• Molecules and Cells
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• 제46권8호
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• pp.496-512
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• 2023

A fructose-enriched diet is thought to contribute to hepatic injury in developing non-alcoholic steatohepatitis (NASH). However, the cellular mechanism of fructose-induced hepatic damage remains poorly understood. This study aimed to determine whether fructose induces cell death in primary hepatocytes, and if so, to establish the underlying cellular mechanisms. Our results revealed that treatment with high fructose concentrations for 48 h induced mitochondria-mediated apoptotic death in mouse primary hepatocytes (MPHs). Endoplasmic reticulum stress responses were involved in fructose-induced death as the levels of phosho-eIF2α, phospho-C-Jun-N-terminal kinase (JNK), and C/EBP homologous protein (CHOP) increased, and a chemical chaperone tauroursodeoxycholic acid (TUDCA) prevented cell death. The impaired oxidation metabolism of fatty acids was also possibly involved in the fructose-induced toxicity as treatment with an AMP-activated kinase (AMPK) activator and a PPAR-α agonist significantly protected against fructose-induced death, while carnitine palmitoyl transferase I inhibitor exacerbated the toxicity. However, uric acid-mediated toxicity was not involved in fructose-induced death as uric acid was not toxic to MPHs, and the inhibition of xanthine oxidase (a key enzyme in uric acid synthesis) did not affect cell death. On the other hand, treatment with inhibitors of the nicotinamide adenine dinucleotide (NAD)⁺-consuming enzyme CD38 or CD38 gene knockdown significantly protected against fructose-induced toxicity in MPHs, and fructose treatment increased CD38 levels. These data suggest that CD38 upregulation plays a role in hepatic injury in the fructose-enriched diet-mediated NASH. Thus, CD38 inhibition may be a promising therapeutic strategy to prevent fructose-enriched diet-mediated NASH.

• Animal Bioscience
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• 제36권7호
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• pp.1101-1119
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• 2023

Objective: This study aimed to evaluate the physicochemical, metabolomic, and sensory qualities of Chikso and Hanwoo beef during 28 days of wet aging. Methods: Rump and loins from Hanwoo and Chikso were obtained and wet-aged for 28 days at 4℃. The samples were collected at 7-day interval (n = 3 for each period). Physicochemical qualities including pH, meat color, shear force value, and myofibrillar fragmentation index, metabolomic profiles, and sensory attributes (volatile organic compounds and relative taste intensities) were measured. Results: Chikso showed a significantly higher shear force value than Hanwoo on day 0; however, no differences between breeds were found after day 14, regardless of the cuts. Overall, Chikso had more abundant metabolites than Hanwoo, especially L-carnitine and tyrosine. Among the volatiles, the ketone ratio was higher in the Chikso rump than the Hanwoo rump; however, Chikso had fewer alcohols and aldehydes than Hanwoo. Chikso rump showed higher taste intensities than the Hanwoo rump on day 0, and sourness decreased in Chikso, but increased in the Hanwoo rump on day 14. Wet aging for 14 days intensified the taste of Chikso loin but reduced the umami intensity of Hanwoo loin. Conclusion: Chikso had different metabolomic and sensory characteristics compared to Hanwoo cattle, and 14 days of wet aging could improve its tenderness and flavor traits.

• Animal Bioscience
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• 제36권8호
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• pp.1199-1208
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• 2023

