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 11ß-hydroxysteroid dehydrogenase type 1 (11ß-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. Nine-month-old rats normofed or overfed during the immediate postnatal period were given pioglitazone (3 mg/kg/day) for 6 weeks. Pioglitazone stimulated weight gain and induced a redistribution of adipose tissue toward epididymal location with enhanced plasma adiponectin. Treatment normalized postnatal overfeeding-induced metabolic alterations (increased fasting insulinemia and free fatty acids) and mesenteric overexpression of GR, 11ß-HSD11, CD 68, and proinflammatory cytokines mRNAs, including plasminogen-activator inhibitor type 1. Mesenteric GR mRNA levels correlated positively with mesenteric proinflammatory cytokines mRNA concentrations. In vitro incubation of MAT obtained from overfed rats demonstrated that pioglitazone induced a down-regulation of GR gene expression and normalized glucocorticoid-induced stimulation of 11ß-HSD1 and plasminogen-activator inhibitor type 1 mRNAs. Our data show for the first time that the metabolic, endocrine, and inflammatory alterations induced by early-onset postnatal obesity can be reversed by pioglitazone at the adulthood. They demonstrate that pioglitazone, in addition to its well-established effect on adipose tissue redistribution and adiponectin secretion, reverses programing-induced adipose GR, 11ß-HSD1, and proinflammatory cytokines overexpression, possibly through a GR-dependent mechanism.

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. RESULTS: Post-natal overfeeding or high-fat feeding lead to overweight with increased visceral fat mass and adipocytes surface. When both paradigms were associated, adipocytes surface showed a disproportionate increase. A strong immunoreactivity for (pro)renin receptor was found in stromal cells. Plasma renin activity increased in programmed animals whereas (pro)renin receptor expressing cells density was stimulated by high-fat diet. There was a positive, linear relationship between plasma renin activity and (pro)renin receptor expressing cells density and adipocytes surface. CONCLUSIONS: Our experiments demonstrate that association of post-natal overfeeding and high-fat diet increased plasma renin activity and adipose (pro)renin receptor expression. Such phenomenon could explain, at least in part, the associated disproportionate adipocyte hypertrophy and its accompanying increased glucose intolerance.

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

[Corticotropic axis and chronic stress in abdominal obesity and metabolic syndrome]. / Axe corticotrope et stress chronique dans l'obésité abdominale et le syndrome métabolique.

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. We note the necessity of methodologically-impeccable clinical studies for an objective evaluation of the role of stress in obesity.

[Gelatinous bone marrow transformation in anorexia nervosa]. / Transformation gélatineuse de la moelle osseuse au cours de l'anorexie mentale.

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). Changes in peripheral blood cell counts are various and moderate, and do not always reflect the severity of bone marrow damage. The pathogenesis is not yet well elucidated but is certainly related to the nutritional status because gelatinous bone marrow transformation is found in anorexia nervosa and in other clinical situations with cachexia. Gelatinous transformation of the marrow is reversible with feeding.