scholarly journals Rhythmic Messenger Ribonucleic Acid Expression of Clock Genes and Adipocytokines in Mouse Visceral Adipose Tissue

Endocrinology ◽  
2005 ◽  
Vol 146 (12) ◽  
pp. 5631-5636 ◽  
Author(s):  
Hitoshi Ando ◽  
Hayato Yanagihara ◽  
Yohei Hayashi ◽  
Yuri Obi ◽  
Shuichi Tsuruoka ◽  
...  

Various peripheral tissues show circadian rhythmicity, which is generated at the cellular level by their own core oscillators that are composed of transcriptional/translational feedback loops involving a set of clock genes. Although the circulating levels of some adipocytokines, i.e. bioactive substances secreted by adipocytes, are on a 24-h rhythmic cycle, it remains to be elucidated whether the clock gene system works in adipose tissue. To address this issue, we investigated the daily mRNA expression profiles of the clock genes and adipocytokines in mouse perigonadal adipose tissues. In C57BL/6J mice, all transcript levels of the clock genes (Bmal1, Per1, Per2, Cry1, Cry2, and Dbp) and adipocytokines (adiponectin, resistin, and visfatin) clearly showed 24-h rhythms. On the other hand, the rhythmic expression of these genes was mildly attenuated in obese KK mice and greatly attenuated in more obese, diabetic KK-Ay mice. Obese diabetes also diminished the rhythmic expression of the clock genes in the liver. Interestingly, a 2-wk treatment of KK and KK-Ay mice with pioglitazone impaired the 24-h rhythmicity of the mRNA expression of the clock genes and adipocytokines despite the antidiabetic effect of the drug. In contrast, pioglitazone improved the attenuated rhythmicity in the liver. These findings suggest that the intracellular clock gene system acts in visceral adipose tissues as well as liver and is influenced by the conditions of obesity/type 2 diabetes and pioglitazone treatment.

Endocrinology ◽  
2016 ◽  
Vol 157 (9) ◽  
pp. 3320-3331 ◽  
Author(s):  
Michaela D. Wharfe ◽  
Caitlin S. Wyrwoll ◽  
Brendan J. Waddell ◽  
Peter J. Mark

Maternal adaptations in lipid metabolism are crucial for pregnancy success due to the role of white adipose tissue as an energy store and the dynamic nature of energy needs across gestation. Because lipid metabolism is regulated by the rhythmic expression of clock genes, it was hypothesized that maternal metabolic adaptations involve changes in both adipose clock gene expression and the rhythmic expression of downstream metabolic genes. Maternal core body temperature (Tc) was investigated as a possible mechanism driving pregnancy-induced changes in clock gene expression. Gonadal adipose tissue and plasma were collected from C57BL/6J mice before and on days 6, 10, 14, and 18 of pregnancy (term 19 d) at 4-hour intervals across a 24-hour period. Adipose expression of clock genes and downstream metabolic genes were determined by quantitative RT-PCR, and Tc was measured by intraperitoneal temperature loggers. Adipose clock gene expression showed robust rhythmicity throughout pregnancy, but absolute levels varied substantially across gestation. Rhythmic expression of the metabolic genes Lipe, Pnpla2, and Lpl was clearly evident before pregnancy; however, this rhythmicity was lost with the onset of pregnancy. Tc rhythm was significantly altered by pregnancy, with a 65% decrease in amplitude by term and a 0.61°C decrease in mesor between days 6 and 18. These changes in Tc, however, did not appear to be linked to adipose clock gene expression across pregnancy. Overall, our data show marked adaptations in the adipose clock in pregnancy, with an apparent decoupling of adipose clock and lipolytic/lipogenic gene rhythms from early in gestation.


2010 ◽  
Vol 504 (1) ◽  
pp. 17-25 ◽  
Author(s):  
Masashi Hosokawa ◽  
Tatsuya Miyashita ◽  
Sho Nishikawa ◽  
Shingo Emi ◽  
Takayuki Tsukui ◽  
...  

2020 ◽  
Vol 112 (4) ◽  
pp. 979-990
Author(s):  
Anish Zacharia ◽  
Daniel Saidemberg ◽  
Chanchal Thomas Mannully ◽  
Natalya M Kogan ◽  
Alaa Shehadeh ◽  
...  

