RESUMO
Plasma metabolites offer insights into aging processes and aging-related biomarkers. Here, the dietary effects of various functional foods on older adult mice were evaluated using metabolomic techniques. Fifty-week-old mice were divided into four groups (n = 4 each) and fed either a normal diet (AC) or the diets from Triticum aestivum sprout (TA), Schisandra chinensis (SZ), or Pisum sativum sprout (PS) extracts. Additionally, a group of 8-week-old mice fed a normal diet (YC; n = 5) was included for the comparison. The PS group had a significantly lower free fatty acid content and higher ornithine, proline, citric acid, and oxalic acid contents than the AC group. The PS group also showed reduced oxidative stress and muscle damage, suggesting the higher anti-aging efficacy of P. sativum sprouts than the other diets. These findings suggest plasma metabolite profiling is an effective tool to assess the anti-aging effects of functional foods. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01479-8.
RESUMO
BACKGROUND/OBJECTIVES: Kaempferol (Ka) is one of the most widely occurring flavonoids found in large amounts in various plants. Ka has anti-obesity, antioxidant, and anti-inflammatory effects. Despite the numerous papers documenting the efficacy of Ka, some controversy remains. Therefore, this study examined the impact of Ka using 3T3-L1 and high-fat diet-induced obese mice. MATERIALS/METHODS: 3T3-L1 cells were treated with 50 µM Ka from the initiation of 3T3-L1 differentiation at D0 until the completion of differentiation on D8. Thirty male mice (C57BL/6J, 4 weeks old) were divided into 3 groups: normal diet (ND), high-fat diet (HFD), and HFD + 0.02% (w/w) Ka (Ka) group. All mice were fed their respective diets ad libitum for 16 weeks. The mice were sacriced, and the plasma and hepatic lipid levels, white adipose tissue weight, hepatic glucose level, lipid level, and antioxidant enzyme activities were analyzed, and immunohistochemistry staining was performed. RESULTS: Ka suppressed the hypertrophy of 3T3-L1 cells, and the Ka-supplemented mice showed a significant decrease in perirenal, retroperitoneal, mesenteric, and subcutaneous fat compared to the HFD group. Ka supplementation in high-fat diet-induced obese mice also improved the overall blood lipid concentration (total cholesterol, non-high-density lipoprotein-cholesterol, phospholipids, and apolipoprotein B). Ka supplementation in high-fat-induced obesity mice reduced hepatic steatosis and insulin resistance by modulating the hepatic lipid (glucose-6-phosphate dehydrogenase, fatty acid synthase, malic enzyme, phosphatidate phosphohydrolase, and ß-oxidation) activities and glucose (glucokinase, phosphoenolpyruvate carboxykinase, and G6pase)-regulating enzymes. Ka supplementation ameliorated the erythrocyte and hepatic mitochondrial H2O2 and inflammation levels (plasma tumor necrosis factor-alpha, monocyte chemoattractant protein-1, interleukin-6, and interferon-gamma and fibrosis of liver and epididymal fat). CONCLUSION: Ka may be beneficial for preventing diet-induced obesity, inflammation, oxidative stress, and diabetes.
RESUMO
Extant research on learners who are d/Deaf or hard of hearing with disabilities who come from Asian immigrant families is extremely sparse. The authors conducted an intrinsic case study of a deaf student with autism who comes from a Korean immigrant family. To acquire a comprehensive understanding of language and communication characteristics, they analyzed (a) interview data of three administrators who worked with the student and family and (b) school documents/reports issued to the parents. Themes are reported across the three components of the tri-focus framework (Siegel-Causey & Bashinski, 1997): the learner, partner, and environment. Implications for practitioners who work with these learners and their families are discussed, including (a) compiling an individualized language and communication profile that encompasses the framework; (b) utilizing culturally and linguistically responsive practices with the family; (c) practicing interprofessional collaboration; and (d) modifying physical and social environments to increase accessibility.
