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See detailAnti-inflammatory agents to treat or prevent type 2 diabetes, metabolic syndrome and cardiovascular disease.
Esser, Nathalie ULg; Paquot, Nicolas ULg; Scheen, André ULg

in Expert opinion on investigational drugs (in press)

Introduction: There is a growing body of evidence to suggest that chronic silent inflammation is a key feature in abdominal obesity, metabolic syndrome, type 2 diabetes (T2DM) and cardiovascular disease ... [more ▼]

Introduction: There is a growing body of evidence to suggest that chronic silent inflammation is a key feature in abdominal obesity, metabolic syndrome, type 2 diabetes (T2DM) and cardiovascular disease (CVD). These observations suggest that pharmacological strategies, which reduce inflammation, may be therapeutically useful in treating obesity, type 2 diabetes and associated CVD. Area covered: The article covers novel strategies, using either small molecules or monoclonal antibodies. These strategies include: approaches targeting IKK-b-NF-kB (salicylates, salsalate), TNF-alpha (etanercept, infliximab, adalimumab), IL-1beta (anakinra, canakinumab) and IL-6 (tocilizumab), AMP-activated protein kinase activators, sirtuin-1 activators, mammalian target of rapamycin inhibitors and C-C motif chemokine receptor 2 antagonists. Expert opinion: The available data supports the concept that targeting inflammation improves insulin sensitivity and beta-cell function; it also ameliorates glucose control in insulin-resistant patients with inflammatory rheumatoid diseases as well in patients with metabolic syndrome or T2DM. Although promising, the observed metabolic effects remain rather modest in most clinical trials. The potential use of combined anti-inflammatory agents targeting both insulin resistance and insulin secretion appears appealing but remains unexplored. Large-scale prospective clinical trials are underway to investigate the safety and efficacy of different anti-inflammatory drugs. Further evidence is needed to support the concept that targeting inflammation pathways may represent a valuable option to tackle the cardiometabolic complications of obesity. [less ▲]

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See detailMetabolically healthy overweight and obesity
Esser, Nathalie ULg; SCHEEN, André ULg; PAQUOT, Nicolas ULg

in Annals of Internal Medicine (2014), 160(7), 514

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See detailInflammation as a link between obesity, metabolic syndrome and type 2 diabetes
ESSER, Nathalie ULg; Legrand, Sylvie ULg; Piette, Jacques ULg et al

in Diabetes Research & Clinical Practice (2014)

It is recognized that a chronic low-grade inflammation and an activation of the immune system are involved in the pathogenesis of obesity-related insulin resistance and type 2 diabetes. Systemic ... [more ▼]

It is recognized that a chronic low-grade inflammation and an activation of the immune system are involved in the pathogenesis of obesity-related insulin resistance and type 2 diabetes. Systemic inflammatory markers are risk factors for the development of type 2 diabetes and its macrovascular complications. Adipose tissue, liver, muscle and pancreas are themselves sites of inflammation in presence of obesity. An infiltration of macrophages and other immune cells is observed in these tissues associated with a cell population shift from an anti-inflammatory to a pro-inflammatory profile. These cells are crucial for the production of pro-inflammatory cytokines, which act in an autocrine and paracrine manner to interfere with insulin signaling in peripheral tissues or induce β-cell dysfunction and subsequent insulin deficiency. Particularly, the pro-inflammatory interleukin-1β is implicated in the pathogenesis of type 2 diabetes through the activation of the NLRP3 inflammasome. The objectives of this review are to expose recent data supporting the role of the immune system in the pathogenesis of insulin resistance and type 2 diabetes and to examine various mechanisms underlying this relationship. If type 2 diabetes is an inflammatory disease, anti-inflammarory therapies could have a place in prevention and treatment of type 2 diabetes. [less ▲]

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See detailObesity phenotype is related to NLRP3 inflammasome activity and immunological profile of visceral adipose tissue
ESSER, Nathalie ULg; L'Homme, Laurent ULg; DE ROOVER, Arnaud ULg et al

in Diabetologia (2013), 56

Aims/hypothesis Obesity is a heterogeneous condition comprising both individuals who remain metabolically healthy (MHO) and those who develop metabolic disorders (metabolically unhealthy, MUO). Adipose ... [more ▼]

