Role of cardiotrophin‐1 in the regulation of metabolic circadian rhythms and adipose core clock genes in mice and characterization of 24‐h circulating CT‐1 profiles in normal‐weight and overweight/obese subjects

Taste plays an important role in processes such as food choices, nutrition status and health. Salivary proteins contribute to taste sensitivity. Taste reduction has been associated with obesity. Gender influences the obesity predisposition and the genetic ability to perceive the bitterness of 6-n-propylthiouracil (PROP), oral marker for food preferences and consumption. We investigated variations in the profile of salivary proteome, analyzed by HPLC-ESI-MS, between sixty-one normal weight subjects (NW) and fifty-seven subjects with obesity (OB), based on gender and PROP sensitivity. Results showed variations of taste-related salivary proteins between NW and OB, which were differently associated with gender and PROP sensitivity. High levels of Ps-1, II-2 and IB-1 proteins belonging to basic proline rich proteins (bPRPs) and PRP-1 protein belonging to acid proline rich proteins (aPRPs) were found in OB males, who showed a lower body mass index (BMI) than OB females. High levels of Ps-1 protein and Cystatin SN (Cyst SN) were found in OB non-tasters, who had lower BMI than OB super-tasters. These new insights on the role of salivary proteins as a factor driving the specific weight gain of OB females and super-tasters, suggest the use of specific proteins as a strategic tool modifying taste responses related to eating behavior.

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BMAL1 but not CLOCK is associated with monochromatic green light-induced circadian rhythm of melatonin in chick pinealocytes

Endocrine Connections ◽

10.1530/ec-18-0377 ◽

2019 ◽

Vol 8 (1) ◽

pp. 57-68 ◽

Cited By ~ 2

Author(s):

Shuhui Ma ◽

Zixu Wang ◽

Jing Cao ◽

Yulan Dong ◽

Yaoxing Chen

Keyword(s):

Circadian Rhythm ◽

Circadian Rhythms ◽

Pineal Gland ◽

Clock Genes ◽

Critical Role ◽

Green Light ◽

Circadian Oscillator ◽

Melatonin Secretion ◽

Expression Levels

The avian pineal gland, an independent circadian oscillator, receives external photic cues and translates them for the rhythmical synthesis of melatonin. Our previous study found that monochromatic green light could increase the secretion of melatonin and expression of CLOCK and BMAL1 in chick pinealocytes. This study further investigated the role of BMAL1 and CLOCK in monochromatic green light-induced melatonin secretion in chick pinealocytes using siRNAs interference and overexpression techniques. The results showed that si-BMAL1 destroyed the circadian rhythms of AANAT and melatonin, along with the disruption of the expression of all the seven clock genes, except CRY1. Furthermore, overexpression of BMAL1 also disturbed the circadian rhythms of AANAT and melatonin, in addition to causing arrhythmic expression of BMAL1 and CRY1/2, but had no effect on the circadian rhythms of CLOCK, BMAL2 and PER2/3. The knockdown or overexpression of CLOCK had no impact on the circadian rhythms of AANAT, melatonin, BMAL1 and PER2, but it significantly deregulated the circadian rhythms of CLOCK, BMAL2, CRY1/2 and PER3. These results suggested that BMAL1 rather than CLOCK plays a critical role in the regulation of monochromatic green light-induced melatonin rhythm synthesis in chicken pinealocytes. Moreover, both knockdown and overexpression of BMAL1 could change the expression levels of CRY2, it indicated CRY2 may be involved in the BMAL1 pathway by modulating the circadian rhythms of AANAT and melatonin.

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The Angiotensin-Melatonin Axis

International Journal of Hypertension ◽

10.1155/2013/521783 ◽

2013 ◽

Vol 2013 ◽

pp. 1-7 ◽

Cited By ~ 32

Author(s):

Luciana A. Campos ◽

Jose Cipolla-Neto ◽

Fernanda G. Amaral ◽

Lisete C. Michelini ◽

Michael Bader ◽

...

