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A simplified diagram of the regulation of feeding behavior at the level of the hypothalamus. There are two main neuronal populations in the hypothalamic arcuate nucleus that are sensitive to signals indicating systemic fuel availability (e. g., leptin, ghrelin and insulin). These populations include the orexigenic neuropeptide Y (NPY) and anorexigenic proopiomelanocortin (POMC) neurons that have projections to key neurons in other hypothalamic nuclei and higher brain centers in order to orchestrate the feeding responses. NPY, neuropeptide Y; AgRP, Agouti related peptide; POMC, Pro-opiomelanocortin; CART, cocaine-and amphetamine-regulated transcript; GABA, -aminobutyric acid; MSH, -melanocyte-stimulating hormone; ARC, arcuate nucleus; PVN, paraventricular nucleus; BBB, blood brain barrier, OBRb, leptin receptor; GHSR1a, ghrelin receptor.
Source publication
Metabolic homeostasis requires a tight balance between energy intake and energy expenditure; hence, the physiological circuits implicated in the regulation of energy metabolism must be able to quickly adjust to changes in either side of the equation. Circulating orexigenic and anorexigenic factors, including ghrelin and leptin, are produced in the...
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Citations
... 18 There are multiple reports indicating that elevated serum leptin concentrations in rodents may be the result of obesity or an HFD. [19][20][21] In this study, an HFD group exhibited elevated leptin levels, whereas combination therapy with UA and RSG reduced leptin levels significantly. In our prior research, we found that the concurrent administration of UA and ...
p class="MsoNormal" style="text-align: justify;"> Background:
The objective of this research endeavor was to assess the effects of rosiglitazone (RSG) and ursolic acid (UA) on hepatic insulin signaling indicators and inflammatory marker concentrations in C57/BL/6J mice that were provided with a high-fat diet (HFD).
Methods:
C57BL/6J mice were fed a HFD for 16 weeks and orally administered UA (5 mg/kg BW), RSG (4 mg/kg BW), and UA (5 mg/kg BW) + RSG (4 mg/kg BW) for the last 6 weeks.
Results:
The HFD groups showed a significant increase in leptin, TNF-α, and IL-6, whereas adiponection level significantly decreased. The expression of insulin signaling markers in the liver also significantly increased in HFD mice.
Conclusions:
Combination treatment improves above said parameters than individual parameters. These data suggest that combination treatment (UA with RSG) has potential benefits for the treatment of HFD-induced insulin resistance, and its effects may be associated with improvements in the inhibition of the expression of inflammatory markers in plasma and liver. </p
... Leptin and ghrelin have been speculated to play a role in development of obesity in sleep deprivation conditions (80) . Leptin is primarily produced by adipose tissue in amounts proportional to body fat masses (81) . It is an important anorexigenic hormone which induces satiety and reduces food intake. ...
Sleep deprivation, which is a decrease in duration and quality of sleep, is a common problem in today’s life. Epidemiological and interventional investigations have suggested a link between sleep deprivation and overweight/obesity. Sleep deprivation affects homeostatic and non-homeostatic regulation of appetite, with the food reward system playing a dominant role. Factors such as sex and weight status affect this regulation; men and individuals with excess weight seem to be more sensitive to reward-driven and hedonistic regulation of food intake. Sleep deprivation may also affect weight through affecting physical activity and energy expenditure. In addition, sleep deprivation influences food selection and eating behaviors, which are mainly managed by the food reward system. Sleep-deprived individuals mostly crave for palatable energy-dense foods and have low desire for fruit and vegetables. Consumption of meals may not change but energy intake from snacks increases. The individuals have more desire for snacks with high sugar and saturated fat content. The relationship between sleep and the diet is mutual, implying that diet and eating behaviors also affect sleep duration and quality. Consuming healthy diets containing fruit and vegetables and food sources of protein and unsaturated fats and low quantities of saturated fat and sugar may be used as a diet strategy to improve sleep. Since the effects of sleep deficiency differ between animals and humans, only evidence from human studies has been included, controversies are discussed, and the need for future investigations is highlighted.
... Leptin, the protein product of the ob gene, is a hormone that is secreted principally by adipose tissue (adipocyte-derived hormone). It is a well-defined afferent satiety factor that suppresses appetite by affecting the hypothalamic nuclei regulating appetite [3]. Ghrelin, growth hormone-releasing peptide, is a hormone which is secreted by the food-deprived stomach and stimulates food intake during starvation [4]. ...
