Effect of LPS preconditioning on mean arterial pressure (MAP) of rats.

<p>Rats were injected vehicle (PBS) or LPS (1 mg/kg) i.p. 24 h prior to HS₉₀ or HS₅₀. The MAP was recorded during the whole experiment. Sham animals were used as control. Data are expressed as mean ± SEM of 8–10 animals. Statistical analysis was performed using two-way ANOVA followed by Bonferroni’s post hoc test. *p < 0.05 versus sham group.</p

Gender dimorphism of the phosphorylation of IκBα, nuclear translocation of the p65 NF-κB subunit, expression of iNOS, TNF-α and IL-6 in the hearts of mice subjected to LPS (3 mg/kg)/PepG (0.1 mg/kg) co-administration.

<p>Male or female mice received either LPS (3 mg/kg)/PepG (0.1 mg/kg) or PBS. Signalling events in heart tissue were assessed at 18 hours. Densitometric analysis of the bands is expressed as relative optical density (O.D.) of (<b>A</b>) phosphorylated IκBα (pSer^32/36) corrected for the corresponding total IκBα content and normalized using the related sham band; (<b>B</b>) NF-κB p65 subunit levels in both, cytosolic and nuclear fractions expressed as a nucleus/cytosol ratio normalized using the related sham bands; (<b>C</b>) iNOS expression corrected for the corresponding tubulin band, and (<b>D</b>) TNF-α expression in heart tissue of mice subjected to LPS/PepG; (<b>E</b>) IL-6 expression in heart tissue of mice subjected to LPS/PepG. Each analysis (<b>A</b>–<b>E</b>) is from a single experiment and is representative of three to four separate experiments. Data are expressed as means ± SEM for n number of observations. ★<i>P</i><0.05 versus the respective sham group, #<i>P</i><0.05 versus male LPS/PepG group.</p

Effect of LPS preconditioning on shed blood and period of time spent at 30 mmHg.

<p>Rats were injected vehicle (PBS) or LPS (1 mg/kg) i.p. 24 h prior to HS₉₀ or HS₅₀. The shed blood (A) and the period of time that animals spent at 30 mmHg (B) are shown. Data are expressed as mean ± SEM of 8–10 animals. Statistical analysis was performed using one-way ANOVA followed by Bonferroni’s post hoc test. * p < 0.05 among the groups.</p

Gastrocnemius colocalization of IMCL and AGEs.

<p>BODIPY stain was used to visualize IMCL in association with immunofluorescence analysis for CML and CEL on gastrocnemius sections from HFHS and OB/OB mice (5 mice per group). Representative 32x/63x magnification photomicrographs of an HFHS mouse show wide overlapping between IMCL positive myofibers (left panels) and CML- or CEL-positive myofibers (right panels).</p

Gender dimorphism of heart rate and temperature of mice responses to septic insults.

<p>Heart rate and temperature were recorded at 18 hours in mice subjected to LPS/PepG co-administration and at 24 hours in mice that underwent CLP. Bpm, beats per minute. Data are expressed as means ± SEM for n number of observations.</p><p>*<i>P</i><0.05 versus the respective sham group,</p>#<p><i>P</i><0.05 versus male LPS/PepG or CLP group.</p

Effect of LPS preconditioning on NF-ĸB activation.

<p>Rats were injected vehicle (PBS) or LPS (1 mg/kg) i.p. 24 h prior to HS₉₀ or HS₅₀. The phosphorylation of IĸBα on Ser^32/36 (A and C) and the nuclear translocation of the p65 NF-ĸB subunit (B and D) on the kidney (A and B) and liver (C and D) were determined by western blotting. Protein expression was measured as relative optical density (O.D.), corrected for the corresponding β-actin contents and normalized using the related Sham band. Data are expressed as mean ± SEM of n observations. Statistical analysis was performed using one-way ANOVA followed by Bonferroni’s post hoc test. *p < 0.05 among the groups.</p

Effect of LPS preconditioning on iNOS expression and serum nitrite and nitrate (NOx).

