Characterized by UCP1 expression and abundant mitochondria, brown adipose tissue (BAT) plays a crucial role in energy balance by converting chemical energy into heat through the cost of ATP production. In this study, it was demonstrated that Trib3 is a critical determinant of BAT-mediated energy expenditure and whole-body energy homeostasis. Under 60% high-fat diet conditions, Trib3 expression in BAT was elevated. Mice deficient in Trib3 are resistant to diet-induced obesity and exhibit improved glucose homeostasis due to enhanced BAT activity. Furthermore, brown adipocyte progenitor cells (APCs) lacking Trib3 exhibited increased proliferation and promoted brown adipocyte differentiation and mitochondrial biogenesis, contributing to the increase in the maximal thermogenic capacity of BAT in Trib3-deficient mice. Mechanistically, it was discovered that Trib3 expression is upregulated by free fatty acids at the transcriptional level and synergistically upregulated by DAG-PKC at the posttranslational level. This occurs through the modulation of COP1-mediated Trib3 protein turnover. Interestingly, the level of Trib3 expression in BAT increased with age. Trib3 knockout mice were protected from aging-related weight gain and impaired glucose homeostasis. These results suggest that Trib3 acts as an obesity- and aging-associated factor that negatively regulates BAT activity and that the loss of Trib3 may provide a beneficial approach to prevent obesity and aging-associated metabolic syndrome by increasing the thermogenic capacity of BAT.

BACKGROUND/OBJECTIVES:Abeliophyllum distichum is a plant endemic to Korea, containing several beneficial natural compounds. This study investigated the effect of A. distichum leaf extract (ALE) on adipocyte differentiation.MATERIALS/METHODS:The cytotoxic effect of ALE was analyzed using cell viability assay. 3T3-L1 preadipocytes were differentiated using induction media in the presence or absence of ALE. Lipid accumulation was confirmed using Oil Red O staining. The mRNA expression of adipogenic markers was measured using RT-PCR, and the protein expressions of mitogen-activated protein kinase (MAPK) and peroxisome proliferator-activated receptor gamma (PPARγ) were measured using western blot. Cell proliferation was measured by calculating the incorporation of Bromodeoxyuridine (BrdU) into DNA.RESULTS:ALE reduced lipid accumulation in differentiated adipocytes, as indicated by Oil Red O staining and triglyceride assays. Treatment with ALE decreased the gene expression of adipogenic markers such as Pparγ, CCAAT/enhancer binding protein alpha (C/ebpα), lipoprotein lipase, adipocyte protein-2, acetyl-CoA carboxylase, and fatty acid synthase. Also, the protein expression of PPARγ was reduced by ALE. Treating the cells with ALE at different time points revealed that the inhibitory effect of ALE on adipogenesis is higher in the early period treatment than in the terminal period. Furthermore, ALE inhibited adipocyte differentiation by reducing the early phase of adipogenesis and mitotic clonal expansion. This was indicated by the lower number of cells in the Synthesis phase of the cell cycle (labeled using BrdU assay) and a decrease in the expression of early adipogenic transcription factors such as C/ebpβ and C/ebpδ. ALE suppressed the phosphorylation of MAPK, confirming that the effect of ALE was through the suppression of early phase of adipogenesis.CONCLUSIONS:Altogether, the results of the present study revealed that ALE inhibits lipid accumulation and may be a potential agent for managing obesity.

The use of natural compounds as anti-obesity agents has been gaining attention over the past few years. Abeliophyllum distichum Nakai is endemic to Korea. In the present study, an A. distichum leaf extract (AE) was analyzed for its anti-obesity effects in mice fed a high-fat diet. Seven-week-old male C57BL/6J mice were divided into five groups, namely, normal diet (ND), high-fat diet (HD), HD + Garcinia (GE300), HD + AE low dose (AE100), and HD + AE high dose (AE300). After 8 weeks of the experimental period, treatment with AE reduced body weight and ameliorated high-fat diet-induced changes in serum lipid levels. Histological analysis revealed that treatment with AE decreased lipid accumulation in the liver and brown adipose tissue. Also, AE reduced the adipocyte size in epididymal fat. The reduction in adipose tissue mass in the AE-treated groups was clearly visible in micro-computed tomography images. The expression levels of lipogenic genes, such as PPARγ, C/EBPα, ACC, and FAS, were significantly reduced in the AE300 group. The levels of p-AMPK and p-ACC were increased in the AE300 group compared to the HD group, indicating that the anti-obesity effect of AE was mediated through the AMPK pathway.

