Ubiquitin signaling regulates virtually all aspects of eukaryotic biology and dynamic processes in which protein substrates are modified by ubiquitin. To regulate these processes, deubiquitinating enzymes (DUBs) cleave ubiquitin or ubiquitin-like proteins from these substrates. DUBs have been implicated in the pathogenesis of cancer, leading to the development of increasing numbers of small-molecule DUB inhibitors. On the other hand, recent studies have focused on the function of DUBs in metabolic diseases such as obesity, diabetes, and fatty liver diseases. DUBs play a positive or negative role in the progression and development of metabolic diseases. Their involvement in cell pathology and regulation of major transcription factors in metabolic syndrome has been examined in vitro and in animal and human biopsies. UCH, USP7, and USP19 were linked to adipocyte differentiation, body weight gain, and insulin resistance in genetic or diet-induced obesity. CYLD, USP4, and USP18 were found to be closely associated with fatty liver diseases. In addition, these liver diseases were accompanied by body weight change in certain cases. Collectively, in this review, we discuss the current understanding of DUBs in metabolic diseases with a particular focus on obesity. We also provide basic knowledge and regulatory mechanisms of DUBs and suggest these enzymes as therapeutic targets for metabolic diseases.
Inae Jeong;Taesang Son;Sang-myeong Jun;Hyun-Jung Chung;Ok-Kyung Kim
Journal of Nutrition and Health
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v.56
no.5
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pp.469-482
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2023
Purpose: Obesity has emerged as a critical global public health concern as it is associated with and increases susceptibility to various diseases. This condition is characterized by the excessive enlargement of adipose tissue, primarily stemming from an inequity between energy intake and expenditure. The purpose of this study was to investigate the potential of sweet pumpkin powder in mitigating obesity and metabolic disorders in leptin-deficient obese (ob/ob) mice and to compare the effects of raw sweet pumpkin powder (HNSP01) and heat-treated sweet pumpkin powder (HNSP02). Methods: Leptin-deficient obese mice were fed a diet containing 10% HNSP01 and another containing 10% HNSP02 for 6 weeks. Results: The supplementation of ob/ob mice with HNSP01 and HNSP02 resulted in decreased body weight gain, reduced adipose tissue weight, and a smaller size of lipid droplets in the adipose tissue and liver. Furthermore, the ob/ob-HNSP01 and ob/ob-HNSP02 supplemented groups exhibited lower levels of triglycerides, total cholesterol, low-density lipoprotein cholesterol, fasting blood glucose, and insulin, as well as a reduced atherogenic index in comparison with the control group. Molecular analysis also demonstrated that the intake of HNSP01 and HNSP02 resulted in a diminished activation of factors associated with fatty acid synthesis, including acetyl-CoA carboxylase and fatty acid synthase, while concurrently enhancing factors associated with lipolysis, including adipose triglyceride lipase and hormone-sensitive lipase, in the adipose tissue. Conclusion: Taken together, these findings collectively demonstrate the potential of sweet pumpkin powder as a functional food ingredient with therapeutic properties against obesity and its associated metabolic disorders, such as insulin resistance and dyslipidemia.
Objective : This study aimed to categorize the lifestyles of older adults into two types - healthy and unhealthy, and use machine learning to identify the personal values that influence these lifestyles. Methods : This cross-sectional study targeting middle-aged and older adults (55 years and above) living in local communities in South Korea. Data were collected from 300 participants through online surveys. Lifestyle types were dichotomized by the Yonsei Lifestyle Profile (YLP)-Active, Balanced, Connected, and Diverse (ABCD) responses using latent profile analysis. Personal value information was collected using YLP-Values (YLP-V) and analyzed using machine learning to identify the relative importance of personal values on lifestyle types. Results : The lifestyle of older adults was categorized into healthy (48.87%) and unhealthy (51.13%). These two types showed the most significant difference in social relationship characteristics. Among the machine learning models used in this study, the support vector machine showed the highest classification performance, achieving 96% accuracy and 95% area under the receiver operating characteristic (ROC) curve. The model indicated that individuals who prioritized a healthy diet, sought health information, and engaged in hobbies or cultural activities were more likely to have a healthy lifestyle. Conclusion : This study suggests the need to encourage the expansion of social networks among older adults. Furthermore, it highlights the necessity to comprehensively intervene in individuals' perceptions and values that primarily influence lifestyle adherence.
