Helene Duez

Helene Duez
University of Lille Nord de France, INSERM, Institut Pasteur Lille

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96
Publications
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Publications

Publications (96)
Article
Full-text available
Liver physiology is circadian and sensitive to feeding and insulin. Food intake regulates insulin secretion and is a dominant signal for the liver clock. However, how much insulin contributes to the effect of feeding on the liver clock and rhythmic gene expression remains to be investigated. Insulin action partly depends on changes in insulin recep...
Chapter
The modern way of life has dramatically affected our biological rhythms. Circadian rhythms, which are generated by an endogenous circadian clock, are observed in a large number of physiological functions including metabolism. Proper peripheral clock synchronization by different signals including appropriate feeding/fasting cycles is essential to co...
Chapter
Innate and adaptive immune cells cooperate to protect the host from exogenous invaders and to maintain body integrity. However, in autoimmune diseases, the immune system turns against the host himself leading to dramatic tissue damage and loss-of-function. The NLRP3 inflammasome is a master regulator of the innate immune system, especially in macro...
Article
Full-text available
Cardiovascular diseases (CVD) are still the first cause of death worldwide. Their main origin is the development of atherosclerotic plaque, which consists in the accumulation of lipids and inflammatory leucocytes within the vascular wall of large vessels. Beyond dyslipidemia, diabetes, obesity, hypertension and smoking, the alteration of circadian...
Preprint
Full-text available
In mammalian cells, gene expression is rhythmic and sensitive to various environmental and physiological stimuli. A circadian clock system helps to anticipate and synchronize gene expression with daily stimuli including cyclic light and food intake, which control the central and peripheral clock programs, respectively. Food intake also regulates in...
Article
Full-text available
The innate immune system is the first line of defense specialized in the clearing of invaders whether foreign elements like microbes or self-elements that accumulate abnormally including cellular debris. Inflammasomes are master regulators of the innate immune system, especially in macrophages, and are key sensors involved in maintaining cellular h...
Article
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The innate immune system senses “non-self” molecules derived from pathogens (PAMPs) as well as endogenous damage-associated molecular patterns (DAMPs) and promotes sterile inflammation that is necessary for injury resolution, tissue repair/regeneration, and homeostasis. The NOD-, LRR- and pyrin domain containing protein 3 (NLRP3) is an innate immun...
Article
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Diet-induced obesity (DIO) is associated with a defect of the orosensory detection of dietary lipids in rodents. This dysfunction is not anecdotic since it might worsen the negative effects of obesity by promoting the overconsumption of energy-dense foods. Previous studies have highlighted a progressive devaluation of reward value of lipid stimuli...
Article
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Liver injury triggers adaptive remodeling of the hepatic transcriptome for repair/regeneration. We demonstrate that this involves particularly profound transcriptomic alterations where acute induction of genes involved in handling of endoplasmic reticulum stress (ERS) is accompanied by partial hepatic dedifferentiation. Importantly, widespread hepa...
Article
AimsNot all people with obesity become glucose intolerant, suggesting differential activation of cellular pathways. The unfolded protein response (UPR) may contribute to the development of insulin resistance in several organs, but its role in skeletal muscle remains debated. Therefore, we explored the UPR activation in muscle from non-diabetic gluc...
Article
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Browning induction or transplantation of brown adipose tissue (BAT) or brown/beige adipocytes derived from progenitor or induced pluripotent stem cells (iPSCs) can represent a powerful strategy to treat metabolic diseases. However, our poor understanding of the mechanisms that govern the differentiation and activation of brown adipocytes limits the...
Chapter
The NLRP3 inflammasome is a cellular sensor of danger signals such as extracellular ATP or abnormally accumulating molecules like crystals. Activation of NLRP3 by such compounds triggers a sterile inflammatory response that may be involved in numerous pathologies including rheumatoid arthritis, atherosclerosis, diabetes, and Alzheimer’s disease. A...
Article
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The nuclear receptor REV-ERBα integrates the circadian clock with hepatic glucose and lipid metabolism by nucleating transcriptional comodulators at genomic regulatory regions. An interactomic approach identified O-GlcNAc transferase (OGT) as a REV-ERBα−interacting protein. By shielding cytoplasmic OGT from proteasomal degradation and favoring OGT...
Article
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Background: Skeletal muscle has the capacity to adapt to environmental changes and regenerate upon injury. To study these processes, most experimental methods use quantification of parameters obtained from images of immunostained skeletal muscle. Muscle cross-sectional area, fiber typing, localization of nuclei within the muscle fiber, the number...
Article
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Circadian misalignment, such as in shift work, has been associated with obesity and type 2 diabetes. However, direct effects of circadian misalignment on skeletal muscle insulin sensitivity and the muscle molecular circadian clock have never been studied in humans. Here, we investigated insulin sensitivity and muscle metabolism in 14 healthy young...
Article
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The nuclear receptors are transcription factors involved in the regulation of a variety of physiological processes whose activity can be modulated by binding to relevant small molecule ligands. Their dysfunction has been shown to play a role in disease states such as diabetes, cancer, inflammatory diseases, and hormonal resistance ailments, which m...
