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  • Food intake adaptation to dietary fat involves PSA-dependent rewiring of the arcuate melanocortin system in mice. 22933782

    Hormones such as leptin and ghrelin can rapidly rewire hypothalamic feeding circuits when injected into rodent brains. These experimental manipulations suggest that the hypothalamus might reorganize continually in adulthood to integrate the metabolic status of the whole body. In this study, we examined whether hypothalamic plasticity occurs in naive animals according to their nutritional conditions. For this purpose, we fed mice with a short-term high-fat diet (HFD) and assessed brain remodeling through its molecular and functional signature. We found that HFD for 3 d rewired the hypothalamic arcuate nucleus, increasing the anorexigenic tone due to activated pro-opiomelanocortin (POMC) neurons. We identified the polysialic acid molecule (PSA) as a mediator of the diet-induced rewiring of arcuate POMC. Moreover, local pharmacological inhibition and genetic disruption of the PSA signaling limits the behavioral and metabolic adaptation to HFD, as treated mice failed to normalize energy intake and showed increased body weight gain after the HFD challenge. Altogether, these findings reveal the existence of physiological hypothalamic rewiring involved in the homeostatic response to dietary fat. Furthermore, defects in the hypothalamic plasticity-driven adaptive response to HFD are obesogenic and could be involved in the development of metabolic diseases.
    Document Type:
    Reference
    Product Catalog Number:
    MAB1501
    Product Catalog Name:
    Anti-Actin Antibody, clone C4

  • Role of the duodenum and macronutrient type in ghrelin regulation. 15528308

    The orexigenic hormone ghrelin is implicated in preprandial hunger and meal initiation in part because circulating levels increase before meals and decrease after food intake. The mechanisms underlying postprandial ghrelin suppression are unknown. Although most ghrelin is produced by the stomach, we have shown that neither gastric nutrients nor gastric distension affect ghrelin levels. We hypothesized that the nutrient-sensing mechanism regulating ghrelin is in the duodenum, the second richest source of ghrelin. To test whether duodenal nutrient exposure is required for ghrelin suppression, we infused nutrients into either the proximal duodenum or proximal jejunum in rats bearing chronic intestinal cannulas. At 0, 30, 60, 90, 120, 180, 240, and 300 min after infusions, blood was sampled via jugular-vein catheters for ghrelin, insulin, and glucose measurements. To elucidate further the mechanisms governing nutrient-related ghrelin suppression, we also assessed the ghrelin responses to isocaloric (3 kcal) infusions of glucose, amino acids, or lipids delivered into the stomach or small intestine of chronically catheterized rats. Regardless of macronutrient type, the depth and duration of ghrelin suppression were equivalent after gastric, duodenal, and jejunal infusions. Glucose and amino acids suppressed ghrelin more rapidly and strongly (by approximately 70%) than did lipids (by approximately 50%). Because jejunal nutrient infusions suppressed ghrelin levels as well as either gastric or duodenal infusions, we conclude that the inhibitory signals mediating postprandial ghrelin suppression are not derived discretely from either the stomach or duodenum. The relatively weak suppression of ghrelin by lipids compared with glucose or amino acids could represent one mechanism promoting high-fat dietary weight gain.
    Document Type:
    Reference
    Product Catalog Number:
    SRI-13K
    Product Catalog Name:
    Sensitive Rat Insulin RIA

  • Appetite responds to changes in meal content, whereas ghrelin, leptin, and insulin track changes in energy availability. 19401375

    CONTEXT: It is uncertain how between-meal variations in energy availability and physiological changes in ghrelin, leptin, and insulin affect appetite. Objective: The aim of the study was to examine the influence on human appetite of the meal size and its nutrient content or changes in energy availability and concentrations of ghrelin, leptin, and insulin. DESIGN: We conducted a crossover study manipulating meal size and energy availability through exercise energy expenditure and iv nutrient replacement (TPN). Setting: The study was performed at a Clinical Research Center. PARTICIPANTS: Ten healthy postmenopausal women (age, 59.7 +/- 1.5 yr; mean body mass index, 26 kg/m(2)) were studied. Interventions: We conducted trials based on different morning meal size (418 vs. 2090 KJ), presence or absence of exercise energy expenditure (2273 to 2361 KJ), energy replacement by TPN (1521 to 1538 KJ), and a midday ad libitum meal. Main Outcome Measures: Changes in hunger, fullness, midday ad libitum food consumption, and concentrations of ghrelin, leptin, insulin, and metabolic fuels were measured. We also performed midday meal tests for the presence of caloric compensation. RESULTS: Appetite was influenced by the size and energy content of the meals, but not by variation in energy availability which also did not trigger consummatory compensation. Exercise reduced hunger and increased fullness. Ghrelin, leptin, and insulin responded to changes in energy availability but not to meal size. Appetite was unaffected by physiological changes in ghrelin, leptin, or insulin. CONCLUSIONS: During rest, appetite is influenced by the size and energy content of meals, but it bears no homeostatic relationship to between-meal changes in energy availability due to small meals, exercise, or TPN, or concentrations of ghrelin, leptin, and insulin.
    Document Type:
    Reference
    Product Catalog Number:
    Multiple
    Product Catalog Name:
    Multiple

