Analysis of polyphenolic metabolites from in vitro gastrointestinal digested soft fruit extracts identify malvidin-3-glucoside as an inhibitor of PTP1B.

Protein-tyrosine phosphatase 1B (PTP1B, EC 3.1.3.

The anthocyanins in black currants regulate postprandial hyperglycaemia primarily by inhibiting α-glucosidase while other phenolics modulate salivary α-amylase, glucose uptake and sugar transporters.

The hypoglycaemic effects of two Ribes sp. i.e.

A randomised, double-blind, cross-over trial to evaluate bread, in which gluten has been pre-digested by prolyl endoprotease treatment, in subjects self-reporting benefits of adopting a gluten-free or low-gluten diet.

The aim of the present study was to determine if the enzyme Aspergillus niger prolyl endoprotease (ANPEP), which degrades the immunogenic proline-rich residues in gluten peptides, can be used in the development of new wheat products, suitable for gluten-sensitive (GS) individuals. We have carried out a double-blind, randomised, cross-over trial with two groups of adults; subjects, self-reporting benefits of adopting a gluten-free or low-gluten diet (GS, n 16) and a control non-GS group (n 12). For the trial, volunteers consumed four wheat breads: normal bread, bread treated with 0·8 or 1 % ANPEP and low-protein bread made from biscuit flour.

Repletion of TNFα or leptin in calorically restricted mice suppresses post-restriction hyperphagia.

The causes of post-restriction hyperphagia (PRH) represent a target for drug-based therapies to prevent obesity. However, the factors causing PRH are poorly understood. We show that, in mice, the extent of PRH was independent of the time under restriction, but depended on its severity, suggesting that PRH was driven by signals from altered body composition.

Diurnal profiles of hypothalamic energy balance gene expression with photoperiod manipulation in the Siberian hamster, Phodopus sungorus.

Hypothalamic energy balance genes have been examined in the context of seasonal body weight regulation in the Siberian hamster. Most of these long photoperiod (LD)/short photoperiod (SD) comparisons have been of tissues collected at a single point in the light-dark cycle. We examined the diurnal expression profile of hypothalamic genes in hamsters killed at 3-h intervals throughout the light-dark cycle after housing in LD or SD for 12 wk.

Hypothalamic neuropeptide gene expression during recovery from food restriction superimposed on short-day photoperiod-induced weight loss in the Siberian hamster.

Previously, 40% food restriction of male Siberian hamsters over 21 days in short-day (SD) photoperiod induced characteristic changes in expression of hypothalamic arcuate nucleus energy balance genes; mRNAs for neuropeptide Y, agouti-related peptide, and leptin receptor were upregulated, and those of proopiomelanocortin and cocaine- and amphetamine-regulated transcript were depressed. The present study examined the effect of refeeding hamsters for 6 days (approximately 50% recovery of weight differential) or 19 days (resumption of appropriate weight trajectory). Hyperphagia continued throughout refeeding, but differences in fat pad weights and leptin levels had disappeared after 19 days.

Solid and liquid obesogenic diets induce obesity and counter-regulatory changes in hypothalamic gene expression in juvenile Sprague-Dawley rats.

Contemporary foods and beverages that constitute the diets of adults and children almost certainly contribute to the obesity problem. To develop a model of childhood obesity, we examined the effects of feeding juvenile rats 2 solid diets, either alone or in combination [nonpurified control diet (C), high-energy (HE), or C+HE] with or without the liquid supplement Ensure (EN). Rats were fed C until 4 wk of age and then were assigned to 1 of 6 weight-matched groups that were fed C, HE, C+HE, C+EN, HE+EN, or C+HE+EN for 5 wk.

Hypothalamic orexigenic peptides are overexpressed in young Long-Evans rats after early life exposure to fat-rich diets.

Nutritional factors have a critical influence during prenatal life on the development and regulation of networks involved in body weight and feeding regulation. To establish the influence of the macronutrient type on feeding regulatory mechanisms and more particularly on stimulatory pathways (galanin and orexins), we fed female rats on either a high-carbohydrate (HC), a high-fat (HF), or a well-balanced control diet during gestation and lactation, and measured peptide expression in the hypothalamus and important hormones (leptin, insulin) in their pups at weaning. HF weanlings were 30% lighter than control and HC pups (P<0.

Photoperiodic regulation of histamine H3 receptor and VGF messenger ribonucleic acid in the arcuate nucleus of the Siberian hamster.

