The Role of the Gastric Hormones Ghrelin and Nesfatin-1 in Reproduction

Ghrelin and nesfatin-1 are enteroendocrine peptide hormones expressed in rat X/A-like and human P/D1cells of the gastric mucosa. Besides their effect on food intake, both peptides are also implicated in various other physiological systems. One of these is the reproductive system. This present review illustrates the distribution of ghrelin and nesfatin-1 along the hypothalamus–pituitary–gonadal (HPG) axis, their modulation by reproductive hormones, and effects on reproductive functions as well as highlighting gaps in current knowledge to foster further research.     

The relationship between the leptin/ghrelin ratio and meals with various macronutrient contents in men with different nutritional status: a randomized crossover study

Background

Hormones, which influence satiety and hunger, play a significant role in body energy balance regulation. Ghrelin is a peptide that plays an important role in short-term appetite regulation, whereas leptin is a factor that controls long-term energy balance and is considered as a satiety hormone. The aim of this study was to evaluate the leptin/ghrelin ratio in a fasting state and after the intake of meals with varying macronutrient contents and to assess the possible differences between normal body weight and overweight/obese men.

Methods

We examined 46 healthy adult men (23 with normal body weight and 23 overweight/obese) aged 21–58, who were divided into two groups. In the crossover study, participants received isocaloric (450?kcal) meals with different macronutrient contents: men from the first group received high-carbohydrate (HC) and normo-carbohydrate (NC) meals, and in the second group, participants received high-carbohydrate and high-fat (HF) meals. The ratio of leptin/ghrelin levels was calculated from leptin and total ghrelin serum concentrations in a fasting state and 30, 60, 120, 180 and 240?min after meal intake. One-way ANOVA and Wilcoxon signed-rank tests were carried out. The normality of the variable distribution was checked with the Shapiro–Wilk test, the homogeneity of variances was verified with the Levene test, and the false discovery rate p-value adjustment method was used.

Results

The leptin/ghrelin ratio was significantly higher in overweight/obese men than individuals with normal body weight in a fasting state, as well as postprandially. We observed trends towards a higher leptin/ghrelin ratio values from the 60?min after HC-meal intake compared to the NC- and HF-meals in normal body weight participants, while in overweight/obese men, we did not note any significant differences dependent on the meal type.

Conclusions

We have observed a significantly different postprandial leptin/ghrelin ratio in normal body weight and overweight/obese men, and our results suggest that in men with normal body weight, a greater feeling of satiety may occur after high-carbohydrate meal intake, which was not noted in the overweight/obese individuals.

     

Effect of Dietary Cholesterol and Fat on Cell Cholesterol Transfer to Postprandial Plasma in Hyperlipidemic Men

Postprandial chylomicrons are potent ultimate acceptors of cell membrane cholesterol and are believed to accelerate reverse cholesterol transport (RCT). We compared the effects of meals rich in polyunsaturated fat (PUFA) and either high (605 mg) or low (151 mg) in cholesterol and a meal rich in dairy fat (DF) in the form of cream on net in vitro transport of red blood cell (RBC) membrane cholesterol to 4 and 6 h postprandial plasma in eight normotriglyceridemic (NTG-H) and eight hypertriglyceridemic (HTG-H) men with mild to moderate hypercholesterolemia. In HTG-H men, cell cholesterol accumulation in 6-h postprandial plasma was significantly (P = 0.02) less after the PUFA-HC meal compared with the other meals. The significant (P < 0.001) increase in cell plus endogenous cholesterol accumulation in the triglyceride-rich lipoprotein (TRL) fraction of 4 h postprandial plasma incubated with RBC was significantly (P = 0.007) higher after the PUFA-HC meal compared with DF meal in HTG-H men. In NTG-H men, cholesterol accumulation in plasma and plasma lipoproteins in the presence and absence of RBC was not significantly affected by the type of meal ingested. These data suggest that addition of large amounts of cholesterol to a PUFA meal may impair diffusion-mediated transport of cell membrane cholesterol to postprandial plasma and that replacing DF with PUFA in a meal increases postprandial lipemia and may potentially increase cholesterol accumulation in atherogenic postprandial TRL in HTG-H men.     