In this study, we investigated the preventive and therapeutic effects of antler-extract for osteoporosis. Rats were ovariectomized bilaterally and were fed up with Ca- and P-free diet in order to induce osteoporosis. Body weight, organ weight, the weight of femur and bone ash quantity were examined for 5 weeks. We also performed histological and electronical microscopic examinations. 1. After adminstration of female and male antler extract to osteoporosis-induced rats at the doses of 625 and 1250 mg/kg, respectively, the body weights were significantly increased compared with those of normal control group's which was 230.2:t2.3-281.0:t2.5g (p<0.05). 2. The weights of both right and left femur of osteoporosis-induced rats, administered with female or male antler-extract, little decreased compared with those of normal control group. 3. The bone ash quanties of femur of osteoporosis-induced rats, administered with female or male antler-extract, little decreased compared with those of normal control group. 4. The weights of liver, spleen, and kidney of osteoporosis-induced rats, administered with female or male antler-extract, decreased compared with those of normal control group. 5. Histological and electronic microscopical findings were (1) that in normal control rats the connectional of lacunae appeared well and were without loss of bone mineral, (2) that in ovariectomized rats the connections of lacunae were mostly broken and were with loss of bone mineral compared with those of normal control rats, (3) that in osteoporosis-induced rats, administrated with female or male antler-extract, the shape of lacunae and the connections of them were similar to those of normal control rats. These findings suggest a possible protective and therapeutic effects of female or male antler extract against bone loss in ovariectomized rats.
Journal of the Korean Society of Food Science and Nutrition
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v.41
no.12
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pp.1708-1715
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2012
The purpose of this study was to investigate whether water extracts of Sparassis crispa (SC) have anti-obesity effects. Treatment of mature adipocytes with SC caused a decrease in lipid accumulation (assessed by Oil Red O staining) and an increase in glycerol release. Mice were induced to obesity by a high fat diet (45% fat in total kcal) and experimental groups were treated with two different dosages of SC extracts, a low SC (LSC, 100 mg/kg/day) or high SC (HSC, 300 mg/kg/day). SC extracts were administered by gavages for 10 weeks in the experimental groups, while the control group was fed with distilled water. The body weight gain of mice fed SC was significantly reduced (11.88% lower in LSC, 14.54% lower in HSC) compared to the control group. Additionally, there were significantly reduced serum levels of triglycerides (13.57% lower in LSC, 19.46% lower in HSC), total cholesterol (32.22% lower in LSC, 24.67% lower in HSC) and glucose (28.85% lower in LSC, 25.82% lower in HSC) in mice fed SC compared to the control group. Hepatic triglycerides in mice fed SC were lower (9.68% lower in LSC, 14.24% lower in HSC) than the control group and total cholesterol levels were also lower in mice fed SC (38.72% lower in LSC, 35.20% in HSC). These results demonstrate that the water extract of SC may enhance lipolysis and up-regulate the expression of lipolytic enzymes in vitro and reduce body weight in vivo. These significant effects were found for both low and high doses of SC treatment, and suggest SC can be used as potential therapeutic substances for the prevention and treatment of obesity.
Purpose : Phenylketonuria(PKU) is an inborn error of metabolism and a genetic disorder resulting from a deficiency of phenylalanine hydroxylase(PAH) and decreased activity of tetrahydrobiopterin(BH4).In this study the correlation between the DNA mutation and clinical manifestations was investigated and PAH DNA mutations were compared bewteen Asian and Caucasian populations. Methods : DNA was isolated from peripheral leukocytes. The PAH gene was amplified by Polymerase Chain Reaction(PCR) and the sequence was analyzed with Multiplex Ligation-dependent Probe Amplification(MLPA). Results : We characterized the PAH gene of 102 independent Korean patients with PKU. PAH nucleotide sequence analysis revealed 44 different mutations, including 10 novel mutations comprising 9 missense mutations(N207D, K95del, A447P, G344D, P69S, S391I, A202T, G103S, and I306L) and 1 novel splice-site variant mutation(IVS10-3C>G). R243Q was the most prevalent mutation in this study. A259T has not previously been reported in Asian populations, but we found that this mutation had a frequency of 10.1% in our study. Furthermore, the genotypes of $BH_4$ responsive patients were analyzed and were divided into two groups: $BH_4$ medication-only group and $BH_4$ medication with diet therapy group. In the $BH_4$ medication-only group and $BH_4$ medication with diet therapy group, R241C was the most common mutation. Conclusion : Novel mutations in the PAH gene of PKU patients are still being discovered. Additional information as to the frequency of mutations in the tetrahydrobiopterine responsive gene is also accumulating. We anticipate that knowledge of these PKU gene mutations will assist the diagnosis, genetic counseling, and therapeutic treatment of PKU patients in future.
