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1.
Biomed Pharmacother ; 176: 116863, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38850650

RESUMO

Pyroptosis is a lytic and pro-inflammatory form of regulated cell death characterized by the formation of membrane pores mediated by the gasdermin protein family. Two main activation pathways have been documented: the caspase-1-dependent canonical pathway and the caspase-4/5/11-dependent noncanonical pathway. Pyroptosis leads to cell swelling, lysis, and the subsequent release of inflammatory mediators, including interleukin-1ß (IL-1ß) and interleukin-18 (IL-18). Chronic inflammation is a well-established foundation and driver for the development of metabolic diseases. Conversely, metabolic pathway dysregulation can also induce cellular pyroptosis. Recent studies have highlighted the significant role of pyroptosis modulation in various metabolic diseases, including type 2 diabetes mellitus, obesity, and metabolic (dysfunction) associated fatty liver disease. These findings suggest that pyroptosis may serve as a promising novel therapeutic target for metabolic diseases. This paper reviews an in-depth study of the current advancements in understanding the role of pyroptosis in the progression of metabolic diseases.


Assuntos
Doenças Metabólicas , Piroptose , Piroptose/fisiologia , Humanos , Doenças Metabólicas/metabolismo , Doenças Metabólicas/patologia , Animais , Transdução de Sinais , Inflamação/metabolismo , Inflamação/patologia
2.
In Vivo ; 38(4): 1917-1926, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38936925

RESUMO

BACKGROUND/AIM: To examine the relationship between the body surface area (BSA) and body composition in patients with metabolic dysfunction-associated steatotic liver disease (MASLD, 2,141 men and 986 women). MATERIALS AND METHODS: BSA and body composition parameters were examined. RESULTS: The median body mass index (BMI) was 25.0 kg/m2 for both men and women (p=0.7754). The median body surface area (BSA) was 1.854 m2 for men and 1.618 m2 for women (p<0.0001). In men, the median fat mass was 17.7 kg, whereas in women, it was 22.1 kg (p<0.0001). Additionally, the median fat-free mass was 55.4 kg in men and 39.3 kg in women (p<0.0001).). In male cases, BSA significantly correlated with fat mass (r=0.82, p<0.0001) and fat-free mass (r=0.95, p<0.0001). In female cases, BSA significantly correlated with fat mass (r=0.87, p<0.0001) and fat-free mass (r=0.94, p<0.0001). CONCLUSION: BSA could be a useful marker for the estimation of body composition in patients with MASLD.


Assuntos
Composição Corporal , Índice de Massa Corporal , Superfície Corporal , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Adulto , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Fígado Gorduroso/complicações , Doenças Metabólicas/metabolismo , Doenças Metabólicas/patologia , Doenças Metabólicas/complicações , Doenças Metabólicas/etiologia
3.
Tissue Cell ; 88: 102396, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38703582

RESUMO

By using a unique animal model of type 2 diabetes mellitus, Psammomys obesus induced by a high-calorie diet (HCD) for nine months, we showed for the first time, in the liver, the impact of inflammation on the remodeling of intercellular junction molecules E-cadherins during the progression of steatohepatitis. Under the effect of HCD, the expressions of immunohistochemical markers, Tumor Necrosis Factor alpha (TNFα) and E-cadherins were inversely correlated. Ultrastructural examination revealed the involvement of destabilization and loss of E-cadherins in the process of hepatic pathogenesis. This mechanical maintenance stress was favored by the recruitment of immune cells which contributed to the triggering and progression of fibrosis by the enlargement of the intercellular space and the invasion of collagen fibers. Furthermore to escape cell death, loss of E-cadherins played a major role in mediating fibrosis. Psammomys obesus is a promising model for experimental research, enabling the extrapolation of observed structural and functional alterations in humans, the objective to find new therapeutic targets. The physiological resemblance between Psammomys obesus and humans enhances the precision and relevance of biomedical research efforts.