Aims/hypothesis Obesity is a heterogeneous condition comprising both individuals who remain metabolically healthy (MHO) and those who develop metabolic disorders (metabolically unhealthy, MUO). Adipose tissue is also heterogeneous in that its visceral component is more frequently associated with metabolic dysfunction than its subcutaneous component. The development of metabolic disorders is partly mediated by the NLR family pyrin domain containing-3 (NLRP3) inflammasome, which increases the secretion of inflammatory cytokines via activation of caspase-1. We compared the immunological profile and NLRP3 activity in adipose tissue between MUO and MHO individuals. Methods MHO and MUO phenotypes were defined, respectively, as the absence and the presence of the metabolic syndrome. Cellular composition and intrinsic inflammasome activity were investigated by flow cytometry, quantitative RTPCR and tissue culture studies in subcutaneous and visceral adipose tissue from 23 MUO, 21 MHO and nine lean individuals. Results We found significant differences between the three study groups, including an increased secretion of IL-1β, increased expression of IL1B and NLRP3, increased number of adipose tissue macrophages and decreased number of regulatory T cells in the visceral adipose tissue of MUO patients compared with MHO and lean participants. In macrophages derived from visceral adipose tissue, both caspase-1 activity and IL-1β levels were higher in MUO patients than in MHO patients. Furthermore, caspase-1 activity was higher in CD11c+CD206+ adipose tissue macrophages than in CD11c−CD206+ cells. Conclusions/interpretation The MUO phenotype seems to be associated with an increased activation of the NLPR3 inflammasome in macrophages infiltrating visceral adipose tissue, and a less favourable inflammatory profile compared with the MHO phenotype. [less ▲]

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See detailUnsaturated fatty acids prevent activation of NLRP3 inflammasome in human monocytes/macrophages
L'Homme, Laurent ULg; Esser, Nathalie ULg; Riva, Laura ULg et al

in Journal of Lipid Research (2013), 54

The NLRP3 inflammasome is involved in many obesity-associated diseases such as type 2 diabetes, atherosclerosis and gouty arthritis through its ability to induce IL-1β release. The molecular link between ... [more ▼]

The NLRP3 inflammasome is involved in many obesity-associated diseases such as type 2 diabetes, atherosclerosis and gouty arthritis through its ability to induce IL-1β release. The molecular link between obesity and inflammasome activation is still unclear but free fatty acids have been proposed as one triggering event. Here we reported opposite effects of saturated fatty acids (SFAs) compared to unsaturated fatty acids (UFAs) on NLRP3 inflammasome in human monocytes/macrophages. Palmitate and stearate, both SFAs, triggered IL-1β secretion in a caspase-1/ASC/NLRP3-dependent pathway. Unlike SFAs, the UFAs oleate and linoleate did not lead to IL-1β secretion. In addition, they totally prevented the IL-1β release induced by SFAs and, with less efficiency, by a broad range of NLRP3 inducers including nigericin, alum and MSU. UFAs did not affect the transcriptional effect of SFAs suggesting a specific effect on the NLRP3 activation. These results provide a new antiinflammatory mechanism of UFAs by preventing the activation of the NLRP3 inflammasome and therefore the IL-1β processing. By this way, UFAs might play a protective role in NLRP3-associated diseases. [less ▲]

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See detailDifférences d’activité de l’inflammasome NLRP3 entre sujets obèses avec et sans anomalies métaboliques
Esser, Nathalie ULg; L'Homme, Laurent ULg; DE ROOVER, Arnaud ULg et al

in Diabètes & Métabolism (2013, March), 39(suppl 1), 102

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See detailLa vignette diagnostique de l'etudiant. Mise au point d'un patient consultant pour obesite.
De Flines, J.; Rorive, M.; Esser, Nathalie ULg et al

in Revue Médicale de Liège (2013), 68(3), 148-53

Obesity is increasingly prevalent in our society and medical consultations for evaluation and management of weight excess are frequent. Before considering a therapeutic strategy, a careful initial ... [more ▼]

Obesity is increasingly prevalent in our society and medical consultations for evaluation and management of weight excess are frequent. Before considering a therapeutic strategy, a careful initial clinical assessment is mandatory. The diagnostic approach of an obese person should be similar as for any other chronic pathology. The objectives of the present clinical description are to report the main steps of an exhaustive anamnesis, the signs to be more specifically detected at the clinical examination and the other useful investigations to be programmed at first glance in a person who is visiting his/her medical doctor because of obesity. Based upon the data collected during this careful evaluation, therapeutic modalities may be defined, ideally in the frame of a multidisciplinary approach. [less ▲]