Assuntos
Transtorno do Espectro Autista , Surdez , Emigrantes e Imigrantes , Criança , Humanos , Transtorno do Espectro Autista/psicologia , Transtorno do Espectro Autista/etnologia , Comunicação , Barreiras de Comunicação , Surdez/psicologia , Surdez/reabilitação , Surdez/etnologia , Educação de Pessoas com Deficiência Auditiva , Emigrantes e Imigrantes/psicologia , Idioma , Pessoas com Deficiência Auditiva/psicologia , República da Coreia , Língua de Sinais , Meio SocialRESUMO
BACKGROUND: Chronic inflammation, which becomes more prevalent during aging, contributes to sarcopenia by reducing muscle mass and strength. PURPOSE: Wheat seedlings extract (WSE) is known for its various physiological activities, including anti-inflammation and antioxidant effects. However, its efficacy against sarcopenia is not well documented. STUDY DESIGN: 8-week-old and 50-week-old C57BL/6 J mice were used as young control (YC group) and aged controls (AC group), respectively. Then, aged mice were randomly divided into 5 groups (WSE100mg/kg, WSE200mg/kg, WSE400mg/kg, and schizandrin as a positive control) and fed each experimental diet for 10 weeks. METHOD: We investigated the effects of WSE on muscle quality and protein homeostasis pathways based on improvements in mitochondrial function and chronic inflammation. We then used TNFα-treated C2C12 to investigate the effects of isoorientin (ISO) and isoschaftoside (ISS), the active substances of WSE, on the myogenic pathway. RESULTS: We administered WSE to aging mice and observed an increase in muscle mass, thickness, protein content, and strength in mice treated with WSE at a dose of 200 mg/kg or 400 mg/kg. Furthermore, the administration of WSE led to a reduction in inflammatory factors (TNFα, IL-1, and IL-6) and an increase in mitochondrial biogenesis (p-AMPK/SIRT3/PGC1α) in muscle. This effect was also observed in TNFα-induced muscle atrophy in C2C12 cells, and we additionally identified the upregulation of myogenic regulatory factors, including Myf5, Myf6, MyoD, and myogenin, by WSE, ISO, and ISS. CONCLUSION: These findings suggest that WSE could function as a dietary anti-inflammatory factor and mitochondrial activator, potentially exerting modulatory effects on the metabolism and mechanical properties of skeletal muscles in the aging population. Furthermore, Our results demonstrate the potential value of ISO and ISS as functional food ingredients for preventing muscle atrophy.
Assuntos
Anti-Inflamatórios , Camundongos Endogâmicos C57BL , Biogênese de Organelas , Extratos Vegetais , Sarcopenia , Plântula , Triticum , Animais , Sarcopenia/tratamento farmacológico , Extratos Vegetais/farmacologia , Anti-Inflamatórios/farmacologia , Masculino , Triticum/química , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Envelhecimento/efeitos dos fármacos , Camundongos , Biossíntese de Proteínas/efeitos dos fármacos , Proteólise/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Lignanas/farmacologiaRESUMO
BACKGROUND AND AIMS: Noninvasive tools assessing steatosis, such as ultrasonography-based 2D-attenuation imaging (ATI), are needed to tackle the worldwide burden of steatotic liver disease. This one-stage individual patient data (IPD) meta-analysis aimed to create an ATI-based steatosis grading system. APPROACH AND RESULTS: A systematic review (EMBASE + MEDLINE, 2018-2022) identified studies, including patients with histologically or magnetic resonance imaging proton-density fat fraction (MRI-PDFF)-verified ATI for grading steatosis (S0 to S3). One-stage IPD meta-analyses were conducted using generalized mixed models with a random study-specific intercept. Created ATI-based steatosis grading system (aS0 to aS3) was externally validated on a prospective cohort of patients with type 2 diabetes and metabolic dysfunction-associated steatotic liver disease (n=174, histologically and MRI-PDFF-verified steatosis). Eleven enrolled studies included 1374 patients, classified into S0, S1, S2, and S3 in 45.4%, 35.0%, 9.3%, and 10.3% of the cases. ATI was correlated with histological steatosis ( r = 0.60; 95% CI: 0.52, 0.67; p < 0.001) and MRI-PDFF ( r = 0.70; 95% CI: 0.66, 0.73; p < 0.001) but not with liver stiffness ( r = 0.03; 95% CI: -0.04, 0.11, p = 0.343). Steatosis grade was an independent factor associated with ATI (coefficient: 0.24; 95% CI: [0.22, 0.26]; p < 0.001). ATI marginal means within S0, S1, S2, and S3 subpopulations were 0.59 (95% CI: [0.58, 0.61]), 0.69 (95% CI [0.67, 0.71]), 0.78 (95% CI: [0.76, 0.81]), and 0.85 (95% CI: [0.83, 0.88]) dB/cm/MHz; all contrasts between grades were significant ( p < 0.0001). Three ATI thresholds were calibrated to create a new ATI-based steatosis grading system (aS0 to aS3, cutoffs: 0.66, 0.73, and 0.81 dB/cm/MHz). Its external validation showed Obuchowski measures of 0.84 ± 0.02 and 0.82 ± 0.02 with histologically based and MRI-PDFF-based references. CONCLUSIONS: ATI is a reliable, noninvasive marker of steatosis. This validated ATI-based steatosis grading system could be valuable in assessing patients with metabolic dysfunction-associated steatotic liver disease.