Park, Jin Yeong;Kim, Wi-Sik;Kim, Heung Yun;Kim, Eunheui
Journal of fish pathology
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v.29
no.1
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pp.35-43
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2016
In comparison to the numbers of such studies of fish, few studies have been carried out on the immunity, physiology and ecology of abalone, while studies on abalone disease are also extremely rare. Moreover, mass mortality of cultured abalone due to pathogenic bacteria has not been reported in the southern coast of Korea. However, Vibrio-like bacteria have been isolated from dead abalone, which indicates that a review is required in order to determine the cause of abalone mortality. Use of an antimicrobial agent to minimize the damage caused by disease in abalone farms is common, but the therapeutic effects are insignificant. Demand for probiotics has increased, but research on the development of probiotics for use in abalone culture is very rare. Therefore, the present study isolated KC16-2 from fermented kimchi soup and investigated the characteristics of the isolate as a candidate probiotic bacterium in abalone. KC16-2 was identified as Bacillus amyloliquefaciens (B. amyloliquefaciens KC16-2) based on its biochemical properties and 16S rRNA gene sequence. B. amyloliquefaciens KC16-2 showed inhibitory effects against the growth of various vibrios in vitro, and kept the numbers constant until four days after inoculation in marine water at a temperature of $15{\sim}25^{\circ}C$, indicating the possible use of KC16-2 as a probiotic, except in the winter. The growth of KC16-2 was inhibited by bile salt, but the numbers increased over time suggesting the bacteria were still alive in the abalone's digestive tract. Abalone fed with a diet including KC16-2 for 12 weeks showed good growth, but showed no significant differences from the control group. However, the mortality of the abalone supplied the probiotic diet was reduced to half that of the control group in a challenge test with Vibrio tubiashii. Therefore, we suggest that B. amyloliquefaciens KC16-2 could be used as a probiotic bacterium for control of the mortality of abalone caused by opportunistic pathogenic vibrios.
Journal of agricultural medicine and community health
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v.30
no.1
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pp.15-28
/
2005
Objectives: The purpose of this cross-sectional study was aimed to investigate the status of bowel health behaviors, prevalence of constipation and risk factors related to self-reported constipation in high school students. Methods: The study subjects were 1,882 students of six high schools located in a metropolitan city, who were selected by the accidental sampling from June to August, 2002. We analyzed the data by frequency analysis, chi-square test, and multivariate logistic regression using SPSS ver. 10.0. Results: The result of this study were summarized as follows: 1. A prevalence rate of self-reported constipation was 25.2%. A rate in male students was 13.4% and in female students 36.5%. 2. In regard to therapeutic behavior, 52.1% of study student with change in bowel habit had not find particular counsellor, 38.9% of the student had counselling with parents. 16.3% of students in constipation group had taken laxative medicine for treating the constipation. 73.5% of the student in constipation group had suffered from anal pain during defecation, but 48.0% in normal group. 41.6% of the student in constipation group had a experience of rectal bleeding after defecation, but 23.7% in normal group. So constipation related symptoms distribution had showed statistically significant difference between two group. 3. From the multivariate analysis by self-reported method, the risk factors related to the constipation were sex(female), experience of diet for weight reduction, absence of the breakfast and intake of vegetable more than 3 times per weeks. Conclusions: we had reconfirmed that we should improve eating habits to prevent and treat the constipation in a result of this study. Intervention that is target to girl students, abstain from weight reduction diet, regularity of taking meals, intake more vegetables, stress management should be provided to prevent the constipation especially in Korean high school students. Further prospective designed study are needed to establish the causal-effect relationship between so many risk factors with constipation.