Assuntos
Caderinas , Diabetes Mellitus Tipo 2 , Modelos Animais de Doenças , Gerbillinae , Fígado , Fator de Necrose Tumoral alfa , Animais , Fator de Necrose Tumoral alfa/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Caderinas/metabolismo , Fígado/metabolismo , Fígado/patologia , Fígado/ultraestrutura , Doenças Metabólicas/patologia , Doenças Metabólicas/metabolismo , Masculino
4.
Biochim Biophys Acta Mol Basis Dis ; 1870(6): 167247, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38762059

RESUMO

Cardiometabolic diseases (CMDs) denote a cadre of chronic and devastating cardiovascular anomalies routed from metabolic derangements including obesity, type 2 diabetes mellitus, and hypertension. Recent studies have demonstrated the association between histone lactylation, a unique form of post-translational modification, and pathogenesis of CMDs, apparently through epigenetic mechanisms. Lactylation has been indicated to regulate key aspects of metabolism, inflammation, and cardiovascular function in the realm of CMDs in a cellular and tissue-specific manner. A better understanding of the molecular, cellular and physiological domains of lactylation in the etiology of CMDs is expected to offer new insights into etiopathogenesis, hazardous factor control and therapeutic development for these challenging ailments.


Assuntos
Doenças Cardiovasculares , Epigênese Genética , Processamento de Proteína Pós-Traducional , Humanos , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/patologia , Animais , Ácido Láctico/metabolismo , Histonas/metabolismo , Histonas/genética , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Obesidade/genética , Obesidade/metabolismo , Doenças Metabólicas/genética , Doenças Metabólicas/metabolismo , Doenças Metabólicas/patologia
5.
Hepatol Commun ; 8(6)2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38727678

RESUMO

BACKGROUND: Few studies have examined the risk of long-term clinical outcomes in patients with metabolic dysfunction-associated steatohepatitis in relation to liver histology. We aimed to study this using a real-world cohort. METHODS: Adults (N = 702) recorded on Vanderbilt University Medical Center's Synthetic Derivative database (1984-2021) with evidence of metabolic dysfunction-associated steatohepatitis on liver biopsy were followed from the first biopsy until the first clinical event or last database entry (median: 4.7 y). Risks of cirrhosis (N = 650), other noncirrhotic liver-related (N = 702) and cardiovascular-related outcomes (N = 660), and mortality due to liver, cardiovascular, or cancer events (N = 660) were determined as a function of baseline histology (fibrosis stage [F], lobular inflammation grade [LI], hepatocyte ballooning grade [HB], and steatosis score) adjusting for sex, age, diabetes, and weight-loss surgery. RESULTS: Cirrhosis risk was reduced for lower versus higher fibrosis stage (HR: F0-1 vs. F3: 0.22 [95% CI: 0.12-0.42]), LI1 versus LI2-3 (0.42 [0.19-0.97]), and HB1 versus HB2 (0.20 [0.08-0.50]). Lower fibrosis stage was associated with significantly lower risks of liver-related outcomes versus F4 cirrhosis (eg, F0-1: 0.12 [0.05-0.25]), whereas no differences were seen across baseline lobular inflammation, hepatocyte ballooning, and steatosis grades/scores. Lower versus higher lobular inflammation grade was associated with lower risks for liver-related outcomes in patients with weight-loss surgery. There was a trend for lower risks for cardiovascular-related and any long-term outcomes with lower versus higher fibrosis stage. CONCLUSIONS: Fibrosis stage and lobular inflammation and hepatocyte ballooning grades predict the risk of long-term outcomes, supporting the use of these histological features as potential surrogate markers of disease progression or clinical outcomes.


Assuntos
Cirrose Hepática , Fígado , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Cirrose Hepática/patologia , Fígado/patologia , Adulto , Biópsia , Hepatopatia Gordurosa não Alcoólica/patologia , Hepatopatia Gordurosa não Alcoólica/complicações , Idoso , Doenças Metabólicas/patologia , Doenças Metabólicas/complicações , Fígado Gorduroso/patologia , Doenças Cardiovasculares/etiologia
6.
Metabolism ; 155: 155911, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38609037

