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

ObjectivesThis study investigated the effect of bariatric surgery (BS)–induced weight loss on cardiac ectopic fat using 3T magnetic resonance imaging in morbid obesity.BackgroundHeart 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. Whether sustained weight loss can modulate epicardial fat or myocardial fat is unknown.MethodsTwenty-three morbidly obese patients underwent 1H-magnetic resonance spectroscopy to determine myocardial triglyceride content (MTGC), magnetic resonance imaging to assess epicardial fat volume (EFV), cardiac function, and computed tomography visceral abdominal fat (VAF) measurements at baseline and 6 months after BS.ResultsThe BS reduced body mass index significantly, from 43.1 ± 4.5 kg/m2 to 32.3 ± 4.0 kg/m2, subcutaneous fat from 649 ± 162 cm2 to 442 ± 127 cm2, VAF from 190 ± 83 cm2 to 107 ± 44 cm2, and EFV from 137 ± 37 ml to 98 ± 25 ml (all p < 0.0001). There was no significant change in MTGC: 1.03 ± 0.2% versus 1.1 ± 0.2% (p = 0.85). A significant reduction in left ventricular mass (118 ± 24 g vs. 101 ± 18 g) and cardiac output (7.1 ± 1.6 l/min vs. 5.4 ± 1.0 l/min) was observed and was statistically associated with weight loss (p < 0.05). The loss in EFV was limited (−27 ± 11%) compared to VAF diminution (−40 ± 19%). The EFV variation was not correlated with percentage of body mass index or VAF loss (p = 0.007). The ratio of %EFV to %VAF loss decreased with sleep apnea syndrome (1.34 ± 0.3 vs. 0.52 ± 0.08, p < 0.05).ConclusionsSix-month BS modulates differently cardiac ectopic fat deposition, with a significant decrease in epicardial fat and no change in myocardial fat. Epicardial fat volume loss was limited in patients with sleep apnea. (Impact of Bariatric Surgery on Epicardial Adipose Tissue and on Myocardial Function; NCT01284816

Neonatal overfeeding by small-litter rearing sensitises hippocampal microglial responses to immune challenge:Reversal with neonatal repeated injections of saline or minocycline

The early-life period is extremely vulnerable to programming effects from the environment, many of which persist into adulthood. We have previously demonstrated that adult rats overfed as neonates have hypothalamic microglia that are hyper-responsive to an immune challenge, as well as hippocampal microglia that respond less efficiently to learning. We therefore hypothesised that neonatal overfeeding would alter the ability of hippocampal microglia to respond to an immune challenge with lipopolysaccharide (LPS) and that concomitant minocycline, a tetracycline antibiotic that suppresses microglial activity, could restore these responses. We induced neonatal overfeeding by manipulating the litter sizes in which Wistar rat pups were raised, so the pups were suckled in litters of four (neonatally overfed) or 12 (control-fed). We then examined the hippocampal microglial profiles 24 hour after an immune challenge with LPS and found that the neonatally overfed rats had dramatically increased microglial numbers in the hippocampus after immune challenge compared to control-fed rats. Attempts to reverse these effects with minocycline revealed repeated that neonatal injections, whether with minocycline or with saline, markedly suppressed microglial number and density throughout the hippocampus and abolished the difference between the groups in their responses to LPS. These data suggest that neonatal overfeeding not only can have lasting effects on hippocampal immune responses, but also that neonatal exposure to a protocol of repeated injections, irrespective of treatment, has a pronounced long-term impact, highlighting the importance of considering these effects when interpreting experimental data

Neonatal Overfeeding Induced by Small Litter Rearing Causes Altered Glucocorticoid Metabolism in Rats