To survive winter the Siberian hamster has evolved profound physiological and behavioral adaptations, including a moult to winter pelage, regression of the reproductive axis, onset of daily torpor and increased capacity for thermogenesis. However, one of the most striking adaptations is the catabolism of intraabdominal and sc fat reserves contributing to the loss of up to 40% of body weight. These physiological and behavioral adaptations are photoperiodically driven, yet neither the site(s) in the brain nor the molecular mechanism(s) involved in the regulation of these profound adaptations is known.

Photoperiodic regulation of leptin sensitivity in the Siberian hamster, Phodopus sungorus, is reflected in arcuate nucleus SOCS-3 (suppressor of cytokine signaling) gene expression.

We present the first evidence that suppressor of cytokine signaling-3 (SOCS3), a protein inhibiting Janus kinase/signal transducer and activator of transcription (STAT) signaling distal of the leptin receptor, conveys seasonal changes in leptin sensitivity in the Siberian hamster. Food deprivation (48 h) reduced SOCS3 gene expression in hamsters acclimated to either long (LD) or short (SD) photoperiods, suggesting that leptin signals acute starvation regardless of photoperiod. However, SOCS3 mRNA levels were substantially lower in the hypothalamic arcuate nucleus of hamsters acclimated to SD than in those raised in LD.

Age-dependent hypothalamic expression of neuropeptides in wild-type and melanocortin-4 receptor-deficient mice.

In young (35- to 56-day-old) and middle-aged (9-mo-old) wild-type (+/+) and melanocortin-4 receptor (MC4R)-deficient (+/-, -/-) mice, expressions of neuropeptide Y (NPY), agouti-related protein (AGRP), pro-opiomelanocortin (POMC), and cocaine-and-amphetamine-regulated transcript (CART) were analyzed in the arcuate nucleus (ARC) and adjacent regions comprising the dorsomedial (DMN) and ventromedial (VMN) nucleus. In the ARC of young mice, NPY and AGRP expression increased and POMC and CART expression decreased with body fat content. Adjusting for the influence of body fat content by ANCOVA showed that the levels of NPY, POMC, and CART were highest and of AGRP lowest in young -/- mice.

Photoperiodic regulation of hypothalamic retinoid signaling: association of retinoid X receptor gamma with body weight.

This study reports novel events related to photoperiodic programming of the neuroendocrine hypothalamus. To investigate photoperiod-responsive genes, Siberian hamsters were maintained in long or short photoperiods that generate physiological states of obesity or leanness. Microarray expression analysis first identified CRBP1 as a photoperiod-responsive gene, and then further studies using in situ hybridization and immunocytochemistry revealed that expression levels of several related retinoid-signaling genes were modulated in response to photoperiod changes.

Hyperphagia, not hypometabolism, causes early onset obesity in melanocortin-4 receptor knockout mice.

Previous studies on mice with melanocortin-4 receptor gene (MC4r) knockout have focused on obese adults. Because humans with functional MC4r mutations show early-onset obesity, we determined the onset of excessive fat deposition in 10- to 56-day-old mice, taking into account sex and litter influences. Total body fat content of MC4r-/- on day 35 and MC4r+/- on day 56 significantly exceeds that of MC4r+/+.

Early regulation of hypothalamic arcuate nucleus CART gene expression by short photoperiod in the Siberian hamster.

Cocaine- and amphetamine-regulated transcript (CART) mRNA is expressed in a number of hypothalamic nuclei including the arcuate nucleus (ARC). An increase in CART gene expression in the ARC of juvenile female Siberian hamsters (Phodopus sungorus) 14 days after transfer to short photoperiod at weaning and prior to major divergence of body weight trajectory in this seasonal mammal implicates CART in the induction of programmed weight change. In the current series of experiments, elevated CART mRNA in short photoperiod juvenile female animals relative to long photoperiod controls was apparent throughout the caudal-rostral extent of the ARC after 14 days, but was not observed when short photoperiod exposure was limited to 4-7 days.

Pituitary adenylate cyclase-activating polypeptide acts as a paracrine regulator of melatonin-responsive cells of the ovine pars tuberalis.

The pars tuberalis (PT) region of the anterior pituitary plays a physiological role in seasonal animals. The primary signal transduction mechanism of the melatonin receptor in this tissue is an inhibition of cAMP signaling. However, nothing is known about the endocrine signals that activate cAMP synthesis in the cells of the PT, as previous studies relied on the pharmacological tool, forskolin, to stimulate cAMP synthesis.