RESUMO

BACKGROUND: The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing year by year and has become one of the leading causes of end-stage liver disease worldwide. Triggering Receptor Expressed on Myeloid Cells 2 (Trem2) has been confirmed to play an essential role in the progression of MASLD, but its specific mechanism still needs to be clarified. This study aims to explore the role and mechanism of Trem2 in MASLD. METHODS: Human liver tissues were obtained from patients with MASLD and controls. Myeloid-specific knockout mice (Trem2mKO) and myeloid-specific overexpression mice (Trem2TdT) were fed a high-fat diet, either AMLN or CDAHFD, to establish the MASLD model. Relevant signaling molecules were assessed through lipidomics and RNA-seq analyses after that. RESULTS: Trem2 is upregulated in human MASLD/MASH-associated macrophages and is associated with hepatic steatosis and inflammation progression. Hepatic steatosis and inflammatory responses are exacerbated with the knockout of myeloid Trem2 in MASLD mice, while mice overexpressing Trem2 exhibit the opposite phenomenon. Mechanistically, Trem2mKO can aggravate macrophage pyroptosis through the PI3K/AKT signaling pathway and amplify the resulting inflammatory response. At the same time, Trem2 promotes the inflammation resolution phenotype transformation of macrophages through TGFß1, thereby promoting tissue repair. CONCLUSIONS: Myeloid Trem2 ameliorates the progression of Metabolic dysfunction-associated steatotic liver disease by regulating macrophage pyroptosis and inflammation resolution. We believe targeting myeloid Trem2 could represent a potential avenue for treating MASLD.


Assuntos
Progressão da Doença , Fígado Gorduroso , Inflamação , Macrófagos , Glicoproteínas de Membrana , Piroptose , Receptores Imunológicos , Animais , Humanos , Masculino , Camundongos , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Fígado Gorduroso/genética , Inflamação/metabolismo , Inflamação/patologia , Fígado/metabolismo , Fígado/patologia , Macrófagos/metabolismo , Glicoproteínas de Membrana/metabolismo , Glicoproteínas de Membrana/genética , Doenças Metabólicas/metabolismo , Doenças Metabólicas/patologia , Doenças Metabólicas/genética , Camundongos Endogâmicos C57BL , Camundongos Knockout , Piroptose/fisiologia , Receptores Imunológicos/metabolismo , Receptores Imunológicos/genética
7.
J Assist Reprod Genet ; 41(5): 1245-1259, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38470552

RESUMO

BACKGROUND: Preimplantation genetic testing for monogenic disorders (PGT-M) is now widely used as an effective strategy to prevent various monogenic or chromosomal diseases. MATERIAL AND METHODS: In this retrospective study, couples with a family history of hereditary neurological diseases or metabolic diseases dominated by nervous system phenotypes and/or carrying the pathogenic genes underwent PGT-M to prevent children from inheriting disease-causing gene mutations from their parents and developing known genetic diseases. After PGT-M, unaffected (i.e., normal) embryos after genetic detection were transferred into the uterus of their corresponding mothers. RESULTS: A total of 43 carrier couples with the following hereditary neurological diseases or metabolic diseases dominated by nervous system phenotypes underwent PGT-M: Duchenne muscular dystrophy (13 families); methylmalonic acidemia (7 families); spinal muscular atrophy (5 families); infantile neuroaxonal dystrophy and intellectual developmental disorder (3 families each); Cockayne syndrome (2 families); Menkes disease, spinocerebellar ataxia, glycine encephalopathy with epilepsy, Charcot-Marie-Tooth disease, mucopolysaccharidosis, Aicardi-Goutieres syndrome, adrenoleukodystrophy, phenylketonuria, amyotrophic lateral sclerosis, and Dravet syndrome (1 family each). After 53 PGT-M cycles, the final transferable embryo rate was 12.45%, the clinical pregnancy rate was 74.19%, and the live birth rate was 89.47%; a total of 18 unaffected (i.e., healthy) children were born to these families. CONCLUSIONS: This study highlights the importance of PGT-M in preventing children born with hereditary neurological diseases or metabolic diseases dominated by nervous system phenotypes.


