Active Ghrelin Concentrations Research Articles

Restricted Feeding Of Weight Control Diets Induces Weight Loss And Affects Body Composition, Voluntary Physical Activity, Blood Metabolites, Hormones, And Oxidative Stress Markers, And Fecal Metabolites And Microbiota Of Obese Cats.

Feline obesity puts many cats at risk for comorbidities such as hepatic lipidosis, diabetes mellitus, urinary tract diseases, and others. Restricted feeding of specially formulated diets may improve feline health and safely support weight loss while maintaining lean mass. The objective of this study was to determine the effects of restricted intake of weight control diets on weight loss, body composition, voluntary physical activity, serum metabolic and inflammatory markers, and fecal metabolites and microbiota of obese cats. Twenty-four obese adult domestic shorthair cats [body weight (BW) = 5.51 ± 0.92kg; body condition score (BCS) = 8.44 ± 0.53] were used. A leading grocery brand diet was fed during a 4-wk baseline to identify intake needed to maintain BW. After baseline (wk 0), cats were allotted to one of two weight control diets (DRY or CAN) and fed to lose 1.5% BW per wk for 18wk. At baseline and 6, 12, 18wk after weight loss, dual-energy x-ray absorptiometry scans were performed, blood and fecal samples were collected, and voluntary physical activity was measured. Change from baseline data were analyzed statistically using the Mixed Models procedure of SAS, with P<0.05 being significant and P<0.10 being trends. BW was reduced by 1.54 ± 0.51% per wk. Restricted feeding of both diets led to BW (P<0.01) and fat mass loss (P<0.01), reduced BCS (P<0.01), reduced leptin (P<0.01) and insulin (P<0.01) concentrations, and increased superoxide dismutase (P<0.01) and active ghrelin (P<0.01) concentrations. Change from baseline fecal scores were reduced (P<0.01) with restricted feeding and weight loss, while total short-chain fatty acid, acetate, and propionate concentration reductions were greater (P<0.05) in cats fed CAN than those fed DRY. Fecal bacterial alpha diversity measures increased (P<0.01) with restricted feeding and weight loss. Fecal bacterial beta diversity was altered by time in all cats, with wk 0 being different (P<0.05) than wk 6, 12, and 18. Change from baseline relative abundances of 3 fecal bacterial phyla and over 30 fecal bacterial genera were impacted (P<0.05) or tended to be impacted (P<0.10) by dietary treatment. Our data demonstrate that restricted feeding of both weight control diets was an effective means for weight loss in obese adult domestic cats. Some changes were also impacted by diet, highlighting the importance of diet formulation and format, and nutrient composition in weight control diets.

Motilin fluctuations in healthy volunteers determined by liquid chromatography mass spectrometry.

Motilin is a hormone secreted by specialised enteroendocrine cells in the small intestine, and is known to modulate gastrointestinal motility in humans, regulating the migratory motor complex. It is understudied at least in part due to the lack of commercially available immunoassays. A multiplexed liquid chromatography mass spectrometry (LC-MS/MS) method was optimised to measure motilin, insulin, C-peptide, GIP (1-42) and GIP (3-42). Corresponding active ghrelin concentrations were determined by immunoassay. Ten healthy volunteers with no prior history of gastroenterological or endocrine condition attended after overnight fast and had blood samples taken every 15 minutes for 4 hours whilst continuing to fast, and then further sampling for 2 hours following a liquid mixed meal. Hunger scores were taken at each time point using a visual analogue scale. Normal bowel habit was confirmed by 1 week stool diary. Motilin levels fluctuated in the fasting state with an average period between peaks of 109.5 mins (SD:30.0), but with no evidence of a relationship with either ghrelin levels or hunger scores. The mixed meal interrupted cyclical motilin fluctuations, increased concentrations of motilin, insulin, C-peptide, GIP(1-42) and GIP(3-42), and suppressed ghrelin levels. This study highlights the utility of LC-MS/MS for parallel measurement of motilin alongside other peptide hormones, and supports previous reports of the cyclical nature of motilin levels in the fasting state and interruption with feeding. This analytical method has utility for further clinical studies into motilin and gut hormone physiology in human volunteers.

Measurement of Ghrelin as a Marker of Appetite Dysregulation in Cats with and without Chronic Kidney Disease.

