Effects of sleeve gastrectomy in high fat diet-induced obese mice: respective role of reduced caloric intake,white adipose tissue inflammation and changes in adipose tissue and ectopic fat depots

Background

Sleeve gastrectomy (SG) has become a popular bariatric procedure. The mechanisms responsible for weight loss and improvement of metabolic disturbances have still not been completely elucidated. We investigated the effect of SG on body weight, adipose tissue depots, glucose tolerance, and liver steatosis independent of reduced caloric intake in high-fat-diet-induced obese mice.

Methods

C57BI/6 J mice fed a high fat diet (45 %) for 33 weeks were divided into three groups: sleeve gastrectomy (SG, 13 mice), sham-operated ad libitum fed (SALF, 13 mice) and sham-operated pair fed (PFS, 13 mice). The animals were humanely killed 23 days after surgery.

Results

In SG mice, food intake was reduced transiently, but weight loss was significant and persistent compared to controls (SG vs. PFS, P < 0.05; PFS vs. SALF, P < 0.05). SG mice showed improved glucose tolerance and lower levels of liver steatosis compared with controls (area under the curve, SG vs. PFS, P < 0.01; PFS vs. SALF, P < 0.05) (liver steatosis, SG vs. PFS, P < 0.05; PFS vs. SALF, P < 0.01). This was associated with a decrease in the ratios of the weight of pancreas, epididymal and inguinal adipose tissues to body weight, and an increase in the ratio of brown adipose tissue weight to body weight. Epididymal adipose tissue was also infiltrated by fewer activated T cells and by more anti-inflammatory regulatory T cells. Serum levels of fasting acyl ghrelin were still significantly decreased 3 weeks after surgery in SG mice compared to PFS mice (P < 0.05).

Conclusions

Reduced white adipose tissue inflammation, modification of adipose tissue development (brown vs. white adipose tissue), and ectopic fat are potential mechanisms that may account for the reduced caloric intake independent effects of SG.     

The role of PLC beta 1 in the control of oocyte meiosis during folliculogenesis

The dynamics of the subcellular distribution of PLCbeta1 was investigated during meiosis competence acquisition and meiosis resumption in relation to oocyte diameter and to nonsurrounded-nucleolus or surrounded-nucleolus chromatin configurations. Oocytes collected after both in vivo and in vitro folliculogenesis were studied. In both conditions, at the beginning of the process, most oocytes exhibited a nuclear PLCbeta 1 associated with a nonsurrounded-nucleolus chromatin configuration. Then at the final stage of the process, the factors shifted mainly toward a cytoplasmic PLCbeta1 and a surrounded-nucleolus chromatin configuration, typical of a preovulatory fertilizable oocyte. Additionally, only germinal vesicle oocytes with a diameter > 75 microm, and exhibiting cytoplasmic PLC beta1 distribution and surrounded-nucleolus chromatin configuration, resumed meiosis. Our findings demonstrate a strong correlation between oocyte diameter, chromatin configuration, and PLCbeta1 localization. Thus, PLCbeta1 localization appears to be a key factor determining the progressive acquisition of meiotic competence and final resumption of meiosis.     

Urocortins improve dystrophic skeletal muscle structure and function through both PKA- and Epac-dependent pathways

In Duchenne muscular dystrophy, the absence of dystrophin causes progressive muscle wasting and premature death. Excessive calcium influx is thought to initiate the pathogenic cascade, resulting in muscle cell death. Urocortins (Ucns) have protected muscle in several experimental paradigms. Herein, we demonstrate that daily s.c. injections of either Ucn 1 or Ucn 2 to 3-week-old dystrophic mdx(5Cv) mice for 2 weeks increased skeletal muscle mass and normalized plasma creatine kinase activity. Histological examination showed that Ucns remarkably reduced necrosis in the diaphragm and slow- and fast-twitch muscles. Ucns improved muscle resistance to mechanical stress provoked by repetitive tetanizations. Ucn 2 treatment resulted in faster kinetics of contraction and relaxation and a rightward shift of the force-frequency curve, suggesting improved calcium homeostasis. Ucn 2 decreased calcium influx into freshly isolated dystrophic muscles. Pharmacological manipulation demonstrated that the mechanism involved the corticotropin-releasing factor type 2 receptor, cAMP elevation, and activation of both protein kinase A and the cAMP-binding protein Epac. Moreover, both STIM1, the calcium sensor that initiates the assembly of store-operated channels, and the calcium-independent phospholipase A(2) that activates these channels were reduced in dystrophic muscle by Ucn 2. Altogether, our results demonstrate the high potency of Ucns for improving dystrophic muscle structure and function, suggesting that these peptides may be considered for treatment of Duchenne muscular dystrophy.     