RESUMO
Marine biogenic calcium carbonate (CaCO3) cycles play a key role in ecosystems and in regulating the ocean's ability to absorb atmospheric carbon dioxide (CO2). However, the drivers and magnitude of CaCO3 cycling are not well understood, especially for the upper ocean. Here, we provide global-scale evidence that heterotrophic respiration in settling marine aggregates may produce localized undersaturated microenvironments in which CaCO3 particles rapidly dissolve, producing excess alkalinity in the upper ocean. In the deep ocean, dissolution of CaCO3 is primarily driven by conventional thermodynamics of CaCO3 solubility with reduced fluxes of CaCO3 burial to marine sediments beneath more corrosive North Pacific deep waters. Upper ocean dissolution, shown to be sensitive to ocean export production, can increase the neutralizing capacity for respired CO2 by up to 6% in low-latitude thermocline waters. Without upper ocean dissolution, the ocean might lose 20% more CO2 to the atmosphere through the low-latitude upwelling regions.
RESUMO
BACKGROUND/OBJECTIVES: An increasing life expectancy in society has burdened healthcare systems substantially because of the rising prevalence of age-related metabolic diseases. This study compared the effects of animal protein hydrolysate (APH) and casein on metabolic diseases using aged mice. MATERIALS/METHODS: Eight-week-old and 50-week-old C57BL/6J mice were used as the non-aged (YC group) and aged controls (NC group), respectively. The aged mice were divided randomly into 3 groups (NC, low-APH [LP], and high-APH [HP] and fed each experimental diet for 12 weeks. In the LP and HP groups, casein in the AIN-93G diet was substituted with 16 kcal% and 24 kcal% APH, respectively. The mice were sacrificed when they were 63-week-old, and plasma and hepatic lipid, white adipose tissue weight, hepatic glucose, lipid, and antioxidant enzyme activities, immunohistochemistry staining, and mRNA expression related to the glucose metabolism on liver and muscle were analyzed. RESULTS: Supplementation of APH in aging mice resulted in a significant decrease in visceral fat (epididymal, perirenal, retroperitoneal, and mesenteric fat) compared to the negative control (NC) group. The intraperitoneal glucose tolerance test and area under the curve analysis revealed insulin resistance in the NC group, which was alleviated by APH supplementation. APH supplementation reduced hepatic gluconeogenesis and increased glucose utilization in the liver and muscle. Furthermore, APH supplementation improved hepatic steatosis by reducing the hepatic fatty acid and phosphatidate phosphatase activity while increasing the hepatic carnitine palmitoyltransferase activity. Furthermore, in the APH supplementation groups, the red blood cell (RBC) thiobarbituric acid reactive substances and hepatic H2O2 levels decreased, and the RBC glutathione, hepatic catalase, and glutathione peroxidase activities increased. CONCLUSIONS: APH supplementation reduced visceral fat accumulation and alleviated obesity-related metabolic diseases, including insulin resistance and hepatic steatosis, in aged mice. Therefore, high-quality animal protein APH that reduces the molecular weight and enhances the protein digestibility-corrected amino acid score has potential as a dietary supplement for healthy aging.
