Search Results

You are looking at 1 - 10 of 17 items for

  • Author: Jing Wang x
  • Refine by access: All content x
Clear All Modify Search
Kai Wang
Search for other papers by Kai Wang in
Google Scholar
PubMed
Close
and
Jing Zheng Clinical and Translational Research Center, Perinatal Research Laboratories, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 200040, China

Search for other papers by Jing Zheng in
Google Scholar
PubMed
Close

During normal pregnancy, dramatically increased placental blood flow is critical for fetal growth and survival as well as neonatal birth weights and survivability. This increased blood flow results from angiogenesis, vasodilatation, and vascular remodeling. Locally produced growth factors including fibroblast growth factor 2 (FGF2) and vascular endothelial growth factor A (VEGFA) are key regulators of placental endothelial functions including cell proliferation, migration, and vasodilatation. However, the precise signaling mechanisms underlying such regulation in fetoplacental endothelium are less well defined, specifically with regard to the interactions amongst protein kinases (PKs), protein phosphatase, and nitric oxide (NO). Recently, we and other researchers have obtained solid evidence showing that different signaling mechanisms participate in FGF2- and VEGFA-regulated fetoplacental endothelial cell proliferation and migration as well as NO production. This review will briefly summarize currently available data on signaling mediating fetoplacental angiogenesis with a specific emphasis on PKs, ERK1/2, AKT1, and p38 MAPK and protein phosphatases, PPP2 and PPP3.

Free access
Miao Hou Departments of, Child Health Care, General Surgery, Institute of Pediatric Research, Department of Public Health and Clinical Medicine, Nanjing Children's Hospital, Nanjing Medical University, 72 Guangzhou Road, Nanjing 210008, People's Republic of China

Search for other papers by Miao Hou in
Google Scholar
PubMed
Close
,
Chenlin Ji Departments of, Child Health Care, General Surgery, Institute of Pediatric Research, Department of Public Health and Clinical Medicine, Nanjing Children's Hospital, Nanjing Medical University, 72 Guangzhou Road, Nanjing 210008, People's Republic of China

Search for other papers by Chenlin Ji in
Google Scholar
PubMed
Close
,
Jing Wang Departments of, Child Health Care, General Surgery, Institute of Pediatric Research, Department of Public Health and Clinical Medicine, Nanjing Children's Hospital, Nanjing Medical University, 72 Guangzhou Road, Nanjing 210008, People's Republic of China

Search for other papers by Jing Wang in
Google Scholar
PubMed
Close
,
Yanhua Liu Departments of, Child Health Care, General Surgery, Institute of Pediatric Research, Department of Public Health and Clinical Medicine, Nanjing Children's Hospital, Nanjing Medical University, 72 Guangzhou Road, Nanjing 210008, People's Republic of China

Search for other papers by Yanhua Liu in
Google Scholar
PubMed
Close
,
Bin Sun Departments of, Child Health Care, General Surgery, Institute of Pediatric Research, Department of Public Health and Clinical Medicine, Nanjing Children's Hospital, Nanjing Medical University, 72 Guangzhou Road, Nanjing 210008, People's Republic of China

Search for other papers by Bin Sun in
Google Scholar
PubMed
Close
,
Mei Guo Departments of, Child Health Care, General Surgery, Institute of Pediatric Research, Department of Public Health and Clinical Medicine, Nanjing Children's Hospital, Nanjing Medical University, 72 Guangzhou Road, Nanjing 210008, People's Republic of China

Search for other papers by Mei Guo in
Google Scholar
PubMed
Close
,
Jonas Burén Departments of, Child Health Care, General Surgery, Institute of Pediatric Research, Department of Public Health and Clinical Medicine, Nanjing Children's Hospital, Nanjing Medical University, 72 Guangzhou Road, Nanjing 210008, People's Republic of China

Search for other papers by Jonas Burén in
Google Scholar
PubMed
Close
, and
Xiaonan Li Departments of, Child Health Care, General Surgery, Institute of Pediatric Research, Department of Public Health and Clinical Medicine, Nanjing Children's Hospital, Nanjing Medical University, 72 Guangzhou Road, Nanjing 210008, People's Republic of China
Departments of, Child Health Care, General Surgery, Institute of Pediatric Research, Department of Public Health and Clinical Medicine, Nanjing Children's Hospital, Nanjing Medical University, 72 Guangzhou Road, Nanjing 210008, People's Republic of China