... Ghrelin, growth hormone-releasing peptide, is a hormone which is secreted by the food-deprived stomach and stimulates food intake during starvation [4]. Its application by either the central or peripheral process increases appetite, food intake, adiposity and glucose metabolism [2,3]. Metabolic homeostasis requires a tight balance between energy intake and energy expenditure. ...
Background
It is known that iron deficiency anemia effects appetite and growth negatively. The aim of this study was to investigate the effect of iron therapy on appetite, growth and plasma ghrelin and leptin levels in children aged between 12 and 24 months with isolated nutritional iron deficiency anemia.
Methods
Iron deficiency anemia was diagnosed by clinic and laboratory findings. All 19 cases were given 5 mg/kg/day iron therapy for 3 months.
Results
The mean plasma ghrelin level was 936.7±428.8 pg/mL before therapy and it increased to 1284.7±533.3 pg/mL (p<0.001) while the mean plasma leptin level decreased from 3.4±1.6 ng/mL to 1.9±1.0 ng/mL (p<0.01) after therapy. The amount of daily caloric intake, carbohydrate and protein intake were significantly increased after therapy (p<0.001). Δ body weight was correlated with plasma ghrelin levels before and after therapy significantly.
Conclusions
In conclusion, the findings of this study indicate that plasma ghrelin level increases and leptin level decreases and growth accelerates because of an increase in appetite and daily calories, carbohydrate and protein amount in children with nutritional iron deficiency anemia after iron therapy. The increase in appetite and acceleration on growth in iron deficiency anemia might result from decreased leptin and increased plasma ghrelin levels. The most important finding of this study is significantly increased plasma ghrelin levels after iron therapy, and this finding might be related to both the improved appetite and catch-up growth.
... Its main role is to inhibit appetite via interaction with receptors within the hypothalamus; thus, leptin is often referred to as the "satiety hormone." 12 Other important effects of leptin include increase in glucose utilization, inhibition of lipogenesis, stimulation of fatty acid oxidation, and reduction of trigliceride accumulation in liver and skeletal muscles, accounting for leptin's insulin-sensitizing properties. 13 Leptin is synthesized and released predominantly by adipocytes, and its serum concentrations correlate positively with body mass index (BMI) and the amount of adipose tissue. ...
Purpose
To investigate the association of leptin, resistin and tumor necrosis factor α (TNF‐α) with prognosis in type 2 diabetes (T2D).
Methods
Analysis included 284 T2D patients. Apart from routine laboratory parameters, baseline leptin, resistin and TNF‐α concentrations were measured. Patients were followed for a median of 5.4 years. The primary endpoint was all‐cause death at follow‐up. The secondary endpoint was a composite of death, acute coronary syndrome and stroke or transient ischemic attack.
Results
At baseline, median age was 68 years and 48% of patients were female. Data on the primary endpoint were obtained for all patients: 32 (11%) died during follow‐up. Data on the secondary endpoint were available for 230 patients, of whom 45 (20%) reached the secondary endpoint. In univariate analyses, older age, heart failure, lower glomerular filtration rate, and higher resistin, TNF‐α and NT‐proBNP concentrations were predictors of the study endpoints. Of these variables, only resistin remained an independent predictor of both study endpoints in multivariate models. In receiver operating characteristic analysis, area under the curve for resistin was 0.7. Resistin concentration of ≥11.4 ng/mL had sensitivity of 41% and specificity of 91% for prediction of death at follow‐up (Youden's index).
Conclusions
Higher resistin is associated with reduced survival in T2D, irrespectively of TNF‐α. Resistin concentration of above 11 ng/mL indicates T2D patients at an increased risk of unfavorable outcomes. Leptin was not a prognostic factor. These results suggest that in T2D, association of resistin with unfavorable outcomes might, at least in part, result from its pro‐inflammatory properties.
... In many studies, leptin and ghrelin seemed to play the most important role in energy metabolism. [1][2][3][4]12 There are many factors that influence the serum level of appetite hormones. Leptin synthesis and expression are influenced, for example, by fasting, sympathetic activity insulin, and exercise. ...
Aim
We wanted to investigate serum levels of ghrelin and leptin – appetite‐regulating hormones – and their correlation with the nutritional status of children with neurogenic bladder (NB) due to myelomeningocele (MMC) in comparison to healthy individuals.
Methods
This prospective analysis was conducted on 67 children with NB after MMC and 20 healthy children. Children's medical charts were analysed to determine age, gender, anthropometric measurements, body mass index (BMI), activity assessment using Hoffer's scale and renal function parameters. Serum total ghrelin and leptin levels were measured using the enzyme‐linked immunosorbent assay.