Keyword(s):

Circadian Rhythms ◽

Metabolic Disorders ◽

Clock Genes ◽

Renin Angiotensin System ◽

Angiotensin System ◽

Beneficial Effects ◽

Progression Of Disease ◽

The Central Nervous System ◽

Peripheral Clocks

Accumulating evidence indicates that various biological and neuroendocrine circadian rhythms may be disrupted in cardiovascular and metabolic disorders. These circadian alterations may contribute to the progression of disease. Our studies direct to an important role of angiotensin II and melatonin in the modulation of circadian rhythms. The brain renin-angiotensin system (RAS) may modulate melatonin synthesis, a hormone with well-established roles in regulating circadian rhythms. Angiotensin production in the central nervous system may not only influence hypertension but also appears to affect the circadian rhythm of blood pressure. Drugs acting on RAS have been proven effective in the treatment of cardiovascular and metabolic disorders including hypertension and diabetes mellitus (DM). On the other hand, since melatonin is capable of ameliorating metabolic abnormalities in DM and insulin resistance, the beneficial effects of RAS blockade could be improved through combined RAS blocker and melatonin therapy. Contemporary research is evidencing the existence of specific clock genes forming central and peripheral clocks governing circadian rhythms. Further research on the interaction between these two neurohormones and the clock genes governing circadian clocks may progress our understanding on the pathophysiology of disease with possible impact on chronotherapeutic strategies.

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REVIEW OF RESEARCH ON THE RELATIONSHIP BETWEEN CIRCADIAN RHYTHMS AND CARCINOGENESIS USING ANIMAL MODELS

Siberian Journal of Oncology ◽

10.21294/1814-4861-2021-20-3-134-143 ◽

2021 ◽

Vol 20 (3) ◽

pp. 134-143

Author(s):

G. S. Kireeva ◽

E. A. Gubareva ◽

M. A. Maydin ◽

A. V. Panchenko ◽

M. L. Tyndyk ◽

...

Keyword(s):

Circadian Rhythms ◽

Animal Models ◽

Clock Gene ◽

Clock Genes ◽

Tumor Development ◽

Malignant Neoplasms ◽

Light Cycle ◽

Gene System ◽

The Relationship

Purpose of the study: to review in vivo studies on the relationship and role of various molecular genetic components of the circadian rhythm system in the initiation and development of malignant neoplasms. in contrast to clinical and epidemiological studies, animal models, including transgenic animal models, can model various changes and disturbances in the activity of clock genes and track the results of these changes.Material and Methods. the review includes data from studies carried out over the past 10 years in animal models, studying the mechanisms and effects of disturbances in the system of circadian rhythms related to the formation and development of tumors. the data sources for the review were the Medline, embase and scopus databases.Results. analysis of the literature has shown that interference with the work of the «biological clock» by changing the light cycle, disrupting the expression of clock genes and other manipulations is a factor predisposing to the development of tumors. in tumors of various types, the expression of clock genes is often mismatched, and it is unclear at what stage of their formation this occurs. in addition, the development of tumors disrupts the circadian homeostasis of the body. there are three key areas of research aimed at studying the role of circadian rhythms in tumor development: disturbance of circadian rhythms as a carcinogenic factor, disturbances in the clock gene system in a tumor, disturbances in the clock gene system of the whole organism, provoked by tumor development.Conclusion. the results of studies on animal models demonstrate that the relationship between the disturbance of circadian rhythms and the tumor process is complex since the causal relationship has not yet been studied. in this regard, the prospect of targeted pharmacological correction of circadian rhythms in clinical practice in cancer patients does not seem to be the nearest one.

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Duodenal Metatranscriptomics to Define Human and Microbial Functional Alterations Associated with Severe Obesity: A Pilot Study

Microorganisms ◽

10.3390/microorganisms8111811 ◽

2020 ◽

Vol 8 (11) ◽

pp. 1811

Author(s):

Ilaria Granata ◽

Carmela Nardelli ◽

Valeria D’Argenio ◽

Salvatore Tramontano ◽

Debora Compare ◽

...

