De quelques maux de la prévention contemporaine. Le cas de l’obésité et du surpoids

Overweight and obesity are considered major public health issues, and many preventive campaigns are designed to prevent unhealthy eating habits among the French. But these campaigns may be ineffective, and even sometimes counterproductive. Firstly, because prevention is a moral enterprise that can lead to stigmatizing targeted people. Secondly, because the ‘merchandization’ of prevention fuels a ‘dietary cacophony’. Thirdly, the medicalisation of overweight/obesity involves some shortcomings: it can prevent us from understanding eating habits, and many general physicians are insufficiently trained to take care of overweight or obese patients.     

Obésité sarcopénique et altérations du métabolisme protéique musculaire

The increasing prevalence of obesity among elderly people has led to the definition of the concept of sarcopenic obesity. This concept is defined as the potential to combine muscle metabolic changes associated with both aging and obesity. Several definitions have been proposed, but the absence of a consensus led to great variability in the prevalence of this phenomenon in literature. However, the proportion of the older obese population is not negligible, representing 5 to 15% of elderly people. The study of metabolic abnormalities associated with sarcopenic obesity is of importance, since these subjects are at increased risk of developing functional disability. However, very few studies evaluated the mechanisms involved in the cumulating and aggravating effect of obesity in the elderly, particularly at muscle level. Of note, significant alterations of muscle protein anabolism were observed in elderly people but also in obese subjects. Impairment in muscle protein metabolism, including protein synthesis rate, could be involved in the loss of functional capacity during sarcopenic obesity.     

Les cellules endothéliales du tissu adipeux

The adipose tissue plays a major role in energy homeostasis through the storage and release of fatty acids as well as adipokine production. The endothelial cells of the adipose tissue vascular network constitute a barrier between the blood and the adipocyte compartments. They are key players in the metabolic status of the fat mass controlling the exchanges of nutrients, hormones, oxygen and immune-inflammatory cells. Recent data highlight the process of lipid handling at the endothelial cell surface and of the transendothelial transit of fatty acids. The extension of the vascular network and its functionality are necessary for the adipose tissue integrity. Insufficient oxygen supply generates hypoxic area within the tissue that favors metabolic abnormalities and the recruitment of immuno-inflammatory cells. The present review relates to the role of adipose tissue endothelial cells in the adipose tissue physiology. Their involvement and more particularly the role of accelerated ageing, in the link between obesity and associated metabolic and cardiovascular pathologies are described.     

Myosite localisée chez un diabétique : penser à l’infarctus musculaire

Diabetic muscle infarction is a rare and often unrecognized complication of diabetes mellitus. It usually occurs in patients with long-term diabetic complications, particularly microangiopathy. It is characterized by sudden muscle pain, most often located in one lower limb. The magnetic resonance imaging (MRI) makes it possible to confirm the diagnosis without the need for muscular biopsy. We report the case of a 21-year-old woman with type 1 diabetes and degenerative complications who presented a muscle infarction. The clinical picture mainly consisted in a painful left thigh. The laboratory test showed an inflammatory syndrome without increase in muscle enzymes. MRI signal abnormalities from the affected muscle area confirmed the diagnosis of diabetic myonecrosis.     

Physiopathologie de l’insulinorésistance dans le muscle squelettique et implication des fonctions mitochondriales

In modern societies, decreased physical activity, nutritional transition and aging contribute to the increase in the prevalence of obesity and its associated pathologies (as cardiovascular diseases and type 2 diabetes). Obesity is tightly correlated with insulin resistance, which appears in the early stages of type 2 diabetes. As skeletal muscle is quantitatively the main tissue involved in glucose transport in response to insulin, muscle insulin resistance is a key step in the etiology of type 2 diabetes. Several alterations of skeletal muscle insulin signaling in various models of obesity or type 2 diabetes have been evidenced and numerous underlying mechanisms have been hypothesized. Among them, muscle lipotoxicity, obesity-induced adipose tissue inflammation and oxidative stress following excess of energetic substrates could be involved, independently or synergically, in the development of muscle insulin resistance. Moreover, mitochondrial alterations have been reported in the skeletal muscle of obese or diabetic patients and animals. This suggests that mitochondrion, through its capacity of regulating cellular fatty acids flux and redox state, may play a key role in obesity-induced skeletal muscle insulin resistance.     