Objective: The purpose of this study was to perform a comparative analysis of metabolite levels in serum and milk obtained from cows fed on different concentrate to forage feed ratios. Methods: Eight lactating Holstein cows were divided into two groups: a high forage ratio diet (HF; 80% Italian ryegrass and 20% concentrate of daily intake of dry matter) group and a high concentrate diet (HC; 20% Italian ryegrass and 80% concentrate) group. Blood was collected from the jugular vein, and milk was sampled using a milking machine. Metabolite levels in serum and milk were estimated using proton nuclear magnetic resonance and subjected to qualitative and quantitative analyses performed using Chenomx 8.4. For statistical analysis, Student's t-test and multivariate analysis were performed using Metaboanalyst 4.0. Results: In the principal component analysis, a clear distinction between the two groups regarding milk metabolites while serum metabolites were shown in similar. In serum, 95 metabolites were identified, and 13 metabolites (include leucine, lactulose, glucose, betaine, etc.) showed significant differences between the two groups. In milk, 122 metabolites were identified, and 20 metabolites (include urea, carnitine, acetate, butyrate, arabinitol, etc.) showed significant differences. Conclusion: Our results show that different concentrate to forage feed ratios impact the metabolite levels in the serum and milk of lactating Holstein cows. A higher number of metabolites in milk, including those associated with milk fat synthesis and the presence of Escherichia coli in the rumen, differed between the two groups compared to that in the serum. The results of this study provide a useful insight into the metabolites associated with different concentrate to forge feed ratios in cows and may aid in the search for potential biomarkers for subacute ruminal acidosis.

• 한방재활의학과학회지
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• 제33권3호
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• pp.33-46
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• 2023

Objectives We investigated anti-obesity effects of Menthae Herba hydrosol in obese mice. Methods Animals were divided into four groups, and treatments were performed for 7 weeks. After the treatment, serum lipid profiles, weight and pathological morphology in liver, kidney, adipose tissue were measured. Also, hepatic protein and gene expression levels of lipid metabolism-related factors were analyzed. Results Body weight was decreased in P3% group. In P1% (group fed high-fat diet and 1% Menthae Herba hydrosol) and P3% (group fed high-fat diet and 3% Menthae Herba hydrosol) group, weight of white adipose tissue, serum levels of triglyceride and blood urea nitrogen were decreased, and weight of muscle was increased. Also, liver, kidney and epididymal adipocyte size were reduced in P1% and P3% group. Adenosine monophosphate-activated protein kinase was increased and sterol regulatory element binding protein-1c (SREBP-1c) was decreased in P3% group. mPeroxisome proliferator-activator receptor-γ, mMonocyte chemotactic protein-1 were decreased in P1% and P3% group. In P3% group, mSREBP-1c was decreased and mCarnitine palmitoyl transferase-1 was increased. And mUncoupling protein 1 in brown adipose tissue was increased. Conclusions These results suggest that Menthae Herba hydrosol has a worthy effect on anti-obesity.

• Journal of Nutrition and Health
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• 제56권6호
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• pp.641-654
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• 2023

Purpose: Sour cherry (Prunus cerasus L.) contains abounding phytochemicals, such as polyphenols and anthocyanins, and has antioxidative effects. Adenosine monophosphate-activated protein kinase (AMPK) is a crucial regulator in enhancing the lipid metabolism. This study hypothesized that the intake of sour cherry affects AMPK signaling. Therefore, this study examined whether sour cherry regulates AMPK to balance the hepatic lipid metabolism and exert ameliorating effects. Methods: Male C57BL/6J mice had obesity induced with a 45% fat diet. The mice were divided into four groups: control (CON), high-fat diet (HFD), low percentage sour cherry powder (LSC), and high percentage sour cherry powder (HSC). The mice in the sour cherry groups were fed 1% sour cherry or 5% sour cherry in their respective diets for 12 weeks. Results: The body weight, visceral fat weight, and lipid droplet size significantly decreased in the treatment groups. The serum and hepatic triglyceride and total cholesterol levels improved significantly in the HSC group. The low-density lipoprotein cholesterol levels were also reduced significantly, whereas the high-density lipoprotein cholesterol levels were increased significantly in both treatment groups. The sterol regulator binding protein-1c and fatty acid synthase expression levels as fatty acid synthesis-related enzymes were significantly lower in the treatment groups than in the high-fat diet group. Furthermore, the adipose triglyceride lipase and hormone-sensitive lipase expression levels as lipolytic enzyme activity and AMPK/acetyl-CoA carboxylase/carnitine palmitoyltransferase-1 as fatty acid β-oxidation-related pathway were upregulated significantly in both sour cherry groups. Conclusions: These results show that sour cherry intake improves hepatic lipid synthesis and chronic diseases by activating AMPK signaling. Therefore, this study suggests that phytochemical-rich sour cherry can be developed as a healthy functional food.