Article
Metabolic stresses such as dietary energy restriction or physical activity exert beneficial metabolic effects. In the liver, endospanin-1 and endospanin-2 cooperatively modulate calorie restriction-mediated (CR-mediated) liver adaptations by controlling growth hormone sensitivity. Since we found CR to induce endospanin protein expression in skeleta...
Article
Full-text available
Background & aims: The innate immune system responds not only to bacterial signals, but also to non-infectious danger-associated molecular patterns that activate the NLRP3 inflammasome complex after tissue injury. Immune functions vary over the course of the day, but it is not clear whether these changes affect the activity of the NLRP3 inflammaso...
Article
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The nuclear receptor Rev-erb-α modulates hepatic lipid and glucose metabolism, adipogenesis and thermogenesis. We have previously demonstrated that Rev-erb-α is also an important regulator of skeletal muscle mitochondrial biogenesis and function, and autophagy. As such, Rev-erb-α over-expression in skeletal muscle or its pharmacological activation...
Article
Background: On-pump cardiac surgery provokes a predictable perioperative myocardial ischaemia-reperfusion injury which is associated with poor clinical outcomes. We determined the occurrence of time-of-the-day variation in perioperative myocardial injury in patients undergoing aortic valve replacement and its molecular mechanisms. Methods: We st...
Article
Most organisms have developed an autonomous time-keeping system that generates self-sustained daily fluctuations in behavior and physiological processes. These biological clocks are reset every day by light to adjust physiology to the day/night cycle generated by the rotation of the Earth. Clocks present in organs involved in glucose and lipid meta...
Article
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Cell and animal studies have demonstrated that circadian rhythm is governed by autonomous rhythmicity of clock genes. Although disturbances in circadian rhythm have been implicated in metabolic disease development, it remains unknown whether muscle circadian rhythm is altered in human models of type 2 diabetes. Here we used human primary myotubes (...
Article
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To maintain energy homeostasis despite variable energy supply and consumption along the diurnal cycle, the liver relies on a circadian clock synchronized to food timing. Perturbed feeding and fasting cycles have been associated with clock disruption and metabolic diseases; however, the mechanisms are unclear. To address this question, we have const...
Article
Biological rhythms of around 24 hours can be identified both in our behaviour and in the main physiological functions, as shown by the daily variations of body temperature, blood pressure, hormonal secretions and metabolic reactions. Disruptions to these rhythms due, for example, to shift work or snacking have repercussions on the metabolic level,...
Article
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Objective: A disturbed day-night rhythm is associated with metabolic perturbations that can lead to obesity and type 2 diabetes mellitus (T2DM). In skeletal muscle, a reduced oxidative capacity is also associated with the development of T2DM. However, whether oxidative capacity in skeletal muscle displays a day-night rhythm in humans has so far not...
Article
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In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring au...
Article
In mammals, the central clock localized in the central nervous system imposes a circadian rhythmicity to all organs. This is achieved thanks to a well-conserved molecular clockwork, involving interactions between several transcription factors, whose pace is conveyed to peripheral tissues through neuronal and humoral signals. The molecular clock pla...
Article
Circadian rhythms are oscillations which occur with a period of approximately one day to match the rotation of the Earth and the day/light alternance. They are generated by the molecular clockwork that exists in every single cell. Many physiological processes are subjected to circadian variations, ranging from the sleep/wake alternance to lipid and...
Article
Circadian rhythms are generated by oscillators operating in the brain and peripheral organs to temporally gate physiological processes to the right time window. For instance, glucose and lipid metabolism, body temperature and hormonal secretion oscillate diurnally. Circadian disorders, either due to genetic defects or environmental risk factors suc...
Article
Background: Obesity and diabetes mellitus are independently associated with the development of heart failure. In this study, we determined the respective effects of obesity, insulin resistance, and diabetes mellitus on the intrinsic contraction and mitochondrial function of the human myocardium before the onset of cardiomyopathy. Methods and resu...
Article
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Context: Obesity is characterized by the excessive accumulation of dysfunctional white adipose tissue (WAT), leading to a strong perturbation of metabolic regulations. However, the molecular events underlying this process are not fully understood. Objective: MicroRNAs (miRNAs) are small noncoding RNAs acting as posttranscriptional regulators of...
Article
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The "mechanistic target of rapamycin" (mTOR) is a central controller of growth, proliferation and/or motility of various cell-types ranging from adipocytes to immune cells, thereby linking metabolism and immunity. mTOR signaling is overactivated in obesity, promoting inflammation and insulin resistance. Therefore, great interest exists in the devel...
Article
Circadian rhythms are generated by oscillators operating in the brain and peripheral organs to temporally gate physiological processes to the right time window. For instance, glucose and lipid metabolism, body temperature and hormonal secretion oscillate diurnally. Circadian disorders, either due to genetic defects or environmental risk factors suc...
Article
Circadian rhythms are generated by an internal molecular clock which synchronizes daily physiological variations to the day/night alternance. Many behavioral and physiological processes display circadian rhythmicity, including locomotor activity, sleep/wake cycles and metabolic and endocrine pathways. In peripheral tissues, the molecular clock sens...
