👤 J A Boutin

Proteomics provides an opportunity for detection and monitoring of anorexia nervosa (AN) and its related variant, atypical-AN (atyp-AN). However, research to date has been limited by the small number of proteins explored, exclusive focus on adults with AN, and lack of replication across studies. This study performed Olink Proseek Multiplex profiling of 92 proteins involved in inflammation among females with AN and atyp-AN (N = 64), all < 90% of expected body weight, and age-matched healthy controls (HC; N=44). After correction for multiple testing, nine proteins differed significantly in the AN/atyp-AN group relative to HC group ( Show less

Production conditions of layer chicken can vary in terms of temperature or diet energy content compared to the controlled environment where pure-bred selection is undertaken. The aim of this study was to better understand the long-term effects of a 15%-energy depleted diet on egg-production, energy homeostasis and metabolism via a multi-tissue transcriptomic analysis. Study was designed to compare effects of the nutritional intervention in two layer chicken lines divergently selected for residual feed intake. Chicken adapted to the diet in terms of production by significantly increasing their feed intake and decreasing their body weight and body fat composition, while their egg production was unchanged. No significant interaction was observed between diet and line for the production traits. The low energy diet had no effect on adipose tissue and liver transcriptomes. By contrast, the nutritional challenge affected the blood transcriptome and, more severely, the hypothalamus transcriptome which displayed 2700 differentially expressed genes. In this tissue, the low-energy diet lead to an over-expression of genes related to endocannabinoid signaling (CN1R, NAPE-PLD) and to the complement system, a part of the immune system, both known to regulate feed intake. Both mechanisms are associated to genes related polyunsaturated fatty acids synthesis (FADS1, ELOVL5 and FADS2), like the arachidonic acid, a precursor of anandamide, a key endocannabinoid, and of prostaglandins, that mediate the regulatory effects of the complement system. A possible regulatory role of NR1H3 (alias LXRα) has been associated to these transcriptional changes. The low-energy diet further affected brain plasticity-related genes involved in the cholesterol synthesis and in the synaptic activity, revealing a link between nutrition and brain plasticity. It upregulated genes related to protein synthesis, mitochondrial oxidative phosphorylation and fatty acid oxidation in the hypothalamus, suggesting reorganization in nutrient utilization and biological synthesis in this brain area. We observed a complex transcriptome modulation in the hypothalamus of chicken in response to low-energy diet suggesting numerous changes in synaptic plasticity, endocannabinoid regulation, neurotransmission, lipid metabolism, mitochondrial activity and protein synthesis. This global transcriptomic reprogramming could explain the adaptive behavioral response (i.e. increase of feed intake) of the animals to the low-energy content of the diet. Show less

Because the cost of cereals is unstable and represents a large part of production charges for meat-type chicken, there is an urge to formulate alternative diets from more cost-effective feedstuff. We have recently shown that meat-type chicken source is prone to adapt to dietary starch substitution with fat and fiber. The aim of this study was to better understand the molecular mechanisms of this adaptation to changes in dietary energy sources through the fine characterization of transcriptomic changes occurring in three major metabolic tissues - liver, adipose tissue and muscle - as well as in circulating blood cells. We revealed the fine-tuned regulation of many hepatic genes encoding key enzymes driving glycogenesis and de novo fatty acid synthesis pathways and of some genes participating in oxidation. Among the genes expressed upon consumption of a high-fat, high-fiber diet, we highlighted CPT1A, which encodes a key enzyme in the regulation of fatty acid oxidation. Conversely, the repression of lipogenic genes by the high-fat diet was clearly associated with the down-regulation of SREBF1 transcripts but was not associated with the transcript regulation of MLXIPL and NR1H3, which are both transcription factors. This result suggests a pivotal role for SREBF1 in lipogenesis regulation in response to a decrease in dietary starch and an increase in dietary PUFA. Other prospective regulators of de novo hepatic lipogenesis were suggested, such as PPARD, JUN, TADA2A and KAT2B, the last two genes belonging to the lysine acetyl transferase (KAT) complex family regulating histone and non-histone protein acetylation. Hepatic glycogenic genes were also down-regulated in chickens fed a high-fat, high-fiber diet compared to those in chickens fed a starch-based diet. No significant dietary-associated variations in gene expression profiles was observed in the other studied tissues, suggesting that the liver mainly contributed to the adaptation of birds to changes in energy source and nutrients in their diets, at least at the transcriptional level. Moreover, we showed that PUFA deposition observed in the different tissues may not rely on transcriptional changes. We showed the major role of the liver, at the gene expression level, in the adaptive response of chicken to dietary starch substitution with fat and fiber. Show less