Le syndrome métabolique : une entité à haut risque métabolique et cardiovasculaire

The association between abdominal obesity, insulin-resistance, type 2 diabetes, arterial hypertension and dyslipidemia has been known for many years. Metabolic syndrome has been recently recognized by both WHO and NCEP ATP III with the definition including a cluster of metabolic abnormalities. Metabolic syndrome is common with its prevalence increasing with age. Metabolic syndrome represents an averse metabolic state since it confers an increased risk for both type 2 diabetes and cardiovascular disease. Targeting physical inactivity and obesity with lifestyle changes is the cornerstone of the prevention and treatment of the metabolic syndrome. Further studies are warranted to better determine the value of therapies directed specifically at insulin-resistance in individuals with metabolic syndrome.     

Place et impact des régimes chez les personnes très âgées

Successful ageing promotion is a major goal of care in geriatrician patients, even in old age. Cardiovascular prevention strategy, diabetes care or kidney protection involve dietary management. However, mortality and morbidity risk factors are modified in the oldest old, and on the other hand, dietary restrictions could impair health status of the older. Studies devoted to the oldest old are scarce. In most situations, exercise training promotion seems to better address the prevention goals than do diets.     

Que devient le tissu adipeux dans l’obésité ?

Adipose tissue exerts multiples functions related to glucose and lipid homeostasis. The adipose tissue is a site of low-grade inflammation in obese subjects, evidenced by immune cells accumulation, mainly macrophages. Pro-inflammatory factors produced by macrophages alter adipocytes biology and may contribute to the severity of metabolic complications, including insulin resistance and hepatic diseases. However, macrophages might also be beneficial to tissue homeostasis through the elimination of deficient adipocytes or pro-angiogenic effects. The cellular and molecular mechanisms of macrophage infiltration are related, at least in part, to a dialogue among hypertrophied adipocytes, macrophages and other cell-types, including lymphocytes, pre-adipocytes and endothelial cells within adipose tissue. A newly discovered consequence of adipose tissue inflammation is fibrosis that is organized both in bundles and around adipocytes. These cellular and structural alterations are only partly reversible after weight loss and reflect the pathology of adipose tissue that may contribute to the chronicity of obesity. In this context, identification of pharmacological means to maintain adipose tissue integrity remains a major challenge in the field.     

L’endothéliopathie : son risque et rôle des facteurs métaboliques

Endothelial dysfunction (ED) has been demonstrated in diabetics, insulin resistant obese patients, patients with hypercholesterolemia or hypertension, and also in smokers. The role played by hyperglycemia, and an excess in free fatty acids and leptin has been evoked. ED may be considered as a vascular integrator of various metabolic disorders and some nutritional factors. Evidence for ED is based on pharmacological tests using acetylcholine in particular, or functional tests like the forearm-mediated vasodilation, but also on the measurement of blood markers or microalbuminuria. ED plays a pathophysiological role in atherothrombosis, tissue ischemia, hypertension and microangiopathic complications of diabetes. ED is an ubiquitous disorder which involves the whole artery network and microcirculation. ED may also contribute to insulin resistance. It may be reversed when improving metabolic disorders and lowering blood pressure. In addition, some oral hypoglycemic agents, lipid or blood pressure lowering drugs are able to improve endothelium function through pleiotropic effects. Various antioxidant agents exert also short-term beneficial effects on the endothelium but their therapeutic effects remain to be defined.     

Mesures objectives de l’environnement bâti et statut pondéral des enfants et adolescents : revue de la littérature

In the framework of the study of the Environmental links to physical activity, nutrition and health (ELIANE), we performed a systematic review of the associations between objective spatial measurements of the built environment and weight status in youth. Of the 25 identified papers, 18 reported at least one significant relationship, although only almost one-third of the associations tested were significant. Inverse relationships of weight with different walkability indices were the most consistent (7/9 papers). Weight was also positively related to spatial accessibility to convenience stores (3/6 papers), and inversely to the accessibility to recreational physical activity facilities (4/9 papers). Relationships with parks, other food retail outlets and restaurants were inconsistent. Reasons for such discrepant results are discussed. Better-built environment measures are needed. The challenge lies also in better understanding the complex pathways through which the built environment, the socioeconomic context, and the perception of their environment by the subjects impact childhood behaviors and weight status.     

