Pioglitazone in adult rats reverses immediate postnatal overfeeding-induced metabolic, hormonal, and inflammatory alterations.

Immediate postnatal overfeeding in rats, obtained by reducing the litter size, results in early-onset obesity. Such experimental paradigm programs overweight, insulin resistance, dyslipidemia, increased adipose glucocorticoid metabolism [up-regulation of glucocorticoid receptor (GR) and 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1)], and overexpression of proinflammatory cytokines in mesenteric adipose tissue (MAT) in adulthood. We studied the effects of pioglitazone, a PPARγ agonist, treatment on the above-mentioned overfeeding-induced alterations.

[Corticotherapy withdrawal in older people].

Synthetic glucocorticoids treatment for their antiinflammatory and immunosuppressive activities for more than 3 weeks decreases corticotropic axis and induces a risk of adrenal insufficiency upon treatment withdrawal. Dose, duration and unknown individual factors play a role in the occurrence of adrenal insufficiency. Serum cortisol at 7-8 am, possibly completed by an 1-24 ACTH stimulation test makes the diagnosis.

Effects of bariatric surgery on cardiac ectopic fat: lesser decrease in epicardial fat compared to visceral fat loss and no change in myocardial triglyceride content.

Objectives: This study investigated the effect of bariatric surgery (BS)-induced weight loss on cardiac ectopic fat using 3T magnetic resonance imaging in morbid obesity.

Background: Heart disease is one of the leading causes of mortality and morbidity in obese patients. Deposition of cardiac ectopic fat has been related to increased heart risk.

Expression and nutritional regulation of the (pro)renin receptor in rat visceral adipose tissue.

Background: Early life nutritional environment plays an important role in the development of visceral adipose tissue and interacts with nutritional regulations in adulthood, leading to metabolic dysregulations.

Aim: We hypothesized that the renin-angiotensin system may play a role in the programming-induced development of visceral adipose tissue.

Material And Methods: We studied, using a model of programming of overweight and glucose intolerance, obtained by post-natal overfeeding with consecutive highfat diet, the status of plasma renin activity and mesenteric adipose renin-angiotensin system, including the recently identified (pro)renin receptor, in adult rats.

[What can we do with genetic screening of obesity in clinical practice?].

The discovery of genetic abnormalities in obesity improves the knowledge on the physiology of energetic homeostasis, and demonstrates that it is a fully recognized disease and not only a behavioral problem. In cases of early obesity and very severe degree, with severely abnormal dietary behavior, endocrine abnormalities, and a ground of parental consanguinity, monogenic obesity or a syndromic obesity (in the case of a rare genetic disease) must be suspected. In that case, a genetic screening is necessary because it helps the global care of the patient and sometimes an effective specific therapeutics can be proposed.

Perinatal programming of central obesity and the metabolic syndrome: role of glucocorticoids.

Intrauterine growth retardation (IUGR) is associated with increased prevalence, at the adult age, of central obesity, the metabolic syndrome, and its complications (type 2 diabetes and coronary heart disease). Programming of the corticotropic function is one of the mechanisms underlying the above-mentioned phenomenon. An increased passage of active glucocorticoids from the mother to the fetus can act, at the central nervous system level, to program an enhanced response to stress and, at the peripheral level, in adipose tissue to induce an increased local glucocorticoid exposure and sensitivity.

Postnatal programming of glucocorticoid metabolism in rats modulates high-fat diet-induced regulation of visceral adipose tissue glucocorticoid exposure and sensitivity and adiponectin and proinflammatory adipokines gene expression in adulthood.

Objective: Alterations of the perinatal environment, which lead to increased prevalence of the metabolic syndrome in adulthood, program an upregulation of systemic and/or adipose tissue glucocorticoid metabolism (11 beta-hydroxysteroid dehydrogenase type 1 [11 beta-HSD-1]-induced corticosterone reactivation). We hypothesized that postnatal programming could modulate high-fat diet-induced adipose tissue dysregulation in adulthood.

Research Design And Methods: We compared the effects of chronic (since weaning) high- or low-fat diet in postnatally normofed (control) or overfed (programmed) rats.

Effect of sleep apnea syndrome on the circadian profile of cortisol in obese men.

It has been hypothesized that sleep apnea syndrome (SAS) increases hypothalamic-pituitary-adrenal axis activity and, through increased cortisol levels, participates in the pathophysiology of metabolic and cardiovascular complications. We compared the circadian profiles of cortisol in obese men with [obSAS+; apnea-hypopnea index (AHI) >or= 20/h] and without SAS (obSAS-; AHI View Article and Find Full Text PDF

Renin receptor expression in human adipose tissue.