Effects of soy or milk protein durign a high-fat feeding challenge on oxidative stress, inflammation, and lipids in healthy men

Soy isoflavones may impede atherogenic processes associated with cardiovascular disease. Research suggests that the postprandial generation of TG-rich remnants contributes to the development of atherosclerosis. The purpose of the current study was to determine if 39 g soy (85 mg aglycone isoflavones, treatment) compared with 40 g milk protein (0 mg aglycone isoflavones, control) in combination with a high-fat meal can modify postprandial, atherogenic-associated events and biomarkers for oxidative stress, inflammation, and thrombosis. Fifteen healthy men (20–47 yr) participated in a double-blind cross-over meal-challenge study occurring on two nonconsecutive days. The study meals consisted of two high-fat apple muffins consumed with either a soy or milk shake (229 mL, 41% fat, 41% carbohydrate, and 18% protein). Blood samples were obtained at base-line (fasted) and hours two, four, and six postprandial. Plasma TG significantly increased in both treatment and control meal challenges compared with baseline. There were no significant differences (P>0.05) between treatment (soy) and control (milk) for ex vivo copper-induced LDL oxidation, serum C-reactive protein, serum interleukin-6 (IL-6), serum fibrinogen, or plasma lipids (total cholesterol, HDL, LDL, TG). IL-6-concentrations significantly decreased as a function of time during either meal challenge (P=0.005). These data suggest that consumption of soy or milk protein in conjunction with a high-fat meal does not acutely modify postprandial oxidative stress, inflammation, or plasma lipid concentrations in young, healthy men.     

Dietary Cocoa Butter or Refined Olive Oil Does Not Alter Postprandial hsCRP and IL-6 Concentrations in Healthy Women

Contrary to other long chain saturated fatty acids (SFA), fats high in stearic acid do not raise plasma cholesterol concentrations, however, a slight elevation in inflammatory markers, plasma fibrinogen and interleukin-6 (IL-6), has been observed in the fasting state. The effect of stearic acid on inflammation in the postprandial state has not yet been reported. We conducted a single blind crossover, randomized, postprandial study to compare the effects of a fat load of cocoa butter high in stearic acid and olive oil in ten healthy women. The test meals contained 1 g of fat per kg body weight (mean 62 g). Blood samples were collected at 0 (fasting), 4 and 6 h. Both diets resulted in a significant increase in serum triacylglycerol (TAG) concentration over time (P = 0.003) and a decrease in serum IL-6 concentration after 4 h followed by an increase to post absorptive values after 6 h (P < 0.001); whereas serum high sensitivity C-reactive protein (hsCRP) concentration was not affected. There was no difference between diets in effects on serum TAG, hsCRP and IL-6 concentrations and no association between postprandial lipemia and inflammatory markers. High intake of dietary fats increase postprandial serum TAG, however, may not affect inflammatory markers postprandially. Thus, fat rich in stearic acid does not seem to increase postprandial inflammation.     

Palm Olein and Olive Oil Cause a Higher Increase in Postprandial Lipemia Compared with Lard but Had No Effect on Plasma Glucose,Insulin and Adipocytokines

Postprandial lipemia impairs insulin sensitivity and triggers the pro-inflammatory state which may lead to the progression of cardiovascular diseases. A randomized, crossover single-blind study (n = 10 healthy men) was designed to compare the effects of a high-fat load (50 g fat), rich in palmitic acid from both plant (palm olein) or animal source (lard) versus an oleic acid-rich fat (virgin olive oil) on lipemia, plasma glucose, insulin and adipocytokines. Serum triacylglycerol (TAG) concentrations were significantly lower after the lard meal than after the olive oil and palm olein meals (meal effect P = 0.003; time effect P < 0.001). The greater reduction in the plasma non-esterified free fatty acids levels in the lard group compared to the olive oil meal was mirrored by the changes observed for serum TAG levels (P < 0.05). The magnitude of response for plasma glucose, insulin and adipocytokines [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and leptin] were not altered by the type of dietary fats. A significant difference in plasma IL-1β was found over time following the three high fat loads (time effect P = 0.036). The physical characteristics and changes in TAG structure of lard may contribute to the smaller increase in postprandial lipemia compared with palm olein. A high fat load but not the type of fats influences concentrations of plasma IL-1β over time but had no effect on other pro-inflammatory markers tested in the postprandial state.     