• Nutrition Research and Practice
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• 제17권6호
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• pp.1043-1055
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• 2023

BACKGROUND/OBJECTIVES: The fruit of Cydonia oblonga Miller (COM) is used traditionally in Mediterranean region medicine to prevent or treat obesity, but its mechanism of action is still unclear. Beyond a demonstrated anti-obesity effect, the fruit was tested for the mechanism of adipogenesis in 3T3-L1 preadipocytes. MATERIALS/METHODS: 3T3-L1 preadipocytes were cultured for 8 days with COM fruit extract (COME) at different concentrations (0-600 ㎍/mL) with adipocyte differentiation medium. The cell viability was measured using an MTT assay; triglyceride (TG) was stained with Oil Red O. The expression levels of the adipogenesis-related genes and protein expression were analyzed by reverse transcription polymerase chain reaction and Western blotting, respectively. RESULTS: COME inhibited intracellular TG accumulation during adipogenesis. A COME treatment in 3T3-L1 cells induced upregulation of the adenosine monophosphate-activated protein kinase (AMPK)α phosphorylation and downregulation of the adipogenic transcription factors, such as sterol regulatory element-binding protein 1c, peroxisome proliferator-activated receptor γ, and CCAAT/enhancer binding protein α. The COME treatment reduced the mRNA expression of fatty acyl synthetase, adenosine triphosphate-citrate lyase, adipocyte protein 2, and lipoprotein lipase. It increased the mRNA expression of hormone-sensitive lipase and carnitine palmitoyltransferase I in 3T3-L1 cells. CONCLUSIONS: COME inhibits adipogenesis via the AMPK signaling pathways. COME may be used to prevent and treat obesity.

• Nutrition Research and Practice
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• 제18권1호
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• pp.46-61
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• 2024

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.

• 한방비만학회지
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• 제24권1호
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• pp.13-24
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• 2024

Objectives: The objective of this study was to explore the anti-obesity effect of Cydonia oblonga Miller fruit extract (COME) and to compare its anti-obesity efficacy with Garcinia cambogia extract (GCE) in diet-induced obese mice. Methods: Five-week-old male C57BL/6 were allocated into four groups: control diet (CD), high-fat diet (HFD), HFD + 400 mg/kg body weight (BW)/day COME (H+C), or HFD + 400 mg/kg BW/day GCE (H+G) groups. COME or GCE was administered once a day by oral gavage for eight weeks. Body weight, body fat percentage, fat weight, and biochemical parameters in serum were measured. The expressions of transcription factors and their target genes in epididymal adipose tissues were analyzed by reverse transcription polymerase chain reaction. Results: COME reduced body weight, weight gain, body fat percentage, total white adipose tissue weight, adipocyte size, and serum levels of insulin and leptin in high-fat diet-induced obese C57BL/6 mice. COME suppressed the mRNA expressions of CCAAT/enhancer binding proteinα, peroxisome proliferator-activated receptorγ, sterol-regulatory element-binding protein-1c, fatty acid synthase, and adipocyte protein 2 and increased carnitine palmitoyl transferase 1 mRNA expression in epidydimal adipose tissues. The anti-obesity efficacy of COME was found to be similar to that of GCE at the same dose. However, COME more effectively decreased adipose tissue weights, epididymal adipocyte size, serum insulin and leptin compared to GCE. Conclusions: These results demonstrated that COME is not toxic and exhibits anti-obesity efficacy at a level similar to that of GCE, suggesting that COME may be applicable as an anti-obesity agent.