  • Active ghrelin levels across time and associations with leptin and anthropometrics in healthy ache Amerindian women of Paraguay. 18161038

    Active (acylated) ghrelin is a peptide hormone secreted primarily by the stomach, positively associated with fasting, orexigenic, and promotes growth hormone secretion. It is therefore important to energy intake management. The objective of this pilot research was to (1) compare active ghrelin with previous measurements of leptin and anthropometrics; (2) assess the consistency of active ghrelin across time in this population; (3) extend our understanding of potential population variation in active ghrelin. Two serum samples separated by 10 days at the same time between meals were collected from healthy Ache women (n = 12, mean age 32.2 +/- 14.0 SD) to determine consistency over time, associations with leptin, and anthropmetric values. Mean active ghrelin was 72.9 +/- 23.0 pg/ml, highly correlated (r(2) = 0.95, P 0.0001) between collections, and showed no paired mean differences (P 0.18). There was no significant correlation with leptin, age, or anthropometric measures. Active ghrelin appears to be consistent over time in this population, perhaps reflecting regimented meal schedules and less interpopulation variation compared to leptin.
    Document Type:
    Reference
    Product Catalog Number:
    GHRA-88HK
    Product Catalog Name:
    Human Ghrelin (ACTIVE) RIA

  • Restricting time at pasture: effects on dairy cow herbage intake, foraging behavior, hunger-related hormones, and metabolite concentration during the first grazing sessio ... 19700720

    This study investigated the effect of restricting grazing time on circulating concentrations of ghrelin, nonesterified fatty acids (NEFA), and glucose before, and foraging behavior of dairy cows during, the first grazing session of the day (GS, 0800-1200 h). Forty-eight Holstein-Friesian cows (470 +/- 47 kg of BW; 35 +/- 9 d in milk) were strip-grazed on a perennial ryegrass pasture for either 4 h after each milking (2 x 4), 8 h between milkings (1 x 8), or the 24-h period excluding milking times (CTL). Cows were bled before the GS; plasma was analyzed for ghrelin and serum for glucose and NEFA. Herbage mass was measured pregrazing (0730 h), during and at the end of the GS (1200 h), and postgrazing (24 h after the first measurement). Herbage mass data were fitted to a model to estimate herbage disappearance rates. Herbage intake and bite mass were calculated using herbage mass disappearance and behavioral measurements. Bite rate, eating, searching, ruminating, and idling time were determined during the GS for each cow. No difference in glucose concentration was found between treatments. Concentrations of NEFA and ghrelin were the greatest for cows in the 1 x 8 treatment. Daily herbage intake did not differ between treatments; however, during the GS 1 x 8 had a greater herbage intake than 2 x 4 and CTL. Bite mass differed between treatments and throughout the GS. Bite mass was smallest for CTL during the first 60 min and greatest during the last 90 min, when cows in the 2 x 4 treatment had the smallest bite mass. Cows in 1 x 8 spent the longest time eating and the least time searching and ruminating. Eating time was greatest for 1 x 8 during the first 60 and last 90 min of the GS. Searching time only differed in the second 60 min, when it was the lowest for 1 x 8. Cows from all treatments did not ruminate during the first 120 min. Cows in CTL had the greatest rumination time during the last 90 min. The model fitted to represent dynamics of herbage mass disappearance presented differences in the fractional herbage disappearance rate. There was an interaction between treatment and time in herbage depletion rate. The results of this study present a fuller picture of foraging dynamics during the first 4 h of grazing and its potential relationship with physiological markers of hunger as affected by grazing management.
    Document Type:
    Reference
    Product Catalog Number:
    GHRA-88HK
    Product Catalog Name:
    Human Ghrelin (ACTIVE) RIA

