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Shih-torng Ding - One of the best experts on this subject based on the ideXlab platform.

  • Adiponectin and Adiponectin Receptor 1 overexpression enhance inflammatory bowel disease
    Journal of Biomedical Science, 2018
    Co-Authors: Yuju Peng, Harry J Mersmann, Tanglong Shen, Yushan Chen, Binghsien Liu, Shih-torng Ding
    Abstract:

    Adiponectin (ADN) is an adipokine derived from adipocytes. It binds to Adiponectin Receptor 1 and 2 (AdipoR1 and R2) to exert its function in regulating whole-body energy homeostasis and inflammatory responses. However, the role of ADN-AdipoR1 signaling in intestinal inflammation is controversial, and its role in the regulation of neutrophils is still unclear. Our goal was to clarify the role of AdipoR1 signaling in colitis and the effects on neutrophils. We generated porcine AdipoR1 transgenic mice (pAdipoR1 mice) and induced murine colitis using dextran sulfate sodium (DSS) to study the potential role of AdipoR1 in inflammatory bowel disease. We also treated a THP-1 macrophage and a HT-29 colon epithelial cell line with ADN recombinant protein to study the effects of ADN on inflammation. After inducing murine colitis, pAdipoR1 mice developed more severe symptoms than wild-type (WT) mice. Treatment with ADN increased the expression of pro-inflammatory factors in THP-1 and HT-29 cells. Moreover, we also observed that the expression of cyclooxygenase2 (cox2), neutrophil chemokines (CXCL1, CXCL2 and CXCL5), and the infiltration of neutrophils were increased in the colon of pAdipoR1 mice. Our study showed that ADN-AdipoR1 signaling exacerbated colonic inflammation through two possible mechanisms. First, ADN-AdipoR1 signaling increased pro-inflammatory factors. Second, AdipoR1 enhanced neutrophil chemokine expression and recruited neutrophils into the colonic tissue to increase inflammation.

  • Adiponectin Receptor 1 resists the decline of serum osteocalcin and GPRC6A expression in ovariectomized mice.
    PloS one, 2017
    Co-Authors: Yuan-yu Lin, Ching-yi Chen, Shih-torng Ding
    Abstract:

    Hormonal changes that cause metabolic complications are a common problem in postmenopausal women. Adiponectin and osteocalcin are cytokines associated with glucose regulatory and insulin sensitized function in postmenopausal stages. The current study investigated the role of Adiponectin signaling and osteocalcin mediated function in glucose metabolism in ovariectomized mice. In a mouse menopausal-related metabolic disorder model, overexpression of Adiponectin Receptor 1 improved glucose tolerance and caused resistance to body weight increase and decline of serum osteocalcin. Furthermore, Adiponectin Receptor 1 transgenic ovariectomized mice had higher GPRC6A (the putative osteocalcin Receptor) expression in muscle tissue. Immunofluorescence indicated that GPRC6A and Adiponectin Receptor 1 were co-localized in mouse muscle tissues. The present finding suggested Adiponectin Receptor 1 can mediate the improvement of glucose metabolism by osteocalcin in ovariectomized mice. Our findings imply the possibility to ameliorate menopause-induced metabolic disorder by GPRC6A and Adiponectin signaling.

  • Adiponectin Receptor 1 regulates bone formation and osteoblast differentiation by gsk 3β β catenin signaling in mice
    Bone, 2014
    Co-Authors: Yuan-yu Lin, Ching-yi Chen, Tai Yuan Chuang, Yun Lin, Hui Yu Liu, Harry J Mersmann, Shih-torng Ding
    Abstract:

    Adiponectin and its Receptors are expressed in bone marrow-derived osteoblasts. Previous studies in vivo and in vitro have produced controversial results. The purpose of this study was to use porcine Adiponectin Receptor 1 transgenic mice (pAdipoR1) as a model to evaluate the role of AdipoR1 on bone physiology at different ages. pAdipoR1 transgenic mice had higher bone mineral density than wild-type mice in both genders at 56 weeks of age. The bone volume and trabecular number, measured by micro-computed tomography (μCT) was significantly greater in transgenic than in wild-type female mice at both 8 and 56 weeks of age. ELISA analysis revealed that both serum osteocalcin and osteoprotegerin (OPG) were significantly increased in 8-week old pAdipoR1 transgenic mice of both genders. Furthermore, serum OPG was elevated at 32 and 56 weeks of age in female and male pAdipoR1 transgenic mice. Serum TRAP5b concentration was reduced in 8 and 56 weeks old male pAdipoR1 mice compared with wild-type male mice. Knock-down of AdipoR1 significantly decreased gene expression of osteocalcin, OPG, alkaline phosphatase and msh homeobox 2 and the mineralization in MC3T3-E1 cells and mesenchymal stem cells. In addition, pathscan analysis and real-time PCR analysis suggest AdipoR1 regulates osteoblast differentiation through GSK-3 β and β-Catenin signaling. Consequently, the lack of AdipoR1 impaired osteoblast differentiation and bone formation. We conclude that AdipoR1 is a critical factor for the osteoblast differentiation and bone homeostasis.

  • Adiponectin Receptor 1 mediates regulation of bone formation and osteoblast differentiation by gsk 3β β catenin signaling 1027 1
    The FASEB Journal, 2014
    Co-Authors: Yuan-yu Lin, Ching-yi Chen, Harry J Mersmann, Shih-torng Ding
    Abstract:

    The purpose of this study was to evaluate the role of Adiponectin Receptor 1 (adipoR1) on bone physiology using porcine AdipoR1 transgenic mice (pAdipoR1) as a model. We found that pAdipoR1 transgenic mice have higher bone mineral density than wild-type mice in older ages. The percent bone volume and trabecular number determined by micro-CT, was also significantly higher in pAdipoR1 transgenic mice than in wild-type female mice at both young and older ages. ELISA analysis revealed that serum osteocalcin (Oc) and osteoprotegrin (OPG) were significantly increased in young pAdipoR1 transgenic mice in both genders. Furthermore, serum OPG also elevated at 8 week and 32 week in female and male pAdipoR1 transgenic mice at young and old ages. Serum TRAP5b concentration was reduced in male pAdipoR1 mice compared with wild-type mice. Knock-down AdipoR1 significantly decreased the gene expression of Oc, OPG, alkaline phosphatase and msh homeobox 2 and mineralization in MC3T3-E1 and mesenchymal stem cells, suggesting...

  • Adiponectin Receptor 1 enhances fatty acid metabolism and cell survival in palmitate treated hepg2 cells through the pi3 k akt pathway
    European Journal of Nutrition, 2014
    Co-Authors: Ipin Chou, Yuan-yu Lin, Shih-torng Ding, Ching-yi Chen
    Abstract:

    Hepatic lipid overloading induces lipotoxicity which can cause hepatocyte damage, fibrosis, and eventually progress to cirrhosis, which is associated with nonalcoholic fatty liver disease. Adiponectin Receptors play important roles in regulating lipid metabolism. In this study, we used a lentivirus system to overexpress the Adiponectin Receptor 1 (AdipoR1) in HepG2 cells to define the role of Adiponectin and its Receptor 1 in the development of fatty liver syndrome. Exposure of human hepatocytes, HepG2 cells, to palmitate (0.2 or 0.4 mM) for 16 h resulted in elevated apoptosis, whereas AdipoR1 decreased the palmitate-induced apoptosis. Transgene AdipoR1 increased the expression of FATP2, acyl-coA oxidase, and carnitine palmitoyltransferase I in palmitate-treated HepG2 cells. The transcript level of acetyl-CoA carboxylase and fatty acid synthase was upregulated by palmitate treatment, while AdipoR1 reversed the effect induced by palmitate. AdipoR1 increased the gene expression of cytochrome C oxidase, peroxisome proliferator-activated Receptor α, and decreased the gene expression of PGC1α and AMPKα in HepG2 cells under palmitate treatment. Palmitate suppressed ATP production, while transgene AdipoR1 reversed the decreased ATP production by palmitate. Transgene AdipoR1 enhanced AKT phosphorylation in HepG2 cells both with and without palmitate treatment. When PI3 kinase inhibitor was applied, the protective effect of AdipoR1 was absent, such that palmitate again decreased ATP production while also reducing cell viability. AdipoR1 enhances fatty acid metabolism and cell viability in palmitate-treated HepG2 cells partially by activating AKT signaling. Therefore, AdipoR1 has therapeutic potential in the treatment of nonalcoholic fatty liver disease.

