scholarly journals Impairment of Peripheral Circadian Clocks Precedes Metabolic Abnormalities in ob/ob Mice

Endocrinology ◽  
2011 ◽  
Vol 152 (4) ◽  
pp. 1347-1354 ◽  
Author(s):  
Hitoshi Ando ◽  
Masafumi Kumazaki ◽  
Yuya Motosugi ◽  
Kentarou Ushijima ◽  
Tomohiro Maekawa ◽  
...  

Abstract Recent studies have demonstrated relationships between the dysfunction of circadian clocks and the development of metabolic abnormalities, but the chicken-and-egg question remains unresolved. To address this issue, we investigated the cause-effect relationship in obese, diabetic ob/ob mice. Compared with control C57BL/6J mice, the daily mRNA expression profiles of the clock and clock-controlled genes Clock, Bmal1, Cry1, Per1, Per2, and Dbp were substantially dampened in the liver and adipose tissue, but not the hypothalamic suprachiasmatic nucleus, of 10-wk-old ob/ob mice. Four-week feeding of a low-calorie diet and administration of leptin over a 7-d period attenuated, to a significant and comparable extent, the observed metabolic abnormalities (obesity, hyperglycemia, hyperinsulinemia, and hypercholesterolemia) in the ob/ob mice. However, only leptin treatment improved the impaired peripheral clocks. In addition, clock function, assessed by measuring levels of Per1, Per2, and Dbp mRNA at around peak times, was also reduced in the peripheral tissues of 3-wk-old ob/ob mice without any overt metabolic abnormalities. Collectively these results indicate that the impairment of peripheral clocks in ob/ob mice does not result from metabolic abnormalities but may instead be at least partially caused by leptin deficiency itself. Further studies are needed to clarify how leptin deficiency affects peripheral clocks.

2011 ◽  
Vol 96 (4) ◽  
pp. E606-E613 ◽  
Author(s):  
M. Mraz ◽  
Z. Lacinova ◽  
J. Drapalova ◽  
D. Haluzikova ◽  
A. Horinek ◽  
...  

Abstract Context: Low-grade inflammation links obesity, type 2 diabetes mellitus (T2DM), and cardiovascular diseases. Objective: To explore the expression profile of genes involved in inflammatory pathways in adipose tissue and peripheral monocytes (PM) of obese patients with and without T2DM at baseline and after dietary intervention. Design: Two-week intervention study with very-low-calorie diet (VLCD). Setting: University hospital. Patients: Twelve obese females with T2DM, 8 obese nondiabetic females (OB) and 15 healthy age-matched females. Intervention: Two weeks of VLCD (2500 kJ/d). Main Outcome Measures: Metabolic parameters, circulating cytokines, hormones, and mRNA expression of 39 genes in sc adipose tissue (SCAT) and PM. Results: Both T2DM and OB group had significantly increased serum concentrations of circulating proinflammatory factors (C-reactive protein, TNFα, IL-6, IL-8), mRNA expression of macrophage antigen CD68 and proinflammatory chemokines (CCL-2, -3, -7, -8, -17, -22) in SCAT and complementary chemokine receptors (CCR-1, -2, -3, -5) and other proinflammatory receptors (toll-like receptor 2 and 4, TNF receptor superfamily 1A and 1B, IL-6R) in PM, with OB group showing less pronounced chemoattracting and proinflammatory profile compared to T2DM group. In T2DM patients VLCD decreased body weight, improved metabolic profile, and decreased mRNA expression of up-regulated CCRs in PM and chemokines [CCL 8, chemokine (C-X-C motif) ligand 10] in SCAT. VLCD markedly increased mRNA expression of T-lymphocyte attracting chemokine CCL-17 in SCAT. Conclusion: Obese patients with and without T2DM have increased mRNA expression of chemotactic and proinflammatory factors in SCAT and expression of corresponding receptors in PM. Two weeks of VLCD significantly improved this profile in T2DM patients.


2012 ◽  
Vol 302 (2) ◽  
pp. E226-E232 ◽  
Author(s):  
Katrien Koppo ◽  
Michaela Siklová-Vitková ◽  
Eva Klimčáková ◽  
Jan Polák ◽  
Marie A. Marques ◽  
...  