RESUMO
BACKGROUND/OBJECTIVES: Obesity is a major risk factor for metabolic syndrome, a global public health problem. Mentha canadensis (MA), a traditional phytomedicine and dietary herb used for centuries, was the focus of this study to investigate its effects on obesity. MATERIALS/METHODS: Thirty-five male C57BL/6J mice were randomly divided into 2 groups and fed either a normal diet (ND, n = 10) or a high-fat diet (HFD, n = 25) for 4 weeks to induce obesity. After the obesity induction period, the HFD-fed mice were randomly separated into 2 groups: one group continued to be fed HFD (n = 15, HFD group), while the other group was fed HFD with 1.5% (w/w) MA ethanol extract (n = 10, MA group) for 13 weeks. RESULTS: The results showed that body and white adipose tissue (WAT) weights were significantly decreased in the MA-supplemented group compared to the HFD group. Additionally, MA supplementation enhanced energy expenditure, leading to improvements in plasma lipids, cytokines, hepatic steatosis, and fecal lipids. Furthermore, MA supplementation regulated lipid-metabolism-related enzyme activity and gene expression, thereby suppressing lipid accumulation in the WAT and liver. CONCLUSIONS: These findings indicate that MA has the potential to improve diet-induced obesity and its associated complications, including adiposity, dyslipidemia, hepatic steatosis, and inflammation.
RESUMO
D-allulose, a rare sugar, has been proposed to have potential benefits in addressing metabolic disorders such as obesity and type 2 diabetes (T2D). However, the precise mechanisms underlying these effects remain poorly understood. We aimed to elucidate the mechanisms by which D-allulose influences obesity-induced insulin resistance. We conducted gene set enrichment analysis on the liver and white adipose tissue of mice exposed to a high-fat diet (HFD) along with the white adipose tissue of individuals with obesity. Our study revealed that D-allulose effectively suppressed IFN-γ, restored chemokine signaling, and enhanced macrophage function in the livers of HFD-fed mice. This implies that D-allulose curtails liver inflammation, alleviating insulin resistance and subsequently impacting adipose tissue. Furthermore, D-allulose supplementation improved mitochondrial NADH homeostasis and translation in both the liver and white adipose tissue of HFD-fed mice. Notably, we observed decreased NADH homeostasis and mitochondrial translation in the omental tissue of insulin-resistant obese subjects compared to their insulin-sensitive counterparts. Taken together, these results suggest that supplementation with allulose improves obesity-induced insulin resistance by mitigating the disruptions in macrophage and mitochondrial function. Furthermore, our data reinforce the crucial role that mitochondrial energy expenditure plays in the development of insulin resistance triggered by obesity.
Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Insulinas , Humanos , Animais , Camundongos , NAD/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Obesidade/metabolismo , Tecido Adiposo/metabolismo , Macrófagos/metabolismo , Homeostase , Mitocôndrias/metabolismo , Insulinas/metabolismo , Dieta Hiperlipídica/efeitos adversos , Camundongos Endogâmicos C57BL , Inflamação/metabolismoRESUMO
Age-related muscle loss and dysfunction, sarcopenia, is a common condition that results in poor quality of life in the elderly. Protein supplementation is a potential strategy for preventing sarcopenia and increasing muscle synthesis, but the effectiveness of protein type and level in improving sarcopenia is not well understood. In this study, we compared animal protein hydrolysate (APH), which has a high protein digestibility-corrected amino acid score (PDCAAS) and low molecular weight, with casein as a control group to investigate the effects and mechanisms of sarcopenia improvement, with a particular focus on the gut-muscle axis. APH supplementation improved age-related declines in muscle mass, grip strength, hind leg thickness, muscle protein level, muscle fiber size, and myokine levels, compared to the control group. In particular, levels of plasma cortisol, muscle lipids, and muscle collagen were markedly reduced by APH supplements in the aged mice. Furthermore, APH efficiently recovered the concentration of total SCFAs including acetic, propionic, and isovaleric acids decreased in aged mice. Finally, APH induced changes in gut microbiota and increased production of SCFAs, which were positively correlated with muscle protein level and negatively correlated with pro-inflammatory cytokines. In conclusion, APH can help to inhibit age-related sarcopenia by increasing muscle synthesis, inhibiting muscle breakdown, and potentially modulating the gut-muscle axis.
