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Kracmerova J.,Charles University | Rossmeislova L.,Charles University | Kovacova Z.,Charles University | Klimcakova E.,Charles University | And 10 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2014

Context: Soluble CD163 (sCD163) was suggested as a biomarker of insulin sensitivity and CD163 mRNA expression representing macrophage content in adipose tissue (AT). Objective: The aim of this study was to investigate, in cross-sectional and prospective design, the relationship between sCD163 circulating levels and CD163 mRNA expression in adipose tissue and insulin sensitivity assessed by euglycemic-hyperinsulinemic clamp. Design, Setting, Participants, and Interventions: Two cohorts of subjects were examined in the study. Cohort 1 included 42 women with a wide range of body mass index (17-48 kg/m2); cohort 2 included 27 obese women who followed a dietary intervention consisting of 1 month of a very low-calorie diet and 5 months of a weight-stabilization period. Main Outcome Measures: Serum levels of CD163 and mRNA expression of CD163 and CD68 in sc and visceral (visc)ATwere determined,andinsulin sensitivity [expressed as glucose disposal rate (GDR)]was measured in cohort 1. In cohort 2, serum levels of CD163, mRNA expressions of CD163, CD68, and CD163-shedding factors [TNF-α-converting enzyme (TACE) and tissue inhibitor of metalloproteinase (TIMP3)] in sc AT were examined and GDR was measured before and during dietary intervention. Results: In cohort 1, circulating sCD163 correlated with CD163 mRNA levels in both sc and visc AT. sCD163 and CD163 mRNA expression in both fat depots correlated with GDR. In cohort 2, the diet-induced changes of sCD163 levels did not correlate with those of CD163, CD68, TACE, and TIMP3 mRNA levels. Although the pattern of the diet-induced change of sCD163 paralleled that of GDR, there was no correlation between the changes of these two variables. Conclusion: sCD163 correlates with CD163mRNAexpression in sc and visc AT and with whole-body insulin sensitivity in the steady-state condition. These associations are not observed with respect to the diet-induced changes during a weight-reducing hypocaloric diet. Copyright © 2014 by the Endocrine Society. Source

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In the basement of the Convent of the Jacobins in Rennes, France, archaeologists found five heart-shaped lead urns dating from the 16th and 17th centuries. Ornamented with inscriptions, the urns were identified as carrying embalmed hearts and were found in the vaults of elite-class families. Using magnetic resonance imaging (MRI) and computer tomography (CT), the research team from the National Institute for Preventive Archaeological Research found evidence of present-day heart diseases in the old hearts. “Since four of the five hearts were very well preserved we were able to see signs of present-day heart conditions, such as plaque and atherosclerosis,” said Fatima-Zohra Mokrane, a radiologist at Rangueil Hospital at the Univ. Hospital of Toulouse. In addition to archaeologists and radiologists, the research team included forensic physicians, pathologic physicians and physicists from institutions such as the Molecular Anthropology and Synthesis Imaging and the Institute of Metabolic and Cardiovascular Diseases. First, the team attempted to glean health information from the hearts in their embalmed state. However, the embalming material made imaging difficult. The scans were performed again after the embalming material’s removal. Via the CT images, the researchers identified heart structures, including chambers, valves and coronary arteries. Then, the tissue was rehydrated and an MRI was performed. The MRI allowed the researchers to identify myocardial muscles. Though one heart appeared in good condition, three showed manifestations of disease, such as plaque in the coronary arteries. One of the inscriptions identified the encased heart as belonging to Toussaint Perrien, a Knight of Brefeillac. The heart was removed at the time of his death and later buried with his wife, Louise de Quengo, Lady of Brefeillac. Her preserved body was found at the archaeological site. “It was common during that time period to be buried with the heart of a husband or wife,” Mokrane said. “This was the case with one of our hearts. It’s a very romantic aspect to the burials.”

Louche K.,French Institute of Health and Medical Research | Louche K.,Institute of Metabolic and Cardiovascular Diseases | Badin P.-M.,French Institute of Health and Medical Research | Badin P.-M.,Institute of Metabolic and Cardiovascular Diseases | And 18 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2013