Gastric inhibitory polypeptide (GIP)-dependent Cushing's syndrome has been reported to occur either in unilateral adrenal adenoma or in bilateral macronodular adrenal hyperplasia. A 33-yr-old woman with Cushing's syndrome was found to have two 2.5- to 3-cm nodules in the right adrenal on computed tomography scan; the left adrenal appeared normal except for the presence of a small 0.8 x 0.6-cm nodule. Uptake of iodocholesterol was limited to the right adrenal. Plasma morning cortisol was 279 nmol/L fasting and 991 nmol/L postprandially, and ACTH remained suppressed. Plasma cortisol increased after oral glucose (202%) or a lipid-rich meal (183%), but not after a protein-rich meal (95%) or iv glucose (93%); the response to oral glucose was blunted by pretreatment with 100 microg octreotide, sc. Plasma cortisol and GIP levels were positively correlated (r = 0.95; P = 0.0001); cortisol was stimulated by the administration of human GIP iv (225%), but not by GLP-1, insulin, TRH, GnRH, glucagon, arginine vasopressin, upright posture, or cisapride orally. A right adrenalectomy was performed; GIP receptor messenger ribonucleic acid was overexpressed in both adrenal nodules and in the adjacent cortex. Histopathology revealed diffuse macronodular adrenal hyperplasia without internodular atrophy. Three months after surgery, fasting plasma ACTH and cortisol were suppressed, but cortisol increased 3.6-fold after oral glucose, whereas ACTH remained suppressed; this was inhibited by octreotide pretreatment, suggesting that cortisol secretion by the left adrenal is also GIP dependent. We conclude that GIP-dependent nodular hyperplasia can progress in an asynchronous manner and that GIPR overexpression is an early event in this syndrome. Show less

The major tyrosine protein kinase, HPK40, isolated from HL-60, the preparation of which is described elsewhere (Ernould, A.P., Ferry, G., Barret, J.M., Genton, A. and Boutin, J.A., Eur. J. Biochem., 214, 503-514), was investigated as to its specificity on a number of peptides and proteins. It was found that HPK40 can phosphorylate histones (except histone H4), casein, acid-treated enolase, actin and tubulin but not calmodulin. Phosphorylation specificity of HPK40 was investigated using over a hundred peptidic structures. HPK40 is not related to the 'src' family and does not phosphorylate efficiently either the tetrapeptide NEYT derived from the pp60src autophosphorylation domain or the corresponding peptide RRsrc, RRLIED-NEYTARG. VALYDYESR from the SH3 domain of pp60c-src is recognized as a substrate with a high phosphorylation level. DEDYIQD, derived from the phosvitin/casein kinase II, was also highly phosphorylated. In order to determine the minimal recognition sequence of HPK40, the phosphorylation of about 60 dito tetrapeptides was investigated. Some of the tetrapeptides, such as *EEYE and NEYE, were well phosphorylated. Even some tripeptides, such as EYE, DYM, TYS and KYE, were recognized by HPK40, while none of the tested dipeptides was recognized as substrate. Sequences of peptides from DRVYHPF (angiotensin), LEEEEEAYGWMDF (minigastrin) and QEEYSAM (from H-ras1) were examined as substrates. The presence of one or several acidic residues on the N alpha-side of tyrosine residue was identified as the only apparently favorable determinant.(ABSTRACT TRUNCATED AT 250 WORDS) Show less