Does Glycine max leaves or Garcinia Cambogia promote weight-loss or lower plasma cholesterol in overweight individuals: a randomized control trial

Background

There is conflicting data on the effects of carbon dioxide contained in beverages on stomach functions. We aimed to verify the effect of a pre-meal administration of a 300 ml non-caloric carbonated beverage (B+CO₂) compared to water or a beverage without CO₂ (B-CO₂), during a solid (SM) and a liquid meal (LM) on: a) gastric volume, b) caloric intake, c) ghrelin and cholecystokinin (CCK) release in healthy subjects.

Methods

After drinking the beverages (Water, B-CO₂, B+CO₂), ten healthy subjects (4 women, aged 22-30 years; BMI 23 ± 1) were asked to consume either an SM or an LM, at a constant rate (110 kcal/5 min). Total gastric volumes (TGV) were evaluated by Magnetic Resonance Imaging after drinking the beverage and at maximum satiety (MS). Total kcal intake at MS was evaluated. Ghrelin and CCK were measured by enzyme immunoassay until 120 min after the meal. Statistical calculations were carried out by paired T-test and analysis of variance (ANOVA). The data is expressed as mean ± SEM.

Results

TGV after B+CO₂ consumption was significantly higher than after B-CO₂ or water (p < 0.05), but at MS, it was no different either during the SM or the LM. Total kcal intake did not differ at MS after any of the beverages tested, with either the SM (Water: 783 ± 77 kcals; B-CO₂: 837 ± 66; B+CO₂: 774 ± 66) or the LM (630 ± 111; 585 ± 88; 588 ± 95). Area under curve of ghrelin was significantly (p < 0.05) lower (13.8 ± 3.3 ng/ml/min) during SM following B-CO₂ compared to B+CO₂ and water (26.2 ± 4.5; 27.1 ± 5.1). No significant differences were found for ghrelin during LM, and for CCK during both SM and LM after all beverages.

Conclusions

The increase in gastric volume following a 300 ml pre-meal carbonated beverage did not affect food intake whether a solid or liquid meal was given. The consistency of the meal and the carbonated beverage seemed to influence ghrelin release, but were unable, under our experimental conditions, to modify food intake in terms of quantity. Further studies are needed to verify if other food and beverage combinations are able to modify satiation.     

Biological Aspects of Selected Myokines in Skeletal Muscle: Focus on Aging

In the last decade, clear evidence has emerged that the cellular components of skeletal muscle are important sites for the release of proteins and peptides called “myokines”, suggesting that skeletal muscle plays the role of a secretory organ. After their secretion by muscles, these factors serve many biological functions, including the exertion of complex autocrine, paracrine and/or endocrine effects. In sum, myokines affect complex multi-organ processes, such as skeletal muscle trophism, metabolism, angiogenesis and immunological response to different physiological (physical activity, aging, etc.) or pathological states (cachexia, dysmetabolic conditions, chronic inflammation, etc.). The aim of this review is to describe in detail a number of myokines that are, to varying degrees, involved in skeletal muscle aging processes and belong to the group of proteins present in the functional environment surrounding the muscle cell known as the “Niche”. The particular myokines described are those that, acting both from within the cell and in an autocrine manner, have a defined relationship with the modulation of oxidative stress in muscle cells (mature or stem) involved in the regulatory (metabolic or regenerative) processes of muscle aging. Myostatin, IGF-1, NGF, S100 and irisin are examples of specific myokines that have peculiar features in their mechanisms of action. In particular, the potential role of one of the most recently characterized myokines—irisin, directly linked to an active lifestyle—in reducing if not reversing senescence-induced oxidative damage is discussed in terms of its possible application as an agent able to counteract the deleterious effects of muscle aging.     

