•Chronic energy imbalance impacts olfactory-driven behaviors in response to food.•Fed obese rat strains respond to food odor in the same way as when they are fasted.•Fasting induces alterations in ...food olfactory-driven behaviors in lean strains only.•Expression of olfactory-related metabolic genes varies in different strains.
In most species, food intake is influenced by olfactory cues and metabolic status can affect the olfactory function of animals and regulate feeding-related behaviors. We investigated whether modulation of the endocrine system that regulates or modifies energy balance affected the olfactory system by examining four rat strains, obese Zucker and obesity-resistant Lou/C rats and their counterparts. Such models were chosen because they differ largely in their energy status and in their insulin and leptin blood levels, two hormones known to impact olfactory behaviors. After evaluation of the main metabolic parameters, we analyzed the food-driven olfactory behaviors of the four strains by measuring general activity time and sniffing time in response to food cues together with food reward localization performances in fed and fasted states. In fed conditions, obese Zucker and Wistar rats exhibited a great interest for food odor, which was not enhanced by fasting, in contrast to Lou/C and Zucker lean rats. All strains, except Lou/C, showed decreased latencies to find a hidden food reward with time, whereas a 24-h fasting was necessary to improve food search performances in Lou/C. These metabolic and behavioral changes were partly associated with variations in the transcription profiles of leptin, insulin and orexin and their receptors in the hypothalamus and olfactory system. The results show that variations in metabolic-related genes expression along the olfactory pathways comes with obesity in influencing food odors-driven behaviors. Our data indicate that food-olfactory driven behaviors are clearly affected by the long-term metabolic status.
Developed from presentations given at the Cerisy SVSI (Sciences de la vie, sciences de l information) conference held in 2016, this book presents a broad overview of thought and research at the ...intersection of life sciences and information sciences.
This study aimed to determine the prevalence of genetic and environmental vascular risk factors in non diabetic patients with premature peripheral arterial disease, either peripheral arterial ...occlusive disease or thromboangiitis obliterans, the two main entities of peripheral arterial disease, and to established whether some of them are specifically associated with one or another of the premature peripheral arterial disease subgroups.
This study included 113 non diabetic patients with premature peripheral arterial disease (diagnosis <45-year old) presenting either a peripheral arterial occlusive disease (N = 64) or a thromboangiitis obliterans (N = 49), and 241 controls matched for age and gender. Both patient groups demonstrated common traits including cigarette smoking, low physical activity, decreased levels of HDL-cholesterol, apolipoprotein A-I, pyridoxal 5'-phosphate (active form of B6 vitamin) and zinc. Premature peripheral arterial occlusive disease was characterized by the presence of a family history of peripheral arterial and carotid artery diseases (OR 2.3 and 5.8 respectively, 95% CI), high lipoprotein (a) levels above 300 mg/L (OR 2.3, 95% CI), the presence of the factor V Leiden (OR 5.1, 95% CI) and the glycoprotein Ia(807T,837T,873A) allele (OR 2.3, 95% CI). In thromboangiitis obliterans group, more patients were regular consumers of cannabis (OR 3.5, 95% CI) and higher levels in plasma copper has been shown (OR 6.5, 95% CI).
According to our results from a non exhaustive list of study parameters, we might hypothesize for 1) a genetic basis for premature peripheral arterial occlusive disease development and 2) the prevalence of environmental factors in the development of thromboangiitis obliterans (tobacco and cannabis). Moreover, for the first time, we demonstrated that the 807T/837T/873A allele of platelet glycoprotein Ia may confer an additional risk for development of peripheral atherosclerosis in premature peripheral arterial occlusive disease.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Food odours are major determinants for food choice; their detection is influenced by nutritional status. Among different metabolic signals, insulin plays a major role in food intake regulation. The ...aim of the present study was to investigate a potential role of insulin in the olfactory mucosa (OM), using ex vivo tissues and in vitro primary cultures. We first established the expression of insulin receptor (IR) in rat olfactory mucosa. Transcripts of IR‐A and IR‐B isoforms, as well as IRS‐1 and IRS‐2, were detected in OM extracts. Using immunocytochemistry, IR protein was located in olfactory receptor neurones, sustentacular and basal cells and in endothelium of the lamina propria vessels. Moreover, the insulin binding capacity of OM was quite high compared to that of olfactory bulb or liver. Besides the main pancreatic insulin source, we demonstrated insulin synthesis at a low level in the OM. Interestingly 48 h of fasting, leading to a decreased plasmatic insulin, increased the number of IR in the OM. Local insulin concentration was also enhanced. These data suggest a control of OM insulin system by nutritional status. Finally, an application of insulin on OM, aiming to mimic postprandial insulin increase, reversibly decreased the amplitude of electro‐olfactogramme responses to odorants by approximately 30%. These data provide the first evidence that insulin modulates the most peripheral step of odour detection at the olfactory mucosa level.