Bo Chang - One of the best experts on this subject based on the ideXlab platform.

  • Corrigendum: Adiponectin Receptor 1 conserves docosahexaenoic acid and promotes photoReceptor cell survival.
    Nature communications, 2015
    Co-Authors: Dennis S Rice, Jorgelina M Calandria, William C Gordon, Bokkyoo Jun, Yongdong Zhou, C M Gelfman, Minghao Jin, Eric J Knott, Bo Chang
    Abstract:

    Corrigendum: Adiponectin Receptor 1 conserves docosahexaenoic acid and promotes photoReceptor cell survival

  • Adiponectin Receptor 1 conserves docosahexaenoic acid and promotes photoReceptor cell survival
    Nature Communications, 2015
    Co-Authors: Dennis S Rice, Jorgelina M Calandria, William C Gordon, Bokkyoo Jun, Yongdong Zhou, C M Gelfman, Minghao Jin, Eric J Knott, Bo Chang
    Abstract:

    Docosahexaenoic acid is a major and important retinal fatty acid that is recruited and retained in the photoReceptor membrane via an unknown mechanism. Here, Rice et al. show that Adiponectin Receptor 1 is a key molecular switch for docosahexaenoic acid membrane homeostasis and photoReceptor cell function.

  • Adiponectin Receptor 1 conserves docosahexaenoic acid and promotes photoReceptor cell survival
    Nature Communications, 2015
    Co-Authors: Dennis S Rice, Jorgelina M Calandria, William C Gordon, Bokkyoo Jun, Yongdong Zhou, C M Gelfman, Minghao Jin, Eric J Knott, Bo Chang, Alex Abuin
    Abstract:

    The identification of pathways necessary for photoReceptor and retinal pigment epithelium (RPE) function is critical to uncover therapies for blindness. Here we report the discovery of Adiponectin Receptor 1 (AdipoR1) as a regulator of these cells' functions. Docosahexaenoic acid (DHA) is avidly retained in photoReceptors, while mechanisms controlling DHA uptake and retention are unknown. Thus, we demonstrate that AdipoR1 ablation results in DHA reduction. In situ hybridization reveals photoReceptor and RPE cell AdipoR1 expression, blunted in AdipoR1(-/-) mice. We also find decreased photoReceptor-specific phosphatidylcholine containing very long-chain polyunsaturated fatty acids and severely attenuated electroretinograms. These changes precede progressive photoReceptor degeneration in AdipoR1(-/-) mice. RPE-rich eyecup cultures from AdipoR1(-/-) reveal impaired DHA uptake. AdipoR1 overexpression in RPE cells enhances DHA uptake, whereas AdipoR1 silencing has the opposite effect. These results establish AdipoR1 as a regulatory switch of DHA uptake, retention, conservation and elongation in photoReceptors and RPE, thus preserving photoReceptor cell integrity.

Dennis S Rice - One of the best experts on this subject based on the ideXlab platform.

  • Corrigendum: Adiponectin Receptor 1 conserves docosahexaenoic acid and promotes photoReceptor cell survival.
    Nature communications, 2015
    Co-Authors: Dennis S Rice, Jorgelina M Calandria, William C Gordon, Bokkyoo Jun, Yongdong Zhou, C M Gelfman, Minghao Jin, Eric J Knott, Bo Chang
    Abstract:

    Corrigendum: Adiponectin Receptor 1 conserves docosahexaenoic acid and promotes photoReceptor cell survival

  • Adiponectin Receptor 1 conserves docosahexaenoic acid and promotes photoReceptor cell survival
    Nature Communications, 2015
    Co-Authors: Dennis S Rice, Jorgelina M Calandria, William C Gordon, Bokkyoo Jun, Yongdong Zhou, C M Gelfman, Minghao Jin, Eric J Knott, Bo Chang
    Abstract:

    Docosahexaenoic acid is a major and important retinal fatty acid that is recruited and retained in the photoReceptor membrane via an unknown mechanism. Here, Rice et al. show that Adiponectin Receptor 1 is a key molecular switch for docosahexaenoic acid membrane homeostasis and photoReceptor cell function.