  • A high-legume low-glycemic index diet reduces fasting plasma leptin in middle-aged insulin-resistant and -sensitive men. 21206508

    Fasting leptin and ghrelin levels were measured in 36 insulin-sensitive (IS) and 28 insulin-resistant (IR) men who consumed a legume-enriched low-glycemic index (LG) diet or healthy American (HA) diet in a randomly ordered cross-over feeding study consisting of two 4-week periods. Weight remained stable over the entire study. Fasting plasma leptin was significantly reduced from pre-study levels by both the LG (18.8%, P < 0.001) and HA (16.1%, P < 0.001) diets, whereas fasting ghrelin did not change. By subgroup analysis according to prestudy insulin status, leptin was reduced in IR subjects after both the LG (17.1%, P < 0.01) and the HA (33.3%, P < 0.001) diets, whereas IS subjects responded only after the LG diet (23.1%, P < 0.01). Thus, a legume-rich LG index diet may be a beneficial strategy for reducing circulating leptin concentrations, even under conditions of weight maintenance.
    Document Type:
    Reference
    Product Catalog Number:
    EZHL-80SK
    Product Catalog Name:
    Human Leptin "Dual Range" ELISA

  • Ghrelin and glucagon-like peptide 1 concentrations, 24-h satiety, and energy and substrate metabolism during a high-protein diet and measured in a respiration chamber. 16400055

    BACKGROUND: The mechanism of protein-induced satiety remains unclear. OBJECTIVE: The objective was to investigate 24-h satiety and related hormones and energy and substrate metabolism during a high-protein (HP) diet in a respiration chamber. DESIGN: Twelve healthy women aged 18-40 y were fed in energy balance an adequate-protein (AP: 10%, 60%, and 30% of energy from protein, carbohydrate, and fat, respectively) or an HP (30%, 40%, and 30% of energy from protein, carbohydrate, and fat, respectively) diet in a randomized crossover design. Substrate oxidation, 24-h energy expenditure (EE), appetite profile, and ghrelin and glucagon-like peptide 1 (GLP-1) concentrations were measured. RESULTS: Sleeping metabolic rate (6.40 +/- 0.47 compared with 6.12 +/- 0.40 MJ/d; P 0.05), diet-induced thermogenesis (0.91 +/- 0.25 compared with 0.69 +/- 0.24 MJ/d; P 0.05), and satiety were significantly higher, and activity-induced EE (1.68 +/- 0.32 compared with 1.86 +/- 0.41; P 0.05), respiratory quotient (0.84 +/- 0.02 compared with 0.88 +/- 0.03; P 0.0005), and hunger were significantly lower during the HP diet. There was a tendency for a greater 24-h EE during the HP diet (P = 0.05). Although energy intake was not significantly different between the diet groups, the subjects were in energy balance during the HP diet and in positive energy balance during the AP diet. Satiety was related to 24-h protein intake (r2 = 0.49, P 0.05) only during the HP diet. Ghrelin concentrations were not significantly different between diets. GLP-1 concentrations after dinner were higher during the HP than during the AP diet (P 0.05). CONCLUSION: An HP diet, compared with an AP diet, fed at energy balance for 4 d increased 24-h satiety, thermogenesis, sleeping metabolic rate, protein balance, and fat oxidation. Satiety was related to protein intake, and incidentally to ghrelin and GLP-1 concentrations, only during the HP diet.
    Document Type:
    Reference
    Product Catalog Number:
    EGLP-35K
    Product Catalog Name:
    Glucagon Like Peptide-1 (Active) ELISA

  • Reduced serum acylated ghrelin levels in patients with hyperthyroidism. 16612106

    BACKGROUND AND OBJECTIVE: Recent studies have revealed that circulating ghrelin levels seem to play a role in energy homeostasis. The effect of hyperthyroidism on ghrelin levels is not fully known. METHODS: Serum levels of ghrelin and its relationship with insulin resistance were evaluated in 48 patients with hyperthyroidism and 43 euthyroid healthy controls. Thyroid hormones, insulin, glucose, ghrelin levels and lipid parameters were measured in all subjects. Insulin sensitivity was determined using the homeostasis model assessment. RESULTS: Serum ghrelin levels were significantly decreased in hyperthyroid patients than in controls (32.5 +/- 23.3 vs. 54.1 +/- 35.5 pg/ml, p 0.001). Circulating ghrelin levels significantly correlated with age (r = -0.26, p = 0.01), fasting glucose (r = -0.21, p = 0.01), free triiodothyronine (r = -0.18, p = 0.04), free thyroxine (r = -0.23, p = 0.02) and thyroid stimulating hormone (r = 0.21, p = 0.04), but not with blood pressure, body mass index, lipid parameters, insulin and homeostasis model assessment (p > 0.05). Multiple regression analysis revealed glucose level to be the most important predictor of circulating ghrelin level. CONCLUSION: These results indicate that hyperthyroidism has effect on serum ghrelin levels. Further studies are needed for the exact mechanism.
    Document Type:
    Reference
    Product Catalog Number:
    2100
    Product Catalog Name:
    Protein-Concentrate Kit (Micro)