Adipose tissue synthesizes all components of the renin-angiotensin system. The renin receptor (RenR) is able, on renin binding, to increase its efficiency to generate angiotensin I from angiotensinogen. We demonstrate that RenR is specifically synthesized in the stromal portion of human adipose tissue in both isolated interadipocyte stromal cells and in stromal areas.

11beta-hydroxysteroid dehydrogenase type 1 mRNA is increased in both visceral and subcutaneous adipose tissue of obese patients.

Objective: Data from rodents provide evidence for a causal role of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD-1) in the development of obesity and its complications. In humans, 11beta-HSD-1 is increased in subcutaneous adipose tissue (SAT) of obese patients, and higher adipose 11beta-HSD-1 was associated with features of the metabolic syndrome. To date, there is no evidence for an increased expression of 11beta-HSD-1 in human visceral adipose tissue (VAT), although VAT is the major predictor for insulin resistance and the metabolic syndrome.

Insulin resistance induced by hydrocortisone is increased in patients with abdominal obesity.

Glucocorticoids hypersensitivity may be involved in the development of abdominal obesity and insulin resistance. Eight normal weight and eight obese women received on two occasions a 3-h intravenous infusion of saline or hydrocortisone (HC) (1.5 microg x kg(-1) x min(-1)).

[Obesity: where are we now?].

Overweight and obesity correspond to excess fat, defined and assessed in clinical practice by the body mass index (BMI: ratio of weight in kilograms to height in meters squared). Obesity has numerous negative health consequences: metabolic, cardiovascular, and mechanical complications, predisposition to some cancers, and psychosocial repercussions. In France in 2003, 30% of adults were overweight and 11% obese.

[Corticotropic axis and chronic stress in abdominal obesity and metabolic syndrome].

Several indicators of corticotropic axis hyperactivity have been observed in common abdominal obesity, which is clinically similar to the obesity found in Cushing's syndrome. Corticotropic axis hyperactivity may be involved in the development and metabolic and cardiovascular complications of abdominal obesity. Several mechanisms may be responsible for this hormonal dysregulation: genetic, lifestyle, and nutritional factors, and chronic stress.

Cluster analysis: an alternative method for covariate selection in population pharmacokinetic modeling.

To be analyzed, the heterogeneity characterizing biological data calls for using appropriate models involving numerous variables. A high variable number could become problematic when one needs to determine a priori the most significant variable combination in order to reduce the inter-individual variability (IIV). Alternatively to multiple introductions of single variables, we propose a single introduction of a multivariate variable.

[Gelatinous bone marrow transformation in anorexia nervosa].

Moderate hematologic abnormalities, like anemia or leukopenia, are frequently seen in anorexia nervosa, whereas pancytopenia and bone marrow abnormalities are uncommon. We report a case of tricytopenia with gelatinous bone marrow transformation in anorexia nervosa. Marrow gelatinous transformation (also called serous fat atrophy or starvation marrow) is characterized by the association of marrow hypoplasia and interstitial infiltration of a ground gelatinous substance (acidic mucopolysaccharides).

Postnatal diet-induced obesity in rats upregulates systemic and adipose tissue glucocorticoid metabolism during development and in adulthood: its relationship with the metabolic syndrome.

In humans, a hyperactivity of glucocorticoid metabolism was postulated to be involved in the intrauterine programming of the metabolic syndrome in adulthood. We studied in rats the effects of overfeeding, obtained by reducing the size of the litter in the immediate postnatal period, a time crucial for neuroendocrine maturation such as late gestation in humans. Overfeeding induced early-onset obesity and accelerated the maturation of the hypothalamo-pituitary-adrenal (HPA) axis together with an upregulation of adipose tissue glucocorticoid receptor (GR) mRNA.

Expression of the mRNAs coding for the glucocorticoid receptor isoforms in obesity.

Objective: Glucocorticoids may be a pathophysiological mediator for the development of visceral obesity. In obese patients, adipose tissue reactivation of cortisone to cortisol is enhanced. In addition, changes in glucocorticoid receptor (GR) could also be important, either at the central nervous system level, by modulating the negative glucocorticoid feedback, or at a peripheral level, by regulating adipose tissue activity.

[Glucocorticoids, 11 beta-hydroxysteroid dehydrogenase type 1, and visceral obesity].

Glucocorticoids are implicated as a pathophysiological mediator of obesity and its accompanying metabolic and cardiovascular complications. Obese patients exhibit normal circulating cortisol levels, related to increased glucocorticoid production and degradation. However, it has been demonstrated that local production of active cortisol from inactive cortisone driven by 11 beta-hydroxysteroid dehydrogenase type 1 is exaggerated in adipose tissue of obese subjects.