  • Adiponectin Receptor 1 conserves docosahexaenoic acid and promotes photoReceptor cell survival
    Nature Communications, 2015
    Co-Authors: Dennis S Rice, Jorgelina M Calandria, William C Gordon, Bokkyoo Jun, Yongdong Zhou, C M Gelfman, Minghao Jin, Eric J Knott, Bo Chang, Alex Abuin
    Abstract:

    The identification of pathways necessary for photoReceptor and retinal pigment epithelium (RPE) function is critical to uncover therapies for blindness. Here we report the discovery of Adiponectin Receptor 1 (AdipoR1) as a regulator of these cells' functions. Docosahexaenoic acid (DHA) is avidly retained in photoReceptors, while mechanisms controlling DHA uptake and retention are unknown. Thus, we demonstrate that AdipoR1 ablation results in DHA reduction. In situ hybridization reveals photoReceptor and RPE cell AdipoR1 expression, blunted in AdipoR1(-/-) mice. We also find decreased photoReceptor-specific phosphatidylcholine containing very long-chain polyunsaturated fatty acids and severely attenuated electroretinograms. These changes precede progressive photoReceptor degeneration in AdipoR1(-/-) mice. RPE-rich eyecup cultures from AdipoR1(-/-) reveal impaired DHA uptake. AdipoR1 overexpression in RPE cells enhances DHA uptake, whereas AdipoR1 silencing has the opposite effect. These results establish AdipoR1 as a regulatory switch of DHA uptake, retention, conservation and elongation in photoReceptors and RPE, thus preserving photoReceptor cell integrity.

Yuan-yu Lin - One of the best experts on this subject based on the ideXlab platform.

  • Adiponectin Receptor 1 resists the decline of serum osteocalcin and GPRC6A expression in ovariectomized mice.
    PloS one, 2017
    Co-Authors: Yuan-yu Lin, Ching-yi Chen, Shih-torng Ding
    Abstract:

    Hormonal changes that cause metabolic complications are a common problem in postmenopausal women. Adiponectin and osteocalcin are cytokines associated with glucose regulatory and insulin sensitized function in postmenopausal stages. The current study investigated the role of Adiponectin signaling and osteocalcin mediated function in glucose metabolism in ovariectomized mice. In a mouse menopausal-related metabolic disorder model, overexpression of Adiponectin Receptor 1 improved glucose tolerance and caused resistance to body weight increase and decline of serum osteocalcin. Furthermore, Adiponectin Receptor 1 transgenic ovariectomized mice had higher GPRC6A (the putative osteocalcin Receptor) expression in muscle tissue. Immunofluorescence indicated that GPRC6A and Adiponectin Receptor 1 were co-localized in mouse muscle tissues. The present finding suggested Adiponectin Receptor 1 can mediate the improvement of glucose metabolism by osteocalcin in ovariectomized mice. Our findings imply the possibility to ameliorate menopause-induced metabolic disorder by GPRC6A and Adiponectin signaling.

  • Adiponectin Receptor 1 regulates bone formation and osteoblast differentiation by gsk 3β β catenin signaling in mice
    Bone, 2014
    Co-Authors: Yuan-yu Lin, Ching-yi Chen, Tai Yuan Chuang, Yun Lin, Hui Yu Liu, Harry J Mersmann, Shih-torng Ding
    Abstract:

    Adiponectin and its Receptors are expressed in bone marrow-derived osteoblasts. Previous studies in vivo and in vitro have produced controversial results. The purpose of this study was to use porcine Adiponectin Receptor 1 transgenic mice (pAdipoR1) as a model to evaluate the role of AdipoR1 on bone physiology at different ages. pAdipoR1 transgenic mice had higher bone mineral density than wild-type mice in both genders at 56 weeks of age. The bone volume and trabecular number, measured by micro-computed tomography (μCT) was significantly greater in transgenic than in wild-type female mice at both 8 and 56 weeks of age. ELISA analysis revealed that both serum osteocalcin and osteoprotegerin (OPG) were significantly increased in 8-week old pAdipoR1 transgenic mice of both genders. Furthermore, serum OPG was elevated at 32 and 56 weeks of age in female and male pAdipoR1 transgenic mice. Serum TRAP5b concentration was reduced in 8 and 56 weeks old male pAdipoR1 mice compared with wild-type male mice. Knock-down of AdipoR1 significantly decreased gene expression of osteocalcin, OPG, alkaline phosphatase and msh homeobox 2 and the mineralization in MC3T3-E1 cells and mesenchymal stem cells. In addition, pathscan analysis and real-time PCR analysis suggest AdipoR1 regulates osteoblast differentiation through GSK-3 β and β-Catenin signaling. Consequently, the lack of AdipoR1 impaired osteoblast differentiation and bone formation. We conclude that AdipoR1 is a critical factor for the osteoblast differentiation and bone homeostasis.

  • Adiponectin Receptor 1 mediates regulation of bone formation and osteoblast differentiation by gsk 3β β catenin signaling 1027 1
    The FASEB Journal, 2014
    Co-Authors: Yuan-yu Lin, Ching-yi Chen, Harry J Mersmann, Shih-torng Ding
    Abstract:

    The purpose of this study was to evaluate the role of Adiponectin Receptor 1 (adipoR1) on bone physiology using porcine AdipoR1 transgenic mice (pAdipoR1) as a model. We found that pAdipoR1 transgenic mice have higher bone mineral density than wild-type mice in older ages. The percent bone volume and trabecular number determined by micro-CT, was also significantly higher in pAdipoR1 transgenic mice than in wild-type female mice at both young and older ages. ELISA analysis revealed that serum osteocalcin (Oc) and osteoprotegrin (OPG) were significantly increased in young pAdipoR1 transgenic mice in both genders. Furthermore, serum OPG also elevated at 8 week and 32 week in female and male pAdipoR1 transgenic mice at young and old ages. Serum TRAP5b concentration was reduced in male pAdipoR1 mice compared with wild-type mice. Knock-down AdipoR1 significantly decreased the gene expression of Oc, OPG, alkaline phosphatase and msh homeobox 2 and mineralization in MC3T3-E1 and mesenchymal stem cells, suggesting...

  • Adiponectin Receptor 1 enhances fatty acid metabolism and cell survival in palmitate treated hepg2 cells through the pi3 k akt pathway
    European Journal of Nutrition, 2014
    Co-Authors: Ipin Chou, Yuan-yu Lin, Shih-torng Ding, Ching-yi Chen
    Abstract:

    Hepatic lipid overloading induces lipotoxicity which can cause hepatocyte damage, fibrosis, and eventually progress to cirrhosis, which is associated with nonalcoholic fatty liver disease. Adiponectin Receptors play important roles in regulating lipid metabolism. In this study, we used a lentivirus system to overexpress the Adiponectin Receptor 1 (AdipoR1) in HepG2 cells to define the role of Adiponectin and its Receptor 1 in the development of fatty liver syndrome. Exposure of human hepatocytes, HepG2 cells, to palmitate (0.2 or 0.4 mM) for 16 h resulted in elevated apoptosis, whereas AdipoR1 decreased the palmitate-induced apoptosis. Transgene AdipoR1 increased the expression of FATP2, acyl-coA oxidase, and carnitine palmitoyltransferase I in palmitate-treated HepG2 cells. The transcript level of acetyl-CoA carboxylase and fatty acid synthase was upregulated by palmitate treatment, while AdipoR1 reversed the effect induced by palmitate. AdipoR1 increased the gene expression of cytochrome C oxidase, peroxisome proliferator-activated Receptor α, and decreased the gene expression of PGC1α and AMPKα in HepG2 cells under palmitate treatment. Palmitate suppressed ATP production, while transgene AdipoR1 reversed the decreased ATP production by palmitate. Transgene AdipoR1 enhanced AKT phosphorylation in HepG2 cells both with and without palmitate treatment. When PI3 kinase inhibitor was applied, the protective effect of AdipoR1 was absent, such that palmitate again decreased ATP production while also reducing cell viability. AdipoR1 enhances fatty acid metabolism and cell viability in palmitate-treated HepG2 cells partially by activating AKT signaling. Therefore, AdipoR1 has therapeutic potential in the treatment of nonalcoholic fatty liver disease.