Search for other papers by Xiaonan Li in
Google Scholar
PubMed
Close

Early life nutrition is important in the regulation of metabolism in adulthood. We studied the effects of different fatty acid composition diets on adiposity measures, glucose tolerance, and peripheral glucocorticoid (GC) metabolism in overfed neonatal rats. Rat litters were adjusted to a litter size of three (small litters (SLs)) or ten (normal litters (NLs)) on postnatal day 3 to induce overfeeding or normal feeding respectively. After weaning, SL and NL rats were fed a ω6 polyunsaturated fatty acid (PUFA) diet (14% calories as fat, soybean oil) or high-saturated fatty acid (high-fat; 31% calories as fat, lard) diet until postnatal week 16 respectively. SL rats were also divided into the third group fed a ω3 PUFA diet (14% calories as fat, fish oil). A high-fat diet induced earlier and/or more pronounced weight gain, hyperphagia, glucose intolerance, and hyperlipidemia in SL rats compared with NL rats. In addition, a high-fat diet increased 11β-hsd1 (Hsd11b1) mRNA expression and activity in the retroperitoneal adipose tissue of both litter groups compared with standard chow counterparts, whereas high-fat feeding increased hepatic 11β-hsd1 mRNA expression and activity only in SL rats. SL and a high-fat diet exhibited significant interactions in both retroperitoneal adipose tissue and hepatic 11β-HSD1 activity. Dietary ω3 PUFA offered protection against glucose intolerance and elevated GC exposure in the retroperitoneal adipose tissue and liver of SL rats. Taken together, the results suggest that dietary fatty acid composition in the post-sucking period may interact with neonatal feeding and codetermine metabolic alterations in adulthood.

Free access
Fengyue Wang
Search for other papers by Fengyue Wang in
Google Scholar
PubMed
Close
,
Jing Yang
Search for other papers by Jing Yang in
Google Scholar
PubMed
Close
,
Junfeng Sun
Search for other papers by Junfeng Sun in
Google Scholar
PubMed
Close
,
Yanli Dong
Search for other papers by Yanli Dong in
Google Scholar
PubMed
Close
,
Hong Zhao Laboratory of Cardiovascular Internal Medicine Department, Laboratory of Cardiovascular Internal Medicine Department, First Affiliated Hospital, Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin, Heilongjiang 150001, China

Search for other papers by Hong Zhao in
Google Scholar
PubMed
Close
,
Hui Shi Laboratory of Cardiovascular Internal Medicine Department, Laboratory of Cardiovascular Internal Medicine Department, First Affiliated Hospital, Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin, Heilongjiang 150001, China

Search for other papers by Hui Shi in
Google Scholar
PubMed
Close
, and
Lu Fu
Search for other papers by Lu Fu in
Google Scholar
PubMed
Close

Testosterone can affect cardiovascular disease, but its effects on mitochondrial dynamics in the post-infarct myocardium remain unclear. To observe the effects of testosterone replacement, a rat model of castration-myocardial infarction (MI) was established by ligating the left anterior descending coronary artery 2 weeks after castration with or without testosterone treatment. Expression of mitochondrial fission and fusion proteins was detected by western blot and immunofluorescence 14 days after MI. Cardiac function, myocardial inflammatory infiltration and fibrosis, cardiomyocyte apoptosis, mitochondrial microstructure, and ATP levels were also assessed. Compared with MI rats, castrated rats showed aggravated mitochondrial and myocardial insults, including mitochondrial swelling and disordered arrangement; loss of cristae, reduced mitochondrial length; decreased ATP levels; cardiomyocyte apoptosis; and impaired cardiac function. Results of western blotting analyses indicated that castration downregulated peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1A) and mitofusin 2, but upregulated dynamin-related protein 1. The results were also supported by results obtained using immunofluorescence. However, these detrimental effects were reversed by testosterone supplementation, which also elevated the upstream AMP-activated protein kinase (AMPK) activation of PGC1A. Thus, testosterone can protect mitochondria in the post-infarct myocardium, partly via the AMPK–PGC1A pathway, thereby decreasing mitochondrial dysfunction and cardiomyocyte apoptosis. The effects of testosterone were confirmed by the results of ELISA analyses.