Keyword(s):

Pilot Study ◽

Metabolic Pathways ◽

Severe Obesity ◽

Functional Characterization ◽

Human Genes ◽

Severely Obese ◽

Obese Subjects ◽

And Function

Obesity is a multifactorial disorder, and the gut microbiome has been suggested to contribute to its onset. In order to better clarify the role of the microbiome in obesity, we evaluated the metatranscriptome in duodenal biopsies from a cohort of 23 adult severely obese and lean control subjects using next generation sequencing. Our aim was to provide a general picture of the duodenal metatranscriptome associated with severe obesity. We found altered expressions of human and microbial genes in the obese compared to lean subjects, with most of the gene alterations being present in the carbohydrate, protein, and lipid metabolic pathways. Defects were also present in several human genes involved in epithelial intestinal cells differentiation and function, as well as in the immunity/inflammation pathways. Moreover, the microbial taxa abundance inferred by our transcriptomic data differed in part from the data that we previously evaluated by 16S rRNA in 13/23 individuals of our cohort, particularly concerning the Firmicutes and Proteobacteria phyla abundances. In conclusion, our pilot study provides the first taxonomic and functional characterization of duodenal microbiota in severely obese subjects and lean controls. Our findings suggest that duodenal microbiome and human genes both play a role in deregulating metabolic pathways, likely affecting energy metabolism and thus contributing to the obese phenotype.

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Dyslipidemia, C-reactive protein and leptin levels in non diabetic obese subjects

Bangladesh Liver Journal ◽

10.3329/blj.v1i1.2625 ◽

1970 ◽

Vol 1 (1) ◽

pp. 41-50

Author(s):

Sowbhagya Lakshmi ◽

DM Ravichand

Keyword(s):

Cardiovascular Disease ◽

Total Cholesterol ◽

Protective Factor ◽

Normal Subjects ◽

Normal Weight ◽

Serum Samples ◽

Obese Subjects ◽

Cardio Vascular ◽

Relationship Of

Introduction: The objective of the study is to find the relationship of obesity with dyslipidemia and Leptin levels. Material and Methods: The study was carried out in the Department of clinical Biochemistry, Bangalore Medical College. Cases and controls were chosen from the subjects attending the out patient department of Victoria hospital for their routine check up.The protocol of the study was to study and compare the linear relationship of obesity, dyslipidemia, CRP and Leptin levels is Non Diabetic obese persons to Non Diabetic persons with normal weight. The protocol was based on inclusion and exclusion criteria and is approved by local ethical committee Serum samples were stored at -200C for estimation of Leptin and CRP levels. The samples were thawed on one stretch for the estimation. Leptin was analyzed by DRG Leptin sand witch ELISA method by using kit from DRG Company. Results: About 8.0% of patients had elevated Total cholesterol in normal subjects when compared to 84.0% in Obese subjects, indicates that patients with obesity are 60.37 times more likely to have elevated Total cholesterol (>200 mg/dl) when compared to Normal. Patients with obesity (98.0%) are 46.23 times more likely to have elevated Triglycerides when compared to normal subjects (52.0%). Subjects in Obese groups, 76.0% had decreased HDL when compared to only 12.0% on Normal group, which 8.14 times more likely in obsess group. Subjects with obesity (80.0%) are 29.33 times more likely to have elevated LDL (>150 mg/dl) when compared to Normal subjects (12.0%). The elevated VLDL is 21.0 times more likely in obese subjects (84.0%) when compared to normal subjects (20.0%). Subjects in obese are 46.58 times more likely to have elevated LP (a) when compared to normal subjects. Conclusions: Present study has shown a strong link between obesity, dislipidemia and cardiovascular disease in accordance with other studies. The role of Leptin associated with cardiovascular disease is not well established, so prospective study should be carried out to elucidate the role of Leptin in cardio vascular disease and Diabetes to establish its role as, whether it is causative, additive risk factor or a protective factor. Leptin may play a role to prevent metabolic syndrome by its interaction with neuroendocrine systems to maintain metabolic homeostasis, similar to the role played by Insulin in homeostasis of blood sugar level. doi: 10.3329/blj.v1i1.2625 Bangladesh Liver Journal Vol.1(1) 2009 p.41-50