Assuntos
Testes Genéticos , Doenças Metabólicas , Diagnóstico Pré-Implantação , Humanos , Diagnóstico Pré-Implantação/métodos , Feminino , Gravidez , Testes Genéticos/métodos , Doenças Metabólicas/genética , Doenças Metabólicas/patologia , Estudos Retrospectivos , Masculino , Doenças do Sistema Nervoso/genética , Fenótipo , Adulto , Criança , Transferência Embrionária , Mutação/genética
8.
Front Biosci (Schol Ed) ; 16(1): 5, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38538341

RESUMO

The pathogenesis of type 2 diabetes mellitus (T2DM) is based on the development of insulin resistance, which is a disruption to the ability of the tissues to bind to insulin, leading to a general metabolic disorder. Mitochondria are the main participants in cellular energy metabolism, meaning their dysfunction is associated with the development of insulin resistance in T2DM. Mitochondrial function is affected by insulin resistance in various tissues, including skeletal muscle and the liver, which greatly influence glucose homeostasis throughout the body. This review studies mitochondrial dysfunction in T2DM and its impact on disease progression. In addition, it considers the causes underlying the development of mitochondrial dysfunction in T2DM, including mutations in the mitochondrial genome, mitochondrial DNA methylation, and other epigenetic influences, as well as the impact of impaired mitochondrial membrane potential. New therapeutic strategies for diabetes that have been developed to target the mitochondria will also be presented.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Doenças Metabólicas , Doenças Mitocondriais , Humanos , Diabetes Mellitus Tipo 2/metabolismo , Resistência à Insulina/fisiologia , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Doenças Metabólicas/metabolismo , Doenças Metabólicas/patologia , Metabolismo Energético , Doenças Mitocondriais/metabolismo , Doenças Mitocondriais/patologia
10.
Transl Res ; 266: 1-15, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37433392

RESUMO

Diabetic lipo-toxicity is a fundamental pathophysiologic mechanism in DM and is now increasingly recognized a key determinant of DKD. Targeting lipid metabolic disorders is an important therapeutic strategy for the treatment of DM and its complications, including DKD. This study aimed to explore the molecular mechanism of lipid metabolic regulation in kidney, especially renal PTECs, and elucidate the role of lipid metabolic related molecule lipin-1 in diabetic lipid-related kidney damage. In this study, lipin-1-deficient db/db mouse model and STZ/HFD-induced T2DM mouse model were used to determine the effect of lipin-1 on DKD development. Then RPTCs and LPIN1 knockdown or overexpressed HK-2 cells induced by PA were used to investigate the mechanism. We found that the expression of lipin-1 increased early and then decreased in kidney during the progression of DKD. Glucose and lipid metabolic disorders and renal insufficiency were found in these 2 types of diabetic mouse models. Interestingly, lipin-1 deficiency might be a pathogenic driver of DKD-to-CKD transition, which could further accelerate the imbalance of renal lipid homeostasis, the dysfunction of mitochondrial and energy metabolism in PTECs. Mechanistically, lipin-1 deficiency resulted in aggravated PTECs injury to tubulointerstitial fibrosis in DKD by downregulating FAO via inhibiting PGC-1α/PPARα mediated Cpt1α/HNF4α signaling and upregulating SREBPs to promote fat synthesis. This study provided new insights into the role of lipin-1 as a regulator for maintaining lipid homeostasis in the kidney, especially PTECs, and its deficiency led to the progression of DKD.


Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , Doenças Metabólicas , Camundongos , Animais , Nefropatias Diabéticas/metabolismo , Rim/patologia , Modelos Animais de Doenças , Lipídeos , Ácidos Graxos , Doenças Metabólicas/patologia , Diabetes Mellitus/patologia , Compostos Orgânicos
11.
Biochim Biophys Acta Mol Cell Res ; 1871(2): 119626, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-37977492

RESUMO

Adipose tissue fibrosis has been identified as a novel contributor to the pathomechanism of obesity associated metabolic disorders. Sulforaphane (SFN) has been shown to have an anti-obesity effect. However, the impact of SFN on adipose tissue fibrosis is still not well understood. In this study, obese mice induced by high-fat diets (HFD) were used to examine the effects of SFN on adipose tissue fibrosis. According to the current findings, SFN dramatically enhanced glucose tolerance and decreased body weight in diet-induced-obesity (DIO) mice. Additionally, SFN therapy significantly reduced extracellular matrix (ECM) deposition and altered the expression of genes related to fibrosis. Furthermore, SFN also reduced inflammation and promoted macrophages polarization towards to M2 phenotype in adipose tissue, which protected adipose tissue from fibrosis. Notably, SFN-mediated nuclear factor E2-related factor 2 (Nrf2) activation was crucial in decreasing adipose tissue fibrosis. These results implied that SFN had favorable benefits in adipose tissue fibrosis, which consequently ameliorates obesity-related metabolic problems. Our research provides new treatment strategies for obesity and associated metabolic disorders.