  • Reverse Feeding Suppresses the Activity of the GH Axis in Rats and Induces a Preobesogenic State. 21209022

    Reversed feeding (RF) is known to disrupt hormone rhythmicity and metabolism. Although these effects may be mediated in part by phase inversion of glucocorticoid secretion, the precise mechanism is incompletely characterized. In this study, we demonstrate that acute nocturnal food deprivation in male rats suppressed the amplitude of spontaneous GH secretion during the dark phase by 62% (P < 0.001), without affecting baseline secretion. Prolonged RF, which reduced pituitary weight (by 22%; P < 0.05), also suppressed GH pulse height sufficiently to reduce skeletal growth (by 4-5%; P < 0.01) and terminal liver weight (by 11%; P < 0.001). Despite this suppression of the GH axis, proportionate adiposity was not elevated, probably due to the accompanying 16% reduction in cumulative food intake (P < 0.01). We demonstrate that RF also resulted in phase inversion of core clock gene expression in liver, abdominal white adipose tissue (WAT) and skeletal muscle, without affecting their expression patterns in the suprachiasmatic nucleus. In addition, RF resulted in phase inversion of hepatic peroxisome proliferator-activated receptor γ2 mRNA expression, a 3- to 5-fold elevation in fatty acid synthase mRNA in WAT in both light- and dark-phase samples (P < 0.01) and an elevation in muscle uncoupling protein 3 mRNA expression at the beginning of the light phase (P < 0.01). Consumption of a high-fat diet increased inguinal (by 36%; P < 0.05) and retroperitoneal WAT weight (by 72%; P < 0.01) only in RF-maintained rats, doubling the efficiency of lipid accumulation (P < 0.05). Thus, RF not only desynchronizes central and peripheral circadian clocks, and suppresses nocturnal GH secretion, but induces a preobesogenic state.
    Document Type:
    Reference
    Product Catalog Number:
    GHRT-89HK
    Product Catalog Name:
    Human Ghrelin (TOTAL) RIA

  • Carob pulp preparation rich in insoluble dietary fiber and polyphenols enhances lipid oxidation and lowers postprandial acylated ghrelin in humans. 16702317

    Ghrelin is an orexigenic hormone that may affect substrate utilization in humans. Ghrelin is influenced by macronutrients, but the effects of insoluble dietary fiber and polyphenols are unknown. We investigated the effects of a polyphenol-rich insoluble dietary fiber preparation from carob pulp (carob fiber) on postprandial ghrelin responses and substrate utilization. Dose-dependent effects of the consumption of carob fiber were investigated in a randomized, single-blind, crossover study in 20 healthy subjects, aged 22-62 y. Plasma total and acylated ghrelin, triglycerides, and serum insulin and nonesterified fatty acids (NEFA) levels were repeatedly assessed before and after ingestion of an isocaloric standardized liquid meal with 0, 5, 10, or 20 g of carob fiber over a 300-min period. The respiratory quotient (RQ) was determined after consumption of 0 or 20 g of carob fiber. Carob fiber intake lowered acylated ghrelin to 49.1%, triglycerides to 97.2%, and NEFA to 67.2% compared with the control meal (P 0.001). Total ghrelin and insulin concentrations were not affected by consumption of a carob fiber-enriched liquid meal. Postprandial energy expenditure was increased by 42.3% and RQ was reduced by 99.9% after a liquid meal with carob fiber compared with a control meal (P 0.001). We showed that the consumption of a carob pulp preparation, an insoluble dietary fiber rich in polyphenols, decreases postprandial responses of acylated ghrelin, triglycerides, and NEFA and alters RQ, suggesting a change toward increased fatty acid oxidation. These results indicate that carob fiber might exert beneficial effects in energy intake and body weight.
    Document Type:
    Reference
    Product Catalog Number:
    Multiple
    Product Catalog Name:
    Multiple