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See detailDiabete de type 2 et medicaments anti-inflammatoires: nouvelles perspectives therapeutiques?
Esser, Nathalie ULg; Paquot, Nicolas ULg; SCHEEN, André ULg

in Revue Médicale Suisse (2011), 7(306), 1614-81620

It is now well accepted that a chronic, low-grade inflammation is observed in abdominal obesity, insulin resistance and type 2 diabetes mellitus, and that pro-inflammatory cytokines and oxidative stress ... [more ▼]

It is now well accepted that a chronic, low-grade inflammation is observed in abdominal obesity, insulin resistance and type 2 diabetes mellitus, and that pro-inflammatory cytokines and oxidative stress play a role in the pathogenesis of type 2 diabetes. These new findings raise the question of whether antiinflammatory strategies may have a place in the prevention and treatment of type 2 diabetes. This review article describes the results obtained in studies on patients with metabolic syndrome or type 2 diabetes aiming to test the metabolic effect of anti-inflammatory (salicylates, antagonists of interleukine-1, antagonists of tumor necrosis factor-alpha) and anti-oxydants (succinobucol) drugs. [less ▲]

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See detailAptitude physique versus adiposité : aspects physiopathologiques et impacts cardio-métaboliques chez le sujet adulte non diabétique
Esser, Nathalie ULg; Paquot, Nicolas ULg; Scheen, André ULg

in Médecine des Maladies Métaboliques (2010), 4

L’excès de masse grasse (adiposité), surtout abdominale, induit des effets cardio-métaboliques néfastes, alors que l’exercice musculaire et une bonne aptitude physique exercent globalement une influence ... [more ▼]

L’excès de masse grasse (adiposité), surtout abdominale, induit des effets cardio-métaboliques néfastes, alors que l’exercice musculaire et une bonne aptitude physique exercent globalement une influence favorable. Les effets délétères d’un excès de masse grasse (fatness) pourraient donc être contrecarrés par la pratique régulière d’exercices aboutissant à une bonne forme physique (fitness). Cet article analyse d’abord les différents mécanismes physiopathologiques par lesquels l’exercice physique produit des effets bénéfiques chez la personne avec excès pondéral et fait le distinguo entre la pratique d’une activité physique (exercice musculaire) stricto sensu et aptitude physique (fitness). Ensuite, il décrit les études les plus importantes ayant analysé les relations entre le niveau d’aptitude physique et le degré d’adiposité chez le sujet adulte en surpoids ou obèse non diabétique et leurs influences respectives sur le risque de survenue de troubles métaboliques (syndrome métabolique) et sur la mortalité, en particulier cardiovasculaire. [less ▲]

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See detailAptitude physique versus adiposité : impacts cardio-métaboliques respectifs chez l’enfant/adolescent et chez la personne âgée
Esser, Nathalie ULg; Paquot, Nicolas ULg; Scheen, André ULg

in Médecine des Maladies Métaboliques (2010), 4

Le sujet adulte d’âge moyen en surpoids ou obèse est caractérisé par une adiposité exagérée, généralement combinée à une aptitude physique cardio-respiratoire déficiente. La pratique régulière d’une ... [more ▼]

Le sujet adulte d’âge moyen en surpoids ou obèse est caractérisé par une adiposité exagérée, généralement combinée à une aptitude physique cardio-respiratoire déficiente. La pratique régulière d’une activité physique d’endurance améliore le profil de risque cardio-métabolique dans cette tranche d’âge. Le manque d’activité physique chez les adolescents contribue à augmenter leur masse grasse et à induire des anomalies métaboliques, tandis que la sédentarité marquée des sujets âgés peut conduire à un excès de graisse combiné à une fonte musculaire (obésité sarcopénique). Dans ces deux tranches d’âge, les effets néfastes d’un excès de masse grasse (fatness) pourraient être contrecarrés, voire annulés, par la pratique régulière d’exercices musculaires conduisant à une meilleure aptitude physique (fitness). Cet article décrit les relations entre fitness et fatness, et les impacts cardio-métaboliques respectifs de ces deux composantes, d’une part, dans la population jeune (< 20 ans), d’autre part dans la population âgée (> 60 ans). [less ▲]

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