Irisin,a Link among Fatty Liver Disease,Physical Inactivity and Insulin Resistance

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in industrialized countries. The increasing prevalence of NAFLD mirrors the outbreak of obesity in western countries, highlighting the connection between these two conditions. Nevertheless, there is currently no specific pharmacotherapy for its treatment. Accepted management begins with weight loss and exercise. Moreover, exercise can provide metabolic benefits independently of weight loss. It is known how long-term aerobic training produces improvements in hepatic triglycerides, visceral adipose tissue and free fatty acids, even if there is no weight reduction. A recent study from Boström et al. unravels a potential molecular mechanism that may explain how exercise, independently of weight loss, can potentially improve metabolic parameters through a new messenger system (irisin) linking muscle and fat tissue. Irisin has been proposed to act as a hormone on subcutaneous white fat cells increasing energy expenditure by means of a program of brown-fat-like development. Moreover, it was also shown that irisin plasma concentration was higher in people who exercise, suggesting a molecular mechanism by which exercise may improve metabolism. The present systematic review is based on the possibility that irisin might represent a hypothetical connection between NAFLD pathogenesis and disease progression.     

Effects of highly purified eicosapentaenoic acid and docosahexaenoic acid on fatty acid absorption, incorporation into serum phospholipids and postprandial triglyceridemia

Fourteen healthy volunteers were randomly allocated to receive 4 g highly purified ethyl esters of eicosapentaenoic acid (EPA) (95% pure, n=7) or docosahexaenoic acid (DHA) (90% pure, n=7) daily for 5 wk in supplement to their ordinary diet. The n−3 fatty acids were given with a standard high-fat meal at the beginning and the end of the supplementation period. EPA and DHA induced a similar incorporation into chylomicrons which peaked 6 h after the meal. The relative uptake of EPA and DHA from the meal was >90% compared with the uptake of oleic acid. During absorption, there was no significant elongation or retroconversion of EPA or DHA in total chylomicron fatty acids. The concentration of EPA decreased by 13% and DHA by 62% (P<0.001) between 6 and 8 h after the meal. During the 5-wk supplementation period, EPA showed a more rapid and comprehensive increase in serum phospholipids than did DHA. DHA was retroconverted to EPA, whereas EPA was elongated to docosapentaenoic acid (DPA). The postprandial triglyceridemia was suppressed by 19 and 49% after prolonged intake of EPA and DHA, respectively, indicating that prolonged intake of DHA is equivalent to or even more efficient than that of EPA in lowering postprandial triglyceridemia. This study indicates that there are metabolic differences between EPA and DHA which may have implications for the use of n−3 fatty acids in preventive and clinical medicine.     

Oxytocin and Food Intake Control: Neural,Behavioral, and Signaling Mechanisms

The neuropeptide oxytocin is produced in the paraventricular hypothalamic nucleus and the supraoptic nucleus of the hypothalamus. In addition to its extensively studied influence on social behavior and reproductive function, central oxytocin signaling potently reduces food intake in both humans and animal models and has potential therapeutic use for obesity treatment. In this review, we highlight rodent model research that illuminates various neural, behavioral, and signaling mechanisms through which oxytocin’s anorexigenic effects occur. The research supports a framework through which oxytocin reduces food intake via amplification of within-meal physiological satiation signals rather than by altering between-meal interoceptive hunger and satiety states. We also emphasize the distributed neural sites of action for oxytocin’s effects on food intake and review evidence supporting the notion that central oxytocin is communicated throughout the brain, at least in part, through humoral-like volume transmission. Finally, we highlight mechanisms through which oxytocin interacts with various energy balance-associated neuropeptide and endocrine systems (e.g., agouti-related peptide, melanin-concentrating hormone, leptin), as well as the behavioral mechanisms through which oxytocin inhibits food intake, including effects on nutrient-specific ingestion, meal size control, food reward-motivated responses, and competing motivations.     

Effect of rye bread breakfasts on subjective hunger and satiety: a randomized controlled trial

Background  

Several studies report that dietary fibre from different sources promotes the feeling of satiety and suppresses hunger. However, results for cereal fibre from rye are essentially lacking. The aim of the present study was to investigate subjective appetite during 8 h after intake of iso-caloric rye bread breakfasts varying in rye dietary fibre composition and content.     