Appetite abnormalities and weight loss are important comorbidities in the treatment of chronic kidney disease (CKD) in cats. Ghrelin, a key hormone involved in the regulation of appetite and metabolism, is a potential marker of appetite dysregulation in cats with CKD. The aim of this study was to compare the plasma concentrations of acylated, desacyl, and total ghrelin in normal cats and cats with CKD. Storage methodology was investigated prior to evaluating ghrelin concentrations in normal and CKD cats to facilitate clinical sample collection. Twelve normal cats and twelve cats with CKD were enrolled. Plasma acylated and total ghrelin concentrations were measured using radioimmunoassay. Desacyl ghrelin was calculated (total ghrelin minus acylated ghrelin). Cats with CKD had significantly increased total ghrelin and calculated desacyl ghrelin concentrations in comparison to normal cats (p < 0.0001 and p = 0.0001). There was no significant difference in active ghrelin concentrations between groups. Both total ghrelin and calculated desacyl ghrelin were significantly correlated with serum creatinine concentrations (p < 0.0001, r = 0.70 and p < 0.0001, r = 0.73). Elevated plasma desacyl ghrelin concentrations in cats with CKD provides evidence for dysregulation of appetite in feline CKD.

Acute iv CRH administration significantly increases serum active ghrelin in postmenopausal PCOS women compared to postmenopausal controls.

In women with Polycystic Ovarian Syndrome (PCOS), an increased risk of disordered eating has been described. There is growing interest regarding a possible interconnection between psychological states and increased appetite in women with PCOS. Acute stress is characterized by increased Corticotropin Releasing Hormone (CRH) secretion. The aim was to estimate the ghrelin concentrations during CRH test. Twenty postmenopausal women with PCOS and twenty age- and BMI- matched postmenopausal control women were recruited at Aretaieion University Hospital. In the morning (9 am) all subjects had anthropometric measurements (weight, height, waist circumference) and a fasting sample for hormonal measurements. An intravenous (iv) CRH stimulation test conducted over 1 min. Serum active ghrelin levels were measured at 0, 15, 30, 60, 90, 120 min after iv CRH administration. The postmenopausal PCOS group had a higher waist circumference compared to postmenopausal controls. Active ghrelin concentrations increased significantly from 0 to 15 min, to 30 min, to 60 min, to 90 min and then decreased to 120 min. However, within the postmenopausal control group there were no significant changes in serum active ghrelin levels. Serum active ghrelin concentrations were significantly greater in the postmenopausal control group at 0, 15 and 120 min compared to the postmenopausal PCOS group. At 90 min active ghrelin concentrations were significantly greater in the postmenopausal PCOS group. Delta Area Under the Curve of active ghrelin (ΔAUCghr) was significantly greater in the postmenopausal PCOS group compared to controls. In postmenopausal PCOS, but not in postmenopausal controls, iv CRH administration induces increased serum active ghrelin secretion, suggesting a possible anti-stress adaptive mechanism. An increase in serum active ghrelin may induce hunger as a side-effect of this presumed adaptive mechanism.

PSIX-9 The Effect of Endophyte-Infected Tall Fescue Seed Consumption on gut and Satiety Hormones Related to Intake in Holstein Steers

Abstract The objective of this study was to evaluate the impact of endophyte-infected tall fescue (E+) seed, and ergovaline (ERV), on gut and satiety hormones and investigate changes in post-absorptive metabolism. Holstein steers (n=12; 260 ± 16 kg) were assigned to one of three treatments (ERV concentration in diet dry matter): 0, 1.8, and 2.7 ppm with animals being adapted to an indoor environment for 4 days followed by a 7-day diet adaptation and a 10-day treatment period. On days 16 and 17, blood was collected via jugular catheters at 20-min intervals for 8 hours beginning 1 hour pre-feeding. Plasma was extracted and analyzed for insulin, leptin, and active ghrelin. Non-esterified fatty acids (NEFA), b-hydroxybutyrate (BHB), and glucose were analyzed to evaluate changes in postabsorptive metabolism using plasma from each 60-min interval. DMI decreased linearly with increased ERV concentration (P&amp;lt; 0.0001). A quadratic increase was observed for insulin with the 2.7 ppm ERV treatment having the greatest concentrations (P&amp;lt; 0.0001). A quadratic response was observed for leptin where the 1.8 ppm ERV treatment had the greatest concentrations (P&amp;lt; 0.0001). Active ghrelin concentrations decreased linearly with increasing ERV concentrations (P=0.047). A treatment-by-time interaction was observed for NEFA (P&amp;lt; 0.0001) where the 1.8 ppm ERV decreased from pre-feeding to 1-hour post-feeding and did not differ from control thereafter whereas, the 2.7 ppm ERV treatment increased above the 0 ppm ERV treatment beginning 5 hours post-feeding and was greatest among all treatments at 6 hours post-feeding. The 2.7 ppm ERV treatment exhibited the least BHB concentrations (P=0.029). Glucose concentrations increased linearly with increasing ERV concentrations (P=0.046). These results indicate that consumption of E+ seed decreases intake which may be possible through alteration of hormones and may also alter post-absorptive metabolism.