Assuntos
Sarcopenia , Humanos , Idoso , Animais , Camundongos , Sarcopenia/tratamento farmacológico , Sarcopenia/prevenção & controle , Sarcopenia/metabolismo , Hidrolisados de Proteína/farmacologia , Hidrolisados de Proteína/uso terapêutico , Músculo Esquelético/metabolismo , Qualidade de Vida , Proteínas Musculares/metabolismoRESUMO
Obesity-induced chronic inflammation has been linked to several autoimmune diseases, including rheumatoid arthritis, type 1 diabetes, and multiple sclerosis. The underlying mechanisms are not yet fully understood, but it is believed that chronic inflammation in adipose tissue can lead to the production of pro-inflammatory cytokines and chemokines, which can trigger immune responses and contribute to the development of autoimmune diseases. However, the underlying mechanisms that lead to the infiltration of immune cells into adipose tissue are not fully understood. In this study, we observed a time-dependent response to a high-fat diet in the liver and epididymal white adipose tissue using gene set enrichment analysis. Our findings revealed a correlation between early abnormal innate immune responses in the liver and late inflammatory response in the adipose tissue, that eventually leads to systemic inflammation. Specifically, our data suggest that the dysregulated NADH homeostasis in the mitochondrial matrix, interacting with the mitochondrial translation process, could serve as a sign marking the transition from liver inflammation to adipose tissue inflammation. Taken together, our study provides valuable insights into the molecular mechanisms underlying the development of chronic inflammation and associated autoimmune diseases in obesity.
Assuntos
Doenças Autoimunes , Dieta Hiperlipídica , Animais , Camundongos , Dieta Hiperlipídica/efeitos adversos , Fígado , Inflamação , Tecido Adiposo , ObesidadeRESUMO
The purpose of this study was to investigate the feasibility of the fluid-attenuated inversion recovery sequence with fat suppression (FLAIR-FS) for the assessment of ankle synovitis without contrast enhancement. FLAIR-FS and contrast-enhanced, T1-weighted sequences (CE-T1) of 94 ankles were retrospectively reviewed by two radiologists. Grading of synovial visibility (four-point scale) and semi-quantitative scoring of synovial thickness (three-point scale) were performed in four compartments of the ankle in both sequences. Synovial visibility and thickness in FLAIR-FS and CE-T1 images were compared, and agreement between both sequences was assessed. Synovial visibility grades and synovial thickness scores for FLAIR-FS images were lower than those for CE-T1 images (reader 1, p = 0.016, p < 0.001; reader 2, p = 0.009, p < 0.001). Dichotomized synovial visibility grades (partial vs. full visibility) were not significantly different between both sequences. The agreement in synovial thickness scores between the FLAIR-FS and CE-T1 images was moderate to substantial (κ = 0.41-0.65). The interobserver agreement between the two readers was fair for synovial visibility (κ = 0.27-0.32) and moderate to substantial for synovial thickness (κ = 0.54-0.74). In conclusion, FLAIR-FS is a feasible MRI sequence for the evaluation of ankle synovitis without contrast enhancement.
RESUMO
Metformin, an antidiabetic drug, and Glycyrrhiza uralensis Fischer (GU), an oriental medicinal herb, have been reported to exert anti-obesity effects. This study investigated the synergistic action of metformin and GU in improving diet-induced obesity. Mice were fed a normal diet, a high-fat diet (HFD), or HFD + 0.015% GU water extract for 8 weeks. The HFD and GU groups were then randomly divided into two groups and fed the following diets for the next 8 weeks: HFD with 50 mg/kg metformin (HFDM) and GU with 50 mg/kg metformin (GUM). GUM prevented hepatic steatosis and adiposity by suppressing expression of mRNAs and enzyme activities related to lipogenesis in the liver and upregulating the expression of adipocyte mRNAs associated with fatty acid oxidation and lipolysis, and as a result, improved dyslipidemia. Moreover, GUM improved glucose homeostasis by inducing glucose uptake in tissues and upregulating mRNA expressions associated with glycolysis in the liver and muscle through AMP-activated protein kinase activation. GUM also improved inflammation by increasing antioxidant activity in the liver and erythrocytes and decreasing inflammatory cytokine productions. Here, we demonstrate that GU and metformin exert synergistic action in the prevention of obesity and its complications.
