• Title/Summary/Keyword: insulin signaling

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Comparison of transcriptome between high- and low-marbling fineness in longissimus thoracis muscle of Korean cattle

  • Beak, Seok-Hyeon;Baik, Myunggi
    • Animal Bioscience
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    • v.35 no.2
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    • pp.196-203
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    • 2022
  • Objective: This study compared differentially expressed genes (DEGs) between groups with high and low numbers of fine marbling particles (NFMP) in the longissimus thoracis muscle (LT) of Korean cattle to understand the molecular events associated with fine marbling particle formation. Methods: The size and distribution of marbling particles in the LT were assessed with a computer image analysis method. Based on the NFMP, 10 LT samples were selected and assigned to either high- (n = 5) or low- (n = 5) NFMP groups. Using RNA sequencing, LT transcriptomic profiles were compared between the high- and low-NFMP groups. DEGs were selected at p<0.05 and |fold change| >2 and subjected to functional annotation. Results: In total, 328 DEGs were identified, with 207 up-regulated and 121 down-regulated genes in the high-NFMP group. Pathway analysis of these DEGs revealed five significant (p<0.05) Kyoto encyclopedia of genes and genomes pathways; the significant terms included endocytosis (p = 0.023), protein processing in endoplasmic reticulum (p = 0.019), and adipocytokine signaling pathway (p = 0.024), which are thought to regulate adipocyte hypertrophy and hyperplasia. The expression of sirtuin4 (p<0.001) and insulin receptor substrate 2 (p = 0.043), which are associated with glucose uptake and adipocyte differentiation, was higher in the high-NFMP group than in the low-NFMP group. Conclusion: Transcriptome differences between the high- and low-NFMP groups suggest that pathways regulating adipocyte hyperplasia and hypertrophy are involved in the marbling fineness of the LT.

Cell-cell contacts via N-cadherin induce a regulatory renin secretory phenotype in As4.1 cells

  • Chang, Jai Won;Kim, Soohyun;Lee, Eun Young;Leem, Chae Hun;Kim, Suhn Hee;Park, Chun Sik
    • The Korean Journal of Physiology and Pharmacology
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    • v.26 no.6
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    • pp.479-499
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    • 2022
  • The lack of a clonal renin-secreting cell line has greatly hindered the investigation of the regulatory mechanisms of renin secretion at the cellular, biochemical, and molecular levels. In the present study, we investigated whether it was possible to induce phenotypic switching of the renin-expressing clonal cell line As4.1 from constitutive inactive renin secretion to regulated active renin secretion. When grown to postconfluence for at least two days in media containing fetal bovine serum or insulin-like growth factor-1, the formation of cell-cell contacts via N-cadherin triggered downstream cellular signaling cascades and activated smooth muscle-specific genes, culminating in phenotypic switching to a regulated active renin secretion phenotype, including responding to the key stimuli of active renin secretion. With the use of phenotype-switched As4.1 cells, we provide the first evidence that active renin secretion via exocytosis is regulated by phosphorylation/dephosphorylation of the 20 kDa myosin light chain. The molecular mechanism of phenotypic switching in As4.1 cells described here could serve as a working model for full phenotypic modulation of other secretory cell lines with incomplete phenotypes.

Exploring the quality standard of Phellinus spp through β-glucan content and sensory evaluation (β-glucan 함량과 관능검사를 통한 상황버섯 품질기준 모색)

  • Shin, Yong-Wook
    • The Korea Journal of Herbology
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    • v.32 no.4
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    • pp.47-52
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    • 2017
  • Objective : Phellinus spp. mushroom is an object of interest because it has excellent anticancer effect. Owing to the similalarities in the morphology, Phellinus linteus and Phellinus baumii are often used as same Sang Hwang Mushroom in the Korean market.. The quality control for mushrooms is needed because there are many differences in the efficacy according to cultivation method and cultivation area. Therefore, a reliable authentication method of these herbal medicine is necessary to compare and measure the amount of beta-glucan which is known to have a hypoglycemic effect, from the mushrooms collected in various regions Methods : 7 samples of medicinal mushrooms supplying phellinus spp. were collected in Korea, China and Cambodia. We investigated the hardness, colors, extract ratio, ${\alpha}-amylase$ and ${\alpha}-glucosidase$ inhibitory activities, glucose transporter 4 (GLUT-4) expressions of water extracts from Phellinus spp and also MTT assay were examined for cell toxicity. Results : The results revealed that Phellinus spp.water Ext.inhibited ${\alpha}-glucosidase$ activity. glucose transporter 4 (GLUT-4), the key insulin signaling pathway transcription factor, was remarkably increased by the Phellinus baumii water extract Conclusions : These results suggest that The more yellowish the mushroom is, the lower the hardness, the more the content of ${\beta}-glucan$ is proportional. Because the more ${\beta}-glucan$, the greater the effect of hypoglycemia. compared to the hypoglycemic effect, Phellinus Baumii grown at hanging on selves for 7 month in the green house is the best.