Elevated glucocorticoid (GC) activity may be involved in the development of the metabolic syndrome. Tissue GC exposure is determined by the tissue-specific GC-activating enzyme 11β-hydroxysteriod dehydrogenase type 1 (11β-HSD1) and the GC-inactivating enzyme 5α-reductase type 1 (5αR1), as well as 5β-reductase (5βR). Our aim was to study the effects of neonatal overfeeding induced by small litter rearing on the expression of GC-regulating enzymes in adipose tissue and/or liver and on obesity-related metabolic disturbances during development. Male Sprague-Dawley rat pup litters were adjusted to litter sizes of three (small litters, SL) or ten (normal litters, NL) on postnatal day 3 and then given standard chow from postnatal week 3 onward (W3). Small litter rearing induced obesity, hyperinsulinemia, and higher circulating corticosterone in adults. 11β-HSD1 expression and enzyme activity in retroperitoneal, but not in epididymal, adipose tissue increased with postnatal time and peaked at W5/W6 in both groups before declining. From W8, 11β-HSD1 expression and enzyme activity levels in retroperitoneal fat persisted at significantly higher levels in SL compared to NL rats. Hepatic 11β-HSD1 enzyme activity in SL rats was elevated from W3 to W16 compared to NL rats. Hepatic 5αR1 and 5βR expression was higher in SL compared to NL rats after weaning until W6, whereupon expression decreased in the SL rats and remained similar to that in NL rats. In conclusion, small litter rearing in rats induced peripheral tissue-specific alterations in 11β-HSD1 expression and activity and 5αR1 and 5βR expression during puberty, which could contribute to elevated tissue-specific GC exposure and aggravate the development of metabolic dysregulation in adults

The Early Nutritional Environment of Mice Determines the Capacity for Adipose Tissue Expansion by Modulating Genes of Caveolae Structure

While the phenomenon linking the early nutritional environment to disease susceptibility exists in many mammalian species, the underlying mechanisms are unknown. We hypothesized that nutritional programming is a variable quantitative state of gene expression, fixed by the state of energy balance in the neonate, that waxes and wanes in the adult animal in response to changes in energy balance. We tested this hypothesis with an experiment, based upon global gene expression, to identify networks of genes in which expression patterns in inguinal fat of mice have been altered by the nutritional environment during early post-natal development. The effects of over- and under-nutrition on adiposity and gene expression phenotypes were assessed at 5, 10, 21 days of age and in adult C57Bl/6J mice fed chow followed by high fat diet for 8 weeks. Under-nutrition severely suppressed plasma insulin and leptin during lactation and diet-induced obesity in adult mice, whereas over-nourished mice were phenotypically indistinguishable from those on a control diet. Food intake was not affected by under- or over-nutrition. Microarray gene expression data revealed a major class of genes encoding proteins of the caveolae and cytoskeleton, including Cav1, Cav2, Ptrf (Cavin1), Ldlr, Vldlr and Mest, that were highly associated with adipose tissue expansion in 10 day-old mice during the dynamic phase of inguinal fat development and in adult animals exposed to an obesogenic environment. In conclusion gene expression profiles, fat mass and adipocyte size in 10 day old mice predicted similar phenotypes in adult mice with variable diet-induced obesity. These results are supported by phenotypes of KO mice and suggest that when an animal enters a state of positive energy balance adipose tissue expansion is initiated by coordinate changes in mRNA levels for proteins required for modulating the structure of the caveolae to maximize the capacity of the adipocyte for lipid storage

Métabolisme des glucocorticoïdes du tissu adipeux dans l'obésité et le syndrome métabolique (études chez le rat et l'homme)

AIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

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

International audienceImmediate 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 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1)], and overexpression of proinflammatory cytokines in mesenteric adipose tissue (MAT) in adulthood. We studied the effects of pioglitazone, a PPAR gamma 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, 11 beta-HSD11, CD 68, and proinflammatory cytokines mRNAs, including plasminogen-activator inhibitor type 1. MesentericGRmRNAlevels correlated positively with mesenteric proinflammatory cytokinesmRNAconcentrations. 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 11 beta-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, 11 beta-HSD1, and proinflammatory cytokines overexpression, possibly through a GR-dependent mechanism

Glucocorticoïdes, 11β-hydroxystéroïde déshydrogénase de type 1 et obésité viscérale

L’importance des glucocorticoïdes dans le développement et le maintien de l’obésité ainsi que la genèse de ses complications métaboliques et cardio-vasculaires est maintenant bien reconnue. L’existence, chez l’obèse, de concentrations circulantes de cortisol normales a fait envisager la possibilité d’anomalies du métabolisme local des glucocorticoïdes, en particulier dans le tissu adipeux. Un ensemble de données récentes a mis en évidence, dans ce tissu, une surexpression de la 11β-hydroxystéroïde déshydrogénase de type 1, enzyme qui convertit la cortisone (inactive) en cortisol (actif). Cette surexpression engendre un hypercorticisme local. Le développement d’inhibiteurs spécifiques de la 11β-hydroxystéroïde déshydrogénase de type 1 pourrait constituer une nouvelle approche du traitement de l’obésité viscérale et de ses complications