Recent developments in ghrelin receptor ligands

The 28-amino acid peptide ghrelin is a neuroendocrine hormone synthesized primarily in the stomach. It stimulates growth hormone secretion and appetite, thus promoting food intake and body-weight gain. The pharmacological properties of this peptide are mediated by the growth hormone secretagogue receptor type 1a (GHS-R1a). Given its wide spectrum of biological activities, it is evident that the discovery of ghrelin and its receptor has opened up many perspectives in the fields of neuroendocrine and metabolic research and has had an influence on such fields of internal medicine as gastroenterology, oncology, and cardiology. It is therefore increasingly likely that synthetic, peptidyl, and nonpeptidyl GHS-R1a ligands, acting as agonists, partial agonists, antagonists, or inverse agonists, could have both clinical and therapeutic potential. This review summarizes the various types of GHS-R1a ligands that have been described in the literature and discusses the recent progress made in this research area.     

Assessment of the Validity and Reproducibility of a Novel Standardized Test Meal for the Study of Postprandial Triacylglycerol Concentrations

Lipotest^® is a standardized fat‐rich meal designed for use as a test meal during a fat tolerance test (FTT) for the study of postprandial triacylglycerol (TAG) concentrations. Herein we examined the precision and reproducibility of examination using Lipotest^® on postprandial TAG levels. A total of 26 healthy consenting subjects were examined twice after 8–10 h fasting with an interval of approximately 1 week apart. Blood samples were collected at baseline and 1, 2, 3, and 4 h after consumption of the test meal for measurement of plasma total TAG levels. We examined agreement, precision, and accuracy between the two visits using the Altman plots and correlation coefficient. Reproducibility was tested using the coefficient of variation (CV) and intraclass correlation coefficient (ICC). Moreover, the area under the curve (AUC) as a summary measure of the overall postprandial TAG levels was calculated. The agreement, precision (r ≥ 0.74, p < 0.001), and accuracy (≥0.99) between the measurements in plasma TAG during Lipotest^® testing in the two visits were high. In terms of reproducibility, the values of CV were 15.59–23.83% while those of ICC were ≥0.75. The values of the AUCs in the visits were not different (p = 0.87). A single measurement of plasma TAG levels at 4 h after Lipotest^® consumption depicted peak postprandial TAG concentration. A FTT using Lipotest^® as a standardized meal has good precision and reproducibility for the study of postprandial TAG levels in healthy individuals. A single determination of plasma TAG concentration at 4 h after Lipotest^® consumption captures peak postprandial TAG response.     

Rye kernel breakfast increases satiety in the afternoon - an effect of food structure

Background  

The structure of whole grain cereals is maintained to varying degrees during processing and preparation of foods. Food structure can influence metabolism, including perceived hunger and satiety. A diet that enhances satiety per calorie may help to prevent excessive calorie intake. The objective of this work was to compare subjective appetite ratings after consumption of intact and milled rye kernels.     

Nucleobindin-2/Nesfatin-1—A New Cancer Related Molecule?

Cancer is a heterogeneous disease, and even tumors with similar clinicopathological characteristics show different biology, behavior, and treatment responses. As a result, there is an urgent need to define new prognostic and predictive markers to make treatment options more personalized. According to the latest findings, nucleobindin-2/nesfatin-1 (NUCB2/NESF-1) is an important factor in cancer development and progression. Nucleobindin-2 is a precursor protein of nesfatin-1. As NUCB2 and nesfatin-1 are colocalized in each tissue, their expression is often analyzed together as NUCB2. The metabolic function of NUCB2/NESF-1 is related to food intake, glucose metabolism, and the regulation of immune, cardiovascular and endocrine systems. Recently, it has been demonstrated that high expression of NUCB2/NESF-1 is associated with poor outcomes and promotes cell proliferation, migration, and invasion in, e.g., breast, colon, prostate, endometrial, thyroid, bladder cancers, or glioblastoma. Interestingly, nesfatin-1 is also considered an inhibitor of the proliferation of human adrenocortical carcinoma and ovarian epithelial carcinoma cells. These conflicting results make NUCB2/NESF-1 an interesting target of study in the context of cancer progression. The present review is the first to describe NUCB2/NESF-1 as a new prognostic and predictive marker in cancers.     