Bifidobacterium bifidum DS0908 and Bifidobacterium longum DS0950 Culture-Supernatants Ameliorate Obesity-Related Characteristics in Mice with High-Fat Diet-Induced Obesity

  • M. Shamim Rahman;Youri Lee;Doo-Sang Park;Yong-Sik Kim
    • Journal of Microbiology and Biotechnology
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    • v.33 no.1
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    • pp.96-105
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    • 2023
  • Probiotic supplements have promising therapeutic effects on chronic diseases. In this study, we demonstrated the anti-obesity effects of two potential probiotics, Bifidobacterium bifidum DS0908 (DS0908) and Bifidobacterium longum DS0950 (DS0950). Treatment with DS0908 and DS0950 postbiotics significantly induced the expression of the brown adipocyte-specific markers UCP1, PPARγ, PGC1α, PRDM16 and beige adipocyte-specific markers CD137, FGF21, P2RX5, and COX2 in C3H10T1/2 mesenchymal stem cells (MSCs). In mice with high-fat diet (HFD)-induced obesity, both potential probiotics and postbiotics noticeably reduced body weight and epididymal fat accumulation without affecting food intake. DS0908 and DS0950 also improved insulin sensitivity and glucose use in mice with HFD-induced obesity. In addition, DS0908 and DS0950 improved the plasma lipid profile, proved by reduced triglyceride, low-density lipoprotein, and cholesterol levels. Furthermore, DS0908 and DS0950 improved mitochondrial respiratory function, confirmed by the high expression of oxidative phosphorylation proteins, during thermogenesis induction in the visceral and epididymal fat in mice with HFD-induced obesity. Notably, the physiological and metabolic changes were more significant after treatment with potential probiotic culture-supernatants than those with the bacterial pellet. Finally, gene knockdown and co-treatment with inhibitor-mediated mechanistic analyses showed that both DS0908 and DS0950 exerted anti-obesity-related effects via the PKA/p38 MAPK signaling activation in C3H10T1/2 MSCs. Our observations suggest that DS0908 and DS0950 could potentially alleviate obesity as dietary supplements.

Dietary methionine supplementation to a low-protein diet improved hair follicle development of Angora rabbits

  • Man Zhao;Tongtong Wang;Bin Wang;Chuanhua Liu;Fuchang Li;Lei Liu
    • Animal Bioscience
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    • v.36 no.6
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    • pp.920-928
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    • 2023
  • Objective: Angora rabbits fed a low-protein diet exhibit decreased hair production performance. This study was set out to evaluate the effects of methionine on hair properties and nitrogen metabolism in Angora rabbits fed a low-protein diet and to investigate the gene expression related to hair follicle development to determine the possible molecular mechanism of methionine effects on hair follicle development. Methods: An experiment was conducted to investigate the effects of DL-methionine addition on a low-protein diet on hair development in Angora rabbits. Angora rabbits were divided into 5 groups: fed a normal diet (control), fed a low-protein diet (LP), or fed an LP supplemented with 0.2%, 0.4%, or 0.6% DL-methionine (Met). Results: The results showed that rabbits in the LP group had lower wool yield than the control rabbits, but the addition of 0.4% to 0.6% Met to LP attenuated these effects (p<0.05). Dietary addition of 0.4% to 0.6% Met to LP increased the apparent nitrogen digestibility, nitrogen utilization rate, and feed efficiency (p<0.05). Feeding LP decreased the insulin-like growth factor 1 (IGF1), keratin-associated protein (KAP) 3.1, and KAP 6.1 mRNA levels compared with the control, but the addition of 0.4% Met in LP attenuated these effects (p<0.05). Relative to the LP or control group, dietary addition of 0.4% Met increased versican mRNA levels. Conclusion: In conclusion, the addition of Met to LP could improves wool production performance and feed efficiency and reduce nitrogen emissions in Angora rabbits. Met can promote hair follicle development, which may be associated with IGF1, KAP, and the versican signaling.

