥ 80 cm F antes (30), depois (19), pressão arterial ≥ 130/85 mmHg antes (06), depois (0), triglicéridos ≥ 150 mg/dl antes (30), depois (17), C-HDL < 40 M < 50 F antes (29), depois (24). Com um p-value de 0,004 o PRV diminui os níveis de triglicéridos. Conclusão: Na população em geral, o PRV diminui os níveis de triglicéridos; em pessoas com alguns factores de risco, o PRV controla e regula todos os factores da SM

17.
Vive (El Alto) ; 7(20)ago. 2024.
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1570128

ABSTRACT

El síndrome metabólico (SM) se previene controlando sus factores de riesgo, el programa de reforma de vida (PRV) busca el control y regulación de estos. Objetivo: evaluar el impacto del PRV. Materiales y métodos: Investigación aplicativo, longitudinal, prospectivo, diseño longitudinal, inductivo y deductivo, en una población inicial de 104 trabajadores de una universidad del Perú, la población final fue 31 quienes completaron el programa, los factores de riesgo fueron evaluados por un laboratorista clínico, se utilizó fichas de recolección y se procesó con el programa SPSS V.26, prueba de Wilcoxon y T de Student según el criterio de normalidad. Resultados: el PRV disminuye los niveles de triglicéridos, promedio antes 235,6 mg/dl y después 196,1 mg/dl, no se evidencio efectos positivos en el resto de los factores de riesgo. En personas con algún factor de riesgo el PRV impacto positivamente; antes del PRV 2 personas tenían la glucosa >= a 100 mg/dl y después del PRV 1, en cuanto al perímetro abdominal ≥ 90cm M, ≥ 80cm F antes (30), después (19), presión arterial ≥130/85 mmHg antes (06), después (0), triglicéridos ≥ 150 mg/dl antes (30), después (17), C-HDL < 40 M < 50 F antes (29), después (24). Con un p valor de 0,004 el PRV disminuye los niveles de triglicéridos. Conclusión: En la población en general el PRV disminuye el nivel de triglicéridos; en personas con algún factor de riesgo el PRV controla y regula todos los factores SM.


Metabolic syndrome (MS) is prevented by controlling its risk factors; the lifestyle reform program (LRP) seeks to control and regulate them. Objective: to evaluate the impact of the LRP. Materials and methods: Applied, longitudinal, prospective, longitudinal, inductive and deductive design, in an initial population of 104 workers of a Peruvian university, the final population was 31 who completed the program, the risk factors were evaluated by a clinical laboratorist, collection cards were used and processed with the SPSS V.26 program, Wilcoxon and Student's t-test according to the normality criterion. Results: the PRV decreases triglyceride levels, average before 235,6 mg/dl and after 196,1 mg/dl; no positive effects were evidenced in the rest of the risk factors. In people with some risk factor the PRV had a positive impact; before the PRV 2 people had glucose >= 100mg/dl and after the PRV 1, regarding abdominal perimeter ≥ 90cm M, ≥ 80cm F before (30), after (19), blood pressure ≥ 130/85 mmHg before (06), after (0), triglycerides ≥ 150mg/dl before (30), after (17), C-HDL < 40 M < 50 F before (29), after (24). With a p value of 0,004 the PRV decreases triglyceride levels. Conclusion: In the general population the PRV decreases the triglyceride level; in people with some risk factor the PRV controls and regulates all the SM factors.