Assuntos
Glycyrrhiza uralensis , Doenças Metabólicas , Metformina , Animais , Camundongos , Metformina/efeitos adversos , Obesidade/tratamento farmacológico , Obesidade/etiologia , Obesidade/metabolismo , Fígado/metabolismo , Doenças Metabólicas/metabolismo , Dieta Hiperlipídica/efeitos adversos , Camundongos Endogâmicos C57BLRESUMO
SCOPE: Although sarcopenia is mainly caused by aging, sarcopenia due to obesity has become an emerging issue given the increase in obesity among people of various ages. There are studies on obesity or sarcopenia, our understanding of obesity-mediated sarcopenia is insufficient. Luteolin (LU) has exhibited antiobesity effects, but no studies have investigated the LU effects on antisarcopenia. This study therefore investigated the effects of LU on obese sarcopenia in mice with high-fat diet (HFD)-induced obesity. METHODS AND RESULTS: To evaluate its inhibitory efficacy against obese sarcopenia, 5-week-old mice are fed an HFD supplemented with LU for 20 weeks. LU exerts suppressive effects on obesity, inflammation, and protein degradation in the HFD-fed obese mice. It also inhibits lipid infiltration into the muscle and decreases p38 activity and the mRNA expression of inflammatory factors, including TNF-α, Tlr2, Tlr4, MCP1, and MMP2, in the muscle. The suppression of muscle inflammation by LU leads to the inhibition of myostatin, FoxO, atrogin, and MuRF expression. These effects of LU affect inhibition of protein degradation and improvement of muscle function. CONCLUSION: Here, it demonstrates that LU's antiobesity and antiinflammatory functionality affect inhibition of muscle protein degradation, and consequently, these interactions by LU exerts a protective effect against obese sarcopenia.
Assuntos
Resistência à Insulina , Sarcopenia , Animais , Camundongos , Sarcopenia/tratamento farmacológico , Sarcopenia/etiologia , Sarcopenia/prevenção & controle , Luteolina/farmacologia , Luteolina/metabolismo , Proteólise , Dieta Hiperlipídica/efeitos adversos , Obesidade/etiologia , Inflamação/tratamento farmacológico , Inflamação/etiologia , Músculo Esquelético/metabolismo , Camundongos Endogâmicos C57BL , Camundongos ObesosRESUMO
d/Deaf or hard of hearing (d/Dhh) students with autism spectrum disorder (ASD) may require specific approaches to promote social inclusion. The purpose of this study was to investigate the effects of reading social stories with American Sign Language vocabulary to students who are d/Dhh with ASD (d/Dhh-ASD) and their peers in inclusive settings, using a non-concurrent multiple baseline design across participants. To examine the effectiveness of the intervention, the frequency of four communicative social behaviors and the duration of social engagement with peers were recorded for each participant during lunchtime and recess. The results did not show an immediate effect across all participants. Implications for promoting social inclusion for students who are d/Dhh-ASD in general education classrooms are discussed.
Assuntos
Transtorno do Espectro Autista , Surdez , Perda Auditiva , Pessoas com Deficiência Auditiva , Humanos , Interação Social , EstudantesRESUMO
The ATP-binding cassette subfamily 4 (ABCA4), a transporter, is localized within the photoreceptors of the retina, and its genetic variants cause retinal dystrophy. Despite the clinical importance of the ABCA4 transporter, a few studies have investigated the function of each variant. In this study, we functionally characterized ABCA4 variants found in Korean patients with Stargardt disease or variants of the ABCA4 promoter region. We observed that four missense variants-p.Arg290Gln, p.Thr1117Ala, p.Cys1140Trp, and p.Asn1588Tyr-significantly decreased ABCA4 expression on the plasma membrane, which could be due to intracellular degradation. There are four major haplotypes in the ABCA4 proximal promoter. We observed that the H1 haplotype (c.-761C>A) indicated significantly increased luciferase activity compared to that of the wild-type, whereas the H3 haplotype (c.-1086A>C) indicated significantly decreased luciferase activity (P < 0.01 and 0.001, respectively). In addition, c.-900A>T in the H2 haplotype exhibited significantly increased luciferase activity compared with that of the wild-type. Two transcription factors, GATA-2 and HLF, were found to function as enhancers of ABCA4 transcription. Our findings suggest that ABCA4 variants in patients with Stargardt disease affect ABCA4 expression. Furthermore, common variants of the ABCA4 proximal promoter alter the ABCA4 transcriptional activity, which is regulated by GATA-2 and HLF transcription factors.