  • modulation of glucose and lipid metabolism by porcine Adiponectin Receptor 1 transgenic mesenchymal stromal cells in diet induced obese mice
    Cytotherapy, 2013
    Co-Authors: Yuan-yu Lin, Ching-yi Chen, Yun Lin, Harry J Mersmann, Binghsien Liu, Chihchien Chen, Yao Pang Chiu, Shih-torng Ding
    Abstract:

    Abstract Background aims Obesity and its associated diseases demand better therapeutic strategies. Regenerative medicine combined with gene therapy has emerged as a promising approach in various clinical applications. Adiponectin (ApN) and its Receptors have been demonstrated to play beneficial roles in modulating glucose and lipid homeostasis. In the current study, we tested such an approach by transplanting mesenchymal stromal cells (MSCs) from porcine ApN Receptor (pAdipoR) 1-transgenic mice into high-fat/sucrose diet (HFSD)-fed mice. Methods Twenty 6-week-old Friend virus B/NJNarl male mice were randomly assigned into four groups with the control fed a chow diet (chow) and others HFSD for 10 months. The HFSD groups were then intraperitoneally injected once per week for 8 weeks with placebo (200 μL phosphate-buffered saline), wild-type MSC (WT-MSC, 2 × 10 6 cells/200 μL phosphate-buffered saline) or pAdipoR1-transgenic MSC (pR1-tMSC, 2 × 10 6 cells/200 μL phosphate-buffered saline), respectively. Body weights, blood samples, tissue histology, and gene expression and protein levels of metabolism-associated genes were analyzed. Results Both WT-MSC and pR1-tMSC transplantations restored the messenger RNA expression of AdipoR1, with those of glucose transporter 4 and 5′-adenosine monophosphate-activated protein kinase catalytic subunit α-1 and protein levels of pyruvate kinase induced by pR1-tMSC in the muscles of HFSD-fed mice. In the liver, both WT-MSC and pR1-tMSC ameliorated HFSD-induced hepatosteatosis, with the gene expression of lipoprotein lipase and hormone-sensitive lipase upregulated by the latter. Lastly, pR1-tMSC transplantation reduced fatty acid synthase mRNA levels in the adipose tissues of HFSD-fed mice. Conclusions This study demonstrates the modulatory actions of MSC and pR1-tMSC on genes associated with glucose and lipid metabolism and provides insights into its therapeutic application for obesity-associated metabolic complication.

Ching-yi Chen - One of the best experts on this subject based on the ideXlab platform.

  • Adiponectin Receptor 1 resists the decline of serum osteocalcin and GPRC6A expression in ovariectomized mice.
    PloS one, 2017
    Co-Authors: Yuan-yu Lin, Ching-yi Chen, Shih-torng Ding
    Abstract:

    Hormonal changes that cause metabolic complications are a common problem in postmenopausal women. Adiponectin and osteocalcin are cytokines associated with glucose regulatory and insulin sensitized function in postmenopausal stages. The current study investigated the role of Adiponectin signaling and osteocalcin mediated function in glucose metabolism in ovariectomized mice. In a mouse menopausal-related metabolic disorder model, overexpression of Adiponectin Receptor 1 improved glucose tolerance and caused resistance to body weight increase and decline of serum osteocalcin. Furthermore, Adiponectin Receptor 1 transgenic ovariectomized mice had higher GPRC6A (the putative osteocalcin Receptor) expression in muscle tissue. Immunofluorescence indicated that GPRC6A and Adiponectin Receptor 1 were co-localized in mouse muscle tissues. The present finding suggested Adiponectin Receptor 1 can mediate the improvement of glucose metabolism by osteocalcin in ovariectomized mice. Our findings imply the possibility to ameliorate menopause-induced metabolic disorder by GPRC6A and Adiponectin signaling.