High Density Lipoprotein Level is Negatively Associated With the Increase of Oxidized Low Density Lipoprotein Lipids After a Fatty Meal

Recent reports show that a fatty meal can substantially increase the concentration of oxidized lipids in low density lipoprotein (LDL). Knowing the LDL‐specific antioxidant effects of high density lipoprotein (HDL), we aimed to investigate whether HDL can modify the postprandial oxidative stress after a fatty meal. Subjects of the study (n = 71) consumed a test meal (a standard hamburger meal) rich in lipid peroxides, and blood samples were taken before, 120, 240, and 360 min after the meal. The study subjects were divided into four subgroups according to the pre‐meal HDL cholesterol value (HDL subgroup 1, 0.66–0.91; subgroup 2, 0.93–1.13; subgroup 3, 1.16–1.35; subgroup 4, 1.40–2.65 mmol/L). The test meal induced a marked postprandial increase in the concentration of oxidized LDL lipids in all four subgroups. The pre‐meal HDL level was associated with the extent of the postprandial rise in oxidized LDL lipids. From baseline to 6 h after the meal, the concentration of ox‐LDL increased by 48, 31, 24, and 16 % in the HDL subgroup 1, 2, 3, and 4, respectively, and the increase was higher in subgroup 1 compared to subgroup 3 (p = 0.028) and subgroup 4 (p = 0.0081), respectively. The pre‐meal HDL correlated with both the amount and the rate of increase of oxidized LDL lipids. Results of the present study show that HDL is associated with the postprandial appearance of lipid peroxides in LDL. It is therefore likely that the sequestration and transport of atherogenic lipid peroxides is another significant mechanism contributing to cardioprotection by HDL.     

Modulatory Effect of Myokines on Reactive Oxygen Species in Ischemia/Reperfusion

There is a growing body of evidence showing the importance of physical activity against acute ischemic events in various organs. Ischemia/reperfusion injury (I/R) is characterized by tissue damage as a result of restriction and subsequent restoration of blood supply to an organ. Oxidative stress due to increased reactive oxygen species formation and/or insufficient antioxidant defense is considered to play an important role in I/R. Physical activity not only decreases the general risk factors for ischemia but also confers direct anti-ischemic protection via myokine production. Myokines are skeletal muscle-derived cytokines, representing multifunctional communication channels between the contracting skeletal muscle and other organs through an endocrine manner. In this review, we discuss the most prominent members of the myokines (i.e., brain-derived neurotrophic factor (BDNF), cathepsin B, decorin, fibroblast growth factors-2 and -21, follistatin, follistatin-like, insulin-like growth factor-1; interleukin-6, interleukin-7, interleukin-15, irisin, leukemia inhibitory factor, meteorin-like, myonectin, musclin, myostatin, and osteoglycin) with a particular interest in their potential influence on reactive oxygen and nitrogen species formation or antioxidant capacity. A better understanding of the mechanism of action of myokines and particularly their participation in the regulation of oxidative stress may widen their possible therapeutic use and, thereby, may support the fight against I/R.     

Influence of two breakfast meals differing in glycemic load on satiety, hunger, and energy intake in preschool children

Background

Glycemic load (GL) is the product of glycemic index of a food and amount of available carbohydrate in that food divided by 100. GL represents quality and quantity of dietary carbohydrate. Little is known about the role of GL in hunger, satiety, and food intake in preschool children. The aim of this study was to investigate the effect of two breakfast meals differing in GL on hunger, satiety, and subsequent food intake at lunch in preschool children aged 4-6 y.

Methods

Twenty three subjects consumed low-GL (LGL) and high-GL (HGL) breakfast meals according to a randomized crossover design followed by an ad libitum lunch 4 h after consumption of breakfast. Children were asked to consume meals until they are full. Each treatment was repeated twice in non-consecutive days and data were averaged.

Results

Children in LGL group consumed significantly lower amounts of GL, total carbohydrate, energy, energy density, and dietary fiber and higher amounts of protein and fat at the breakfast compared to those in HGL group. Prior to lunch, children were hungrier in the HGL intervention group compared to the LGL intervention group (P < 0.03). However, no significant difference was observed between LGL and HGL intervention groups in the amount of food and energy consumed during lunch.

Conclusions

Decreased hunger in children prior to lunch in LGL group is likely due to higher protein and fat content of LGL breakfast. Diets that are low in GL can be recommended as part of healthy diet for preschool children.