Results
There were no differences in the age, gender, weight and BMI between the studied groups. Median serum levels of ghrelin and leptin were higher compared with the reference group. A significant negative correlation between serum leptin concentration and Hoffer's scale was found in children with NB.
Conclusions
Elevated levels of leptin and ghrelin could be considered factors influencing nutritional status in children with NB due to MMC. Children with NB after MMC may have disturbed endocrine regulation of energy homeostasis. Physical activity may be the factor that affects serum leptin concentration.
... These two hormones are known to be produced in white adipose tissues. 2 After their production, leptin, and ghrelin enter into the blood circulation and crosses the blood brain barrier where they regulate the appetite and energy homeostasis by interacting with specific receptors present in hypothalamus. 3 This hormone was initially misrepresented as "obesity hormone" or "fat hormone" but now the most appropriate term used for leptin is "satiety hormone." 4 Leptin is considered as a long-term regulator of energy balance, it may induce weight loss by suppressing appetite and/or desire to eat. Ghrelin, in contrast is a fast acting short-term regulator of energy homeostasis that stimulates appetite. ...
Leptin is an endogenous protein having 167 amino acids and is derived from adipocytes. It hass tertiary structure that resembles with that of the pro-inflammatory cytokines family. The fundamental role of leptin is to maintain the energy homeostasis with the aid of its counter hormone called ghrelin, known as the “hunger hormone”. Small quantities of leptin are also present in various tissues like ovary, placenta, pituitary gland, mammary gland, skeletal muscle, stomach and lymphoid tissue. Expression of leptin is strongly associated with various inflammatory responses and immune system, and plays crucial role in the pathophysiology of obesity and development of diabetes mellitus (DM) and insulin resistance. The metabolic action of leptin is equally important as that of insulin in the pathophysiology of obesity and DM. Thereby, this review article tends to discuss the diverse and complicated role of leptin in the pathogenesis of DM. Furthermore, this article will highlight the signifying role of leptin as a therapeutic target by indicating the targeted treatment of DM through the appropriate understanding of advanced therapeutic approaches using leptin as a treatment strategy for DM. This article is protected by copyright. All rights reserved
... However, there is less agreement on the mechanisms through which such risk may be conferred (4). Collectively, data to date reveal that leptin, in particular, and ghrelin play key roles in facilitating the normal development of hypothalamic neural circuits and suggest that normal expression of these factors during the fetal/neonatal period is key for lifelong metabolic regulation (55,86,102). Although most work to date has been undertaken in the rodent where the early neonatal period is seen as the critical period for development of the neuroendocrine circuits, in many species the neuropeptide systems which control food intake develop and mature in utero, with large differences across the model species used (90). ...
Evidence from epidemiological, clinical, and experimental studies have clearly shown that disease risk in later life is increased following a poor early life environment, a process preferentially termed developmental programming. In particular, this work clearly highlights the importance of the nutritional environment during early development with alterations in maternal nutrition, including both under- and overnutrition, increasing the risk for a range of cardiometabolic and neurobehavioral disorders in adult offspring characterized by both adipokine resistance and obesity. Although the mechanistic basis for such developmental programming is not yet fully defined, a common feature derived from experimental animal models is that of alterations in the wiring of the neuroendocrine pathways that control energy balance and appetite regulation during early stages of developmental plasticity. The adipokine leptin has also received significant attention with clear experimental evidence that normal regulation of leptin levels during the early life period is critical for the normal development of tissues and related signaling pathways that are involved in metabolic and cardiovascular homeostasis. There is also increasing evidence that alterations in the epigenome and other underlying mechanisms including an altered gut–brain axis may contribute to lasting cardiometabolic dysfunction in offspring. Ongoing studies that further define the mechanisms between these associations will allow for identification of early risk markers and implementation of strategies around interventions that will have obvious beneficial implications in breaking a programmed transgenerational cycle of metabolic disorders.
... Metabolic homeostasis requires a balance between energy intake and expenditure. 63,64 Feeding behavior (intake) and locomotion (expenditure) have both motivational and motor aspects that are involved in striking this balance, and are controlled by two complementary dopamine systems in the striatum. 65 Rhythmic dopamine signals that originate in the VTA and project to the ventral striatum [nucleus accumbens (NAc)] regulate the reward pathways underlying motivation, food craving, and anticipation. ...