  • Adiponectin Receptor 1 regulates bone formation and osteoblast differentiation by gsk 3β β catenin signaling in mice
    Bone, 2014
    Co-Authors: Yuan-yu Lin, Ching-yi Chen, Tai Yuan Chuang, Yun Lin, Hui Yu Liu, Harry J Mersmann, Shih-torng Ding
    Abstract:

    Adiponectin and its Receptors are expressed in bone marrow-derived osteoblasts. Previous studies in vivo and in vitro have produced controversial results. The purpose of this study was to use porcine Adiponectin Receptor 1 transgenic mice (pAdipoR1) as a model to evaluate the role of AdipoR1 on bone physiology at different ages. pAdipoR1 transgenic mice had higher bone mineral density than wild-type mice in both genders at 56 weeks of age. The bone volume and trabecular number, measured by micro-computed tomography (μCT) was significantly greater in transgenic than in wild-type female mice at both 8 and 56 weeks of age. ELISA analysis revealed that both serum osteocalcin and osteoprotegerin (OPG) were significantly increased in 8-week old pAdipoR1 transgenic mice of both genders. Furthermore, serum OPG was elevated at 32 and 56 weeks of age in female and male pAdipoR1 transgenic mice. Serum TRAP5b concentration was reduced in 8 and 56 weeks old male pAdipoR1 mice compared with wild-type male mice. Knock-down of AdipoR1 significantly decreased gene expression of osteocalcin, OPG, alkaline phosphatase and msh homeobox 2 and the mineralization in MC3T3-E1 cells and mesenchymal stem cells. In addition, pathscan analysis and real-time PCR analysis suggest AdipoR1 regulates osteoblast differentiation through GSK-3 β and β-Catenin signaling. Consequently, the lack of AdipoR1 impaired osteoblast differentiation and bone formation. We conclude that AdipoR1 is a critical factor for the osteoblast differentiation and bone homeostasis.

  • Adiponectin Receptor 1 mediates regulation of bone formation and osteoblast differentiation by gsk 3β β catenin signaling 1027 1
    The FASEB Journal, 2014
    Co-Authors: Yuan-yu Lin, Ching-yi Chen, Harry J Mersmann, Shih-torng Ding
    Abstract:

    The purpose of this study was to evaluate the role of Adiponectin Receptor 1 (adipoR1) on bone physiology using porcine AdipoR1 transgenic mice (pAdipoR1) as a model. We found that pAdipoR1 transgenic mice have higher bone mineral density than wild-type mice in older ages. The percent bone volume and trabecular number determined by micro-CT, was also significantly higher in pAdipoR1 transgenic mice than in wild-type female mice at both young and older ages. ELISA analysis revealed that serum osteocalcin (Oc) and osteoprotegrin (OPG) were significantly increased in young pAdipoR1 transgenic mice in both genders. Furthermore, serum OPG also elevated at 8 week and 32 week in female and male pAdipoR1 transgenic mice at young and old ages. Serum TRAP5b concentration was reduced in male pAdipoR1 mice compared with wild-type mice. Knock-down AdipoR1 significantly decreased the gene expression of Oc, OPG, alkaline phosphatase and msh homeobox 2 and mineralization in MC3T3-E1 and mesenchymal stem cells, suggesting...