ABSTRACT Background Adipose tissue plays important roles in health and disease. Given the unique association of visceral adipose tissue with obesity-related metabolic diseases, the distribution of lipids between the major fat depots located in subcutaneous and visceral regions may shed new light on adipose tissue–specific roles in systemic metabolic perturbations. Objective We sought to characterize the lipid networks and unveil differences in the metabolic infrastructure of the 2 adipose tissues that may have functional and nutritional implications. Methods Paired visceral and subcutaneous adipose tissue samples were obtained from 17 overweight patients undergoing elective abdominal surgery. Ultra-performance LC-MS was used to measure 18,640 adipose-derived features; 520 were putatively identified. A stem cell model for adipogenesis was used to study the functional implications of the differences found. Results Our analyses resulted in detailed lipid metabolic maps of the 2 major adipose tissues. They point to a higher accumulation of phosphatidylcholines, triacylglycerols, and diacylglycerols, although lower ceramide concentrations, in subcutaneous tissue. The degree of unsaturation was lower in visceral adipose tissue (VAT) phospholipids, indicating lower unsaturated fatty acid incorporation into adipose tissue. The differential abundance of phosphatidylcholines we found can be attributed at least partially to higher expression of phosphatidylethanolamine methyl transferase (PEMT). PEMT-deficient embryonic stem cells showed a dramatic decrease in adipogenesis, and the resulting adipocytes exhibited lower accumulation of lipid droplets, in line with the lower concentrations of glycerolipids in VAT. Ceramides may inhibit the expression of PEMT by increased insulin resistance, thus potentially suggesting a functional pathway that integrates ceramide, PEMT, and glycerolipid biosynthetic pathways. Conclusions Our work unveils differential infrastructure of the lipid networks in visceral and subcutaneous adipose tissues and suggests an integrative pathway, with a discriminative flux between adipose tissues.


2019 ◽  
Vol 34 (2) ◽  
pp. 131-143 ◽  
Author(s):  
Jiajia Li ◽  
Renee Yin Yu ◽  
Farida Emran ◽  
Brian E. Chen ◽  
Michael E. Hughes

The circadian clock is an evolutionarily conserved mechanism that generates the rhythmic expression of downstream genes. The core circadian clock drives the expression of clock-controlled genes, which in turn play critical roles in carrying out many rhythmic physiological processes. Nevertheless, the molecular mechanisms by which clock output genes orchestrate rhythmic signals from the brain to peripheral tissues are largely unknown. Here we explored the role of one rhythmic gene, Achilles, in regulating the rhythmic transcriptome in the fly head. Achilles is a clock-controlled gene in Drosophila that encodes a putative RNA-binding protein. Achilles expression is found in neurons throughout the fly brain using fluorescence in situ hybridization (FISH), and legacy data suggest it is not expressed in core clock neurons. Together, these observations argue against a role for Achilles in regulating the core clock. To assess its impact on circadian mRNA rhythms, we performed RNA sequencing (RNAseq) to compare the rhythmic transcriptomes of control flies and those with diminished Achilles expression in all neurons. Consistent with previous studies, we observe dramatic upregulation of immune response genes upon knock-down of Achilles. Furthermore, many circadian mRNAs lose their rhythmicity in Achilles knock-down flies, suggesting that a subset of the rhythmic transcriptome is regulated either directly or indirectly by Achilles. These Achilles-mediated rhythms are observed in genes involved in immune function and in neuronal signaling, including Prosap, Nemy and Jhl-21. A comparison of RNAseq data from control flies reveals that only 42.7% of clock-controlled genes in the fly brain are rhythmic in both males and females. As mRNA rhythms of core clock genes are largely invariant between the sexes, this observation suggests that sex-specific mechanisms are an important, and heretofore under-appreciated, regulator of the rhythmic transcriptome.


Obesity Facts ◽  
2012 ◽  
Vol 5 (3) ◽  
pp. 452-459 ◽  
Author(s):  
Thais Ortiz Hammes ◽  
Cíntia dos Santos Costa ◽  
Francieli Rohden ◽  
Rogério Margis ◽  
Jussara Carnevale de Almeida ◽  
...  

2005 ◽  
Vol 21 (3) ◽  
pp. 343-350 ◽  
Author(s):  
Daisuke Hishikawa ◽  
Yeon-Hee Hong ◽  
Sang-gun Roh ◽  
Hisae Miyahara ◽  
Yukihiko Nishimura ◽  
...  