Little is known about mutational landscape of rare breast cancer (BC) subtypes. The aim of the study was to apply next generation sequencing to three different subtypes of rare BCs in order to ...identify new genes related to cancer progression. We performed whole exome and targeted sequencing of 29 micropapillary, 23 metaplastic, and 27 pleomorphic lobular BCs. Micropapillary BCs exhibit a profile comparable to common BCs: PIK3CA, TP53, GATA3, and MAP2K4 were the most frequently mutated genes. Metaplastic BCs presented a high frequency of TP53 (78 %) and PIK3CA (48 %) mutations and were recurrently mutated on KDM6A (13 %), a gene involved in histone demethylation. Pleomorphic lobular carcinoma exhibited high mutation rate of PIK3CA (30 %), TP53 (22 %), and CDH1 (41 %) and also presented mutations in PYGM, a gene involved in glycogen metabolism, in 8 out of 27 samples (30 %). Further analyses of publicly available datasets showed that PYGM is dramatically underexpressed in common cancers as compared to normal tissues and that low expression in tumors is correlated with poor relapse-free survival. Immunohistochemical staining on formalin-fixed paraffin-embedded tissues available in our cohort of patients confirmed higher PYGM expression in normal breast tissue compared to equivalent tumoral zone. Next generation sequencing methods applied on rare cancer subtypes can serve as a useful tool in order to uncover new potential therapeutic targets. Sequencing of pleomorphic lobular carcinoma identified a high rate of alterations in PYGM. These findings emphasize the role of glycogen metabolism in cancer progression.
Development after nuclear transfer (NT) is subjected to defects originating from both the epiblast and the trophoblast parts of the conceptus and is always accompanied by placentomegaly at term. Here ...we have investigated the origin of the reprogramming errors affecting the trophoblast lineage in mouse NT embryos. We show that trophoblast stem (TS) cells can be derived from NT embryos (ntTS cells) and used as an experimental in vitro model of trophoblast proliferation and differentiation. Strikingly, TS derivation is more efficient from NT embryos than from controls and ntTS cells exhibit a growth advantage over control TS cells under self-renewal conditions. While epiblast-produced growth factors Fgf4 and Activin exert a fine-tuned control on the balance between self-renewal and differentiation of control TS cells, ntTS cells exhibit a reduced dependency upon their micro-environment. Since the supply of growth factors is known do decrease at the onset of placental formation in vivo we propose that TS cells in NT embryos continue to self-renew during a longer period of time than in fertilized embryo. The resulting increased pool of progenitors could contribute to the enlarged extra-embryonic region observed in the early trophoblast of in vivo grown mouse NT blastocysts that results in placentomegaly.
The current challenge for the various digital whole-slide imaging (WSI) systems is to be definitively validated for diagnostic purposes. We designed a concordance study between glass slide and ...digital slide diagnosis in real-life conditions, coupled with an ergonomic study.
Three senior pathologists evaluated, first in glass slides and then in digital slides, 119 biopsy cases, including 749 slides, with 332 H&E saffron stains and 417 additional techniques, mainly immunohistochemistry.
All digital slides, including specially stained slides, were interpretable. Concordance between glass slides and digital slides was observed in 87.4% of cases. Minor discordances were observed in 12 (10.1%) cases and major discordances, with therapeutic impact, in three (2.5%), including one related to WSI. The satisfaction of participants was high and increased with time.
Our study confirms the feasibility and accuracy of WSI diagnosis, even for cases having multiple samples and requiring special staining techniques, such as immunohistochemistry and in situ hybridization.
Purpose: Diabetes is a suspected risk factor for pancreatic cancer, but questions remain about whether it is a risk factor or a result of the disease. This study prospectively examined the ...association between diabetes and the risk of pancreatic adenocarcinoma in pooled data from the NCI pancreatic cancer cohort consortium (PanScan). Methods: The pooled data included 1,621 pancreatic adenocarcinoma cases and 1,719 matched controls from twelve cohorts using a nested case–control study design. Subjects who were diagnosed with diabetes near the time (<2 years) of pancreatic cancer diagnosis were excluded from all analyses. All analyses were adjusted for age, race, gender, study, alcohol use, smoking, BMI, and family history of pancreatic cancer. Results: Self-reported diabetes was associated with a forty percent increased risk of pancreatic cancer (OR = 1.40, 95 % CI: 1.07, 1.84). The association differed by duration of diabetes; risk was highest for those with a duration of 2–8 years (OR = 1.79, 95 % CI: 1.25, 2.55); there was no association for those with 9+ years of diabetes (OR = 1.02, 95 % CI: 0.68, 1.52). Conclusions: These findings provide support for a relationship between diabetes and pancreatic cancer risk. The absence of association in those with the longest duration of diabetes may reflect hypoinsulinemia and warrants further investigation.
Previous studies have demonstrated that olfactory-driven behaviors in rats are influenced by short-term caloric restriction, partly through the modulation of olfactory sensitivity by ...appetite-modulating hormones or peptides such as insulin and leptin. Here, we addressed the issue of a long-term modulation of their neuroendocrine status by evaluating the effect of chronic food restriction in rats following a limitation of the duration of daily food intake to 2h (SF) instead of 8h (LF) on the expression of insulin and leptin system in the olfactory mucosa and bulb and on olfactory behaviors. This restriction resulted in a one-third reduction in the daily food intake and a 25% reduction in the body weight of SF rats when compared to controls, and was accompanied by lower levels of triglycerides, glucose, insulin and leptin in SF rats. Under these conditions, we observed a modulation of olfactory-mediated behaviors regarding food odors. In addition, restriction had a differential effect on the expression of insulin receptors, but not that of leptin receptors, in the olfactory mucosa, whereas no transcriptional change was observed at the upper level of the olfactory bulb. Overall, these data demonstrated that long-term changes in nutritional status modulate olfactory-mediated behaviors. Modulation of insulin system expression in the olfactory mucosa of food restricted rats suggests that this hormone could be part of this process.
► Olfactory-driven behaviors are influenced by nutritional status in rats. ► A chronic food restriction impacts neuroendocrine status related to food intake. ► Insulin and leptin are differentially affected in the olfactory system. ► Chronic food restriction modulates olfactory-mediated behavior regarding food odor.
PDF