  • Adiponectin Receptor 1 enhances fatty acid metabolism and cell survival in palmitate treated hepg2 cells through the pi3 k akt pathway
    European Journal of Nutrition, 2014
    Co-Authors: Ipin Chou, Yuan-yu Lin, Shih-torng Ding, Ching-yi Chen
    Abstract:

    Hepatic lipid overloading induces lipotoxicity which can cause hepatocyte damage, fibrosis, and eventually progress to cirrhosis, which is associated with nonalcoholic fatty liver disease. Adiponectin Receptors play important roles in regulating lipid metabolism. In this study, we used a lentivirus system to overexpress the Adiponectin Receptor 1 (AdipoR1) in HepG2 cells to define the role of Adiponectin and its Receptor 1 in the development of fatty liver syndrome. Exposure of human hepatocytes, HepG2 cells, to palmitate (0.2 or 0.4 mM) for 16 h resulted in elevated apoptosis, whereas AdipoR1 decreased the palmitate-induced apoptosis. Transgene AdipoR1 increased the expression of FATP2, acyl-coA oxidase, and carnitine palmitoyltransferase I in palmitate-treated HepG2 cells. The transcript level of acetyl-CoA carboxylase and fatty acid synthase was upregulated by palmitate treatment, while AdipoR1 reversed the effect induced by palmitate. AdipoR1 increased the gene expression of cytochrome C oxidase, peroxisome proliferator-activated Receptor α, and decreased the gene expression of PGC1α and AMPKα in HepG2 cells under palmitate treatment. Palmitate suppressed ATP production, while transgene AdipoR1 reversed the decreased ATP production by palmitate. Transgene AdipoR1 enhanced AKT phosphorylation in HepG2 cells both with and without palmitate treatment. When PI3 kinase inhibitor was applied, the protective effect of AdipoR1 was absent, such that palmitate again decreased ATP production while also reducing cell viability. AdipoR1 enhances fatty acid metabolism and cell viability in palmitate-treated HepG2 cells partially by activating AKT signaling. Therefore, AdipoR1 has therapeutic potential in the treatment of nonalcoholic fatty liver disease.

  • modulation of glucose and lipid metabolism by porcine Adiponectin Receptor 1 transgenic mesenchymal stromal cells in diet induced obese mice
    Cytotherapy, 2013
    Co-Authors: Yuan-yu Lin, Ching-yi Chen, Yun Lin, Harry J Mersmann, Binghsien Liu, Chihchien Chen, Yao Pang Chiu, Shih-torng Ding
    Abstract:

    Abstract Background aims Obesity and its associated diseases demand better therapeutic strategies. Regenerative medicine combined with gene therapy has emerged as a promising approach in various clinical applications. Adiponectin (ApN) and its Receptors have been demonstrated to play beneficial roles in modulating glucose and lipid homeostasis. In the current study, we tested such an approach by transplanting mesenchymal stromal cells (MSCs) from porcine ApN Receptor (pAdipoR) 1-transgenic mice into high-fat/sucrose diet (HFSD)-fed mice. Methods Twenty 6-week-old Friend virus B/NJNarl male mice were randomly assigned into four groups with the control fed a chow diet (chow) and others HFSD for 10 months. The HFSD groups were then intraperitoneally injected once per week for 8 weeks with placebo (200 μL phosphate-buffered saline), wild-type MSC (WT-MSC, 2 × 10 6 cells/200 μL phosphate-buffered saline) or pAdipoR1-transgenic MSC (pR1-tMSC, 2 × 10 6 cells/200 μL phosphate-buffered saline), respectively. Body weights, blood samples, tissue histology, and gene expression and protein levels of metabolism-associated genes were analyzed. Results Both WT-MSC and pR1-tMSC transplantations restored the messenger RNA expression of AdipoR1, with those of glucose transporter 4 and 5′-adenosine monophosphate-activated protein kinase catalytic subunit α-1 and protein levels of pyruvate kinase induced by pR1-tMSC in the muscles of HFSD-fed mice. In the liver, both WT-MSC and pR1-tMSC ameliorated HFSD-induced hepatosteatosis, with the gene expression of lipoprotein lipase and hormone-sensitive lipase upregulated by the latter. Lastly, pR1-tMSC transplantation reduced fatty acid synthase mRNA levels in the adipose tissues of HFSD-fed mice. Conclusions This study demonstrates the modulatory actions of MSC and pR1-tMSC on genes associated with glucose and lipid metabolism and provides insights into its therapeutic application for obesity-associated metabolic complication.