Free access
Xiaonan Yan State Key Laboratory of Reproductive Medicine, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China

Search for other papers by Xiaonan Yan in
Google Scholar
PubMed
Close
,
Xiaonan Dai State Key Laboratory of Reproductive Medicine, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China

Search for other papers by Xiaonan Dai in
Google Scholar
PubMed
Close
,
Jing Wang State Key Laboratory of Reproductive Medicine, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China

Search for other papers by Jing Wang in
Google Scholar
PubMed
Close
,
Nannan Zhao State Key Laboratory of Reproductive Medicine, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China

Search for other papers by Nannan Zhao in
Google Scholar
PubMed
Close
,
Yugui Cui State Key Laboratory of Reproductive Medicine, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China

Search for other papers by Yugui Cui in
Google Scholar
PubMed
Close
, and
Jiayin Liu State Key Laboratory of Reproductive Medicine, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China

Search for other papers by Jiayin Liu in
Google Scholar
PubMed
Close

Owing to the heterogeneity in the clinical symptoms of polycystic ovary syndrome (PCOS), the early pathophysiological mechanisms of PCOS remain unclear. Clinical, experimental, and genetic evidence supports an interaction between genetic susceptibility and the influence of maternal environment in the pathogenesis of PCOS. To determine whether prenatal androgen exposure induced PCOS-related metabolic derangements during pubertal development, we administrated 5α-dihydrotestosterone (DHT) in pregnant rats and observed their female offspring from postnatal 4 to 8 weeks. The prenatally androgenized (PNA) rats exhibited more numerous total follicles, cystic follicles, and atretic follicles than the controls. Fasting glucose, insulin, leptin levels, and homeostatic model assessment for insulin resistance were elevated in the PNA rats at the age of 5–8 weeks. Following intraperitoneal glucose tolerance tests, glucose and insulin levels did not differ between two groups; however, the PNA rats showed significantly higher 30- and 60-min glucose levels than the controls after insulin stimulation during 5–8 weeks. In addition, prenatal DHT treatment significantly decreased insulin-stimulated phosphorylation of AKT in the skeletal muscles of 6-week-old PNA rats. The abundance of IR substrate 1 (IRS1) and IRS2 was decreased in the skeletal muscles and liver after stimulation with insulin in the PNA group, whereas phosphorylation of insulin-signaling proteins was unaltered in the adipose tissue. These findings validate the contribution of prenatal androgen excess to metabolic derangements in pubertal female rats, and the impaired insulin signaling through IRS and AKT may result in the peripheral insulin resistance during pubertal development.

Free access
Jing Xie School of Medicine, State Key Laboratory for Medical Genomics, Laboratory of Development and Diseases, Shanghai Institute of Endocrinology and Metabolism, Shanghai Clinical Center for Endocrine and Metabolic Disease

Search for other papers by Jing Xie in
Google Scholar
PubMed
Close
,
Wei-Qing Wang School of Medicine, State Key Laboratory for Medical Genomics, Laboratory of Development and Diseases, Shanghai Institute of Endocrinology and Metabolism, Shanghai Clinical Center for Endocrine and Metabolic Disease

Search for other papers by Wei-Qing Wang in
Google Scholar
PubMed
Close
,
Ting-Xi Liu School of Medicine, State Key Laboratory for Medical Genomics, Laboratory of Development and Diseases, Shanghai Institute of Endocrinology and Metabolism, Shanghai Clinical Center for Endocrine and Metabolic Disease
School of Medicine, State Key Laboratory for Medical Genomics, Laboratory of Development and Diseases, Shanghai Institute of Endocrinology and Metabolism, Shanghai Clinical Center for Endocrine and Metabolic Disease

Search for other papers by Ting-Xi Liu in
Google Scholar
PubMed
Close
,
Min Deng School of Medicine, State Key Laboratory for Medical Genomics, Laboratory of Development and Diseases, Shanghai Institute of Endocrinology and Metabolism, Shanghai Clinical Center for Endocrine and Metabolic Disease

Search for other papers by Min Deng in
Google Scholar
PubMed
Close
, and
Guang Ning School of Medicine, State Key Laboratory for Medical Genomics, Laboratory of Development and Diseases, Shanghai Institute of Endocrinology and Metabolism, Shanghai Clinical Center for Endocrine and Metabolic Disease

