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Articles by C Ohlsson
Total Records ( 4 ) for C Ohlsson
  E Egecioglu , K Ploj , X Xu , M Bjursell , N Salome , N Andersson , C Ohlsson , M Taube , C Hansson , M Bohlooly Y , D. G. A Morgan and S. L. Dickson
 

To investigate the role of the central neuromedin U (NMU) signaling system in body weight and energy balance regulation, we examined the effects of long-term intracerebroventricular (icv) infusion of NMU in C57Bl/6 mice and in mice lacking the gene encoding NMU receptor 2. In diet-induced obese male and female C57BL/6 mice, icv infusion of NMU (8 µg·day–1·mouse–1) for 7 days decreased body weight and total energy intake compared with vehicle treatment. However, these parameters were unaffected by NMU treatment in lean male and female C57BL/6 mice fed a standard diet. In addition, female (but not male) NMUR2-null mice had increased body weight and body fat mass when fed a high-fat diet but lacked a clear body weight phenotype when fed a standard diet compared with wild-type littermates. Furthermore, female (but not male) NMUR2-null mice fed a high-fat diet were protected from central NMU-induced body weight loss compared with littermate wild-type mice. Thus, we provide the first evidence that long-term central NMU treatment reduces body weight, food intake, and adiposity and that central NMUR2 signaling is required for these effects in female but not male mice.

  J Jiang , N. L. S Tang , C Ohlsson , A. L Eriksson , L Vandenput , C Liao , X Wang , F. W. K Chan , A Kwok , E Orwoll , T. C. Y Kwok , J Woo and P. C. Leung
  BACKGROUND:

Results of recent studies have demonstrated that genetic variants of the enzyme steroid 5 reductase type II (SRD5A2) are associated with serum concentrations of major androgen metabolites such as conjugates of androstane-3,17β-diol-glucuronide (3-diol-G). However, this association was not consistently found among different ethnic groups. Thus, we aimed to determine whether the association with SRD5A2 genetic variations exists in a cohort of healthy Chinese elderly men, by examining 2 metabolite conjugates: androstane-3,l7β-diol-3-glucuronide (3-diol-3G) and androstane-3,17β-diol-17-glucuronide (3-diol-17G).

METHODS:

We used GC-MS and LC-MS to measure serum sex steroid concentrations, including testosterone and dihydrotestosterone, and 3-diol-3G and 3-diol-17G in 1182 Chinese elderly men age 65 and older. Genotyping of the 3 SRD5A2 tagSNPs [rs3731586, rs12470143, and rs523349 (V89L)] was performed by using melting-temperature–shift allele-specific PCR.

RESULTS:

The well-described SRD5A2 missense variant rs523349 (V89L) was modestly associated with the 3-diol-17G concentration (P = 0.040). On the other hand, SNP rs12470143 was found to be significantly correlated with 3-diol-3G concentration (P = 0.021). Results of haplotype analysis suggested that the presence of an A-C-G haplotype leads to an increased 3-diol-3G concentration, a finding consistent with results of single SNP analysis.

CONCLUSIONS:

The genetic variation of SRD5A2 is associated with circulating 3-diol-3G and 3-diol-17G concentrations in Chinese elderly men. In addition, we showed that SRD5A2 haplotypic association, rather than a single SNP alone, might be a better predictor of the 3-diol-G concentration. Thus, the effect of either the haplotype itself or of other ungenotyped SNPs in linkage disequilibrium with the haplotype is responsible for the interindividual variation of 3-diol-G.

  E Grundberg , T Kwan , B Ge , K. C.L Lam , V Koka , A Kindmark , H Mallmin , J Dias , D. J Verlaan , M Ouimet , D Sinnett , F Rivadeneira , K Estrada , A Hofman , J. M van Meurs , A Uitterlinden , P Beaulieu , A Graziani , E Harmsen , O Ljunggren , C Ohlsson , D Mellstrom , M. K Karlsson , O Nilsson and T. Pastinen
 

The common genetic variants associated with complex traits typically lie in noncoding DNA and may alter gene regulation in a cell type-specific manner. Consequently, the choice of tissue or cell model in the dissection of disease associations is important. We carried out an expression quantitative trait loci (eQTL) study of primary human osteoblasts (HOb) derived from 95 unrelated donors of Swedish origin, each represented by two independently derived primary lines to provide biological replication. We combined our data with publicly available information from a genome-wide association study (GWAS) of bone mineral density (BMD). The top 2000 BMD-associated SNPs (P < ~10–3) were tested for cis-association of gene expression in HObs and in lymphoblastoid cell lines (LCLs) using publicly available data and showed that HObs have a significantly greater enrichment (threefold) of converging cis-eQTLs as compared to LCLs. The top 10 BMD loci with SNPs showing strong cis-effects on gene expression in HObs (P = 6 x 10–10 – 7 x 10–16) were selected for further validation using a staged design in two cohorts of Caucasian male subjects. All 10 variants were tested in the Swedish MrOS Cohort (n = 3014), providing evidence for two novel BMD loci (SRR and MSH3). These variants were then tested in the Rotterdam Study (n = 2090), yielding converging evidence for BMD association at the 17p13.3 SRR locus (Pcombined = 5.6 x 10–5). The cis-regulatory effect was further fine-mapped to the proximal promoter of the SRR gene (rs3744270, r2 = 0.5, P = 2.6 x 10–15). Our results suggest that primary cells relevant to disease phenotypes complement traditional approaches for prioritization and validation of GWAS hits for follow-up studies.

  R Shao , M Nutu , L Karlsson Lindahl , A Benrick , B Weijdegard , S Lager , E Egecioglu , J Fernandez Rodriguez , K Gemzell Danielsson , C Ohlsson , J. O Jansson and H. Billig
 

The action of interleukin-6 (IL-6) impacts female reproduction. Although IL-6 was recently shown to inhibit cilia activity in human fallopian tubes in vitro, the molecular mechanisms underlying IL-6 signaling to tubal function remain elusive. Here, we investigate the cellular localization, regulation, and possible function of two IL-6 receptors (IL-6R and gp130) in mouse and human fallopian tubes in vivo. We show that IL-6R is restricted to the cilia of epithelial cells in both mouse and human fallopian tubes. Exogenous 17β-estradiol (E2), but not progesterone (P4), causes a time-dependent decrease in IL-6R expression, which is blocked by the estrogen receptor (ER) antagonist ICI-182,780. Exposure of different ER-selective agonists propyl-(1H)-pyrazole-1,3,5-triyl-trisphenol or 2,3-bis-(4-hydroxyphenyl)-propionitrile demonstrated an ER subtype-specific regulation of IL-6R in mouse fallopian tubes. In contrast to IL-6R, gp130 was detected in tubal epithelial cells in mice but not in humans. In humans, gp130 was found in the muscle cells and was decreased in the periovulatory and luteal phases during the reproductive cycles, indicating a species-specific expression and regulation of gp130 in the fallopian tube. Expression of tubal IL-6R and gp130 in IL-6 knockout mice was found to be normal; however, E2 treatment increased IL-6R, but not gp130, in IL-6 knockout mice when compared with wild-type mice. Furthermore, expression levels of IL-6R, but not gp130, decreased in parallel with estrogenic accelerated oocyte-cumulus complex (OCC) transport in mouse fallopian tubes. Our findings open the posibility that cilia-specific IL-6R may play a role in the regulation of OCC transport and suggest an estrogen-regulatory pathway of IL-6R in the fallopian tube.

 
 
 
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