Assuntos
Dieta Hiperlipídica , Isotiocianatos , Doenças Metabólicas , Sulfóxidos , Camundongos , Animais , Dieta Hiperlipídica/efeitos adversos , Tecido Adiposo , Obesidade/tratamento farmacológico , Obesidade/patologia , Fibrose , Macrófagos , Doenças Metabólicas/patologia
12.
J Physiol Biochem ; 80(2): 249-260, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38158555

RESUMO

N6-methyladenosine (m6A) is one of the most abundant epitranscriptomic modifications on eukaryotic mRNA. Evidence has highlighted that m6A is altered in response to inflammation-related factors and it is closely associated with various inflammation-related diseases. Multiple subpopulations of myeloid cells, such as macrophages, dendritic cells, and granulocytes, are crucial for the regulating of immune process in inflammation-related diseases. Recent studies have revealed that m6A plays an important regulatory role in the functional of multiple myeloid cells. In this review, we comprehensively summarize the function of m6A modification in myeloid cells from the perspective of myeloid cell production, activation, polarization, and migration. Furthermore, we discuss how m6A-mediated myeloid cell function affects the progression of inflammation-related diseases, including autoimmune diseases, chronic metabolic diseases, and malignant tumors. Finally, we discuss the challenges encountered in the study of m6A in myeloid cells, intended to provide a new direction for the study of the pathogenesis of inflammation-related diseases.


Assuntos
Adenosina , Adenosina/análogos & derivados , Inflamação , Células Mieloides , Adenosina/metabolismo , Humanos , Inflamação/metabolismo , Células Mieloides/metabolismo , Animais , Doenças Autoimunes/metabolismo , Doenças Autoimunes/imunologia , Doenças Autoimunes/patologia , Neoplasias/metabolismo , Neoplasias/patologia , Neoplasias/imunologia , Neoplasias/genética , Doenças Metabólicas/metabolismo , Doenças Metabólicas/imunologia , Doenças Metabólicas/patologia
13.
Obesity (Silver Spring) ; 32(3): 612-622, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38151987

RESUMO

OBJECTIVE: The objective of this study was to assess the performance of noninvasive tests (NITs) across different racial and ethnic groups in a large multiethnic cohort. METHODS: Data were derived from the National Health and Nutrition Examination Survey (NHANES) 2017 through 2020. Participants without valid transient elastography measurements or with alternative etiologies of liver steatosis disease were excluded from the study. RESULTS: Among the 6359 adults included in the study, fatty liver index and nonalcoholic fatty liver disease liver fat scores performed well for the prediction of metabolic dysfunction-associated steatotic liver disease, without significant changes across racial and ethnic groups. However, significant differences were observed across racial and ethnic groups for the prediction of advanced fibrosis and cirrhosis. The fibrosis-4 (FIB-4) index, aspartate aminotransferase to platelet ratio index (APRI), and nonalcoholic fatty liver disease fibrosis score underperformed in non-Hispanic Black patients for the detection of cirrhosis. For the detection of advanced fibrosis, their performance was also numerically worse in non-Hispanic Black patients but only reached statistical significance for APRI. Using a cutoff point of 12 kPa for advanced fibrosis, both APRI and the FIB-4 index performed significantly worse in non-Hispanic Black patients. CONCLUSIONS: In a large, diverse national cohort, the performance of NITs was overall poor compared with transient elastography, and NITs showed differences across racial and ethnic groups. Given the widespread use of NITs, it is imperative that the scores are equitable across racial and ethnic groups.