PSVIII-5 Effect of glycemic and endocrine response to feeding time in pregnant sows

Abstract The objective of the study was to determine the glycemic and endocrine responses to feeding time in restrictively fed pregnant sows. Eighteen sows [(Landrace × Yorkshire); BW 229.17 ± 1.34 kg; parity 3.90 ± 0.12; backfat 13.60 ± 0.27 mm)] were sampled from 180 sows. Sows were blocked by parity and BW and randomly assigned to 1 of 3 treatments in a RCBD. Treatments included sows fed once at daily at 0730 h (Control, T1), 1130 h (T2), and 1530 h (T3). The daily feed quantity was kept at 1.25× maintenance energy intake (100 × (BW)0.75) kcal ME/d. On average sows received 2.27 kg corn-soybean meal-based diet which provided 6948 kcal ME/d and SID Lys:ME of 1.71 g/Mcal from d 30 to 60 of gestation. Total area under the curve (AUC) was calculated using Trapezoidal summation method. Data analysis was done using PROC MIXED and GLIMMIX procedure of SAS. Sow was the experimental unit. Adjustment for multiple comparison was by Tukey’s method. Pregnant sows fed at different times of the day had similar fasting levels of glucose, insulin, ghrelin, and PYY (P ˃ 0.10). Sows fed daily at 0730 and 1130 h had increased (P = 0.018) and propensity to increase (P = 0.088) in insulin concentration from fasting to 30 minutes post-prandial, respectively, but not in sows fed daily at 1530 h (P ˃ 0.05). Glucose, active ghrelin, and total PYY concentrations and AUC did not differ with respect to feeding time. In conclusion, plasma insulin response appears to be a function of time of the day at which calories are ingested. Feeding time to elicit maximum insulin response are 0730 and 1130 h but not at 1530 h. Therefore, feeding pregnant sows daily at or before 1130 h may elicit maximum insulin response.

47 Quantitative evaluation of hunger in pregnant sows: metabolic and hormonal responses to feeding frequency under limit-fed regime

Abstract The objectives of the study were to determine the pattern of glucose, insulin, active ghrelin, and total PYY responses and indirectly quantify perceived hunger in pregnant sows under-limit fed conditions. Eighteen sows [(Landrace × Yorkshire); BW 211.86 ± 1.29 kg; parity 3.80 ± 0.16; backfat 13.50 ± 0.25 mm)] were sampled from 180 sows. Sows were blocked by parity and BW and randomly assigned to 1 of 3 treatments in a RCBD. Treatments included sows fed once at [0730 h (Control, T1), twice [half ration at 0730 and 1530 h (T2)], or thrice [one-third portion at 0730, 1130, and 1530 h (T3)]. The daily feed quantity was kept at 1.25× maintenance energy intake (100 × (BW)0.75) kcal ME/d. Sows received corn-soybean meal-based diet which provided 6935 kcal ME/d and SID Lys:ME of 1.71 g/Mcal from d 30 to 60 of gestation. Hunger was quantified using total area under the curve (AUC) of the hormonal responses. Data analysis was done using PROC MIXED and GLIMMIX procedure of SAS. Sow was the experimental unit. Adjustment for multiple comparisons was by Tukey’s method. The control sows had greater 23-h mean glucose concentration than sows fed 3× daily (P = 0.002). Active ghrelin concentration for sows fed 3× daily tended to be lower (P = 0.063) compared with control sows but reduced (P = 0.018) relative to sows fed 2× daily. In conclusion, sows fed 3× daily had 9.0% reduction in 23-h glucose total AUC, 42.5% greater 23-h insulin total AUC, 27.4% reduction in active ghrelin total AUC, and 14.2% greater PYY total AUC compared with pregnant sows fed 1× daily. It is suggested that hunger in pregnant sows occurs at active ghrelin/total PYY ratio of 5.06 ± 0.20 and at a mean plasma glucose concentration of 70.37 ± 1.39 mg/dL and below.