Ginsenoside Rb3 ameliorates podocyte injury under hyperlipidemic conditions via PPARδ- or SIRT6-mediated suppression of inflammation and oxidative stress

  • Heeseung Oh;Wonjun Cho;Seung Yeon Park;A.M. Abd El-Aty;Ji Hoon Jeong;Tae Woo Jung
    • Journal of Ginseng Research
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    • v.47 no.3
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    • pp.400-407
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    • 2023
  • Background: Rb3 is a ginsenoside with anti-inflammatory properties in many cell types and has been reported to attenuate inflammation-related metabolic diseases such as insulin resistance, nonalcoholic fatty liver disease, and cardiovascular disease. However, the effect of Rb3 on podocyte apoptosis under hyperlipidemic conditions, which contributes to the development of obesity-mediated renal disease, remains unclear. In the current study, we aimed to investigate the effect of Rb3 on podocyte apoptosis in the presence of palmitate and explore its underlying molecular mechanisms. Methods: Human podocytes (CIHP-1 cells) were exposed to Rb3 in the presence of palmitate as a model of hyperlipidemia. Cell viability was assessed by MTT assay. The effects of Rb3 on the expression of various proteins were analyzed by Western blotting. Apoptosis levels were determined by MTT assay, caspase 3 activity assay, and cleaved caspase 3 expression. Results: We found that Rb3 treatment alleviated the impairment of cell viability and increased caspase 3 activity as well as inflammatory markers in palmitate-treated podocytes. Treatment with Rb3 dosedependently increased PPARδ and SIRT6 expression. Knockdown of PPARδ or SIRT6 reduced the effects of Rb3 on apoptosis as well as inflammation and oxidative stress in cultured podocytes. Conclusions: The current results suggest that Rb3 alleviates inflammation and oxidative stress via PPARδ-or SIRT6-mediated signaling, thereby attenuating apoptosis in podocytes in the presence of palmitate. The present study provides Rb3 as an effective strategy for treating obesity-mediated renal injury.

Hepatoprotective Effect of Lactiplantibacillus plantarum DSR330 in Mice with High Fat Diet-Induced Nonalcoholic Fatty Liver Disease

  • Na-Kyoung Lee;Yunjung Lee;Da-Soul Shin;Jehyeon Ra;Yong-Min Choi;Byung Hee Ryu;Jinhyeuk Lee;Eunju Park;Hyun-Dong Paik
    • Journal of Microbiology and Biotechnology
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    • v.34 no.2
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    • pp.399-406
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    • 2024
  • Lactiplantibacillus plantarum DSR330 (DSR330) has been examined for its antimicrobials production and probiotics. In this study, the hepatoprotective effects of DSR330 were examined against nonalcoholic fatty liver disease (NAFLD) in a high-fat diet (HFD)-fed C57BL/6 mouse model. To induce the development of fatty liver, a HFD was administered for five weeks, and then silymarin (positive control) or DSR330 (108 or 109 CFU/day) was administered along with the HFD for seven weeks. DSR330 significantly decreased body weight and altered serum and hepatic lipid profiles, including a reduction in triglyceride, total cholesterol, and low-density lipoprotein cholesterol levels compared to those in the HFD group. DSR330 significantly alleviated HFD-related hepatic injury by inducing morphological changes and reducing the levels of biomarkers, including AST, ALT, and ALP. Additionally, DSR330 alleviated the expression of SREBP-1c, ACC1, FAS, ACO, PPARα, and CPT-1 in liver cells. Insulin and leptin levels were decreased by DSR330 compared to those observed in the HFD group. However, adiponectin levels were increased, similar to those observed in the ND group. These results demonstrate that L. plantarum DSR330 inhibited HFD-induced hepatic steatosis in mice with NAFLD by modulating various signaling pathways. Hence, the use of probiotics can lead to hepatoprotective effects.

LPS-Induced Modifications in Macrophage Transcript and Secretion Profiles Are Linked to Muscle Wasting and Glucose Intolerance

  • Heeyeon Ryu;Hyeon Hak Jeong;Seungjun Lee;Min-Kyeong Lee;Myeong-Jin Kim;Bonggi Lee
    • Journal of Microbiology and Biotechnology
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    • v.34 no.2
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    • pp.270-279
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    • 2024
  • Macrophages are versatile immune cells that play crucial roles in tissue repair, immune defense, and the regulation of immune responses. In the context of skeletal muscle, they are vital for maintaining muscle homeostasis but macrophage-induced chronic inflammation can lead to muscle dysfunction, resulting in skeletal muscle atrophy characterized by reduced muscle mass and impaired insulin regulation and glucose uptake. Although the involvement of macrophage-secreted factors in inflammation-induced muscle atrophy is well-established, the precise intracellular signaling pathways and secretion factors affecting skeletal muscle homeostasis require further investigation. This study aimed to explore the regulation of macrophage-secreted factors and their impact on muscle atrophy and glucose metabolism. By employing RNA sequencing (RNA-seq) and proteome array, we uncovered that factors secreted by lipopolysaccharide (LPS)-stimulated macrophages upregulated markers of muscle atrophy and pro-inflammatory cytokines, while concurrently reducing glucose uptake in muscle cells. The RNA-seq analysis identified alterations in gene expression patterns associated with immune system pathways and nutrient metabolism. The utilization of gene ontology (GO) analysis and proteome array with macrophage-conditioned media revealed the involvement of macrophage-secreted cytokines and chemokines associated with muscle atrophy. These findings offer valuable insights into the regulatory mechanisms of macrophage-secreted factors and their contributions to muscle-related diseases.