ëª©ì  본 연구는 ì €ë„자콜라겐과 천연ì”ìœë³µí•©ë¬¼ì„ 이용한 구강용해필름(이너뷰티필름)을 개발하여 in vitro 실험과 ì¸ì²´ì ìš©ì‹œí—˜ì„ 통하여 향장기능성을 ê²€ì¦í•˜ê³ ìž 한다. 방법 이너뷰티필름의 피ë€ì„¸í¬ì—ì„œì˜ ë ì„± 및 procollagen생성능, elastase 및 collagenase ì–µì œëŠ¥, DPPH 라디칼 소거능, tyrosinase ì–µì œëŠ¥ì„ ì¸¡ì •í•˜ì—¬ 시험관시험 및 ì¸ì²´ì ìš©ì‹œí—˜ì„ 통해 피ë€ê°œì„ 효과를 검증하였다. ê²°ê³¼ ì €ë„자콜라겐과 천연ì”ìœë³µí•©ë¬¼ì˜ 혼합에 의한 피ë€ì„¸í¬ë 성을 확인한 ê²°ê³¼ 1000 μg/mL까지 ë ì„±ì€ í™•ì¸í• ìˆ˜ 없었으며 ì£¼ë¦„ê°œì„ ì˜ 지표인 elastase는 125 μg/mL이상 농도에서 7.2%의 효과를 나타내었으며 collagenase는 31.3 μg/mL이상에서 16.3%의 ì–µì œ 효율을 나타내었다. 피ë€ì„¸í¬ë¥¼ 이용한 procollagen생성은 62.5 μg/mL이상일 때 음성대조군 대비 34%의 ìœ ì˜ì ì¸ 생성효과를 보였다. 항산화 활성은 250 μg/mL, 미백은 62.5 μg/mL이상 í•¨ìœ ë˜ì—ˆì„ 때 ìœ ì˜ì ì¸ 효과가 í™•ì¸ë˜ì—ˆê³ 6개월간 ì•ˆì •ì„±í™•ì¸ì—ì„œë„ 변형이나 색도변화는 없었다. ì¸ì²´ì ìš©ì‹œí—˜ì—ì„œë„ 이너뷰티필름의 사용 ì „ê³¼ 후의 ì£¼ë¦„ê°œì„ ì€ 최대 32.2%, ìƒ‰ì†Œìž¡í‹°ê°œì„ ì€ 32.5%, 모공수ì•ì€ 31.5% ê·¸ë¦¬ê³ í”¼ë€ì¹˜ë°€ë„의 ê°œì„ ì—ì„œ 12.8%의 ìœ ì˜ë¯¸í•œ 결과를 확인하였다. ê²°ë¡ ì €ë„자 콜라겐 및 천연ì”ìœë³µí•©ë¬¼ì´ í•¨ìœ ëœ 이너뷰티필름은 ì£¼ë¦„ê°œì„ , ìƒ‰ì†Œìž¡í‹°ê°œì„ , 모공수ì•, 피ë€ì¹˜ë°€ë„ê°œì„ 및 항산화, 미백에 효과가 있는 것으로 확인되어 먹는 화장품 및 식품으로 개발이 가능한 것으로 사료된다. 핵심용어: 이너뷰티필름, ì£¼ë¦„ê°œì„ , 미백, 기능성화장품, ì €ë„자콜라겐

Purpose: This study examined the immunological activity and optimized the mixture conditions of Sargassum horneri (S. horneri) extracts in vitro and in vivo models. Methods: S. horneri was extracted using three different methods: hot water extraction (HWE), 50% ethanol extraction (EE), and supercritical fluid extraction (SFE). Splenocyte proliferation and cytokine production (Interleukin-2 and Interferon-γ) were measured using a WST-1 assay and enzyme-linked immunosorbent assay, respectively. The levels of nitric oxide and T cell activation production were measured using a Griess assay and flow cytometry, respectively. The natural killer (NK) cell activity was determined using an EZ-LDH kit. Results: Among the three different types of extracts, HWE showed the highest levels of splenocyte proliferation and cytokine production in vitro. In the animal model, three different types of extracts were administrated for 14 days (once/day) at 50 and 100 mg/kg body weight. HWE and SFE showed a high level of splenocyte proliferation and cytokine production in the with and without mitogen-treated groups, whereas EE administration did not induce the splenocyte activation. When RAW264.7 macrophage cells were treated with different mixtures (HWE with 5, 10, 15, 20% of SFE) to determine the optimal mixture ratio of HWE and SFE, the levels of nitric oxide and cytokine production increased strongly in the HWE with 5% and 10% of SFE containing group. In the animal model, HWE with 5% and 10% of SFE mixture administration increased the levels of splenocyte proliferation, cytokine production, and activated CD4 + cell population significantly, with the highest level observed in the HWE with 5% of SFE group. Moreover, the NK cell activity was increased significantly in the HWE with 5% of SFE mixture-treated group compared to the control group. Conclusion: The optimal mixture condition of S. horneri with immune-enhancing activity is the HWE with 5% of SFE mixture. These results confirmed that the extracts of S. horneri and its mixtures are potential candidate materials for immune enhancement.