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Circadian rhythms and reproduction

Reproduction ◽

10.1530/rep.1.00614 ◽

2006 ◽

Vol 132 (3) ◽

pp. 379-392 ◽

Cited By ~ 81

Author(s):

Michael J Boden ◽

David J Kennaway

Keyword(s):

Circadian Rhythms ◽

Reproductive Performance ◽

Clock Genes ◽

Strain Differences ◽

Reproductive Function ◽

Circadian Timing ◽

Wide Range ◽

Timing System ◽

Circadian Timing System

There is a growing recognition that the circadian timing system, in particular recently discovered clock genes, plays a major role in a wide range of physiological systems. Microarray studies, for example, have shown that the expression of hundreds of genes changes many fold in the suprachiasmatic nucleus, liver heart and kidney. In this review, we discuss the role of circadian rhythmicity in the control of reproductive function in animals and humans. Circadian rhythms and clock genes appear to be involved in optimal reproductive performance, but there are sufficient redundancies in their function that many of the knockout mice produced do not show overt reproductive failure. Furthermore, important strain differences have emerged from the studies especially between the variousClock(CircadianLocomotorOutputCycleKaput) mutant strains. Nevertheless, there is emerging evidence that the primary clock genes,ClockandBmal1(Brain andMuscleARNT-like protein 1, also known asMop3), strongly influence reproductive competency. The extent to which the circadian timing system affects human reproductive performance is not known, in part, because many of the appropriate studies have not been done. With the role ofClockandBmal1in fertility becoming clearer, it may be time to pursue the effect of polymorphisms in these genes in relation to the various types of infertility in humans.

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Hypomethylation of NANOG promoter in colonic mucosal cells of obese patients: a possible role of NF-κB

British Journal Of Nutrition ◽

10.1017/s000711451800212x ◽

2018 ◽

Vol 122 (5) ◽

pp. 499-508 ◽

Cited By ~ 2

Author(s):

Fatemeh Sedaghat ◽

Makan Cheraghpour ◽

Seyed Ahmad Hosseini ◽

Katayoun Pourvali ◽

Ladan Teimoori-Toolabi ◽

...

Keyword(s):

Transcription Factors ◽

Promoter Methylation ◽

Central Obesity ◽

Normal Weight ◽

Intestinal Cell ◽

Differentiated Cells ◽

Mucosal Cells ◽

Obese Subjects ◽

Ht 29

AbstractObesity and particularly central obesity are the main risk factors of colon cancer. All intestinal cell populations including stem cells, their progenitors and differentiated colonocytes seem to be the origin of colorectal cancer. However, recent data support the role of differentiated cells as cancer origin especially during inflammation. Based on Yamanaka’s seminal work, re-expression of few transcription factors in terminally differentiated cells creates stemness properti'es. Although these transcription factors are involved in tumorigenesis, they are epigenetically repressed in adult tissues. We proposed that obesity might regulate methylation of stemness genes in colonocytes via inflammatory signalling. Obesity-associated inflammation was analysed using Western blot analysis of phospho-IκB (inhibitor of NF-κB). Methylation-sensitive high-resolution melting analysis was performed on colonic mucosal samples of twenty obese and twenty normal-weight men to analyse promoter methylation of POU5F1 (OCT4), NANOG, MYC and CDKN2A. TNF-treated HT-29 cells were used to recapitulate the effect of NF-κB activation on stemness genes methylation. Our results showed that colonic phosphorylation of IκB, as a signal of NF-κB activation, was higher in obese subjects compared with their normal-weight counterparts. Moreover, promoter methylation of NANOG was likely to be lower in obese subjects and correlated with central obesity. HT-29 cells incubated by TNF-α showed hypomethylation of POU5F1 and MYC genes in addition to the NANOG. These results suggest that obesity-induced inflammation might be involved in the regulation of DNA methylation of oncogenic genes such as NANOG in differentiated colonocytes and thus predispose them to later oncogenic alterations.

