The pregnancy and abortion process involves a complex mechanism with various immune cells present in the implantation sites and several hormones associated with pregnancy, such as leptin, ghrelin and <em>nesfatin</em>-<em>1</em>. However, the mechanism underlying spontaneous abortion by maternal T helper <em>1</em>7 (Th<em>1</em>7) present in the implantation sites and <em>nesfatin</em>-<em>1</em>, which is of anorexigenic hormones, is not fully understood so far. Therefore, the purpose of this study was to examine the possible roles of Th<em>1</em>7 cells present in the implantation sites and <em>nesfatin</em>-<em>1</em> expressed in the uterus on spontaneous abortion using the CBA/j × DBA/2 mouse model. Th<em>1</em>7 transcription factor, ROR-γt mRNA expression was significantly increased in the abortion sites compared with the implantation sites of abortion model mice on day <em>1</em>4.5 and <em>1</em>9.5 of pregnancy. In addition, the expression levels of IL(-<em>1</em>)7A mRNA were significantly higher in abortion sites than in implantation sites on day <em>1</em>4.5 and <em>1</em>9.5. Moreover, the <em>nesfatin</em>-<em>1</em>/NUCB2 protein and mRNA levels were increased in abortion sites compared with levels in implantation sites of both normal pregnant and abortion model mice on day <em>1</em>4.5 of pregnancy. Interestingly, <em>nesfatin</em>- <em>1</em>/NUCB2 serum levels were not changed throughout the whole pregnancy in abortion model mice, but its serum level was dramatically increased on day <em>1</em>4.5, and then rapidly decreased on day <em>1</em>9.5 in normal pregnant mice. In this study, we showed for the first time the expression of <em>nesfatin</em>-<em>1</em>/NUCB2 mRNA and protein in implantation sites during pregnancy. The present results suggest that Th<em>1</em>7 cells in the uterus may play an important role in the period of implantation and for maintenance of pregnancy. Furthermore, the present results suggest that Th<em>1</em>7 cells in implantation sites may be a key regulator for maintenance of pregnancy and provides evidence that activation of these cells may be regulated by <em>nesfatin</em>-<em>1</em>/NUCB2. Further study is needed to elucidate the role of <em>nesfatin</em>-<em>1</em> expressed in the uterus during pregnancy.

<em>Nesfatin</em>-<em>1</em> is a hypothalamic anorexigenic peptide processed from nucleobindin 2 (NUCB2). Central and peripheral administration of NUCB2/<em>nesfatin</em>-<em>1</em> enhances glucose metabolism and insulin release. NUCB2/<em>nesfatin</em>-<em>1</em> is also localized in pancreatic islets, while its function remains unknown. To explore the role of pancreatic β-cell-produced NUCB2/<em>nesfatin</em>-<em>1</em>, we developed pancreatic β-cell-specific NUCB2 knockout (βNUCB2 KO) mice and NUCB2 gene knockdown (shNUCB2) MIN6 β-cell line. In βNUCB2 KO mice, casual blood glucose was elevated from <em>1</em>2 weeks of age. In a glucose tolerance test at <em>1</em>2 weeks, insulin secretion at <em>1</em>5 min was reduced and blood glucose at 2 h increased in βNUCB2 KO mice fasted 8 h. In islets isolated from βNUCB2 KO mice, high glucose-stimulated insulin secretion (GSIS) was impaired. In shNUCB2 MIN6 cells, GSIS was reduced and UCP-2 mRNA expression was elevated. These results show impaired GSIS possibly associated with UCP-2 overexpression in NUCB2-silenced β-cells, suggesting that β-cell-produced NUCB2/<em>nesfatin</em>-<em>1</em> maintains GSIS and thereby glycemia.

Obstructive jaundice (OJ) can be defined as cessation of bile flow into the small intestine due to benign or malignant changes. <em>Nesfatin</em>-<em>1</em>, recently discovered anorexigenic peptide derived from nucleobindin-2 in hypothalamic nuclei, was shown to have anti-inflammatory and antiapoptotic effects. This study is aimed to investigate the therapeutic effects of <em>nesfatin</em>-<em>1</em> on OJ in rats. Twenty-four adult male Wistar-Hannover rats were randomly assigned to three groups: sham (n = 8), control (n = 8), and <em>nesfatin</em> (n = 8). After bile duct ligation, the study groups were treated with saline or <em>nesfatin</em>-<em>1</em>, for <em>1</em>0 days. Afterward, blood and liver tissue samples were obtained for biochemical analyses, measurement of cytokines, determination of the oxidative DNA damage, DNA fragmentation, and histopathologic analyses. Alanine aminotransferase and gamma-glutamyl transferase levels were decreased after the <em>nesfatin</em> treatment; however, these drops were statistically non-significant compared to control group (p = 0.345, p = 0.<em>1</em><em>1</em>4). Malondialdehyde levels decreased significantly in <em>nesfatin</em> group compared to control group (p = 0.032). Decreases in interleukin-6 and tumor necrosis factor-α levels from the liver tissue samples were not statistically significant in <em>nesfatin</em> group compared to control group. The level of oxidative DNA damage was lower in <em>nesfatin</em> group, however this result was not statistically significant (p = 0.75). DNA fragmentation results of all groups were similar. Histopathological examination revealed that there was less neutrophil infiltration, edema, bile duct proliferation, hepatocyte necrosis, basement membrane damage, and parenchymal necrosis in <em>nesfatin</em> compared to control group. The <em>nesfatin</em>-<em>1</em> treatment could alleviate cholestatic liver damage caused by OJ due to its anti-inflammatory and antioxidant effects.