Conception et évaluation d’une intervention brève « alimentation et prévention cardiovasculaire » en médecine de premier recours

The goal of our project was to assess acceptability and feasibility of a 5-step brief intervention (BI) on diet and coronary heart disease (CHD) prevention by general practitioners in a primary care setting. The intervention process and its acceptability by patients and physicians were assessed by standardised interviews and questionnaires, measuring the proportion of patients included, BI duration, perceived obstacles, usefulness and relevance of BI, patients’ knowledge and planned behavior change. Of 99 eligible patients, 76 (77 %) participated and 48 received the BI, which took 5–10 minutes in the consultation. Three of the five steps were usually (38 %) performed. The five physicians were interested and motivated but mentioned lack of time. Most patients (77 %) said they had learned something new about their diet in relation to CHD, and 64 % were able to express at least one dietary habit they planned to change. Ninety-eight percent considered it was their physician's role to discuss their diet to prevent CHD. However, BI's implementation proves difficult in physicians’ routine.     

Détection centrale des acides gras et contrôle du bilan d’énergie

Nutrient sensitive neurons (glucose and fatty acids (FA) are present in many sites throughout the brain, including the hypothalamus and brainstem, and play a key role in the neural control of energy and glucose homeostasis. Through neuronal output, FA may modulate feeding behaviour as well as both insulin secretion and action. For example, central administration of oleate inhibits food intake and glucose production in rats. This suggests that daily variations in plasma FA concentrations might be detected by the central nervous system as a signal, which contributes to the regulation of energy balance. At the cellular level, subpopulations of neurons in the ventromedial and arcuate hypothalamic nuclei are selectively either inhibited or activated by FA. Possible molecular effectors of these FA effects likely include chloride or potassium ion channels. While intracellular metabolism and activation of the ATP-sensitive K⁺ channel appear to be necessary for some of the signaling effects of FA, at least half of the FA responses in ventromedial hypothalamic neurons are mediated by interaction with FAT/CD36, a FA transporter/receptor that does not require intracellular metabolism to activate downstream signaling. Thus, FA or their metabolites can modulate neuronal activity as a means of directly monitoring ongoing fuel availability by brain nutrient-sensing neurons involved in the regulation of energy and glucose homeostasis. Besides these physiological effects, FA overload or metabolic dysfunction might impair neural control of energy homeostasis and contribute to obesity and/or type 2 diabetes in predisposed subjects.     

Régulation du métabolisme protéique intestinal par les nutriments

The gut plays a central role in some pathophysiological conditions and the preservation or restoration of gut function, such as gut barrier, is a major issue. Cellular removal and protein turnover are high. Indeed, approximately 50% of proteins are synthesized every day in the human duodenal mucosa. During catabolic or inflammatory states, intestinal protein metabolism seems to be deregulated that could be involved in gut barrier dysfunction. Gut protein metabolism can also be affected by nutrients according to the type or the amount. An increasing number of studies focus on this topic but data are still limited and remain controversial. This paper aims to review the available data on the regulation of intestinal protein metabolism during pathophysiologic conditions and the influence of nutrients.     

Intérêts et limites du Programme National Nutrition Santé (PNNS) en faveur de l’éducation nutritionnelle: Enquête d’opinion auprès de patients diabétiques de type 2 et de type 1

A survey among 104 type 2 and 81 type 1 diabetic patients has explored their opinions on two major national educationnal programs on nutrition launched by the french health authorities: the “Program National Nutrition Santé” (PNNS1) (2001-2005) and the PNNS2 (2006-2010). The majority of the patients has acquired knowledge on the PNNS through the media and at the care setting level. The messages they have the best recorded concern the daily consumption of fruits and vegetables and the obesity. On the other hand, they know nothing on the printed educationnal guides distributed by the PNNS, nor on the local PNNS initiatives. If the half of the type 2 diabetic patients considers that the PNNS helps them to carry out food choices, a little number of patients estimates that PNNS plays an important role in preventing nutritionnal problems among the young people. Few patients considers also that the food industries may have a possible “perverse” influence on the food consumption and eating behaviors. The half of the type 2 diabetics is in favor of alternatives ways to the hospital-based therapeutic patient education programs, for example programs organized by the Health Social Insurance or by Mutual insurance companies, while respecting criteria of quality. Lastly, the majority of the patients estimates that, due to their own experience, they have a role to play in the nutritional education.     