Ghrelin alterations during experimental and human sepsis

BackgroundGhrelin is a hormone mainly produced by cells of the gastric mucosa, which has been shown to possess anti-inflammatory and immunomodulatory properties. The objective of the study was to investigate ghrelin levels during sepsis, as well as in an experimental sepsis model. MethodsAll consecutive admissions to the ICU of a tertiary hospital in Athens, Greece were screened for eligibility during the study. Thirty four non-septic patients upon ICU admission who subsequently developed sepsis were enrolled. Clinical data and scores were recorded, and blood samples were obtained at baseline (upon ICU admission), and at sepsis development. Total and active ghrelin, leptin, and cytokines were measured. Moreover, lipopolysaccharide (LPS) was administered to mice in order to induce endotoxemia and at specified time points, blood and tissue samples were collected. ResultsIn patients, serum total and active ghrelin concentrations were significantly elevated in sepsis compared to baseline (553.8 ± 213.4 vs 193.5 ± 123.2, p < 0.001; 254.3 ± 70.6 vs 56.49 ± 16.3, p < 0.001). Active ghrelin levels at the sepsis stage were inversely correlated with SOFA score and length of stay in the ICU (p = 0.023 and p = 0.027 respectively). In the mouse endotoxemia model ghrelin levels were elevated following LPS treatment, and the same trend was observed for leptin, TNFα and IL-6. Ghrelin administration managed to reduce IL-6 levels in mouse serum and in BALF. Pulmonary expression of ghrelin and its receptor GHSR1a was found decreased in LPS-treated mice. ConclusionsIn a well-defined cohort of ICU patients, we have demonstrated that active and total ghrelin increase in sepsis. The same is true for the experimental sepsis model used in the study. The inverse correlation of active ghrelin levels with SOFA score and length of ICU stay among septic patients is indicative of a potential protective role of active ghrelin during the septic process.

85 Impact of teat order on feed consumption in swine from birth to nursery

Abstract This study evaluated the relationship between teat order and its impact on feed consumption in pigs through nursery. Pigs were observed 48 h after birth to be in either a cranial, middle, or caudal teat position. Growth performance data, and active and total plasma ghrelin concentrations (determined by radioimmunoassay) were analyzed from 2 pigs in each position from 6 litters (n = 36) at 7 d of age, 21 d of age (weaning), and 62 d of age (end of the nursery stage) to determine a relationship with teat order. At weaning, pigs were moved to an off-site nursery and housed 2 pigs/pen based on teat position and litter, resulting in 6 pens/teat position. Overall, no effect of teat order was found on average daily gain (ADG; P = 0.91), average daily feed intake (ADFI; P = 0.67), gain-to-feed ratio (G:F; P = 0.33), or body weight (P = 0.94) among pigs from each teat position. A linear relationship was found between teat order and ADG (P = 0.01) as well as G:F in nursery phase-1 (P = 0.01) with caudal pigs gaining more rapidly and being more efficient than cranial pigs. Yet, in nursery phase-2, cranial pigs had the greatest ADFI (linear, P = 0.05). No difference was seen in active (P = 0.18) or total (P = 0.63) ghrelin concentrations or the active to total ghrelin ratio (P = 0.68) in relation to teat order, although there were differences in active (P = 0.04) and total (P &lt; 0.01) ghrelin concentrations among the sampling days with the least concentrations being on d 21 for active and total ghrelin. Further study should investigate what factors would contribute to these data contradicting previous inferences about the relationship of teat order and feed consumption in pigs

Physiological Predictors of Weight Regain at 1-Year Follow-Up in Weight-Reduced Adults with Obesity.

ObjectiveThis study aimed to assess whether changes in resting metabolic rate (RMR), exercise‐induced energy expenditure (EIEE), and appetite following weight loss (WL) are associated with weight regain at 1 year.MethodsThirty‐six adults with obesity underwent 8 weeks of a very‐low‐energy diet, followed by 4 weeks of refeeding and a 1‐year maintenance program. RMR, EIEE, appetite ratings, and active ghrelin, peptide YY, glucagon‐like peptide‐1, cholecystokinin, and insulin concentrations were measured at baseline, week 13, and 1 year.ResultsA 17% WL (−20 ± 5 kg [mean ± SD]; range: −11.7 to −32.2 kg; P < 0.001) was achieved at week 13. After 1 year, weight regain was 2.5 ± 9.0 kg (not significant), ranging from −18.2 to 22.5 kg. Both fat mass and fat‐free mass were reduced at week 13 (−17.9 ± 4.8 and −2.9 ± 2.7 kg, respectively; P < 0.001), while only loss of fat mass was sustained at 1 year. WL was associated with reduced RMR, EIEE, and fasting/postprandial insulin (all P < 0.001), as well as increased fasting hunger (P < 0.01) and fasting/postprandial active ghrelin (P < 0.001). There were no significant correlations between changes in RMR, EIEE, or appetite with WL and weight regain at 1 year.ConclusionsNo clear evidence emerged that changes in RMR, EIEE, or appetite following WL can predict weight regain at 1 year, but larger studies are needed to confirm these results.

