RESUMO
BACKGROUND & AIMS: Most studies on the role of STAMP2 in metabolism have used adipose tissue. Little knowledge exists concerning the role of STAMP2 in the liver, which is a metabolically central target. We hypothesized that STAMP2 is involved in non-alcoholic fatty liver disease (NAFLD) pathogenesis. METHODS: We examined our hypothesis using human NAFLD patient pathology samples and a high-fat diet (HFD)-induced NAFLD mouse model. The molecular mechanism underlying hepatic STAMP2-mediated lipid imbalance was explored using an oleic acid (OA)-induced NAFLD in vitro model. RESULTS: Noticeably, the expression level of STAMP2 protein was reduced in the livers obtained from NAFLD patients and HFD-induced NAFLD mice. In vivo knockdown of hepatic STAMP2 by siRNA accelerated hepatic steatosis and insulin resistance in mice fed a HFD. Conversely, the delivery of adenoviral STAMP2 (Ad-STAMP2) improved hepatic steatosis in HFD-induced NAFLD mice. The expression of lipogenic or adipogenic factors was increased in both in vitro and in vivo NAFLD models but was reversed by Ad-STAMP2. Adenoviral overexpression of STAMP2 improved insulin resistance in the HFD-induced NAFLD mice. In vivo and in vitro assays demonstrated that STAMP2 modulates insulin sensitivity and glucose metabolism and that STAMP2 counteracts OA-induced insulin resistance by modulating insulin receptor substrate-1 stability. CONCLUSIONS: The present study revealed that hepatic STAMP2 plays a pivotal role in preventing HFD-induced NAFLD and that STAMP2 overexpression improves hepatic steatosis and insulin resistance in NAFLD. Our findings indicate that STAMP2 may represent a suitable target for interventions targeting NAFLD.
Assuntos
Regulação da Expressão Gênica , Resistência à Insulina/genética , Fígado/metabolismo , Proteínas de Membrana/genética , Hepatopatia Gordurosa não Alcoólica/genética , RNA/genética , Animais , Biópsia , Western Blotting , Células Cultivadas , Modelos Animais de Doenças , Humanos , Metabolismo dos Lipídeos , Fígado/patologia , Masculino , Proteínas de Membrana/biossíntese , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Hepatopatia Gordurosa não Alcoólica/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Drought conditions limit agricultural production by preventing crops from reaching their genetically predetermined maximum yields. Here, we present the results of field evaluations of rice overexpressing OsNAC9, a member of the rice NAC domain family. Root-specific (RCc3) and constitutive (GOS2) promoters were used to overexpress OsNAC9 and produced the transgenic RCc3:OsNAC9 and GOS2:OsNAC9 plants. Field evaluations over two cultivating seasons showed that grain yields of the RCc3:OsNAC9 and the GOS2:OsNAC9 plants were increased by 13%-18% and 13%-32% under normal conditions, respectively. Under drought conditions, RCc3:OsNAC9 plants showed an increased grain yield of 28%-72%, whilst the GOS2:OsNAC9 plants remained unchanged. Both transgenic lines exhibited altered root architecture involving an enlarged stele and aerenchyma. The aerenchyma of RCc3:OsNAC9 roots was enlarged to a greater extent than those of GOS2:OsNAC9 and non-transgenic (NT) roots, suggesting the importance of this phenotype for enhanced drought resistance. Microarray experiments identified 40 up-regulated genes by more than threefold (P < 0.01) in the roots of both transgenic lines. These included 9-cis-epoxycarotenoid dioxygenase, an ABA biosynthesis gene, calcium-transporting ATPase, a component of the Ca(2+) signalling pathway involved in cortical cell death and aerenchyma formation, cinnamoyl CoA reductase 1, a gene involved in lignin biosynthesis, and wall-associated kinases¸ genes involved in cell elongation and morphogenesis. Interestingly, O-methyltransferase, a gene necessary for barrier formation, was specifically up-regulated only in the RCc3:OsNAC9 roots. Such up-regulated genes that are commonly and specifically up-regulated in OsNAC9 transgenic roots may account for the altered root architecture conferring increased drought resistance phenotype.
Assuntos
Adaptação Fisiológica , Secas , Oryza/crescimento & desenvolvimento , Oryza/fisiologia , Proteínas de Plantas/metabolismo , Raízes de Plantas/anatomia & histologia , Sementes/crescimento & desenvolvimento , Agricultura , Regulação da Expressão Gênica de Plantas , Oryza/genética , Proteínas de Plantas/genética , Raízes de Plantas/crescimento & desenvolvimento , Plantas Geneticamente Modificadas , Reação em Cadeia da Polimerase em Tempo Real , Estresse Fisiológico , Regulação para Cima/genéticaRESUMO
BACKGROUND: In diagnosis and treatment of obesity, body composition analysis including percent body fat (%BF) is useful in the clinical setting. Because bioelectrical impedance analysis (BIA) could be used quickly, easily and was non-invasive in clinical setting, the purpose of the present study was to evaluate the usefulness of multi-frequency BIA with eight-point tactile electrodes (MF-BIA8; InBody 720, Biospace) compared with dual-energy X-ray absorptiometry (DXA) in healthy children and adolescents. METHODS: A total of 166 children and adolescents under 18 (male, n = 86; female, n = 80) were recruited. Height, weight, body mass index (BMI) and Tanner stage were measured for each subject. The body composition such as fat-free mass (FFM), fat mass (FM), and %BF was measured on BIA and DXA and compared. RESULTS: On linear regression analysis, DXA FFM = 1.006(BIA FFM) + 0.554, R(2) = 0.99 and the standard error of the estimate (SEE) was 1.16 kg; DXA FM = 0.971(BIA FM) - 0.596, R(2) = 0.93; SEE, 1.34 kg; and DXA %BF = 0.940(BIA %BF) - 1.026, R(2) = 0.858; SEE, 3.03%. Limit of agreement in FFM, FM, and %BF was 0.7 +/- 2.3 kg, -0.9 +/- 2.9 kg and -2.2 +/- 6.1%, respectively. CONCLUSIONS: Although the %BF was not interchangeable with DXA, MF-BIA8 (InBody 720; Biospace) could be used to measure body composition of children and adolescents in the clinical field because of its high precision.