Polluants environnementaux et troubles de la reproduction masculine : les phtalates au cœur du débat

Two major functions are assumed by the testis: the production of male gametes (i.e. spermatozoa), and the production of steroid hormones. Those two functions are established during fetal life and are essentials for the adult fertility and the masculinization of the internal tract and genitalia. For many years, our laboratory has been interested in the ontogeny of those two functions in rodents and since 2003, in collaboration with Gynecology and Obstetrics service of Professor R. Frydman in A. Béclère hospital, we have studied them in human. The first aim of this work was to improve the global knowledge of the human fetal testis development by using both our experimental data and the literature. Then we focused on the different defects that can occur during the fetal testis development. Indeed, male reproductive abnormalities have been steadily increasing since the last decades and are thought to be related to the concomitant increase of the concentration of contaminants and particularly of endocrine disruptors in the environment. Thus, we decided to study the effect of endocrine disruptors on human fetal testis, and more particularly the effect of phthalates, by using an organ culture system developed for human. In contrast to the data obtained in rat, mono (ethylhexyl)-phthalate (MEHP), an active metabolite of the most widespread phthalate in the environment, does not disturb the steroidogenic function. On the other hand, it has a negative effect on the male germ cells number. This study is the first experimental demonstration of a negative effect of phthalates directly on human reproductive functions. Using a molecular approach, our aim is now to understand the mechanisms of phthalate's action.     

Promouvoir l’activité physique, lutter contre la sédentarité et prévenir le surpoids chez l’adolescent, c’est possible : les leçons d’ICAPS

Based on a socioecological approach, the Intervention Centered on Adolescents’ Physical activity and Sedentary behavior (ICAPS), a four-year randomized and controlled trial has shown that prevention of sedentariness and of obesity is feasible in youth thanks the mobilization of several partners including actors in the domains of health, education, physical activity, transport and of community agencies in charge of recreational areas and transportation infrastructures. In this article, we present a synthesis of the key data demonstrating the efficacy of ICAPS at the end of the four years of intervention as well as preliminary results of the six-year follow-up study, i.e. two years after the end of the intervention. We discuss a few tracks on elements that may explain the effectiveness of the strategy implemented.     

Obésité : que nous dit l’épidémiologie ?

In most developed and developing countries, a regular increase of the prevalence of obesity has been documented during the last decade(s) of the xxth century. The last figure from the USA is for the first time discordant with this general trend by showing a clear slowing down since year 2000. In children likewise, a rapid increase in the prevalence of obesity took place in the second half of the xxth century but recent publications from France, Switzerland, UK, USA also report a stabilization of childhood overweight and obesity prevalences. The experience of developing countries clearly shows the impact of socioeconomic status improvement and urbanization on the prevalence of obesity. In developed countries like France, a striking element was the diffuse nature of the adult obesity epidemic observed from the 1990s. The general improvement of living conditions after the Second World War probably explains the diffuse nature of the epidemics. Specifically, the changes in the nutritional status of children that happened at that time have long lasting consequences for adult obesity epidemics. Indeed, a new current in epidemiology, lifecourse epidemiology, has prompted over the past decade a new approach of the pathophysiology of chronic diseases, including obesity. Lifecourse epidemiology considers factors affecting the susceptibility to diseases over the whole life with critical periods during developmental phases. Critical periods for the susceptibility to obesity have been documented in prenatal life, during the first 6 months of postnatal life and from 3 years on starting at the time of the adiposity rebound. Parental obesity is involved at each of the critical periods. The transgenerational transmission of obesity is explained by genetic factors, shared lifestyle but also epigenetics especially during the early developmental periods. The slowing down of the childhood obesity epidemics observed in several developed countries may signal that factors affecting the early susceptibility to obesity have recently changed.