Effects of ipragliflozin on glycemic control, appetite and its related hormones: A prospective, multicenter, open-label study (SOAR-KOBE Study).

Aims/IntroductionSodium–glucose cotransporter 2 (SGLT‐2) inhibitors improve blood glucose control, as well as reducing bodyweight by promoting urinary glucose excretion. The weight loss is less than expected from urinary glucose loss, however, likely because of an increase in food intake. To investigate whether SGLT‐2 inhibitors might increase appetite by affecting related hormones, we examined the effects of the SGLT‐2 inhibitor, ipragliflozin, including those on appetite‐regulating hormones, in individuals with suboptimally controlled type 2 diabetes.Materials and MethodsThe present prospective, multicenter, open‐label study was carried out with 96 patients with a body mass index of ≥22 kg/m2 who were treated with ipragliflozin (50 mg/day) for 16 weeks. Parameters including glycated hemoglobin level, bodyweight, circulating leptin and active ghrelin concentrations, and appetite as assessed with a visual analog scale were measured before and during treatment.ResultsBoth glycated hemoglobin level (from 7.9 ± 0.8 to 7.1 ± 0.7%) and bodyweight (from 75.2 ± 12.6 to 72.6 ± 12.4 kg) were significantly decreased after treatment for 16 weeks. The fasting serum leptin level was significantly decreased after 2 weeks (from 19.5 ± 13.1 to 18.1 ± 12.4 ng/mL) and remained decreased up to 16 weeks, even after adjustment for bodyweight, whereas the plasma active ghrelin level showed no significant change. The visual analog scale score for hunger was significantly increased at 2 and 8 weeks.ConclusionsThe present results suggest that ipragliflozin improved glycemic control and reduced bodyweight, but also reduced serum leptin levels and might thereby have increased appetite.

Gastroduodenal Symptoms in Inflammatory Bowel Disease Are Correlated with Gastric Emptying and Serum Levels of Active Ghrelin

Background: Inflammatory bowel disease (IBD) is associated with delay in gastric emptying, increase in ghrelin, and decrease in leptin. The aim was to investigate the correlation between gastroduodenal (GD) symptoms, gastric emptying, and serum levels of active ghrelin and leptin in IBD. Twenty-seven IBD patients and 26 healthy volunteers were asked to complete the Porto Alegre Dyspeptic Symptoms Questionnaire. A gastric emptying test for solids was performed using a C13 octanoic acid breath test. During this test, serum samples were collected for measuring active ghrelin and leptin concentrations by radioimmunoassay. Summary: Patients with IBD demonstrated delayed gastric emptying compared with healthy volunteers. In patients with GD symptoms, the delay in gastric emptying was more pronounced, and there were significant correlations of satiety and vomiting with gastric emptying. Basal leptin, but not active ghrelin, increased in patients with GD symptoms compared with patients without these symptoms. There were negative correlations between basal active ghrelin with total Porto Alegre score and epigastric pain in IBD patients with GD symptoms. Key Messages: In IBD, satiety and vomiting were associated with delay in gastric emptying. Conversely, epigastric pain had a negative correlation with active ghrelin. Our results suggest that different pathophysiological mechanisms contribute to GD symptoms in IBD.

Investigation of the long-term sustainability of changes in appetite after weight loss

Background/ObjectiveDiet-induced weight loss (WL) leads to a compensatory increase in appetite and changes in the plasma concentration of appetite-regulating hormones are likely to play a role. Whether these changes are transient or sustained remains unclear. This study aimed to assess if changes in subjective and objective appetite markers observed with WL are sustained after 1 year (1Y).Subjects/MethodsIn total 100 (45 males) individuals with obesity (BMI: 37 ± 4 kg/m2, age: 43 ± 10 years) underwent 8 weeks (wks) of a very-low energy diet (VLED), followed by 4 wks refeeding, and a 1Y maintenance program. Fasting/postprandial subjective ratings of hunger, fullness, desire to eat, and prospective food consumption (PFC) were assessed, and plasma concentration of active ghrelin (AG), total peptide YY (PYY), active glucagon-like peptide 1, cholecystokinin (CCK), and insulin measured, at baseline, week 13 (Wk13) and 1Y.ResultsAt Wk13, 16% WL (−18 ± 1 kg, P < 0.001) was associated with a significant increase in fasting and postprandial hunger ratings (P < 0.01 and P < 0.05, respectively), and postprandial fullness (P < 0.01) combined with a reduction in PFC (P < 0.001). These were accompanied by a significant rise in basal and postprandial AG concentrations (P < 0.001, for both), a reduction in postprandial CCK (P < 0.01) and in basal and postprandial insulin (P < 0.001). At 1Y follow-up, with sustained WL (15%; −16 ± 1 kg, P < 0.001), fasting hunger and postprandial fullness ratings remained increased (P < 0.05 for both), and postprandial PFC reduced (P < 0.001). Basal and postprandial AG remained elevated and insulin reduced (P < 0.001, for all), while postprandial CCK was increased (P < 0.01) and PYY decreased (P < 0.001).ConclusionWith a 15% sustained WL at 1Y, the drive to eat in the fasting state is increased, but this may be balanced out by raised postprandial feelings of fullness. To assist with WL maintenance, new strategies are required to manage increased hunger and drive to eat.