A síndrome metabólica (SM) é prevenida através do controlo dos seus factores de risco, o programa de reforma do estilo de vida (PRV) visa o seu controlo e regulação. Objetivo: Avaliar o impacto do PRV. Materiais e métodos: Investigação aplicada, longitudinal, prospetiva, longitudinal, desenho indutivo e dedutivo, numa população inicial de 104 trabalhadores de uma universidade do Peru, a população final foi de 31 que completaram o programa, os factores de risco foram avaliados por um laboratorista clínico, foram utilizadas fichas de recolha e processadas com o programa SPSS V.26, teste de Wilcoxon e teste t de Student de acordo com o critério de normalidade. Resultados: O PRV reduz os níveis de triglicéridos, em média antes 235,6 mg/dl e depois 196,1 mg/dl, não se evidenciando efeitos positivos nos restantes factores de risco. Em pessoas com algum fator de risco o PRV teve um impacto positivo; antes do PRV 2 pessoas tinham glicose >= 100 mg/dl e depois do PRV 1, quanto ao perímetro abdominal ≥90cm M, ≥ 80 cm F antes (30), depois (19), pressão arterial ≥ 130/85 mmHg antes (06), depois (0), triglicéridos ≥ 150 mg/dl antes (30), depois (17), C-HDL < 40 M < 50 F antes (29), depois (24). Com um p-value de 0,004 o PRV diminui os níveis de triglicéridos. Conclusão: Na população em geral, o PRV diminui os níveis de triglicéridos; em pessoas com alguns factores de risco, o PRV controla e regula todos os factores da SM.

18.
World J Clin Pediatr ; 13(2): 91478, 2024 Jun 09.
Article in English | MEDLINE | ID: mdl-38947987

ABSTRACT

High-saturated fat (HF) or high-fructose (HFr) consumption in children predispose them to metabolic syndrome (MetS). In rodent models of MetS, diets containing individually HF or HFr lead to a variable degree of MetS. Nevertheless, simultaneous intake of HF plus HFr have synergistic effects, worsening MetS outcomes. In children, the effects of HF or HFr intake usually have been addressed individually. Therefore, we have reviewed the outcomes of HF or HFr diets in children, and we compare them with the effects reported in rodents. In humans, HFr intake causes increased lipogenesis, hypertriglyceridemia, obesity and insulin resistance. On the other hand, HF diets promote low grade-inflammation, obesity, insulin resistance. Despite the deleterious effects of simultaneous HF plus HFr intake on MetS development in rodents, there is little information about the combined effects of HF plus HFr intake in children. The aim of this review is to warn about this issue, as individually addressing the effects produced by HF or HFr may underestimate the severity of the outcomes of Western diet intake in the pediatric population. We consider that this is an alarming issue that needs to be assessed, as the simultaneous intake of HF plus HFr is common on fast food menus.

20.
Physiol Rep ; 12(13): e16126, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39001594

ABSTRACT

Molecular mechanisms associated to improvement of metabolic syndrome (MetS) during exercise are not fully elucidated. MetS was induced in 250 g male Wistar rats by 30% sucrose in drinking water. Control rats receiving tap water were controls, both groups received solid standard diet. After 14 weeks, an endurance exercised group, and a sedentary were formed for 8 weeks. The soleus and extensor digitorum longus (EDL) muscles were dissected to determine contractile performance, expression of myosin heavy chain isoforms, PGC1α, AMPKα2, NFATC1, MEF2a, SIX1, EYA1, FOXO1, key metabolic enzymes activities. Exercise mildly improved MetS features. MetS didn't alter the contractile performance of the muscles. Exercise didn't altered expression of PGC1α, NFATC1, SIX1 and EYA1 on MetS EDL whereas NFATC1 increased in soleus. Only citrate synthase was affected by MetS on the EDL and this was partially reverted by exercise. Soleus α-ketoglutarate dehydrogenase activity was increased by exercise but MetS rendered the muscle resistant to this effect. MetS affects mostly the EDL muscle, and endurance exercise only partially reverts this. Soleus muscle seems more resilient to MetS. We highlight the importance of studying both muscles during MetS, and their metabolic remodeling on the development and treatment of MetS by exercise.


Subject(s)
Energy Metabolism , Metabolic Syndrome , Physical Conditioning, Animal , Rats, Wistar , Animals , Male , Metabolic Syndrome/metabolism , Metabolic Syndrome/physiopathology , Rats , Muscle, Skeletal/metabolism , Sucrose/metabolism , Sucrose/administration & dosage , Muscle Fibers, Skeletal/metabolism , Muscle Contraction , Phenotype
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