Hyperadiponectinemia enhances bone formation in mice

<p>Abstract</p> <p>Background</p> <p>There is growing evidence that adiponectin, a physiologically active polypeptide secreted by adipocytes, controls not only adipose tissue but also bone metabolism. However, a role for adiponectin in bone development remains controversial.</p> <p>Methods</p> <p>We therefore investigated the endocrine effects of adiponectin on bone metabolism using 12-week-old male transgenic (Ad-Tg) mice with significant hyperadiponectinemia overexpressing human full-length adiponectin in the liver.</p> <p>Results</p> <p>In Ad-Tg mice, the serum level of osteocalcin was significantly increased, but the levels of RANKL, osteoprotegerin, and TRAP5b were not. Bone mass was significantly greater in Ad-Tg mice with increased bone formation. In contrast, bone resorption parameters including the number of osteoclasts and eroded surface area did not differ between Ad-Tg and their littermates.</p> <p>Conclusions</p> <p>These findings demonstrate that hyperadiponectinemia enhances bone formation in mice.</p

Selective modulation of Wnt ligands and their receptors in adipose tissue by chronic hyperadiponectinemia.

BACKGROUND: Adiponectin-transgenic mice had many small adipocytes in both subcutaneous and visceral adipose tissues, and showed higher sensitivity to insulin, longer life span, and reduced chronic inflammation. We hypothesized that adiponectin regulates Wnt signaling in adipocytes and thereby modulates adipocyte proliferation and chronic inflammation in adipose tissue. MATERIALS AND METHODS: We examined the expression of all Wnt ligands and their receptors and the activity of Wnt signaling pathways in visceral adipose tissue from wild-type mice and two lines of adiponectin-transgenic mice. The effects of adiponectin were also investigated in cultured 3T3-L1 cells. RESULTS: The Wnt5b, Wnt6, Frizzled 6 (Fzd6), and Fzd9 genes were up-regulated in both lines of transgenic mice, whereas Wnt1, Wnt2, Wnt5a, Wnt9b, Wnt10b, Wnt11, Fzd1, Fzd2, Fzd4, Fzd7, and the Fzd coreceptor low-density-lipoprotein receptor-related protein 6 (Lrp6) were reduced. There was no difference in total β-catenin levels in whole-cell extracts, non-phospho-β-catenin levels in nuclear extracts, or mRNA levels of β-catenin target genes, indicating that hyperadiponectinemia did not affect canonical Wnt signaling. In contrast, phosphorylated calcium/calmodulin-dependent kinase II (p-CaMKII) and phosphorylated Jun N-terminal kinase (p-JNK) were markedly reduced in adipose tissue from the transgenic mice. The adipose tissue of the transgenic mice consisted of many small cells and had increased expression of adiponectin, whereas cyclooxygenase-2 expression was reduced. Wnt5b expression was elevated in preadipocytes of the transgenic mice and decreased in diet-induced obese mice, suggesting a role in adipocyte differentiation. Some Wnt genes, Fzd genes, and p-CaMKII protein were down-regulated in 3T3-L1 cells cultured with a high concentration of adiponectin. CONCLUSION: Chronic hyperadiponectinemia selectively modulated the expression of Wnt ligands, Fzd receptors and LRP coreceptors accompanied by the inhibition of the Wnt/Ca(2+) and JNK signaling pathways, which may be involved in the altered adipocyte cellularity, endogenous adiponectin production, and anti-inflammatory action induced by hyperadiponectinemia

Beneficial effects of metformin on energy metabolism and visceral fat volume through a possible mechanism of fatty acid oxidation in human subjects and rats - Fig 6

<p><b>The protein expressions of pAMPK and pACC in the liver of SD rats at 15 weeks old.inhibo</b> A; Western blot analysis, B; Densitometric quantification. Open bars denote control group and black bars denote metformin-treated group. Data are presented as mean ± S.E. (n = 3 in each group). *P<0.05 vs. control groups.</p

Anthropometric factors, food intake and water consumption in control and metformin-treated rats.

<p>Anthropometric factors, food intake and water consumption in control and metformin-treated rats.</p

Pyruvate tolerance test in SD rats at 15 weeks old.

<p>Data are presented as mean ± S.E. (n = 6 in each group). Paired t-test was used for the comparison between groups. Open circle and dotted line; control group, closed circle and solid line; metformin-treated group. *P<0.05 vs. the value of control group at each time point.</p

Fat oxidation-related gene expressions in the liver of SD rats at 15 weeks old.

<p>A; <i>Cpt1</i>, B; <i>Acs</i>, C; <i>Acad</i>, D; <i>Pdk</i> expression corrected by <i>Gapdh</i> expression. Open bars denote control group and black bars denote metformin-treated group. Data are presented as mean ± S.E. (n = 6 in each group). *P<0.05, **P<0.01 vs. control groups.</p

Vulcan: An example of Redefis

ユーザ機能の実装に適したSoC プラットフォームRedefis の一実施例である，プロセッサVulcan について 紹介し，さらにVulcan 上へのアプリケーション実装例について紹介する．Vulcan は再構成可能なデータパスを持った プロセッサであり，アプリケーションに特化した命令を実行することで柔軟性と高性能化を両立させることができる．Vulcan is an example of a novel SoC design platforms “Redefis”. This paper describes Vulcan architecture and the implementation of two applications on Vulcan. Vulcan realize flexibility and high performance by execution of application specific instruction