Differences in the Postprandial Release of Appetite-Related Hormones Between Active and Inactive Men.

Active, as opposed to inactive, individuals are able to adjust their energy intake after preloads of different energy contents. The mechanisms responsible for this remain unknown. This study examined differences in plasma concentration of appetite-related hormones in response to breakfasts of different energy contents, between active and inactive men. Sixteen healthy nonobese (body mass index = 18.5-27kg/m2) adult males (nine active and seven inactive) participated in this study. Participants were given a high-energy (570kcal) or a low-energy (205kcal) breakfast in a random order. Subjective feelings of appetite and plasma concentrations of active ghrelin, active glucagon-like peptide-1, total peptide YY (PYY), cholecystokinin, and insulin were measured in fasting and every 30min up to 2.5hr, in response to both breakfasts. Mixed analysis of variance (fat mass [in percentage] as a covariate) revealed a higher concentration of active ghrelin and lower concentration of glucagon-like peptide-1, and cholecystokinin after the low-energy breakfast (p < .001 for all). Postprandial concentration of PYY was greater after the high energy compared with the low energy, but for inactive participants only (p = .014). Active participants had lower postprandial concentrations of insulin than inactive participants (p < .001). Differences in postprandial insulin between breakfasts were significantly lower in active compared with inactive participants (p < .001). Physical activity seems to modulate the postprandial plasma concentration of insulin and PYY after the intake of breakfasts of different energy contents, and that may contribute, at least partially, to the differences in short-term appetite control between active and inactive individuals.

Association of cord blood ghrelin, leptin and insulin concentrations in term newborns with anthropometric parameters at birth.

Ghrelin, leptin and insulin, generally considered as regulators of energy homeostasis of the organism may be related to fetal and early postnatal growth. Numerous studies have confirmed the presence of these hormones in the cells of the fetus indicating their importance in development at early stages of life. This study analyzed active and total ghrelin by radioimmunoassay (RIA), leptin and insulin concentrations by enzyme-linked immunosorbent assay (ELISA) in 65 cord blood samples, from term newborns, and measured the birth anthropometric parameters [birth weight (BW), head circumference, chest, stomach, thigh and arm circumference]. Active ghrelin (AG) concentrations correlated negatively with BW, head circumference, stomach and thigh circumference. When divided by gender, AG correlated negatively with males' BW, stomach and thigh circumference. Females' head circumference correlated negatively with AG. Cord leptin correlated positively with arm circumference. When divided by gender, cord leptin was positively associated with BW and stomach circumference in male newborns and with thigh and arm circumference in female newborns. Insulin concentrations tended to correlate positively with BW in male newborns. In summary, it was confirmed that cord blood ghrelin, leptin and insulin correlate with anthropometric parameters at birth. This study showed a negative correlation of AG with anthropometric parameters, which may emphasize that this hormone is an indicator of growth restriction. This is in contrast to cord leptin and insulin, which are more connected with overgrowth. Taking all the results into consideration, the metabolic status of the fetus and newborn is an essential component in understanding the regulation of perinatal development.