Search for other papers by Guang Ning in
Google Scholar
PubMed
Close

Chromogranin A (CHGA), a protein participating in the biogenesis of dense core secretory granules in various neuroendocrine tissues, plays a critical role in the release of hormones/peptides and the pathogenesis of pheochromocytoma. However, little is known about the developmental origin of CHGA-expressing cells during embryogenesis. Here, we report the structural characterization and spatio-temporal expression pattern of zebrafish (Danio rerio) ortholog of mammalian CHGA. The earliest expression of chga transcripts was observed at 16 h post fertilization in the developing cranial ganglia as six distinct cellular masses arranged bilaterally as strings of beads in the dorsal root ganglia (DRG) precursors along the dorsal trunk. With development advancing, the chga transcripts were expressed abundantly in diencephalon, mesencephalon, and rhombencephalon as well as in the DRG. Interestingly, double in situ hybridization assay of chga with genes expressed in pronephros (Wilms' tumor suppressor 1, wt1), adrenal cortex (side-chain cleavage enzyme, scc), and sympathoadrenal neuron/chromaffin cell (dopamine-β-hydroxylase, dbh), respectively, showed that the chga-expressing cells are spatially separated from wt1-, scc-, and dbh-positive cell populations during early embryonic development. The pronephros region does not express chga even up to 7 days post fertilization, while chga positive-staining cells bind in the brain and DRG, indicating that chga may play an important role in nervous system development during the early embryonic stages.

Free access
Jing Li Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, China

Search for other papers by Jing Li in
Google Scholar
PubMed
Close
,
Pan-Pan Zhao Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, China

Search for other papers by Pan-Pan Zhao in
Google Scholar
PubMed
Close
,
Ting Hao Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, China

Search for other papers by Ting Hao in
Google Scholar
PubMed
Close
,
Dan Wang Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, China

Search for other papers by Dan Wang in
Google Scholar
PubMed
Close
,
Yu Wang Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, China

Search for other papers by Yu Wang in
Google Scholar
PubMed
Close
,
Yang-Zi Zhu Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, China

Search for other papers by Yang-Zi Zhu in
Google Scholar
PubMed
Close
,
Yu-Qing Wu Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, China
Department of Anesthetic Pharmacology, Xuzhou Medical University, Xuzhou, China

Search for other papers by Yu-Qing Wu in
Google Scholar
PubMed
Close
, and
Cheng-Hua Zhou Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, China
Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China

Search for other papers by Cheng-Hua Zhou in
Google Scholar
PubMed
Close

Urotensin II (U-II), a cyclic peptide originally isolated from the caudal neurosecretory system of fishes, can produce proinflammatory effects through its specific G protein-coupled receptor, GPR14. Neuropathic pain, a devastating disease, is related to excessive inflammation in the spinal dorsal horn. However, the relationship between U-II and neuropathic pain has not been reported. This study was designed to investigate the effect of U-II antagonist on neuropathic pain and to understand the associated mechanisms. We reported that U-II and its receptor GPR14 were persistently upregulated and activated in the dorsal horn of L4–6 spinal cord segments after chronic constriction injury (CCI) in rats. Intrathecal injection of SB657510, a specific antagonist against U-II, reversed CCI-induced thermal hyperalgesia and mechanical allodynia. Furthermore, we found that SB657510 reduced the expression of phosphorylated c-Jun N-terminal kinase (p-JNK) and nuclear factor-κB (NF-κB) p65 as well as subsequent secretion of interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α (TNF-α). It was also showed that both the JNK inhibitor SP600125 and the NF-κB inhibitor PDTC significantly attenuated thermal hyperalgesia and mechanical allodynia in CCI rats. Our present research showed that U-II receptor antagonist alleviated neuropathic pain possibly through the suppression of the JNK/NF-κB pathway in CCI rats, which will contribute to the better understanding of function of U-II and pathogenesis of neuropathic pain.