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Hypercoagulability in overweight and obese subjects who are asymptomatic for thrombotic events

Thrombosis and Haemostasis ◽

10.1160/th14-02-0156 ◽

2015 ◽

Vol 113 (01) ◽

pp. 85-96 ◽

Cited By ~ 45

Author(s):

Claudia M. Radu ◽

Luca Spiezia ◽

Sabrina Gavasso ◽

Mariangela Fadin ◽

Barry Woodhams ◽

...

Keyword(s):

Metabolic Syndrome ◽

Annexin V ◽

Normal Weight ◽

Obese Patients ◽

Inflammatory Parameters ◽

Circulating Microparticles ◽

Obese Subjects ◽

And Gender ◽

Control Study

SummaryThe role of circulating microparticles (MP) of different origin and tissue factor (TF)-bearing in overweight and obese patients with and without metabolic syndrome is still a matter of debate. In a case-control study, the presence of hypercoagulability was evaluated in overweight and obese patients by measuring MP, thrombin generation (TG) and FVIIa-AT complexes. Twenty overweight patients (body mass index [BMI] range 25–29.9 kg/m2), 20 with I degree (30–34.9 kg/m2), 20 with II degree (35–39.9 kg/m2) and 20 with III degree obesity (≥ 40 kg/m2) were enrolled and compared to 40 age and gender-matched normal weight individuals. A significant increase in median levels of all MP subtypes was observed in the three degrees of obese patients compared to controls. Overweight patients had higher levels of annexin V-MP (AMP), endothelial-derived, leukocyte-derived and TF-bearing MP than controls. Obese patients had a significantly shorter median lag time (p< 0.05), higher median peak thrombin (p< 0.01) and increased median endogenous thrombin potential [ETP] (p< 0.001) compared to controls. Overweight subjects had significantly increased ETP compared to controls (p< 0.05). Both AMP levels and ETP were found to positively correlate with BMI, waist circumference, and inflammatory parameters. No significant increase in FVIIa-AT complex was seen in cases compared to controls. We conclude that obesity is associated with overproduction of procoagulant MP and increase TG. Interestingly, hypercoagulability is found in overweight patients free of metabolic syndrome and increases with the severity of obesity. Assessment of MP and TG may be helpful in the early characterisation of the prothrombotic state in obese patients.

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Digital x-ray mapping of nanometer-size supported bimetallic catalysts

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100104716 ◽

1988 ◽

Vol 46 ◽

pp. 530-531

Author(s):

L. T. Germinario

Keyword(s):

Background Radiation ◽

Metal Cluster ◽

Single Element ◽

Beam Diameter ◽

X Rays ◽

X Ray ◽

Major Interest ◽

Induced Changes

Understanding the role of metal cluster composition in determining catalytic selectivity and activity is of major interest in heterogeneous catalysis. The electron microscope is well established as a powerful tool for ultrastructural and compositional characterization of support and catalyst. Because the spatial resolution of x-ray microanalysis is defined by the smallest beam diameter into which the required number of electrons can be focused, the dedicated STEM with FEG is the instrument of choice. The main sources of errors in energy dispersive x-ray analysis (EDS) are: (1) beam-induced changes in specimen composition, (2) specimen drift, (3) instrumental factors which produce background radiation, and (4) basic statistical limitations which result in the detection of a finite number of x-ray photons. Digital beam techniques have been described for supported single-element metal clusters with spatial resolutions of about 10 nm. However, the detection of spurious characteristic x-rays away from catalyst particles produced images requiring several image processing steps.

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