Timeline of changes in appetite during weight loss with a ketogenic diet

Background/objective:Diet-induced weight loss (WL) leads to increased hunger and reduced fullness feelings, increased ghrelin and reduced satiety peptides concentration (glucagon-like peptide-1 (GLP-1), cholecystokinin (CCK) and peptide YY (PYY)). Ketogenic diets seem to minimise or supress some of these responses. The aim of this study was to determine the timeline over which changes in appetite occur during progressive WL with a ketogenic very-low-energy diet (VLED).Subjects/methods:Thirty-one sedentary adults (18 men), with obesity (body mass index: 37±4.5 kg m−2) underwent 8 weeks (wks) of a VLED followed by 4 wks of weight maintenance. Body weight and composition, subjective feelings of appetite and appetite-related hormones (insulin, active ghrelin (AG), active GLP-1, total PYY and CCK) were measured in fasting and postprandially, at baseline, on day 3 of the diet, 5 and 10% WL, and at wks 9 and 13. Data are shown as mean±s.d.Results:A significant increase in fasting hunger was observed by day 3 (2±1% WL), (P<0.01), 5% WL (12±8 days) (P<0.05) and wk 13 (17±2% WL) (P<0.05). Increased desire to eat was observed by day 3 (P<0.01) and 5% WL (P<0.05). Postprandial prospective food consumption was significantly reduced at wk 9 (16±2% WL) (P<0.01). Basal total PYY was significantly reduced at 10% WL (32±8 days) (P<0.05). Postprandial active GLP-1 was increased at 5% WL (P<0.01) and CCK reduced at 5 and 10% WL (P<0.01, for both) and wk 9 (P<0.001). Basal and postprandial AG were significantly increased at wk 13 (P<0.001, both).Conclusions:WL with a ketogenic VLED transiently increases the drive to eat up to 3 weeks (5% WL). After that, and while participants are ketotic, a 10–17% WL is not associated with increased appetite. However, hunger feelings and AG concentrations increase significantly from baseline, once refeeding occurs.

Effect of sterilization and of dietary fat and carbohydrate content on food intake, activity level, and blood satiety-related hormones in female dogs.

Animal sterilization is suggested to promote food overconsumption, although it is unknown whether this effect is mediated by variations in satiety-related hormones, which are released in response to food intake. The aim of this study was to evaluate the effect of sterilization and of the main energy-delivery nutrients, fat and nonstructural carbohydrates, on food intake, blood concentration of satiety-related hormones, and activity level in dogs. In a 2-phase experiment (phase I [Ph.I], 74 d, and Ph.II, 84 d), 12 female Beagle dogs were assigned to a control group (intact in both phases) and a sterilization group (spayed 20 d before Ph.II). In each phase, dogs received a high-carbohydrate (HC) diet (313 and 105 g/kg DM starch and fat, respectively) and a high-fat (HF) diet (191 and 213 g/kg DM starch and fat, respectively), both high in total dietary fiber (>200 g/kg DM) and providing 27% ME as protein, in 2 consecutive periods following a crossover arrangement. During each period, dogs' voluntary DMI and activity level were recorded during 5 d. Then, energy allowance was restricted to 0.7 maintenance and the level of intake of a common challenge food offered 4 h after feeding the experimental diets (challenge food intake [ChFI]) was used as an index of the satiety state of dogs. Blood concentration of active ghrelin, cholecystokinin (CCK), total peptide YY (PYY), and insulin were determined before and 15, 60, 120, 240, and 360 min after feeding. Voluntary DMI was greater ( < 0.05) in HF-fed dogs, but ChFI did not differ between diets ( > 0.10). Dogs fed the HF diet showed a lower increase of CCK at 120 ( < 0.01) and 240 min ( < 0.05), resulting in a lower ( < 0.001) total area under the curve from 0 to 240 min (tAUC). A lower PYY elevation ( < 0.05) was also found in HF-fed dogs at 120 min. Only active ghrelin concentration at 240 min and insulin tAUC correlated ( < 0.05) with ChFI (r = 0.357 and r = -0.364, respectively), suggesting a role of these hormones in appetite. Dog sterilization did not affect voluntary DMI, ChFI, or blood hormones ( > 0.10) but led to a reduced activity level compared with control dogs ( < 0.05). In summary, dog sterilization was not associated with an impaired appetite control. Feeding dogs the HF diet led to energy overconsumption and to a lower blood elevation of CCK and PYY but was not associated with a weaker satiating effect 4 h later compared with the HC diet.

Ghrelin Octanoylation Is Completely Stabilized in Biological Samples by Alkyl Fluorophosphonates.