Nam, Da-Eun;Kim, Ok Kyung;Shim, Tae Jin;Kim, Ji Hoon;Lee, Jeongmin
Journal of the Korean Society of Food Science and Nutrition
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v.43
no.5
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pp.631-640
/
2014
The inhibitory effects of Boswellia serrata (BW) extracts on degenerative osteoarthritis were investigated in primary-cultured rat cartilage cells and a monosodium-iodoacetate (MIA)-induced osteoarthritis rat model. To identify the protective effects of BW extract against $H_2O_2$ ($800{\mu}M$, 2 hr) in vitro, cell survival was measured by MTT assay. Cell survival after $H_2O_2$ treatment was elevated by BW extract at a concentration of $20{\mu}g/mL$. In addition, BW extract treatment significantly reduced and normalized the productions of pro-inflammatory factors, nuclear transcription factor ${\kappa}B$, cyclooxygenase-2, tumor necrosis factor-${\alpha}$, and interleukin-6 at a concentration of $20{\mu}g/mL$. Treatment of chondrocytes with BW extract significantly reduced 5-lipoxygenase activity and production of prostaglandin E2, especially at a concentration of $10{\sim}20{\mu}g/mL$. For the in vivo animal study, osteoarthritis was induced by intra-articular injection of MIA into knee joints of rats. Consumption of a diet containing BW extract (100 and 200 mg/kg) for 35 days significantly inhibited the development and severity of osteoarthritis in rats. To determine the genetic expression of arthritic factors in articular cartilage, real-time PCR was applied to measure matrix metalloproteinases (MMP-3, MMP-9, and MMP-13), collagen type I, collagen type II, and aggrecan, and BW extract had protective effects at a concentration of 200 mg/kg. In conclusion, BW extract was able to inhibit articular cartilage degeneration by preventing extracellular matrix degradation and chondrocyte injury. One can consider that BW extract may be a potential therapeutic treatment for degenerative osteoarthritis.
The present study was carried out in order to investigate the effects of antler extract on hormone concentration, Ca, P and alkaline phosphatase (ALP) levels in ovariectomized rats. Rats were ovariectomized bilaterally and were fed up with Ca- and P-free diet in order to induce osteoporosis. Osteoporosis was determined by the extent of density of bone mineral and lowering the concentrations of serum Ca and P. Male or female antler extract were administrated for 5 weeks to elucidate the protective and therapeutic effects for osteoporosis. The serum concentrations of estradiol, progesterone, calcitonin, osteocalcin, Ca and P, and the activities of ALP of ovariectomized rats were examined for 5 weeks. 1. After administration of female or male antler extract to osteoporosis-induced rats at the doses of 625 mg/kg and 1,250 mg/kg, respectively, the levels of the serum estradiol of the ovariectomized rat significantly decreased from 40.50$\pm$3.34 pg/$m\ell$ to 20.80$\pm$1.86 pg/$m\ell$ for 5 weeks, the levels of serum estradiol were a signigicant lower than those of control group (49.50$\pm$2.70~50.80$\pm$3.l3 pg/$m\ell$). 2. After administration of female or male antler extract to osteoporosis-induced rats at the doses of 625 mg/kg and 1,250 mg/kg, respectively, the levels of serum progesterone were didn't show significant differences. 3. After administration of female or male antler extract to osteoporosis-induced rats at the doses of 625 mg/kg and 1,250 mg/kg, respectively, the levels of serum calcitonin were a little higher than those of control group (0.64$\pm$0.03 ~0.68$\pm$0.04 pg/$m\ell$). 4. After administration of female or male antler extract to osteoporosis-induced rats at the doses of 625 mg/kg and 1,250 mg/kg, respectively, the levels of serum osteocalcin were little higher than those of control groups (0.28$\pm$0.02~0.31$\pm$0.02 ng/$m\ell$). In addition, the levels of serum osteocalcin of female antler extract administered group were little higher than those of male antler extract administered group. 5. The levels of serum Ca and P in osteoporosisinduced rats, administered with male or female antler extract, were little higher than those of control group. However, the levels of serum Ca and P in ovariectomized rats were significantly higher than those of control group (p<0.05). 6. After administration of female or male antler extract to osteoporosis-induced rats, the activities of serum ALP increased compared with those of normal control group. There were significant differences between the serum ALP activities of FA 1,250 and 625 groups (p<0.05). These findings suggest a possible protective and therapeutic effects of female or male antler extract against bone loss in ovariectomized rats, associated with a significant increase of serum estradiol level.
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