Free access
Bin Li School of Basic Medical Sciences, Capital Medical University, Beijing, China

Search for other papers by Bin Li in
Google Scholar
PubMed
Close
,
Jiming Yin Beijing You An Hospital, Capital Medical University, Beijing, China
Beijing Institute of Hepatology, Beijing, China

Search for other papers by Jiming Yin in
Google Scholar
PubMed
Close
,
Jing Chang Beijing You An Hospital, Capital Medical University, Beijing, China

Search for other papers by Jing Chang in
Google Scholar
PubMed
Close
,
Jia Zhang School of Basic Medical Sciences, Capital Medical University, Beijing, China

Search for other papers by Jia Zhang in
Google Scholar
PubMed
Close
,
Yangjia Wang School of Basic Medical Sciences, Capital Medical University, Beijing, China

Search for other papers by Yangjia Wang in
Google Scholar
PubMed
Close
,
Haixia Huang School of Basic Medical Sciences, Capital Medical University, Beijing, China

Search for other papers by Haixia Huang in
Google Scholar
PubMed
Close
,
Wei Wang School of Basic Medical Sciences, Capital Medical University, Beijing, China
Beijing Lab for Cardiovascular Precision Medicine, Beijing, China

Search for other papers by Wei Wang in
Google Scholar
PubMed
Close
, and
Xiangjun Zeng School of Basic Medical Sciences, Capital Medical University, Beijing, China

Search for other papers by Xiangjun Zeng in
Google Scholar
PubMed
Close

Microcirculatory injuries had been reported to be involved in diabetic cardiomyopathy, which was mainly related to endothelial cell dysfunction. Apelin, an adipokine that is upregulated in diabetes mellitus, was reported to improve endothelial cell dysfunction and attenuate cardiac insufficiency induced by ischemia and reperfusion. Therefore, it is hypothesized that apelin might be involved in alleviating endothelial cell dysfunction and followed cardiomyopathy in diabetes mellitus. The results showed that apelin improved endothelial cell dysfunction via decreasing apoptosis and expression of adhesion molecules and increasing proliferation, angiogenesis, and expression of E-cadherin, VEGFR 2 and Tie-2 in endothelial cells, which resulted in the attenuation of the capillary permeability in cardiac tissues and following diabetic cardiomyopathy. Meanwhile, the results from endothelial cell-specific APJ knockout mice and cultured endothelial cells confirmed that the effects of apelin on endothelial cells were dependent on APJ and the downstream NFκB pathways. In conclusion, apelin might reduce microvascular dysfunction induced by diabetes mellitus via improving endothelial dysfunction dependent on APJ activated NFκB pathways.

Open access
Jiannan Zhang Key Laboratory of Bio-resources and Eco-environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, People’s Republic of China

Search for other papers by Jiannan Zhang in
Google Scholar
PubMed
Close
,
Xin Li Key Laboratory of Bio-resources and Eco-environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, People’s Republic of China

Search for other papers by Xin Li in
Google Scholar
PubMed
Close
,
Yawei Zhou Key Laboratory of Bio-resources and Eco-environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, People’s Republic of China

Search for other papers by Yawei Zhou in
Google Scholar
PubMed
Close
,
Lin Cui Key Laboratory of Bio-resources and Eco-environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, People’s Republic of China

Search for other papers by Lin Cui in
Google Scholar
PubMed
Close
,
Jing Li Key Laboratory of Bio-resources and Eco-environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, People’s Republic of China

Search for other papers by Jing Li in
Google Scholar
PubMed
Close
,
Chenlei Wu Key Laboratory of Bio-resources and Eco-environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, People’s Republic of China

Search for other papers by Chenlei Wu in
Google Scholar
PubMed
Close
,
Yiping Wan Key Laboratory of Bio-resources and Eco-environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, People’s Republic of China

Search for other papers by Yiping Wan in
Google Scholar
PubMed
Close
,
Juan Li Key Laboratory of Bio-resources and Eco-environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, People’s Republic of China

Search for other papers by Juan Li in
Google Scholar
PubMed
Close
, and
Yajun Wang Key Laboratory of Bio-resources and Eco-environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, People’s Republic of China