ëª©ì  본 연구는 천연추출복합물을 이용한 기능성 화장품 소재개발을 위한 íš¨ë ¥ì‹œí—˜ì„ 통해 ê²€ì¦í•˜ê³ ìž 한다. 방법 천연추출복합물의 ê°œë³„ì ì¸ elasterase ì–µì œëŠ¥, DPPH 라디칼 소거능, nitric oxide ì–µì œëŠ¥, tyrosinase ì–µì œëŠ¥, ROS 생성 ì–µì œëŠ¥ì„ ì¸¡ì •í•˜ì—¬ design of experiment (DOE)를 통한 ìµœì ì˜ 배합비를 ì°¾ê³ ìµœì¢ ë°°í•©ë¹„ì— 따른 효능을 확인 하였다. ê²°ê³¼ 천연추출복합물을 이용한 DOE는 각 천연물의 효능을 극대화 하여 ìµœì ì˜ 배합비를 예측했을 때 비타민나무열매:ë¸”ëž™ë² ë¦¬ìžŽ:약용들깨잎(0.25:0.7:0.05)의 배합비에서 ìµœì ì˜ 효능을 나타냈다. 도출된 배합비를 바탕으로 ì£¼ë¦„ê°œì„ ì˜ 지표인 elesterase ì–µì œ 효능을 확인하였을 때 음성대조군 대비 28% (500 μg/mL)의 ì–µì œ 효과를 나타내었다. 항산화 지표인 2,2-diphenyl-1-picrylhydrazyl (DPPH) 라디칼 소거능도 음성 대조군 대비 71.8% 의 활성 효능을 나타내었다. 또한 염증 모델인 RAW 264.7세포에 lipopolysaccharides (LPS) 로 ìœ ë„ëœ nitric oxide(NO)의 ì–µì œ 효능도 대조구 대비 87.1%의 활성을 ë‚˜íƒ€ë‚´ì—ˆê³ ë¯¸ë°± 지표인 tyrosinase ì–µì œ 효능도 대조군 대비 24.4%의 효과를 확인하였다. 활성 ì‚°ì†Œì¢ ì— 의한 세포 보호 효능을 알아 보기 위한 human dermal fibroblast (HDF) 세포에 hydrogen peroxide (H2O2)로 reactive oxygen species (ROS)를 ìœ ë„í•œ 모델에서도 ìœ ì˜ì ì¸ 활성 ì‚°ì†Œì¢ ì˜ ì–µì œ 효능을 나타내었다. ê²°ë¡ ë¹„íƒ€ë¯¼ë‚˜ë¬´ì—´ë§¤, ë¸”ëž™ë² ë¦¬ìžŽ, 약용들깨잎의 천연 추출 복합물은 ì£¼ë¦„ê°œì„ ê³¼ 항산화 항염과 미백에 효과가 있는 것으로 확인되어 기능성 화장품 소재로의 개발이 가능한 것으로 사료된다. 핵심용어: 비타민나무열매, ë¸”ëž™ë² ë¦¬ìžŽ, 약용들깨잎, ì£¼ë¦„ê°œì„ , 미백