Antipsychotic drugs are widely prescribed medications, used for numerous psychiatric illnesses. However, antipsychotic drugs cause serious metabolic side effects that can lead to substantial weight gain and increased risk for type 2 diabetes. While individual drugs differ, all antipsychotic drugs may cause these important side effects to varying degrees. Given that the single unifying property shared by these medications is blockade of dopamine D 2 and D 3 receptors, these receptors likely play a role in antipsychotic drug-induced metabolic side effects. Dopamine D 2 and dopamine D 3 receptors are expressed in brain regions critical for metabolic regulation and appetite. Surprisingly, these receptors are also expressed peripherally in insulin-secreting pancreatic beta cells. By inhibiting glucose-stimulated insulin secretion, dopamine D 2 and dopamine D 3 receptors are important mediators of pancreatic insulin release. Crucially, antipsychotic drugs disrupt this peripheral metabolic regulatory mechanism. At the same time, disruptions to circadian timing have been increasingly recognized as a risk factor for metabolic disturbance. Reciprocal dopamine and circadian signaling is important for the timing of appetitive/feeding behaviors and insulin release, thereby coordinating cell metabolism with caloric intake. In particular, circadian regulation of dopamine D 2 receptor/dopamine D 3 receptor signaling may play a critical role in metabolism. Therefore, we propose that antipsychotic drugs' blockade of dopamine D 2 receptor and dopamine D 3 receptors in pancreatic beta cells, hypothalamus, and striatum disrupts the cellular timing mechanisms that regulate metabolism. Ultimately, understanding the relationships between the dopamine system and circadian clocks may yield critical new biological insights into mechanisms of antipsychotic drug action, which can then be applied into clinical practice.
... Jin Kwon Jeong et al. and the hypothalamus has long been highlighted for its participation in feeding behavior and whole body metabolism regulation (Frago and Chowen, 2015;Hassouna et al., 2016). Our data show that the expression of NELL2 in the hypothalamus is directly associated with the metabolic state, as fasting enhanced NELL2 synthesis in this brain region. ...
A brain-enriched secreting signal peptide, NELL2, has been suggested to play multiple roles in the development, survival, and activity of neurons in mammal. We investigated here a possible involvement of central NELL2 in regulating feeding behavior and metabolism. In situ hybridization and an immunohistochemical approach were used to determine expression of NELL2 as well as its colocalization with proopiomelanocortin (POMC) and neuropeptide Y (NPY) in the rat hypothalamus. To investigate the effect of NELL2 on feeding behavior, 2 nmole of antisense NELL2 oligodeoxynucleotide was administered into the lateral ventricle of adult male rat brains for 6 consecutive days, and changes in daily body weight, food, and water intake were monitored. Metabolic state-dependent NELL2 expression in the hypothalamus was tested in vivo using a fasting model. NELL2 was noticeably expressed in the hypothalamic nuclei controlling feeding behavior. Furthermore, all arcuatic POMC and NPY positive neurons produced NELL2. The NELL2 gene expression in the hypothalamus was up-regulated by fasting. However, NELL2 did not affect POMC and NPY gene expression in the hypothalamus. A blockade of NELL2 production in the hypothalamus led to a reduction in daily food intake, followed by a loss in body weight without a change in daily water intake in normal diet condition. NELL2 did not affect short-term hunger dependent appetite behavior. Our data suggests that hypothalamic NELL2 is associated with appetite behavior, and thus central NELL2 could be a new therapeutic target for obesity.
... Leptin is an adipose derived protein hormone that plays important roles in regulating food intake and energy expenditure, including appetite and metabolism [57]. It is a circulatory biomarker that is proportional to body fat. ...
AGEs are a heterogeneous group of molecules formed from the nonenzymatic reaction of reducing sugars with free amino groups of proteins, lipids, and/or nucleic acids. AGEs have been shown to play a role in various conditions including cardiovascular disease and diabetes. In this study, we hypothesized that AGEs play a role in the “multiple hit hypothesis” of nonalcoholic fatty liver disease (NAFLD) and contribute to the pathogenesis of hepatosteatosis. We measured the effects of various mouse chows containing high or low AGE in the presence of high or low fat content on mouse weight and epididymal fat pads. We also measured the effects of these chows on the inflammatory response by measuring cytokine levels and myeloperoxidase activity levels on liver supernatants. We observed significant differences in weight gain and epididymal fat pad weights in the high AGE-high fat (HAGE-HF) versus the other groups. Leptin, TNF-
α
, IL-6, and myeloperoxidase (MPO) levels were significantly higher in the HAGE-HF group. We conclude that a diet containing high AGEs in the presence of high fat induces weight gain and hepatosteatosis in CD-1 mice. This may represent a model to study the role of AGEs in the pathogenesis of hepatosteatosis and steatohepatitis.
