Aging and obesity induce distinct gene expression adaptation in the liver of C57BL/6J mice.

BACKGROUND: Aging and obesity induce complex transcriptomic changes in the liver, promoting the development of insulin resistance and type 2 diabetes. In spite of an increasing amount of studies on the role of aging and nutrient excess in metabolic disorders, the specific molecular events leading to insulin resistance are still poorly understood. METHODS: This study presents a comparative analysis of hepatic gene expression profiles between young adult C57BL/6J mice fed with a low- or a high-fat diet for 1 and 12 months. We evaluated the expression of a defined set of genes implicated in glucose and lipid metabolism as well as key nuclear receptors and their target genes, IGF1 signaling and clock genes. RESULTS: Aging and short-term high-fat consumption induced insulin resistance, albeit through two distinct processes. Hepatic gene expression changes were more pronounced in the context of aging. We further analyzed expression profiles together with plasma parameters by principal component analysis with regard to diet condition. CONCLUSIONS: Our results suggest that in the liver of C57BL/6J mice, the molecular mechanisms underlying high-fat feeding or aging which mediated insulin resistance were not identical.

The nucleus tractus solitari (NTS) participates in peripheral ghrelin glucostatic hunger signalling mediated by insulin.

Three extrahypothalamic areas, the nucleus of the tractus solitari (NTS), the central nucleus of the amygdala (CeA) and the dorsal raphe nucleus (DRN), all potentially involved in peripheral ghrelin signalling of appetite control mediated by the glucose levels were examined. Thus, a specific anti-ghrelin antibody (AGA) was intravenously administered in order to remove the ghrelin signalling and then, subsequently, 4-h food intake, plasma glucose levels and the brain c-fos expression in the NTS, CeA and DRN were assessed. Food intake significantly decreased when the AGA was administered. NTS c-Fos expression was significantly augmented by insulin, while it was significantly decreased by the AGA. These results suggest that the NTS is a part of the ghrelin pathway that regulates the orexigenic signalling cascade, which may be triggered by a drop in blood glucose levels mediated by insulin.

Control del apetito y peso corporal: la ghrelina y la señalización orexigénica / appetite and body weight regulation: ghrelin and the orexigenic signalling

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Meal-induced changes in extracellular 5-HT in medial hypothalamus of lean (Fa/Fa) and obese (fa/fa) Zucker rats.

Hypothalamic serotonin (5-HT) is involved in appetite regulation and sympathetic stimulation of thermogenesis. This study tested the hypothesis that the enhanced energetic efficiency of obese Zucker rats involves blunted serotonergic release within the medial hypothalamus (MH). We used microdialysis and HPLC-EC to measure dynamic changes in extracellular 5-HT levels in the MH of 10-13-week-old male lean (Fa/Fa) and obese (fa/fa) Zucker rats before and after a meal. No differences were noted in basal levels of 5-HT between lean and obese rats. Consistent with the suggestion that hypothalamic 5-HT plays a physiological role in feeding, extracellular 5-HT levels increased significantly in both lean and obese rats given a meal. This increase was observed in the 20 min interval in which they ate the 8.1 kcal meal and remained for an additional 60 min. The net release of 5-HT during the meal interval was comparable in the lean (1.46+/-0.38 fmol/microl) and obese (1.21+/-0.82 fmol/microl) rats. However, the 5-HT levels of the leans (1.80+/-0.29 fmol/microl) plateaued in the next 20 min interval, whereas they continued rising (2.74+/-0.53 fmol/microl) in obese rats and were significantly higher than those in the leans during the 40 and 60 min intervals after the meal was presented. This resulted in a total net release during the meal plus the next three 20 min intervals that was significantly higher in obese (9.83+/-1.16 fmol/microl) than in lean (5.59+/-0.85 fmol/microl) rats. Thus, the enhanced energetic efficiency of the obese Zucker rats may not be associated with attenuated serotonin release in response to a meal. Rather their enhanced release of 5-HT in the MH may reflect compensatory mechanisms for the elevated orexigen NPY, the reduction in meal-induced CCK release, and/or a functional resistance to 5-HT.

Extracellular hypothalamic serotonin levels after dorsal raphe nuclei stimulation of lean (Fa/Fa) and obese (fa/fa) Zucker rats.