Assuntos
Transportadores de Cassetes de Ligação de ATP , Doença de Stargardt , Humanos , Transportadores de Cassetes de Ligação de ATP/genética , Mutação de Sentido Incorreto , Retina/patologia , Distrofias Retinianas/genética , Doença de Stargardt/genéticaRESUMO
Artemisiae argyi is a well-known traditional herbal medicine used in East Asia. Although the antibacterial and anti-inflammatory effects of A. argyi have been reported, its efficacy in improving obesity has not been yet evaluated. In this study, mice were fed a normal diet (AIN-93), a high-fat diet (HFD, 60% of kcal from fat), and an HFD with 0.1% of A. argyi water extract for 16 weeks. The body weight and body fat in A. argyi-fed mice significantly decreased via upregulation of the mRNA expression of fatty acid oxidation-related genes, with a simultaneous decrease in plasma lipid content and leptin levels. A. argyi water extract also ameliorated hepatic steatosis by restricting lipogenesis via lowering the activities of fatty acid synthase and phosphatidic acid phosphatase. Consistently, hepatic histological analysis indicated that A. argyi water extract decreased hepatic lipid accumulation in accordance with the hepatic H, E and Oil Red O-stained area. Additionally, A. argyi ameliorated the impaired glucose homeostasis by increasing the mRNA expression of AMP-activated kinase and glycolysis-related genes. In conclusion, our results indicate that A. argyi can be used to treat obesity-related metabolic conditions.
RESUMO
Annually, marine phytoplankton convert approximately 50 billion tons of dissolved inorganic carbon to particulate and dissolved organic carbon, a portion of which is exported to depth via the biological carbon pump. Despite its important roles in regulating atmospheric carbon dioxide via carbon sequestration and in sustaining marine ecosystems, model-projected future changes in marine net primary production are highly uncertain even in the sign of the change. Here, using an Earth system model, we show that frugal utilization of phosphorus by phytoplankton under phosphate-stressed conditions can overcompensate the previously projected 21st century declines due to ocean warming and enhanced stratification. Our results, which are supported by observations from the Hawaii Ocean Time-series program, suggest that nutrient uptake plasticity in the subtropical ocean plays a key role in sustaining phytoplankton productivity and carbon export production in a warmer world.
RESUMO
The enhanced seasonal amplitude of atmospheric CO2 has been viewed so far primarily as a Northern Hemisphere phenomenon. Yet, analyses of atmospheric CO2 records from 49 stations between 1980 and 2018 reveal substantial trends and variations in this amplitude globally. While no significant trends can be discerned before 2000 in most places, strong positive trends emerge after 2000 in the southern high latitudes. Using factorial simulations with an atmospheric transport model and analyses of surface ocean Pco2 observations, we show that the increase is best explained by the onset of increasing seasonality of air-sea CO2 exchange over the Southern Ocean around 2000. Underlying these changes is the long-term ocean acidification trend that tends to enhance the seasonality of the air-sea fluxes, but this trend is modified by the decadal variability of the Southern Ocean carbon sink. The seasonal variations of atmospheric CO2 thus emerge as a sensitive recorder of the variations of the Southern Ocean carbon sink.
RESUMO
Obesity is characterized by excessive body fat accumulation due to unbalanced energy intake and expenditure. Potential therapeutic targets for anti-obesity include the inhibition of white adipose tissue (WAT) hypertrophy and hyperplasia and the activation of brown adipose tissue (BAT). Not only the activation of BAT but also the browning of WAT have gained increasing attention in research fields as an alternative method in the prevention and treatment of obesity. Here, we investigated possible mechanisms underlying the anti-obesity effect of Phlomis umbrosa Turcz. root ethanol extract (PUE) in an obesogenic animal model. PUE treatment can reduce diet-induced obesity and modulate obesity-associated metabolic disorders, including insulin resistance, hepatic steatosis, and inflammation. In the liver, PUE improved hepatic steatosis by suppressing hepatic lipogenesis and lipid absorption while increasing biliary sterol excretion and hepatic fatty acid oxidation compared to the high-fat group. Moreover, PUE increased energy expenditure and regulated fecal lipid excretion, leading to reduced body weight gain. In particular, PUE remarkably activated the browning of subWAT via upregulation of the browning-related protein and gene expression and promoted BAT activation. In conclusion, these findings provide the potential therapeutic usefulness into the effects of PUE in the treatment of obesity and metabolic disorders. Furthermore, it suggests that PUE treatment can regulate energy metabolism via activating BAT and browning subWAT.