The factors that control fat deposition in adipose tissues are poorly understood. It is known that visceral adipose tissues display a range of biochemical properties that distinguish them from adipose tissues of subcutaneous origin. However, we have little information on gene expression, either in relation to fat deposition or on interspecies variation in fat deposition. The first step in this study was to identify genes expressed in fat depot of cattle using the differential display RT-PCR method. Among the transcripts identified as having differential expression in the two adipose tissues were cell division cycle 42 homolog (CDC42), prefoldin-5, decorin, phosphate carrier, 12S ribosomal RNA gene, and kelch repeat and BTB domain containing 2 (Kbtbd2). In subsequent experiments, we determined the expression levels of these latter genes in the pig and in mice fed either a control or high-fat diet to compare the regulation of fat accumulation in other animal species. The levels of CDC42 and decorin mRNA were found to be higher in visceral adipose tissue than in subcutaneous adipose tissue in cattle, pig, and mice. However, the other genes studied did not show consistent expression patterns between the two tissues in cattle, pigs, and mice. Interestingly, all genes were upregulated in subcutaneous and/or visceral adipose tissues of mice fed the high-fat diet compared with the control diet. The data presented here extend our understanding of gene expression in fat depots and provide further proof that the mechanisms of fat accumulation differ significantly between animal species.


2005 ◽  
Vol 84 (12) ◽  
pp. 1193-1197 ◽  
Author(s):  
M. Furukawa ◽  
T. Kawamoto ◽  
M. Noshiro ◽  
K.K. Honda ◽  
M. Sakai ◽  
...  

Clock genes, which mediate molecular circadian rhythms, are expressed in a circadian fashion in the suprachiasmatic nucleus and in various peripheral tissues. To establish a molecular basis for circadian regulation in the salivary glands, we examined expression profiles of clock-related genes and salivary gland-characteristic genes. Clock-related genes—including Per1, Per2, Cry1, Bmal1, Dec1, Dec2, Dbp, and Reverbα—showed robust circadian expression rhythms in the submandibular glands in 12:12-hour light-dark conditions. In addition, a robust circadian rhythm was observed in amylase 1 mRNA levels, whereas the expression of other salivary-gland-characteristic genes examined was not rhythmic. The Clock mutation resulted in increased or decreased mRNA levels of Per2, Bmal1, Dec1, Dec2, and Dbp, and in Cry1− /− background, Cry2 disruption also increased or decreased mRNA levels of these clock-related genes and the amylase 1 gene. These findings indicate that the Clock- and Cry-dependent molecular clock system is active in the salivary glands.


2004 ◽  
pp. 579-584 ◽  
Author(s):  
E Schoof ◽  
A Stuppy ◽  
F Harig ◽  
R Carbon ◽  
T Horbach ◽  
...  

OBJECTIVE: Adipose tissue displays depot-specific metabolic properties and a predominant gene expression of leptin in subcutaneous tissue. The aim of the study was to evaluate leptin mRNA expression in various adipose tissues and to relate it to plasma leptin concentrations. Furthermore, developmental changes in leptin gene expression from childhood to adulthood were examined. DESIGN AND METHODS: Thoracic subcutaneous and intrathoracic adipose tissue specimens were obtained in 22 adults (51-81 years) and 23 children (0.1-17 years) undergoing cardiac surgery, and abdominal subcutaneous, omental and mesenterial fat specimens were collected from 21 adults (38-79 years) and 22 children (0.2-17 years) before abdominal surgery. Preoperative plasma leptin concentrations were measured by RIA. Leptin mRNA expression was quantified by TaqMan real-time PCR. RESULTS: In adults, there was no difference between leptin gene expression in subcutaneous and intrathoracic fat, whereas in children leptin mRNA expression was significantly higher in subcutaneous adipose tissue. In omental fat, leptin mRNA levels were significantly lower compared with subcutaneous and mesenterial sites in both children and adults. Adults revealed a significantly higher leptin gene expression in subcutaneous, omental and mesenterial adipose tissues than children. Subcutaneous and omental leptin gene expression are independent factors for plasma leptin concentrations in children and adults. CONCLUSION: Leptin is differentially expressed at different adipose tissue sites, a situation which is even more pronounced in children. There is a developmental increase in leptin mRNA expression in adipose tissue during childhood, reaching maximal capacity in adulthood.