Article
Full-text available
The nuclear receptor Rev-erb-α modulates hepatic lipid and glucose metabolism, adipogenesis and the inflammatory response in macrophages. We show here that Rev-erb-α is highly expressed in oxidative skeletal muscle and that its deficiency in muscle leads to reduced mitochondrial content and oxidative function, as well as upregulation of autophagy....
Article
Although being a primary objective in the management of type 2 diabetes, optimal glycaemic control is difficult to achieve and usually not maintained over time. Type 2 diabetes is a complex pathology, comprising altered insulin sensitivity and impaired insulin secretion. Recent advances in the understanding of the physiological functions of increti...
Article
### A Circadian Rhythm Orchestrated by Histone Deacetylase 3 Controls Hepatic Lipid Metabolism Feng et al Science . 2011;331:1315–1319. A new study in Science reveals how circadian epigenetic modification of DNA drives diurnal gene expression in mouse liver and is required for the maintenance of lipid homeostasis. Numerous physiological processe...
Article
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Bile acids (BA) participate in the maintenance of metabolic homeostasis acting through different signaling pathways. The nuclear BA receptor farnesoid X receptor (FXR) regulates pathways in BA, lipid, glucose, and energy metabolism, which become dysregulated in obesity. However, the role of FXR in obesity and associated complications, such as dysli...
Article
Many behavioral and physiological processes, including locomotor activity, blood pressure, body temperature, sleep (fasting)/wake (feeding) cycles, and metabolic regulation display diurnal rhythms. The biological clock ensures proper metabolic alignment of energy substrate availability and processing. Studies in animals and humans highlight a stron...
Article
The endogenous circadian clock ensures daily rhythms in diverse behavioral and physiological processes, including locomotor activity and sleep/wake cycles, but also food intake patterns. Circadian rhythms are generated by an internal clock system, which synchronizes these daily variations to the day/night alternance. In addition, circadian oscillat...
Article
Full-text available
Here we show that gene expression of the nuclear receptor RORalpha is induced during adipogenesis, with RORalpha4 being the most abundantly expressed isoform in human and murine adipose tissue. Over-expression of RORalpha4 in 3T3-L1 cells impairs adipogenesis as shown by the decreased expression of adipogenic markers and lipid accumulation, accompa...
Article
Circadian variations are observed in many physiological processes, and alterations in these oscillations are closely linked to mood disorders, metabolic abnormalities and cardiovascular complications. The nuclear receptor Rev-erba is a crucial component of the clock mechanism. It is an important metabolic regulator and a target for lithium, a drug...
Article
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Pharmacological approaches that enhance incretin action for the treatment of type 2 diabetes mellitus have recently been developed, i.e. injectable glucagon-like peptide-1 receptor (GLP-1R) agonists with prolonged plasma half-lives and orally available inhibitors of dipeptidyl peptidase (DPP)-4, the main enzyme responsible for the rapid degradation...
Article
Triglyceride-rich lipoproteins (TRLs) derived from the intestine are increased in insulin resistant states both in the post-prandial and fasted state and are associated with increased cardiovascular risk. Impaired clearance has long been invoked to explain this accumulation of intestinal TRLs, but more recent studies have highlighted the fact that...
Article
Insulin resistant states are associated with increased fatty acid flux to liver and intestine, which stimulates the production of triglyceride-rich lipoproteins (TRL). ApoC-III production and plasma and TRL concentrations are increased in insulin resistance and may contribute to the hypertriglyceridemia of these conditions. The mechanism underlying...
Article
Circadian rhythms are normal variations in physiological processes that occur over the period of a day. These rhythms are essential for the organism since they allow anticipatory metabolic regulations to prepare for the up-coming feeding or rest period. Disturbances of the biological clock predispose to metabolic disorders such as dyslipidaemia, in...
Article
Full-text available
A role of the nuclear receptor Rev-erbalpha in the regulation of transcription pathways involving other nuclear receptors is emerging. Indeed, Rev-erbalpha is a negative regulator of transcription by binding to overlapping response elements shared with various nuclear receptors, including the peroxisome proliferator-activated receptors and the reti...
Article
Hepatic lipoprotein production has been shown previously to be regulated by free fatty acid (FFA) flux to the liver, whereas intestinal lipoprotein production is stimulated mainly by ingested fat absorbed from the intestinal lumen. Emerging evidence indicates that intestinal lipoprotein production is increased in insulin resistance and type 2 diabe...
Article
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Despite its potent, well-documented insulin-sensitizing effects, rosiglitazone (RSG) does not effectively ameliorate the hypertriglyceridemia of insulin-resistant or diabetic individuals and has even been shown to slightly but significantly increase triglyceride-rich lipoproteins (TRL) in some studies. The mechanism of this effect is currently not...
Article
Full-text available
Conversion into bile acids represents an important route to remove excess cholesterol from the body. Rev-erbalpha is a nuclear receptor that participates as one of the clock genes in the control of circadian rhythmicity and plays a regulatory role in lipid metabolism and adipogenesis. Here, we investigate a potential role for Rev-erbalpha in the co...