Context: Skeletal muscle lipase and intramyocellular triglyceride (IMTG) play a role in obesityrelated metabolic disorders. Objectives: The aim of the present study was to investigate the impact of 8 weeks of endurance exercise training on IMTG content and lipolytic proteins in obese male subjects. Design and Volunteers: Ten obese subjects completed an 8-week supervised endurance exercise training intervention in which vastus lateralis muscle biopsy samples were collected before and after training. Main Outcome Measures: Clinical characteristics and ex vivo substrate oxidation rates were measured pre-and posttraining. Skeletal muscle lipid content and lipolytic protein expression were also investigated. Results: Our data show that exercise training reduced IMTG content by42%(P<.01) and increased skeletal muscle oxidative capacity, whereas no change in total diacylglycerol content and glucose oxidation was found. Exercise training up-regulated adipose triglyceride lipase, perilipin (PLIN) 3 protein, and PLIN5 protein contents in skeletal muscle despite no change in mRNA levels. Training also increased hormone sensitive-lipase Ser660 phosphorylation. No significant changes in comparative gene identification 58, G0/G1 switch gene 2, and PLIN2 protein and mRNA levels were observed in response to training. Interestingly, we noted a strong relationship between skeletal muscle comparative gene identification 58 and mitochondrial respiratory chain complex I protein contents at baseline (r = 0.87, P < .0001). Conclusions: Endurance exercise training coordinately up-regulates fat oxidative capacity and lipolytic protein expression in skeletal muscle of obese subjects. This physiological adaptation probably favors fat oxidation and may alleviate the lipotoxic lipid pressure in skeletal muscle. Enhancement of IMTG turnover may be required for the beneficial metabolic effects of exercise in obesity. © 2013 by The Endocrine Society. Source

Koc M.,Franco Czech Laboratory for Clinical Research on Obesity | Koc M.,Charles University | Mayerova V.,Franco Czech Laboratory for Clinical Research on Obesity | Mayerova V.,Charles University | And 14 more authors.
Biochemical and Biophysical Research Communications | Year: 2015

Background Adipocytes are cells specialized for storage of neutral lipids. This storage capacity is dependent on lipogenesis and is diminished in obesity. The reason for the decline in lipogenic activity of adipocytes in obesity remains unknown. Recent data show that lipogenesis in liver is regulated by pathways initiated by endoplasmic reticulum stress (ERS). Thus, we aimed at investigating the effect of ERS on lipogenesis in adipose cells. Methods Preadipocytes were isolated from subcutaneous abdominal adipose tissue from obese volunteers and in vitro differentiated into adipocytes. ERS was induced pharmacologically by thapsigargin (TG) or tunicamycin (TM). Activation of Unfolded Protein Response pathway (UPR) was monitored on the level of eIF2α phosphorylation and mRNA expression of downstream targets of UPR sensors. Adipogenic and lipogenic capacity was evaluated by Oil Red O staining, measurement of incorporation of radio-labelled glucose or acetic acid into lipids and mRNA analysis of adipogenic/lipogenic markers. Results Exposition of adipocytes to high doses of TG (100 nM) and TM (1 μg/ml) for 1-24 h enhanced expression of several UPR markers (HSPA5, EDEM1, ATF4, XBP1s) and phosphorylation of eIF2α. This acute ERS substantially inhibited expression of lipogenic genes (DGAT2, FASN, SCD1) and glucose incorporation into lipids. Moreover, chronic exposure of preadipocytes to low dose of TG (2.5 nM) during the early phases of adipogenic conversion of preadipocytes impaired both, lipogenesis and adipogenesis. On the other hand, chronic low ERS had no apparent effect on lipogenesis in mature adipocytes. Conclusions Acute ERS weakened a capacity of mature adipocytes to store lipids and chronic ERS diminished adipogenic potential of preadipocytes. © 2015 Elsevier Inc. All rights reserved. Source

Rossmeislova L.,Franco Czech Laboratory for Clinical Research on Obesity | Rossmeislova L.,French Institute of Health and Medical Research | Rossmeislova L.,Charles University | Malisova L.,Franco Czech Laboratory for Clinical Research on Obesity | And 29 more authors.
Diabetes | Year: 2013

Calorie restriction-induced weight loss is accompanied by profound changes in adipose tissue characteristics. To determine the effect of weight loss on differentiation of preadipocytes and secretory capacity of in vitro differentiated adipocytes, we established cultures of these cells from paired subcutaneous adipose tissue biopsies obtained before and at the end of weight-reducing dietary intervention (DI) in 23 obese women. Based on lipid accumulation and the expression of differentiation markers, in vitro adipogenesis increased after weight loss and it was accompanied by enhanced expression of genes involved in de novo lipogenesis. This effect of weight loss was not driven by changes of peroxisome proliferator-activated receptor γ sensitivity to rosiglitazone. Weight loss also enhanced the expression of adiponectin and leptin while reducing that of monocyte chemoattractant protein 1 and interleukin-8 by cultured adipocytes. Thus, the weight-reducing (DI) increased adipogenic capacity of preadipocytes and shifted their secretion toward lower inflammatory profile. Reprogramming of preadipocytes could represent an adaptation to weight loss leading to partial restoration of preobese adipose tissue traits and thus contribute to the improvement of metabolic status. However, enhanced adipogenesis could also contribute to the unwanted weight regain after initial weight loss. © 2013 by the American Diabetes Association. Source

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