Search for other papers by Yajun Wang in
Google Scholar
PubMed
Close

The interaction of melanocortin-4 (MC4R) and melanocortin-3 (MC3R) receptors with proopiomelanocortin (POMC)-derived peptides (e.g. α-MSH), agouti-related protein (AgRP) and melanocortin-2 receptor accessory protein 2 (MRAP2) is suggested to play critical roles in energy balance of vertebrates. However, evidence on their interaction in birds remains scarce. Our study aims to reveal their interaction in chickens and the results showed that (1) chicken (c-)MC3R and cMC4R expressed in Chinese hamster ovary (CHO) cells can be activated by α-MSH and ACTH1–39 equipotently, monitored by a pGL3-CRE-luciferase reporter system; (2) cMC3R and cMC4R, when co-expressed with cMRAP2 (or cMRAP, a cMRAP2 homolog), show increased sensitivity to ACTH treatment and thus likely act as ACTH-preferring receptors, and the interaction between cMC3R/cMC4R and cMRAP2 was demonstrated by co-immunoprecipitation assay; (3) both cMC3R and cMC4R display constitutive activity when expressed in CHO cells, as monitored by dual-luciferase reporter assay, and cMRAP2 (and cMRAP) can modulate their constitutive activity; (4) AgRP inhibits the constitutive activity of cMC3R/cMC4R, and it also antagonizes ACTH/α-MSH action on cMC4R/cMC3R, indicating that AgRP functions as the inverse agonist and antagonist for both receptors. These findings, together with the co-expression of cMC4R, cMC3R, cMRAP2, cAgRP and cPOMC in chicken hypothalamus detected by quantitative real-time PCR, suggest that within the hypothalamus, α-MSH/ACTH, AgRP and MRAP2 may interact at the MC4R(/MC3R) interface to control energy balance. Furthermore, our data provide novel proof for the involvement of MRAP2 (and MRAP) in fine-tuning the constitutive activity and ligand sensitivity and selectivity of both MC3R and MC4R in vertebrates.

Free access
Qinghua Wang State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing, Jiangsu, China
Laboratory Animal Center, Nantong University, Nantong, Jiangsu, China

Search for other papers by Qinghua Wang in
Google Scholar
PubMed
Close
,
Jing Tang State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing, Jiangsu, China

Search for other papers by Jing Tang in
Google Scholar
PubMed
Close
,
Shujun Jiang State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing, Jiangsu, China
School of Traditional Chinese Medicine, China Pharmaceutical University, Nanjing, Jiangsu, China

Search for other papers by Shujun Jiang in
Google Scholar
PubMed
Close
,
Zan Huang State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing, Jiangsu, China
Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, Jiangsu, China

Search for other papers by Zan Huang in
Google Scholar
PubMed
Close
,
Anying Song State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing, Jiangsu, China

Search for other papers by Anying Song in
Google Scholar
PubMed
Close
,
Siyuan Hou State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing, Jiangsu, China

Search for other papers by Siyuan Hou in
Google Scholar
PubMed
Close
,
Xiang Gao State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing, Jiangsu, China

Search for other papers by Xiang Gao in
Google Scholar
PubMed
Close
, and
Hai-Bin Ruan Department of Integrative Biology and Physiology, University of Minnesota Medical School, Minneapolis, Minnesota, USA

Search for other papers by Hai-Bin Ruan in
Google Scholar
PubMed
Close

Peroxisome proliferator-activated receptor-γ (PPARγ) is a master regulator of adipogenesis and a target of the thiazolidinedione (TZD) class of antidiabetic drugs; therefore, identifying novel regulators of PPARγ action in adipocytes is essential for the future development of therapeutics for diabetes. MAGE family member D1 (MAGED1), by acting as an adaptor for ubiquitin-dependent degradation pathways and a co-factor for transcription, plays an important role in neural development, cell differentiation and circadian rhythm. Here, we showed that MAGED1 expression was downregulated during adipogenesis and loss of MAGED1 promoted preadipocyte proliferation and differentiation in vitro. MAGED1 bound to PPARγ and suppressed the stability and transcriptional activity of PPARγ. Compared to WT littermates, MAGED1-deficient mice showed increased levels of PPARγ protein and its target genes, more CD29+CD34+Sca-1+ adipocyte precursors and hyperplasia of white adipose tissues (WATs). Moreover, MAGED1-deficient mice developed late-onset obesity as a result of decreased energy expenditure and physical activity. However, these mice were metabolically healthy as shown by improved glucose clearance and insulin sensitivity, normal levels of serum lipids and enhanced secretion of adipokines such as leptin and adiponectin. Taken together, our data identify MAGED1 as a novel negative regulator of PPARγ activity, adipogenesis and insulin sensitivity in mice. MAGED1 might therefore serve as a novel pharmaceutical target to treat obesity-associated insulin resistance.

