Effects of harmine on hepatic SAHH and NQO1 activities, and on plasma Hcy levels in Tg 189N3 mice.

<p>Hepatic SAHH (A) and NQO1 (B) activities are presented as percent of untreated (Vehicle) non-transgenic (Tg –) mice activities. (C) Plasma Hcy level. Data correspond to means ± SEM and the statistical analysis was done with one-way ANOVA followed by Student's unpaired <i>t</i>-test. n = number of mice.</p

DYRK1A protein expression in liver of CBS-deficient mice crossbred with 152F7 transgenic mice.

<p>(A) Western immunoblots showing DYRK1A expression in liver of wild type mice (<i>Cbs</i>^+/+ Tg -), heterozygous mice (<i>Cbs</i>^+/− Tg -), 152F7 transgenic mice (<i>Cbs</i>^+/+ Tg 152F7), and heterozygous mice crossbred with 152F7 transgenic mice (<i>Cbs</i>^+/− Tg 152F7). Proteins were subjected to immunoblot analysis using antibodies specific to DYRK1A (85.5 kDa). After stripping, the membranes were reprobed with anti-β-actin antibody (41.7 kDa) for the control. (B) Relative protein expression was determined by normalization of the density of images from DYRK1A with that of β-actin of the same blot. The values of <i>Cbs</i>^+/− Tg -, <i>Cbs</i>^+/+ Tg 152F7, or <i>Cbs</i>^+/− Tg 152F7 were normalized to the mean of <i>Cbs</i>^+/+ Tg - mice. The blots are representative of three independent experiments. Data correspond to means ± SEM and the statistical analysis was done with one-way ANOVA followed by Student's unpaired <i>t</i>-tests. n = number of mice.</p

Hepatic SAHH activity is increased in Tg 189N3 and Ts65Dn transgenic mice.

<p>SAHH activity in (A) Tg 189N3 and (B) Ts65Dn transgenic mice. The values were normalized to the mean of Tg – mice from each line. Data correspond to means ± SEM and the statistical analysis was done by Student's unpaired <i>t</i>-test. n = number of mice.</p

Primer sequences for real-time quantitative reverse transcription-polymerase chain reaction (Q-PCR) (all primers are listed 5′ to 3′).

<p>Primer sequences for real-time quantitative reverse transcription-polymerase chain reaction (Q-PCR) (all primers are listed 5′ to 3′).</p

Plasma Hcy level is decreased in 152F7 transgenic mice and in CBS-deficient mice crossbred with 152F7 transgenic mice.

<p>(A) Plasma Hcy level, (B) hepatic CBS, (C) SAHH and (D) NQO1 activity in wild type mice (<i>Cbs</i>^+/+ Tg -), heterozygous mice (<i>Cbs</i>^+/− Tg -), 152F7 transgenic mice (<i>Cbs</i>^+/+ Tg 152F7), and heterozygous mice crossbred with 152F7 transgenic mice (<i>Cbs</i>^+/− Tg 152F7). The values were normalized to the mean of <i>Cbs</i>^+/+ Tg - mice. Data correspond to means ± SEM and the statistical analysis was done with one-way ANOVA followed by Student's unpaired <i>t</i>-tests. n = number of mice.</p

Relative expression of SAHH, BHMT, MS and MTHFR gene based upon Q-PCR data obtained from non-transgenic and Tg189N3 mice.

<p>The values of Tg189N3 were normalized to the mean Tg – mice. Data correspond to means ± SEM and the statistical analysis was done by Student's unpaired <i>t</i>-tests. n = number of mice. *<i>p</i> = 0.068; <b>^†</b><i>p</i>< 0.03.</p

Hepatic DYRK1A mRNA and protein expression in liver of transgenic mice.

<p>Relative expression of DYRK1A gene was based on Q-PCR data and protein expression was determined by normalization of the density of images from DYRK1A with that of β-actin of the same blot. The values of Tg 152F7, Tg189N3 and Ts65Dn were normalized to the mean Tg – mice from each lines. The blots are representative of three independent experiments. Data correspond to means ± SEM and the statistical analysis was done by Student's unpaired <i>t</i>-tests. n = number of mice.</p

Deficiency of Interleukin-15 Confers Resistance to Obesity by Diminishing Inflammation and Enhancing the Thermogenic Function of Adipose Tissues

<div><p>Objective</p><p>IL-15 is an inflammatory cytokine secreted by many cell types. IL-15 is also produced during physical exercise by skeletal muscle and has been reported to reduce weight gain in mice. Contrarily, our findings on IL-15 knockout (KO) mice indicate that IL-15 promotes obesity. The aim of this study is to investigate the mechanisms underlying the pro-obesity role of IL-15 in adipose tissues.</p><p>Methods</p><p>Control and IL-15 KO mice were maintained on high fat diet (HFD) or normal control diet. After 16 weeks, body weight, adipose tissue and skeletal mass, serum lipid levels and gene/protein expression in the adipose tissues were evaluated. The effect of IL-15 on thermogenesis and oxygen consumption was also studied in primary cultures of adipocytes differentiated from mouse preadipocyte and human stem cells.</p><p>Results</p><p>Our results show that IL-15 deficiency prevents diet-induced weight gain and accumulation of lipids in visceral and subcutaneous white and brown adipose tissues. Gene expression analysis also revealed elevated expression of genes associated with adaptive thermogenesis in the brown and subcutaneous adipose tissues of IL-15 KO mice. Accordingly, oxygen consumption was increased in the brown adipocytes from IL-15 KO mice. In addition, IL-15 KO mice showed decreased expression of pro-inflammatory mediators in their adipose tissues.</p><p>Conclusions</p><p>Absence of IL-15 results in decreased accumulation of fat in the white adipose tissues and increased lipid utilization via adaptive thermogenesis. IL-15 also promotes inflammation in adipose tissues that could sustain chronic inflammation leading to obesity-associated metabolic syndrome.</p></div

Relative expression of DYRK1A, SAHH and NQO1 and SAHH and NQO1 activities obtained from lymphoblastoid cell lines.

<p>The values of lymphoblastoid cell lines (LCLs) from patients with DS (T21) were normalized to the mean lymphoblastoid cell lines from control individuals (control). Data correspond to means ± SEM and the statistical analysis was done by Student's unpaired <i>t</i>-tests. n = number of LCLs. * <i>p</i><0.05; <b>^†</b><i>p</i><0.006.</p

Plasma Hcy level, DYRK1A protein expression and SAHH activity are correlated.

<p>Hepatic DYRK1A expression and SAHH activity are presented as percent of <i>Cbs</i>^+/+ Tg – mice. Correlation of plasma Hcy level vs. (A) hepatic DYRK1A protein expression or (B) hepatic SAHH activity. Increasing levels of plasma Hcy and hepatic DYRK1A protein expression or SAHH activity are negatively correlated at <i>p</i><0.04 and <i>p</i><0.006 with a ρ = −0.48 and ρ = −0.61 respectively. Correlation of hepatic DYRK1A protein expression vs. SAHH activity (C). Increasing levels of hepatic DYRK1A protein expression and hepatic SAHH activity are positively correlated at <i>p</i><0.05 with a ρ = 0.47. (D) Graph of PCA. The three quantitative variables corresponding of plasma Hcy level, hepatic DYRK1A protein expression and hepatic SAHH activity are represented by vectors.</p