• Journal of Animal Science and Technology
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• 제66권3호
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• pp.614-629
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• 2024

Hanwoo beef is in high demand because of its unique flavor, freshness, and high-fat content. However, the longer rearing period required to enhance marbling in Hanwoo cattle has adverse environmental consequences, such as greenhouse gas emissions and overall rearing costs. To address consumer preferences for leaner and healthier meat, the Korean meat industry has recently introduced Hanwoo heifer meat as an alternative source, but its quality traits are still unclear. Nevertheless, there is a limited body of research exploring the impact of Hanwoo gender (steer, heifer, and cow) and their corresponding slaughter ages on meat quality traits. This study looked into how gender affected the physicochemical and qualitative features of Hanwoo striploin at their respective slaughter ages. Results revealed that cow striploin has higher levels of moisture (66.81%) and protein (20.76%), whereas it contains lower levels of fat (10.66%) and cholesterol (34.66 mg/100 g). Regarding the physicochemical properties, cow striploin exhibited significantly lower shear force, color indexes, and soluble collagen (p < 0.05). However, chondroitin (1.19%) and muscle fiber area (1,545.23 ㎛²) were significantly higher in steer striploin than in heifer and cow (p < 0.05). Cow striploin exhibited significantly higher levels of oleic acid, unsaturated fatty acids (UFAs), and monounsaturated fatty acids (MUFAs) while having lower levels of eicosadienoic acid and atherogenic index compared to the other two groups. Cows and heifers had higher concentrations of amino acid metabolites than striploin from steers. Furthermore, bioactive metabolites such as carnitine and carnosine content were found higher in cow and heifer respectively. Overall, Hanwoo cattle gender influences the qualitative attributes of striploin; nevertheless, compared to steer and heifer striploin, cow striploin is a relatively good source of protein, fatty acid content, and metabolites conducive to a healthy diet.

• 한국식품영양과학회지
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• 제36권4호
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• pp.405-410
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• 2007

본 연구에서는 우리나라 장려 품종인 청일뽕잎을 이용하여 고지방식이(열량의 37%를 지방으로 대체)를 급여한 C57BL/6 마우스의 지질 함량과 지질대사를 측정함으로써 뽕잎분말과 열수추출물의 지질 개선작용을 검증하고자 하였다. 4주령의 C57BL/6마우스(n=32)를 1주일간 적응시킨 후 정상식이를 급여한 정상군, 고지방을 급여한 고지방대조군(HF), 고지방-뽕잎분말군(HF-PML)과 고지방-뽕잎열수 추출물군(HF-WML)으로 나누어 6주간 사육하였다. 뽕잎은 사람의 섭취량을 고려하여 뽕잎 1%수준이 섭취되도록 분말(1g/100g diet)과 열수추출물(0.22g/100g diet)을 식이에 첨가 조제하여 급여하였다. 뽕잎분말과 열수추출물은 고지 방을 급여 한 마우스의 체중과 장기 무게에는 영향을 미치지 않았다. 뽕잎분말만 일일 식이섭취량과 에너지 섭취를 고지방 대조군에 비하여 감소시켰다 실험 6주 후 고지방 대조군의 혈장과 간조직 중의 콜레스테롤과 중성지질 함량이 정상군에 비하여 유의적으로 높았으나 뽕잎분말과 열수추출물 급여시 혈장과 간조직 중의 지질 함량이 유의적으로 개선되었고 총 콜레스테롤 함량에 대한 HDL-콜레스테롤 비는 정상 수준이었다(p<0.05). 뽕잎분말과 열수추출물은 변으로의 콜레스테롤과 중성지질 배설을 증가시켰다. 간조직 중의 fatty acid synthase, fatty acid ${\beta}-oxidation$과 carnitine palmitoyl transferase 활성은 고지방 대조군이 정상군에 비하여 유의적으로 낮았으나 뽕잎분말과 열수추출물은 이들 효소들의 활성을 증가시키는 것으로 나타났다(p<0.05). 이와 같이 고지방을 급여한 마우스에서 뽕잎분말과 열수추출물은 변으로의 지질 배설을 증가시키고 간조직의 지질대사 관련 효소 활성에 영향을 미침으로써 혈장과 간조직의 지질 함량을 개선하는데 효과적인 것으로 검증되었다.