Free access
Elisabete A Forsberg The Rolf Luft Research Center for Diabetes and Endocrinology, Department of Endocrinology, Center for Pediatric and Adolescent Medicine, Karolinska Institutet, Stockholm, Sweden

Search for other papers by Elisabete A Forsberg in
Google Scholar
PubMed
Close
,
Ileana R Botusan The Rolf Luft Research Center for Diabetes and Endocrinology, Department of Endocrinology, Center for Pediatric and Adolescent Medicine, Karolinska Institutet, Stockholm, Sweden

Search for other papers by Ileana R Botusan in
Google Scholar
PubMed
Close
,
Jing Wang The Rolf Luft Research Center for Diabetes and Endocrinology, Department of Endocrinology, Center for Pediatric and Adolescent Medicine, Karolinska Institutet, Stockholm, Sweden

Search for other papers by Jing Wang in
Google Scholar
PubMed
Close
,
Verena Peters The Rolf Luft Research Center for Diabetes and Endocrinology, Department of Endocrinology, Center for Pediatric and Adolescent Medicine, Karolinska Institutet, Stockholm, Sweden

Search for other papers by Verena Peters in
Google Scholar
PubMed
Close
,
Ishrath Ansurudeen The Rolf Luft Research Center for Diabetes and Endocrinology, Department of Endocrinology, Center for Pediatric and Adolescent Medicine, Karolinska Institutet, Stockholm, Sweden

Search for other papers by Ishrath Ansurudeen in
Google Scholar
PubMed
Close
,
Kerstin Brismar The Rolf Luft Research Center for Diabetes and Endocrinology, Department of Endocrinology, Center for Pediatric and Adolescent Medicine, Karolinska Institutet, Stockholm, Sweden
The Rolf Luft Research Center for Diabetes and Endocrinology, Department of Endocrinology, Center for Pediatric and Adolescent Medicine, Karolinska Institutet, Stockholm, Sweden

Search for other papers by Kerstin Brismar in
Google Scholar
PubMed
Close
, and
Sergiu Bogdan Catrina The Rolf Luft Research Center for Diabetes and Endocrinology, Department of Endocrinology, Center for Pediatric and Adolescent Medicine, Karolinska Institutet, Stockholm, Sweden
The Rolf Luft Research Center for Diabetes and Endocrinology, Department of Endocrinology, Center for Pediatric and Adolescent Medicine, Karolinska Institutet, Stockholm, Sweden

Search for other papers by Sergiu Bogdan Catrina in
Google Scholar
PubMed
Close

IGF binding protein 1 (IGFBP1) is a member of the binding proteins for the IGF with an important role in glucose homeostasis. Circulating IGFBP1 is derived essentially from the liver where it is mainly regulated negatively by insulin. Carnosine, a natural antioxidant, has been shown to improve metabolic control in different animal models of diabetes but its mechanisms of action are still not completely unraveled. We therefore investigate the effect of carnosine treatment on the IGFBP1 regulation in db/db mice. Db/db mice and heterozygous non-diabetic mice received for 4 weeks regular water or water supplemented with carnosine. Igfbp1 mRNA expression in the liver was evaluated using qPCR and the protein levels in plasma by western blot. Plasma IGF1 and insulin were analyzed using immunoassays. HepG2 cells were used to study the in vitro effect of carnosine on IGFBP1. The modulation of hypoxia inducible factor-1 alpha (HIF-1α) which is the central mediator of hypoxia-induction of IGFBP1 was analyzed using: WB, reporter gene assay and qPCR. Carnosine decreased the circulating IGFBP1 levels and the liver expression Igfbp1, through a complex mechanism acting both directly by suppressing the HIF-1α-mediated IGFBP1 induction and indirectly through increasing circulating insulin level followed by a decrease in the blood glucose levels and increased the plasma levels or IGF1. Reduction of IGFBP1 in diabetes through insulin-dependent and insulin-independent pathways is a novel mechanism by which carnosine contributes to the improvement of the metabolic control in diabetes.

Free access