Lysophosphatidic Acid Stimulates SKOV-3 Cell Migration through the Generation of Reactive Oxygen Species via the mTORC2/Akt1/NOX Signaling Axis (리소포스타티드산은 SKOV-3 난소암세포의 mTORC2/Akt1/NOX 신호전달 기전을 통해 활성산소를 형성하고 이를 통해 세포의 이동을 촉진)

  • Eun Kyoung Kim;Seo Yeon Jin;Jung Min Ha;Sun Sik Bae
    • Journal of Life Science
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    • v.33 no.2
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    • pp.129-137
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    • 2023
  • Reactive oxygen species (ROS) play an essential role in a variety of cellular physiological phenomena. The present study assessed the signaling axis that mediates the lysophosphatidic acid (LPA)-induced migration of SKOV-3 cells. Insulin-like growth factor-1 (IGF-1) stimulated SKOV-3 cell migration in a time- and dose-dependent manner. Similarly, LPA stimulated SKOV-3 cell migration and the phosphorylation of Akt in a time- and dose-dependent manner. The pharmacological inhibition of LPA receptors (LPA1/LPA3) significantly suppressed LPA-induced SKOV-3 cell migration. However, IGF-1-induced SKOV-3 cell migration was not affected by the inhibition of LPA1 and LPA3. Pharmacological inhibition of phosphoinositide 3-kinase (PI3K) or Rho-associated kinase (ROCK) significantly suppressed LPA-induced migration, whereas the inhibition of MAPK kinase (MEK) had no effect. Inhibition of PI3K or ROCK completely suppressed LPA-induced ROS generation, and suppression of nicotinamide adenine dinucleotide phosphate oxidase (NOX) or chelation of ROS by N-acetylcysteine (NAC) blocked LPA-induced SKOV-3 cell migration. LPA-induced ROS generation was suppressed by silencing Rictor or Akt1 but not Raptor or Akt2. Silencing Rictor or Akt1 significantly suppressed LPA-induced SKOV-3 cell migration, whereas silencing Raptor or Akt2 had no effect. Finally, the overexpression of the constitutively active form Akt1 (CA-Akt1) significantly enhanced the LPA-induced migration of SKOV-3 cells. Given these results, we suggest that LPA stimulates SKOV-3 cell migration by ROS generation, which is mediated by the mTORC2/Akt1/NOX signaling axis.

Triptolide Mimics the Effect of Dietary Restriction on Lifespan and Retards Age-related Diseases in Caenorhabditis elegans (트립톨라이드가 식이제한에 의한 수명연장과 노화관련 질환에 미치는 영향)

  • Beak, Sun-Mi;Park, Sang-Kyu
    • Journal of Life Science
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    • v.28 no.8
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    • pp.931-937
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    • 2018
  • Triptolide is a compound found in Tripterygium wilfordii and reported to have an anti-inflammatory and anti-oxidant activities. A previous study shows that the dietary supplementation with triptolide increases resistance to environmental stressors, including oxidative stress, heat shock, and ultraviolet irradiation, and extends lifespan in C. elegans. Here, we investigated the underlying mechanisms involved in the lifespan-extending effect of triptolide. The effect of triptolide on age-related diseases, such as diabetes mellitus and Alzheimer's disease, was also examined using animal disease models. The longevity phenotype conferred by triptolide was not observed in the eat-2 mutant, a well-known genetic model of dietary restriction, while there was an additional lifespan extension with triptolide in age-1 and clk-1 mutants. The long lifespan of age-1 mutant is resulted from a reduced insulin/IGF-1-like signaling and the clk-1 mutant lives longer than wild-type due to dysfunction of mitochondrial electron transport chain reaction. The effect of dietary restriction using bacterial dilution on lifespan also overlapped with that of triptolide. The toxicity of high glucose diet or transgenic human amyloid beta gene was significantly suppressed by the supplementation with triptolide. These findings suggest that triptolide can mimic the effect of dietary restriction on lifespan and onset of age-related diseases. We conclude that triptolide can be a strong candidate for the development of dietary restriction mimetics.