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Front Immunol ; 12: 669629, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34305899


Background and aims: Group 2 innate lymphoid cells (ILC2s) have been implicated in the regulation of metabolic homeostasis in mice. Methods: In this study, the role of ILC2s in white adipose tissue (WAT) was investigated using ST2, an IL-33 receptor that is expressed on ILC2 knockout mice. Results: The deficiency of ST2 decreased ILC2s in WAT, whereas ex-ILC2, which acquired group 1 innate lymphoid cell (ILC1)-like traits, was increased. This led to significant metabolic disorders such as visceral fat obesity, decreased browning in WAT, reduction of energy metabolism, and impaired glucose tolerance, compared to wild type (WT) mice. Those metabolic abnormalities of ST2-knockout (ST2KO) mice were not ameliorated by IL-33 administration, but impaired glucose tolerance and visceral fat obesity were significantly improved by transplantation of ILCs from the bone marrow of WT mice. The relative expression of Cd36 in WAT increased due to the deficiency of ST2, and the storage of saturated fatty acids in WAT of ST2KO mice was significantly higher than that of WT mice. Moreover, saturated fatty acids aggravated the chronic inflammation in adipocytes, promoted the differentiation of M1-like macrophages, and inhibited that of M2-like macrophages. Conclusions: Our results indicated that ILC2 regulates diet-induced obesity and chronic inflammation through the regulation of saturated fatty acid absorption in visceral adipose tissue.

Glicemia/metabolismo , Ácidos Graxos/metabolismo , Intolerância à Glucose/metabolismo , Imunidade Inata , Resistência à Insulina , Gordura Intra-Abdominal/metabolismo , Linfócitos/metabolismo , Absorção Fisiológica , Transferência Adotiva , Animais , Glicemia/efeitos dos fármacos , Antígenos CD36/metabolismo , Intolerância à Glucose/tratamento farmacológico , Intolerância à Glucose/genética , Intolerância à Glucose/imunologia , Homeostase , Imunidade Inata/efeitos dos fármacos , Inflamação/imunologia , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Proteína 1 Semelhante a Receptor de Interleucina-1/genética , Proteína 1 Semelhante a Receptor de Interleucina-1/metabolismo , Interleucina-33/farmacologia , Gordura Intra-Abdominal/efeitos dos fármacos , Gordura Intra-Abdominal/imunologia , Linfócitos/efeitos dos fármacos , Linfócitos/imunologia , Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Obesidade/imunologia , Obesidade/metabolismo , Células RAW 264.7
PLoS One ; 16(3): e0247886, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33684119


OBJECTIVES: To investigate the growth velocity-improving effects of vitamin D replacement therapy in pediatric patients diagnosed with vitamin D deficiency and insufficiency. STUDY DESIGN: A retrospective cohort study was conducted in 34 pediatric patients diagnosed with vitamin D deficiency/insufficiency. Based on the clinical findings, the subjects were divided into two groups: a bowed leg (BL) group and a non-bowed leg (non-BL) group. After the initiation of alfacalcidol, the standard deviation score (SDS) of their heights, weights and growth velocities in each group were monitored. RESULTS: The median age at the first visit was significantly lesser in the BL group (1.58 years old [interquartile range (IQR): 1.33, 2.17]) than that in the non-BL group (3.00 years old [IQR: 2.33, 3.67]). On the contrary, the SDS for height was significantly lower in the non-BL group (-2.27 [IQR: -2.63, -1.94]) than that in the BL group (-1.37 [IQR: -1.91, -1.07]). One-year treatment with alfacalcidol showed significant improvements in both height SDSs and growth velocity SDSs not only in the BL group but also in the non-BL group. CONCLUSIONS: The current study revealed that vitamin D replacement therapy improved the growth rate in children with vitamin D deficiency/insufficiency, regardless of the presence of BL. This study emphasizes the importance of assessing the vitamin D status in children with poor growth rates and suggests that alfacalcidol could be a valid option for the treatment of short stature.

Desenvolvimento Infantil/efeitos dos fármacos , Hidroxicolecalciferóis/administração & dosagem , Deficiência de Vitamina D/tratamento farmacológico , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos , Deficiência de Vitamina D/diagnóstico , Deficiência de Vitamina D/fisiopatologia
Clin Pediatr Endocrinol ; 29(4): 189-193, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33088019


We report a case of 15-yr-old phenotypically normal male with short stature associated with the chromosomal abnormalities of 46,X,psu idic(Y)(q11.2)/45,X. At 3 yr of age, he underwent urethroplasty for scrotal hypospadias. At 15 yr of age, he was referred to our hospital due to short stature (-3.71 SD). The results of blood examination were mostly normal. A radiological examination revealed his bone age was 15.7 yr (based on the TW2-RUS method). Chromosome analysis of peripheral lymphocytes revealed 46,X,psu idic(Y)(q11.2)[16]/45,X[14], and array comparative genomic hybridization (aCGH) showed a large deletion of Yq which was located distal to the Y chromosome growth-control gene (GCY) region. It is likely that these structural abnormalities in the Y chromosome were responsible for the short stature. This case might provide new insights regarding GCY and emphasizes the importance of chromosome analysis in not only females but also males with short stature, especially when associated with genital anomalies.