Ghrelin is a peptide hormone involved in multiple physiological processes related to energy homeostasis. This hormone features a unique posttranslational serine octanoylation modification catalyzed by the enzyme ghrelin O-acyltransferase, with serine octanoylation essential for ghrelin to bind and activate its cognate receptor. Ghrelin deacylation rapidly occurs in circulation, with both ghrelin and desacyl ghrelin playing important roles in biological signaling. Understanding the regulation and physiological impact of ghrelin signaling requires the ability to rapidly protect ghrelin from deacylation in biological samples such as blood serum or cell lysates to preserve the relative concentrations of ghrelin and desacyl ghrelin. In in vitro ghrelin O-acyltransferase activity assays using insect microsomal protein fractions and mammalian cell lysate and blood serum, we demonstrate that alkyl fluorophosphonate treatment provides rapid, complete, and long-lasting protection of ghrelin acylation against serine ester hydrolysis without interference in enzyme assay or ELISA analysis. Our results support alkyl fluorophosphonate treatment as a general tool for stabilizing ghrelin and improving measurement of ghrelin and desacyl ghrelin concentrations in biochemical and clinical investigations and suggest current estimates for active ghrelin concentration and the ghrelin to desacyl ghrelin ratio in circulation may underestimate in vivo conditions.

Ghrelin, GLP-1, and leptin responses during exposure to moderate hypoxia.

Severe hypoxia has been indicated to cause acute changes in appetite-related hormones, which attenuate perceived appetite. However, the effects of moderate hypoxia on appetite-related hormonal regulation and perceived appetite have not been elucidated. Therefore, we examined the effects of moderate hypoxia on appetite-related hormonal regulation and perceived appetite. Eight healthy males (21.0 ± 0.6 years; 173 ± 2.3 cm; 70.6 ± 5.0 kg; 23.4 ± 1.1 kg/m(2)) completed two experimental trials on separate days: a rest trial in normoxia (FiO2 = 20.9%) and a rest trial in hypoxia (FiO2 = 15.0%). The experimental trials were performed over 7 h in an environmental chamber. Blood samples and scores of subjective appetite were collected over 7 h. Standard meals were provided 1 h (745 kcal) and 4 h (731 kcal) after initiating exposure to hypoxia or normoxia within the chamber. Although each meal significantly reduced plasma active ghrelin concentrations (P < 0.05), the response did not differ significantly between the trials over 7 h. No significant differences in the area under the curves for plasma active ghrelin concentrations over 7 h were observed between the two trials. No significant differences were observed in glucagon-like peptide 1 or leptin concentrations over 7 h between the trials. The subjective feeling of hunger and fullness acutely changed in response to meal ingestions. However, these responses were not affected by exposure to moderate hypoxia. In conclusion, 7 h of exposure to moderate hypoxia did not change appetite-related hormonal responses or perceived appetite in healthy males.

Association of circulating active and total ghrelin concentrations with dry matter intake, growth, and carcass characteristics of finishing beef cattle.

Ghrelin is a gut peptide that when acylated is thought to stimulate appetite. Circulating ghrelin concentrations could potentially be used as a predictor of DMI in cattle. The objective of this experiment was to determine the association of circulating ghrelin concentrations with DMI and other production traits. Steers and heifers were fed a finishing diet, and individual intake was recorded for 84 d. Blood samples were collected via jugular venipuncture following the DMI and ADG measurement period. Plasma active ghrelin and total ghrelin were quantified using commercial RIA. Active ghrelin was not correlated to DMI (P=0.36), but when DMI was modeled using a multivariate analysis including plasma metabolites and sex, active ghrelin was shown to be positively associated with DMI (P<0.01) and accounted for 6.2% of the variation accounted for by the regression model (R2=0.33). Total ghrelin was negatively correlated to DMI (P<0.01), but was not significant in a multivariate regression analysis (P=0.13). The ratio of active:total ghrelin was positively associated with DMI (P<0.01) and accounted for 10.2% of the variation in the model (R2=0.35). Active ghrelin was positively associated with ADG (P<0.05), while total ghrelin was negatively associated with ADG (P<0.01), and the ratio of active:total ghrelin was positively associated with ADG (P<0.01). Active ghrelin was not associated with G:F (P=0.88), but total ghrelin concentrations were negatively associated with G:F (P<0.01) and accounted for 10.24% of the variation (R2=0.25). Heifers consumed less feed than steers (P<0.01), tended to have greater active ghrelin concentrations (P=0.06), and had greater total ghrelin concentrations than steers (P=0.04). Total ghrelin concentrations were not different between sire breeds (P=0.80), but active ghrelin concentrations and the ratio of active:total ghrelin differed between breeds (P<0.01), indicating that genetics have an effect on the amount and form of circulating ghrelin. Total ghrelin concentrations tended (P=0.08) to be correlated with HCW, but no other carcass characteristics were correlated with active or total ghrelin concentrations (P>0.10). Results indicated that ghrelin concentrations are associated with DMI in beef cattle and that there is genetic variation that leads to differences in the amount and form of circulating ghrelin which could contribute to variation observed in DMI of beef cattle.