Assuntos
Doenças Metabólicas , Hepatopatia Gordurosa não Alcoólica , Adulto , Humanos , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/patologia , Inquéritos Nutricionais , Cirrose Hepática/diagnóstico , Cirrose Hepática/complicações , Fibrose , Doenças Metabólicas/patologia , Aspartato Aminotransferases , Biópsia/efeitos adversos , Fígado/patologia
15.
Ageing Res Rev ; 88: 101963, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37245633

RESUMO

Ageing is a physiological/pathological process accompanied by the progressive damage of cell function, triggering various ageing-related disorders. Phosphatidylinositol 3-kinase (PI3K), which serves as one of the central regulators of ageing, is closely associated with cellular characteristics or molecular features, such as genome instability, telomere erosion, epigenetic alterations, and mitochondrial dysfunction. In this review, the PI3K signalling pathway was firstly thoroughly explained. The link between ageing pathogenesis and the PI3K signalling pathway was then summarized. Finally, the key regulatory roles of PI3K in ageing-related illnesses were investigated and stressed. In summary, we revealed that drug development and clinical application targeting PI3K is one of the focal points for delaying ageing and treating ageing-related diseases in the future.


Assuntos
Envelhecimento , Fosfatidilinositol 3-Quinase , Fosfatidilinositol 3-Quinase/metabolismo , Humanos , Animais , Transdução de Sinais , Envelhecimento/patologia , Envelhecimento/fisiologia , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/patologia , Doenças Metabólicas/metabolismo , Doenças Metabólicas/patologia , Cardiopatias/metabolismo , Cardiopatias/patologia , Neoplasias/metabolismo , Neoplasias/patologia
16.
Biochemistry (Mosc) ; 88(2): 280-288, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37072333

RESUMO

Diseases associated with the disorders of carbohydrate and lipid metabolism are widespread in the modern world. Interaction between the cells of adipose tissue - adipocytes - and immune system cells is an essential factor in pathogenesis of such diseases. Long-term increase in the glucose and fatty acid levels leads to adipocyte hypertrophy and increased expression of pro-inflammatory cytokines and adipokines by these cells. As a result, immune cells acquire a pro-inflammatory phenotype, and new leukocytes are recruited. Inflammation of adipose tissue leads to insulin resistance and stimulates formation of atherosclerotic plaques and development of autoimmunity. New studies show that different groups of B lymphocytes play an essential role in regulation of adipose tissue inflammation. Decrease in the number of B-2 lymphocytes suppresses development of a number of metabolic diseases, whereas decreased numbers of the regulatory B lymphocytes and B-1 lymphocytes are associated with more severe pathology. Recent studies showed that adipocytes influence B lymphocyte activity both directly and by altering activity of other immune cells. These findings provide better understanding of the molecular mechanisms of human pathologies associated with impaired carbohydrate and lipid metabolism, such as type 2 diabetes mellitus.


Assuntos
Diabetes Mellitus Tipo 2 , Doenças Metabólicas , Humanos , Diabetes Mellitus Tipo 2/metabolismo , Adipócitos/metabolismo , Tecido Adiposo/metabolismo , Doenças Metabólicas/patologia , Glucose/metabolismo , Inflamação/metabolismo , Linfócitos B/metabolismo
17.
Cells ; 12(4)2023 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-36831262

RESUMO

Aging is a major risk factor for the leading causes of mortality, and the incidence of age-related diseases including cardiovascular disease, kidney disease and metabolic disease increases with age. NAD+ is a classic coenzyme that exists in all species, and that plays a crucial role in oxidation-reduction reactions. It is also involved in the regulation of many cellular functions including inflammation, oxidative stress and differentiation. NAD+ declines with aging in various organs, and the reduction in NAD+ is possibly involved in the development of age-related cellular dysfunction in cardiorenal metabolic organs through the accumulation of inflammation and oxidative stress. Levels of NAD+ are regulated by the balance between its synthesis and degradation. CD38 is the main NAD+-degrading enzyme, and CD38 is activated in response to inflammation with aging, which is associated with the reduction in NAD+ levels. In this review, focusing on CD38, we discuss the role of CD38 in aging and the pathogenesis of age-related diseases, including cardiorenal metabolic disease.