<p>Rats were injected vehicle (PBS) or LPS (1 mg/kg) i.p. 24 h prior to HS₉₀ or HS₅₀. The iNOS expression on the kidney (A) and liver (B) was determined by western blotting. Protein expression was measured as relative optical density (O.D.), corrected for the corresponding β-actin contents and normalized with the Sham band. (C) The concentration of serum NOx was measured as described at Methods. (D) The basal mean arterial pressure (MAP) of all groups is shown. Data are expressed as mean ± SEM of n observations. Statistical analysis was performed using one-way ANOVA followed by Bonferroni’s post hoc test. *p < 0.05 among the groups.</p

Gender dimorphism of the phosphorylation of Akt and eNOS in the hearts of mice subjected to LPS (3 mg/kg)/PepG (0.1 mg/kg) co-administration.

<p>Male or female mice received either LPS (3 mg/kg)/PepG (0.1 mg/kg) or PBS. Signalling events in heart tissue were assessed at 18 hours. Densitometric analysis of the bands is expressed as relative optical density (O.D.) of (<b>A</b>) phosphorylated Akt (pSer⁴⁷³) corrected for the corresponding total Akt content and normalized using the related sham band; (<b>B</b>) phosphorylated eNOS (pSer¹¹⁷⁷), corrected for the corresponding total eNOS content and normalized using the related sham band. Each analysis (<b>A–B</b>) is from a single experiment and is representative of three to four separate experiments. Data are expressed as means ± SEM for n number of observations. ★<i>P</i><0.05 versus the respective sham group, #<i>P</i><0.05 versus male LPS/PepG group.</p

Accumulation of Advanced Glycation End-Products and Activation of the SCAP/SREBP Lipogenetic Pathway Occur in Diet-Induced Obese Mouse Skeletal Muscle

<div><p>Aim of this study was to investigate whether advanced glycation end-products (AGEs) accumulate in skeletal myofibers of two different animal models of diabesity and whether this accumulation could be associated to myosteatosis. Male C57Bl/6j mice and leptin-deficient ob/ob mice were divided into three groups and underwent 15 weeks of dietary manipulation: standard diet-fed C57 group (C57, n = 10), high-fat high-sugar diet-fed C57 group (HFHS, n = 10), and standard diet-fed ob/ob group (OB/OB, n = 8). HFHS mice and OB/OB mice developed glycometabolic abnormalities in association with decreased mass of the gastrocnemius muscle, fast-to-slow transition of muscle fibers, and lipid accumulation (that occurred preferentially in slow compared to fast fibers). Moreover, we found in muscle fibers of HFHS and OB/OB mice accumulation of AGEs that was preferential for the lipid-accumulating cells, increased expression of the lipogenic pathway SCAP/SREBP, and co-localisation between AGEs and SCAP-(hyper)expressing cells (suggestive for SCAP glycosylation). The increased expression of the SCAP/SREBP lipogenic pathway in muscle fibers is a possible mechanism underlying lipid accumulation and linking myosteatosis to muscle fiber atrophy and fast-to-slow transition that occur in response to diabesity.</p></div

Gender dimorphism of cardiac dysfunction was blunted in response to high dose of LPS (9 mg/kg)/PepG (1 mg/kg) co-administration.

<p>Panel <b>A</b>–<b>D</b>: Male or female mice received either LPS (9 mg/kg)/PepG (1 mg/kg) or PBS intraperitoneally. Cardiac function was assessed at 18 hours. (<b>A</b>) Representative M-mode echocardiograms; percentage (%) (<b>B</b>) ejection fraction (EF); (<b>C</b>) fractional shortening (FS); and (<b>D</b>) fractional area of change (FAC). The following groups were studied: Male+vehicle (n = 5); Female+vehicle (n = 4); Male+LPS/PepG (n = 11); Female+LPS/PepG (n = 6). Data are expressed as means ± SEM for n number of observations. ★<i>P</i><0.05 versus the respective sham group, #<i>P</i><0.05 versus male LPS/PepG group.</p