Comprehensive NF1 screening on cultured Schwann cells from neurofibromas

Neurofibromatosis type 1 (NF1) is mainly characterized by the occurrence of benign peripheral nerve sheath tumors or neurofibromas. Thorough investigation of the somatic mutation spectrum has thus far been hampered by the large size of the NF1 gene and the considerable proportion of NF1 heterozygous cells within the tumors. We developed an improved somatic mutation detection strategy on cultured Schwann cells derived from neurofibromas and investigated 38 tumors from nine NF1 patients. Twenty-nine somatic NF1 lesions were detected which represents the highest NF1 somatic mutation detection rate described so far (76%). Furthermore, our data strongly suggest that the acquired second hit underlies reduced NF1 expression in Schwann cell cultures. Together, these data clearly illustrate that two inactivating NF1 mutations, in a subpopulation of the Schwann cells, are required for neurofibroma formation in NF1 tumorigenesis. The observed somatic mutation spectrum shows that intragenic NF1 mutations (26/29) are most prevalent, particularly frameshift mutations (12/29, 41%). We hypothesize that this mutation signature might reflect slightly reduced DNA repair efficiency as a trigger for NF1 somatic inactivation preceding tumorigenesis. Joint analysis of the current and previously published NF1 mutation data revealed a significant difference in the somatic mutation spectrum in patients with a NF1 microdeletion vs. non-microdeletion patients with respect to the prevalence of loss of heterozygosity events (0/15 vs. 41/81). Differences in somatic inactivation mechanism might therefore exist between NF1 microdeletion patients and the general NF1 population.     

Personality disorders in oncology: characteristic and management

Confronted with a patient with a personality disorder, the oncologist must recognize it and adapt his treatment accordingly. Some pathological character types require interpersonal adjustments to ensure a good understanding of the cancer disease and also to obtain the best compliance with supportive care. Given the fact that specific pharmacological treatment does not exist, collaboration between oncologists and the psycho-oncology team is paramount. The interaction between the somatic disease and the psychiatric disorder demand collaboration among caregivers sharing explanations and recommendations. Clinical examples will illustrate each personality disorder and will focus on the several problems raised by the psychiatric disorder. Treatment principles will be addressed in a second section.     

EEG spectral power and cognitive performance during sleep inertia: the effect of normal sleep duration and partial sleep deprivation

Sleep inertia (SI) is a transient period occurring immediately after awakening, usually characterized by performance decrement. When sleep is sufficient, SI is moderate, and produces few or no deficit. When it is associated with prior sleep deprivation, SI shows dose-dependent negative effects on cognitive performance, especially when subjects have been awaken in slow wave sleep (SWS). In the present study, spectral analysis was applied during the last 10 min before and the first 10 min after awakening, and during 1 h after awakening while subjects performed the Stroop test. Seventeen subjects were divided into a Control group who slept 8 h, and a Sleep Deprived group who slept only 2 h. The results show that performance was normal in the Control group, whereas reaction time was increased during the first half hour and error level during the second half hour in the Sleep Deprived group. Spectral analysis applied on the waking EEG during the whole test session showed that alpha activity was increased in both groups, but theta power only in the Sleep Deprived group. There was a high positive correlation in sleep deprived subjects between delta power during the last 10 min of sleep and subsequent performance decrement in speed and accuracy. Comparison of individual records showed a high positive correlation between spectral power before and after awakening in the Control group (generally in the sense of an increased frequency band), but no correlation was found in the Sleep Deprived group who exhibited a rather disorganized pattern. We discuss these results in terms of incoherence in the EEG continuity during sleep offset after prior sleep loss, which could partly account for the performance decrement observed during SI in sleep deprived subjects.     

Is an irritable ADHD profile traceable using personality dimensions? Replicability,stability, and predictive value over time of data-driven profiles

Pediatric attention deficit/hyperactivity disorder (ADHD) is a heterogeneous condition. In particular, children with ADHD display varying profiles of dispositional traits, as assessed through temperament and personality questionnaires. Previous data-driven community detection analyses based on temperament dimensions identified an irritable profile of patients with ADHD, uniquely characterized by elevated emotional dysregulation symptoms. Belonging to this profile increased the risk of developing comorbid disorders. Here, we investigated whether we could replicate this profile in a sample of 178 children with ADHD, using community detection based on personality dimensions. Stability of the identified profiles, of individual classifications, and clinical prediction were longitudinally assessed over a 1-year interval. Three personality profiles were detected: The first two profiles had high levels of neuroticism, with the first displaying higher ADHD severity and lower openness to experience (profile 1; N = 38), and the second lower agreeableness (profile 2; N = 73). The third profile displayed scores closer to the normative range on all five factors (profile 3; N = 67). The identified profiles did only partially replicate the temperament-based profiles previously reported, as higher levels of neuroticism were found in two of the three detected profiles. Nonetheless, despite changes in individual classifications, the profiles themselves were highly stable over time and of clinical predictive value. Whereas children belonging to profiles 1 and 2 benefited from starting medication, children in profile 3 did not. Hence, belonging to an emotionally dysregulated profile at baseline predicted the effect of medication at follow-up over and above initial ADHD symptom severity. This finding suggests that personality profiles could play a role in predicting treatment response in ADHD.