Serotonin (5-HT), acting in the medial hypothalamus (MH), is involved in appetite/satiety and sympathetic stimulation of thermogenesis. This study tested the hypothesis that the enhanced energetic efficiency of obese Zucker rats is associated with a reduced capacity of activated dorsal raphe (DR) neurons to release 5-HT in the MH. We used microdialysis and HPLC-EC to measure dynamic changes in extracellular 5-HT levels in the MH of urethane-anesthetized, 10-14 week old male lean and obese Zucker rats. These concentrations did not differ significantly between the two genotypes prior to stimulation (mean+/-S.E.M.=3.8+/-0.5 fmol/microl, lean; 3.6+/-1.0 fmol/microl, obese) or following DR stimulation at 25 Hz (200 microA). The latter elicited initial net increases of 0.54+/-0.15 fmol/microl in lean and 0.58+/-0.20 fmol/microl in obese rats; and 20 min post-stimulus, 5-HT values were still elevated and comparable in the two genotypes. Although a 50-Hz (200 microA) stimulus evoked initial increases that were similar in lean (1.37+/-0.23 fmol/microl) and obese (0.95+/-0.24 fmol/microl,) rats, the net increase in 5-HT concentration during the next 20-40 min period was higher in the lean (2.03+/-0.55 fmol/microl vs. 1.18+/-0.24 fmol/microl in the obese animals). Also, in the lean, but not obese rats, extracellular 5-HT levels were significantly greater at 50 vs. 25 Hz. These results support the hypothesis that the capacity of midbrain serotonergic neurons to release 5-HT at the MH is reduced in obese Zucker rats, consistent with their blunted responsiveness to dietary stimuli and greater energetic efficiency.

Lean (Fa/Fa) but not obese (fa/fa) Zucker rats release cholecystokinin at PVN after a gavaged meal.

Neuropeptides play an important role in the integration of dietary signals. Cholecystokinin (CCK) has been implicated in regulating ingestive behavior, particularly satiety. The primary objective of this study was to examine whether the hyperphagia characteristic of obese (fa/fa) rats involves impaired neural CCK secretion. Dynamic release of CCK at the hypothalamic paraventricular nucleus (PVN) of age-matched lean (Fa/Fa) and obese Zucker rats was determined using push-pull perfusion. The gavage of a 10.3-kcal (6 ml) liquid diet during lights off was followed by increased CCK release in lean rats (from 13.6 +/- 1.1 to 22.1 +/- 1.4 fmol in the 1st postprandial period and 18.4 +/- 2.5 fmol in the 2nd postprandial period). An identical meal load resulted in no postprandial increase in CCK release in obese rats, despite the fact that high-K+ artificial cerebrospinal fluid evoked CCK outflow in all animals. Intubation of 6 ml of nonnutritive 1% carboxymethylcellulose had no effect. These results are consistent with the suggestion that hypothalamic CCK plays a physiological role in satiety, and they demonstrate that obese Zucker rats have blunted hypothalamic CCK release in response to dietary cues.

[Gastromiro vs gastrografin vs prontobario CAT for computerized tomography. Multicenter study]. / Gastromiro vs gastrografin vs Prontobario TAC per Tomografia Computerizzata. Studio multicentrico.

The opacification of intestinal loops is mandatory, during CT examination of the abdomen, to prevent the gut from being mistaken for a pathological process or vice versa. The authors compared Gastrografin and Prontobarium-CT with a new, orally administrable, non-ionic contrast medium (Gastromiro) to investigate whether the non-ionic molecule presents any advantages over the other contrast media usually employed with CT. Five hundred ml of water solution/suspension at 11.1% (Gastromiro or Gastrografin) and 1.7% (Prontobarium-CT) were administered 20 minutes before examination to 818 consecutive patients. Different parameters were considered--i.e., patient tolerance as far as "taste and vomiting" were concerned, gut opacification, and any reaction which might have occurred to the patients within 24 hours after examination. The results, statistically analyzed, are the following: no significant difference in the quality of opacification of stomach, duodenum, and large bowel; significant difference in the quality of opacification of small bowel, where Gastromiro proved to have the highest contrast resolution; Gatromiro stimulated diarrhea significantly less than Gastrografin and Prontobarium-CT.

[Anesthesia problems in children with cleft lip, maxilla and palate]. / Problemi di anestesia nei bambini portatori di schisi labio-maxillo-palatina.

The technical and physiopathological problems associated with labiomaxillopalatine schisis in children are discussed. Personal experience, involving the choice of a type of anaesthesia based on the use of an analgesic (pentazocine), and the exclusion of halogenated anaesthetics in most cases, is reported. Stress is laid on the simplicity of the technique. Coupled with careful intraoperative monitoring, it has enabled this type of surgery to be handled both serenely and successfully.