The aim of this study was to investigate the evolution of the adrenergic and insulin-mediated regulation of lipolysis during different phases of a 6-mo dietary intervention. Eight obese women underwent a 6-mo dietary intervention consisting of a 1-mo very low-calorie diet (VLCD) followed by a 2-mo low-calorie diet (LCD) and 3-mo weight maintenance (WM) diet. At each phase of the dietary intervention, microdialysis of subcutaneous adipose tissue (SCAT) was performed at rest and during a 3-h hyperinsulinemic euglycemic clamp. Responses of dialysate glycerol concentration (DGC) were determined at baseline and during local perfusions with adrenaline or adrenaline and phentolamine before and during the last 30 min of the clamp. Dietary intervention induced a body weight reduction and an improved insulin sensitivity. DGC progressively decreased during the clamp, and this decrease was similar during the different phases of the diet. The adrenaline-induced increase in DGC was higher at VLCD and LCD compared with baseline condition and returned to prediet levels at WM. In the probe with adrenaline and phentolamine, the increase in DGC was higher than that in the adrenaline probe at baseline and WM, but it was not different at VLCD and LCD. The results suggest that the responsiveness of SCAT to adrenaline-stimulated lipolysis increases during the calorie-restricted phases due to a reduction of the α2-adrenoceptor-mediated antilipolytic action of adrenaline. At WM, adrenaline-stimulated lipolysis returned to the prediet levels. Furthermore, no direct relationship between insulin sensitivity and the diet-induced changes in the regulation of lipolysis was found.


2014 ◽  
pp. 73-82 ◽  
Author(s):  
L. MALIŠOVÁ ◽  
L. ROSSMEISLOVÁ ◽  
Z. KOVÁČOVÁ ◽  
J. KRAČMEROVÁ ◽  
M. TENCEROVÁ ◽  
...  

Accumulation of adipose tissue in lower body lowers risk of cardiovascular and metabolic disorders. The molecular basis of this protective effect of gluteofemoral depot is not clear. The aim of this study was to compare the profile of expression of inflammation-related genes in subcutaneous gluteal (sGAT) and abdominal (sAAT) adipose tissue at baseline and in response to multiphase weight-reducing dietary intervention (DI). 14 premenopausal healthy obese women underwent a 6 months’ DI consisting of 1 month very-low-calorie-diet (VLCD), subsequent 2 months’ low-calorie-diet and 3 months’ weight maintenance diet (WM). Paired samples of sGAT and sAAT were obtained before and at the end of VLCD and WM periods. mRNA expression of 17 genes (macrophage markers, cytokines) was measured using RT-qPCR on chip-platform. At baseline, there were no differences in gene expression of macrophage markers and cytokines between sGAT and sAAT. The dynamic changes induced by DI were similar in both depots for all genes except for three cytokines (IL6, IL10, CCL2) that differed in their response during weight maintenance phase. The results show that, in obese women, there are no major differences between sGAT and sAAT in expression of inflammation-related genes at baseline conditions and in response to the weight-reducing DI.


2016 ◽  
Vol 101 (12) ◽  
pp. 5021-5029 ◽  
Author(s):  
Veronika Šrámková ◽  
Lenka Rossmeislová ◽  
Eva Krauzová ◽  
Jana Kračmerová ◽  
Michal Koc ◽  
...  

2009 ◽  
Vol 160 (4) ◽  
pp. 585-592 ◽  
Author(s):  
Zuzana Kovacova ◽  
Michaela Vitkova ◽  
Michaela Kovacikova ◽  
Eva Klimcakova ◽  
Magda Bajzova ◽  
...  

ObjectiveAdiponectin is a protein abundantly secreted by the adipose tissue (AT). Plasma adiponectin levels are decreased in obese, insulin-resistant, and type 2 diabetic patients. Various multimeric complexes, i.e. high-, middle-, and low-molecular weight isoforms (HMW, MMW and LMW), are present in plasma. Here, we investigated the effect of weight reducing diet on the distribution of adiponectin isoforms in plasma and on their secretion in AT explants from obese subjects.DesignA total of 20 obese subjects (age 37.8±7.3 years, body mass index 33.9±5.0 kg/m2) underwent eight weeks of very low-calorie diet (VLCD). A needle biopsy of subcutaneous abdominal AT and blood samples were taken before and after dietary intervention. AT explants were incubated in culture medium for 4 h. ELISA assay and western blot analyses were used to identify adiponectin complexes in culture media and in plasma.ResultsThe distribution of adiponectin polymers in plasma was different from that secreted in human AT explants. Before VLCD, the relative amount of HMW isoform was 75.5±9.1% of total adiponectin in culture media and 52.2±11.2% in plasma. Despite the diet-induced weight loss and improvement of insulin sensitivity, VLCD neither induced change in total adiponectin level nor in the ratio of HMW to total adiponectin in plasma and in culture media of AT explants.ConclusionsThe profile of adiponectin polymeric isoforms secreted by AT explants into culture media differs from the plasma profile. A dietary intervention leading to weight loss and improvement of insulin sensitivity was not associated with modifications of AT secretion of total or HMW adiponectin.


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