Background/Aims: Obesity is a serious health risk factor strongly associated with insulin resistance and type 2 diabetes; however, the underlying mechanisms associating obesity with insulin resistance remain unknown. In this study, we explored the physiological role of Trib3 in regulating glucose metabolism in skeletal muscle tissues in a Trib3 transgenic mice model. Methods: Glucose metabolism in transgenic mice overexpressing Trib3 specifically in the skeletal muscle was examined by glucose/insulin tolerance test, metabolic cage studies, and glucose uptake assay. The effect of Trib3 overexpression on AKT phosphorylation and AKT protein turnover were assessed by RT-PCR and immunoblot analysis. Subcellular distribution of Trib3 and AKT1/2 was determined by microscopic analysis, co-immunoprecipitation experiments, and limited-detergent extraction of subcellular organelles. Ubiquitin assay was performed and ATG7 deficient cell line was employed to address the mechanisms of Trib3-dependent AKT protein homeostasis. Results: We found that Trib3 expression in skeletal muscle is elevated in obese conditions, and transgenic mice that overexpressed Trib3, specifically in skeletal muscle tissues, displayed impaired glucose homeostasis by suppressing insulin-stimulated glucose uptake. Disruption of insulin signaling in skeletal muscle Trib3 transgenic mice may occur due to the specific downregulation of AKT2 but not AKT1. Autophagy regulated AKT2 protein turnover, and Trib3 overexpression stimulated autophagic degradation of AKT2 by promoting AKT2 ubiquitination. Conclusion: Because diet-induced obesity upregulates Trib3 and downregulates AKT2 in skeletal muscle tissues, Trib3 may play a key role in establishing an association between obesity and insulin resistance by regulating AKT2 protein homeostasis.

본 연구에서는 모자반목 모자반과 갈조류인 괭생이 모자반의 3가지 서로 다른 추출물의 면역활성 가능성을 비교연구하기 위하여 RWA264.7 대식세포에 서로 다른 괭생이 모자반 추출물을 처리하여 $TNF-{\alpha}$ , IL-6 및 NO 분비능과 MAPK 신호전달경로 및 $NF-{\kappa}B$ 활성화 수준을 측정하였다. 괭생이 모자반 ...

Mammalian ghrelin is derived from stomach and regulates growth hormone release and appetite by modulating GHS-R (Growth hormone secretagogue receptor) activity. Zebrafish has been developed as a forward genetic screening model system and previous screening identified a number of genes involved in multiple signaling pathways. In this system, ghrelin has been identified and its function and regulation have been shown to be highly conserved to that of mammals. Here, we identified three isoforms of zGHS-R1 and one of zGHS-R2 (zGHS-R2a), and characterized their expression, regulation and function. Three isoforms of zGHS-R1, which we named zGHS-R1a, zGHS-R1b, and zGHS-R1c, are generated by alternative splicing. The expression of zGHS-R1 is highly enriched in brain, intestine tissue, and skin tissues. Compared to zGHS-R1, the expression pattern of zGHS-R2a is rather evenly distributed. A 15 day fasting elevated expression of zGHS-R1 and zGHS-R2 transcripts in anterior intestine tissues, but not in brain. Whereas zGHS-R1a, zGHS-R1c, and zGHS-R2a appear to be presented on the plasma membrane, the localization of zGHS-R1b seems to be restricted in the intracellular region. Treatment of ghrelin agonist, L692,585 or goldfish ghrelin peptides but not rat ghrelin, elevated intracellular Ca(2+) level and phosphorylation of ERK in HEK-293 cells expressing zGHS-R1a, but not zGHS-R1b, zGHS-R1c, or zGHS-R2a. It appears that besides core ghrelin peptide sequence of GS/TSF additional amino acids are required for the activation of zGHS-R1a, as rat ghrelin induces neither intracellular Ca(2+) mobilization nor ERK phosphrylation. These results suggest that ghrelin system in zebrafish is highly conserved to that of mammals, and thus is an ideal in vivo model for dissecting ghrelin system.

Mammalian ghrelin is a stomach-derived peptide that stimulates secretion of growth hormone and food intake. Zebrafish is an excellent model system for forward genetic studies, and many aspects of energy homeostasis characterized in mammals appear to be conserved in the zebrafish. In this study, we investigated the expression and regulation of zebrafish ghrelin by metabolic status. Quantitative RT-PCR revealed that zebrafish ghrelin is highly enriched in anterior gut associated tissues. Using in situ hybridization with adult zebrafish tissues, we found that zebrafish ghrelin mRNA was not expressed in intestine tissue, but rather in clusters of endocrine pancreas cells distinct from insulin-expressing islets. Fasting specifically upregulated pancreatic ghrelin but not brain ghrelin expression by 3- to 4-fold and refeeding restored ghrelin transcript to control levels seen in the fed group within 5 h. These results demonstrate that although ghrelin is expressed in a different site in zebrafish, it is responsive to metabolic state in a similar manner as mammalian ghrelin, suggesting a role in the regulation of feeding in teleosts, and thus validate the utility of zebrafish as a genetic model system for the analysis of the ghrelin system and energy homeostasis.