Assuntos
ADP-Ribosil Ciclase 1 , Envelhecimento , Doenças Metabólicas , Humanos , ADP-Ribosil Ciclase 1/metabolismo , Inflamação , Doenças Metabólicas/metabolismo , Doenças Metabólicas/patologia , NAD/metabolismo , Envelhecimento/metabolismo , Envelhecimento/patologia
18.
Biomed Pharmacother ; 161: 114417, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36812714

RESUMO

Poor control of metabolic diseases induces kidney injury, resulting in microalbuminuria, renal insufficiency and, ultimately, chronic kidney disease. The potential pathogenetic mechanisms of renal injury caused by metabolic diseases remain unclear. Tubular cells and podocytes of the kidney show high expression of histone deacetylases known as sirtuins (SIRT1-7). Available evidence has shown that SIRTs participate in pathogenic processes of renal disorders caused by metabolic diseases. The present review addresses the regulatory roles of SIRTs and their implications for the initiation and development of kidney damage due to metabolic diseases. SIRTs are commonly dysregulated in renal disorders induced by metabolic diseases such as hypertensive nephropathy and diabetic nephropathy. This dysregulation is associated with disease progression. Previous literature has also suggested that abnormal expression of SIRTs affects cellular biology, such as oxidative stress, metabolism, inflammation, and apoptosis of renal cells, resulting in the promotion of invasive diseases. This literature reviews the research progress made in understanding the roles of dysregulated SIRTs in the pathogenesis of metabolic disease-related kidney disorders and describes the potential of SIRTs serve as biomarkers for early screening and diagnosis of these diseases and as therapeutic targets for their treatment.


Assuntos
Nefropatias Diabéticas , Doenças Metabólicas , Insuficiência Renal Crônica , Sirtuínas , Humanos , Sirtuínas/metabolismo , Rim/patologia , Nefropatias Diabéticas/metabolismo , Insuficiência Renal Crônica/patologia , Doenças Metabólicas/patologia
19.
Curr Aging Sci ; 16(2): 97-111, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36815652

RESUMO

Aging is characterized by progressive regression in tissue and organ functions and an increased risk of disease and death. Aging is also accompanied by chronic low-grade inflammation. Both obesity and aging are associated with the development of metabolic diseases, leading to an increase in the senescent cell burden in multiple organs. Chronic low-grade inflammation of adipose tissue is one of the mechanisms implicated in the progression of these diseases. As a real endocrine organ, adipose tissue secretes many mediators and hormones (adipokines) to maintain metabolic homeostasis, and their dysfunction has been causally linked to a wide range of metabolic diseases. Dysfunctional adipose tissue participates in interorgan communication both by producing new signaling mediators and by transforming or disrupting signal mediators, reaching from other organs. In addition to obesity and similar metabolic diseases, this situation causes dysfunction in more organs in the aging process, and the complexity of the problem causes challenges in the diagnosis and treatment processes. This review aims to highlight recent developments and current information supporting the relationship between obesity and adipose tissue dysfunction with aging and the role of homeostatic and physio-pathological processes that mediate interorgan communication in aging progress. More understanding clearly of interorgan communication in the process of obesity and aging will facilitate the early diagnosis as well as the management of treatment practices in short- and long-term organ dysfunction.


Assuntos
Doenças Metabólicas , Obesidade , Humanos , Obesidade/metabolismo , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Inflamação/metabolismo , Doenças Metabólicas/complicações , Doenças Metabólicas/metabolismo , Doenças Metabólicas/patologia , Envelhecimento
20.
Mol Genet Metab ; 137(3): 223-229, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36183456

RESUMO

Damages to the ear are very diverse and can depend on the type of inherited metabolic diseases (IMD). Indeed, IMDs can affect all parts of the auditory system, from the outer ear to the central auditory process. We have identified 219 IMDs associated with various types of ear involvement which we classified into five groups according to the lesion site of the auditory system: congenital external ear abnormalities, acquired external ear abnormalities, middle ear involvement, inner ear or retrocochlear involvement, and unspecified hearing loss. This represents the ninth issue in a series of educational summaries providing a comprehensive and updated list of metabolic differential diagnoses according to system involvement.


Assuntos
Orelha Interna , Perda Auditiva Neurossensorial , Perda Auditiva , Doenças Metabólicas , Humanos , Orelha Interna/patologia , Perda Auditiva/genética , Doenças Metabólicas/genética , Doenças Metabólicas/patologia , Perda Auditiva Neurossensorial/patologia
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