Am J Physiol Endocrinol Metab ; 317(6): E1140-E1149, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31638856


The angiotensin II (ANG II)-ANG II type 1 receptor (AT1R) axis is a key player in the pathophysiology of obesity. Angiotensin-converting enzyme 2 (ACE2) counteracts the ANG II/AT1R axis via converting ANG II to angiotensin 1-7 (Ang 1-7), which is known to have an anti-obesity effect. In this study, we hypothesized that ACE2 exerts a strong anti-obesity effect by increasing Ang 1-7 levels. We injected intraperitoneally recombinant human ACE2 (rhACE2, 2.0 mg·kg-1·day-1) for 28 days to high-fat diet (HFD)-induced obesity mice. rhACE2 treatment decreased body weight and improved glucose metabolism. Furthermore, rhACE2 increased oxygen consumption and upregulated thermogenesis in HFD-fed mice. In the rhACE2 treatment group, brown adipose tissue (BAT) mass increased, accompanied with ameliorated insulin signaling and increased protein levels of uncoupling protein-1 (UCP-1) and PRD1-BF1-RIZ1 homologous domain containing 16. Importantly, subcutaneous white adipose tissue (sWAT) mass decreased, concomitant with browning, which was established by the increase of UCP-1 expression. The browning is the result of increased H3K27 acetylation via the downregulation of histone deacetylase 3 and increased H3K9 acetylation via upregulation of GCN5 and P300/CBP-associated factor. These results suggest that rhACE2 exerts anti-obesity effects by stimulating BAT and inducing browning in sWAT. ACE2 and the Ang 1-7 axis represent a potential therapeutic approach to prevent the development of obesity.

Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Branco/efeitos dos fármacos , Angiotensina I/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Obesidade/metabolismo , Fragmentos de Peptídeos/efeitos dos fármacos , Peptidil Dipeptidase A/farmacologia , Termogênese/efeitos dos fármacos , Acetilação/efeitos dos fármacos , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/metabolismo , Angiotensina I/metabolismo , Enzima de Conversão de Angiotensina 2 , Animais , Dieta Hiperlipídica , Regulação para Baixo , Código das Histonas/efeitos dos fármacos , Histona Desacetilases/efeitos dos fármacos , Histona Desacetilases/metabolismo , Humanos , Insulina/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fragmentos de Peptídeos/metabolismo , Proteínas Recombinantes , Gordura Subcutânea/efeitos dos fármacos , Gordura Subcutânea/metabolismo , Proteína Desacopladora 1/efeitos dos fármacos , Proteína Desacopladora 1/metabolismo , Fatores de Transcrição de p300-CBP/efeitos dos fármacos , Fatores de Transcrição de p300-CBP/metabolismo
Yonago Acta Med ; 62(1): 8-13, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30962739


Background: Autism spectrum disorders (ASD) with intellectual disabilities may be associated with many factors. This study focused on patients with ASD with intellectual disabilities, defined by a threshold intelligence quotient (IQ) or development quotient (DQ) of 70. We also discuss comorbidities and other factors related to ASD. Methods: We extracted case records of patients born between April 1995 and March 2001 who lived in Yonago City, as of January 2011, and had visited the two specialist institutions for consultation regarding developmental issues. The list was further narrowed down to patients identified, as having ASD by pediatric neurologists based on Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (DSM-5). We selected patients with < IQ/DQ 70 using the most recent intelligence/development test to determine comorbidities and other factors related to ASD. Results: The data of 81 patients (59 males and 22 females) were extracted, corresponding to an incidence of 76.2 patients out of every 10,000 births. The male-to-female ratio was 2.7:1. Comorbidities and related factors of ASD were observed in 25 cases (30.9%). Eleven cases had perinatal abnormalities. Other abnormalities were observed in 17 cases, including epilepsies in 7, chromosomal abnormalities in 4, familial mental retardation in 1, and acquired brain injury in 1. Conclusion: It is important to treat and support individuals with ASD and intellectual disabilities taking into account the characteristics and prognosis of the comorbidities and related factors.