Endocrinology ◽  
2008 ◽  
Vol 149 (4) ◽  
pp. 1454-1461 ◽  
Author(s):  
F. J. Valenzuela ◽  
C. Torres-Farfan ◽  
H. G. Richter ◽  
N. Mendez ◽  
C. Campino ◽  
...  

The circadian production of glucocorticoids involves the concerted action of several factors that eventually allow an adequate adaptation to the environment. Circadian rhythms are controlled by the circadian timing system that comprises peripheral oscillators and a central rhythm generator located in the suprachiasmatic nucleus (SCN) of the hypothalamus, driven by the self-regulatory interaction of a set of proteins encoded by genes named clock genes. Here we describe the phase relationship between the SCN and adrenal gland for the expression of selected core clock transcripts (Per-2, Bmal-1) in the adult capuchin monkey, a New World, diurnal nonhuman primate. In the SCN we found a higher expression of Bmal-1 during the h of darkness (2000–0200 h) and Per-2 during daytime h (1400 h). The adrenal gland expressed clock genes in oscillatory fashion, with higher values for Bmal-1 during the day (1400–2000 h), whereas Per-2 was higher at nighttime (about 0200 h), resulting in a 9- to 12-h antiphase pattern. In the adrenal gland, the oscillation of clock genes was accompanied by rhythmic expression of a functional output, the steroidogenic enzyme 3β-hydroxysteroid dehydrogenase. Furthermore, we show that adrenal explants maintained oscillatory expression of Per-2 and Bmal-1 for at least 36 h in culture. The acrophase of both transcripts, but not its overall expression along the incubation, was blunted by 100 nm melatonin. Altogether, these results demonstrate oscillation of clock genes in the SCN and adrenal gland of a diurnal primate and support an oscillation of clock genes in the adrenal gland that may be modulated by the neurohormone melatonin.


2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 571-571
Author(s):  
Wen-Hao Xu ◽  
Yuan-Yuan Qu ◽  
Jun Wang ◽  
Hai-Liang Zhang ◽  
Dingwei Ye

571 Background: Growing evidence has proved obesity one of the confirmed important etiologic indicators for renal cell carcinoma (RCC). CD36 is underpinned to be involved in adipose absorption, but its role in clear cell renal cell carcinoma (ccRCC) remains unclear. This study aimed to investigate the mRNA expression of CD36 in anthropometric measures of adipose tissue and defining its value in predicting prognosis in ccRCC patients. Methods: Real-Time qPCR was detected from 367 paired ccRCC and adjacent normal tissues. Distributions of categorical clinical-pathological data together with levels of CD36 expression were compared with χ2-test. Subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) were measured by MRI. Pearson’s correlation coefficient was utilized to quantify relations between body mass index (BMI), VAT%, SAT and CD36 expression respectively. Cox regression analysis were developed to address the influence of independent factors on prognostic value. Gene Set Enrichment Analysis (GSEA) was performed to select related genes and pathways from TCGA database. Results: In the current study, we demonstrated that CD36 mRNA was highly expressed in ccRCC tissues, and was found significantly increased in patients with advanced TNM stage ( p= 0.003, p< 0.001, p< 0.001), and high VAT% ( p= 0.004). Pearson’s correlation coefficient indicated CD36 amplification positively correlated with BMI ( r= 0.117, p= 0.025), VAT% ( r= 0.465, p< 0.001), while negatively with SAT ( r= -0.296, p= 0.002). Furthermore, ccRCC patients with elevated CD36 expression held shorter PFS and OS, with HR of 4.873 (3.300-7.196, p< 0.001) and 4.610 (2.956-7.189, p< 0.001). In 104 cases whose MRI scans were available, VAT was significantly correlated with poor PFS and OS. Significant genes were obtained from GSEA, and CD36 was found involved in the most significant pathways including fatty acid metabolism, angiogenesis and TGF-β signaling pathways. Conclusions: In conclusion, our study first reveal that elevated CD36 mRNA expression is positively correlated to distribution of abdominal adipose, particularly VAT%, which, in addition, notably predicts poor prognosis in ccRCC patients.


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