<em>Nesfatin</em>-<em>1</em> was discovered a decade ago and despite the fact that it represents just one of a multitude of food intake-inhibiting factors it received increasing attention. This led to a detailed characterization of NUCB2/<em>nesfatin</em>-<em>1</em>'s physiological property to reduce food intake and also gave rise to an involvement in the long term regulation of body weight, especially under conditions of obesity. In addition, studies indicated the involvement of NUCB2/<em>nesfatin</em>-<em>1</em> in other homeostatic functions as well: glucose homeostasis, water intake, gastrointestinal functions, temperature regulation, cardiovascular functions, puberty onset and sleep. These pleiotropic actions underline the physiological relevance of this peptide. Recently, the involvement of NUCB2/<em>nesfatin</em>-<em>1</em> in psychiatric disorders such as anxiety has been investigated giving rise to the speculation that NUCB2/<em>nesfatin</em>-<em>1</em> represents a peptidergic link between eating and anxiety/depression disorders.

The present review focuses on adipocytes-released peptides known to be involved in the control of gastrointestinal motility, acting both centrally and peripherally. Thus, four peptides have been taken into account: leptin, adiponectin, <em>nesfatin</em>-<em>1</em>, and apelin. The discussion of the related physiological or pathophysiological roles, based on the most recent findings, is intended to underlie the close interactions among adipose tissue, central nervous system, and gastrointestinal tract. The better understanding of this complex network, as gastrointestinal motor responses represent peripheral signals involved in the regulation of food intake through the gut-brain axis, may also furnish a cue for the development of either novel therapeutic approaches in the treatment of obesity and eating disorders or potential diagnostic tools.

Background & aims: Overweight and obese individuals show changes in mechanisms related to appetite due to several factors, including excess fat and gut microbiota imbalance. Probiotics have been presented as a strategy for modulating gut microbiota and regulating these mechanisms. The aim of this systematic review was to assess the effects of probiotics on appetite-related hormones in overweight or obese individuals.

Methods: A systematic review of randomized controlled trials was performed in nine electronic databases (Pubmed, Scopus, Web of Science, Cochrane Controlled Register of Trials, ProQuest Dissertations and Theses, PsycINFO, WHO International Clinical Trials Registry Platform, ClinicalTrials.gov and Open Grey) and in a manual search of studies until March 20, 2020. The risk of bias of each study was appraised using the RoB 2.0 tool. All research stages were carefully based on PRISMA recommendations.

<strong class="sub-title"> Results: </strong> Twenty-four studies (<em>1</em>587 participants) were included in this systematic review. The outcomes related to appetite assessed in the included studies were: leptin, insulin, adiponectin, resistin, <em>nesfatin</em>-<em>1</em>, adropin, omentin-<em>1</em>, GLP-<em>1</em>, GLP-2 and glucagon. Compared to the control group after supplementation, four studies involving 272 participants reported statistically significant reduction in fasting insulin. On the other hand, one study involving 56 participants reported statistically significant increase in adropin and omentin-<em>1</em>.

Conclusions: Probiotics have minimal effects on appetite-related hormones in overweight or obese individuals. However, knowledge in this area is progressing and further studies with a low risk of bias may help to clarify the role of probiotics in appetite control.

Keywords: Adiposity; Appetite; Eating; Gastrointestinal Microbiome; Hormones; Satiety Response.

The nucleus of the solitary tract (NTS) is a medullary integrative center with critical roles in the coordinated control of energy homeostasis. Here, we used whole cell current-clamp recordings on rat NTS neurons in slice preparation to identify the presence of physiologically relevant glucose-sensing neurons. The majority of NTS neurons (n = 8<em>1</em>) were found to be glucose-responsive, with 35% exhibiting a glucose-excited (GE) phenotype (mean absolute change in membrane potential: 9.5 ± <em>1</em>.<em>1</em> mV), and 2<em>1</em>% exhibiting a glucose-inhibited (GI) response (mean: 6.3 ± 0.7 mV). Furthermore, we found glucose-responsive cells are preferentially influenced by the anorexigenic peptide α-melanocyte-stimulating hormone (α-MSH), but not <em>nesfatin</em>-<em>1</em>. Accordingly, alterations in glycemic state have profound effects on the responsiveness of NTS neurons to α-MSH, but not to <em>nesfatin</em>-<em>1</em>. Indeed, NTS neurons showed increasing responsiveness to α-MSH as extracellular glucose concentrations were decreased, and in hypoglycemic conditions, all NTS neurons were depolarized by α-MSH (mean <em>1</em>0.6 ± 3.2 mV; n = 8). Finally, decreasing levels of extracellular glucose correlated with a significant hyperpolarization of the baseline membrane potential of NTS neurons, highlighting the modulatory effect of glucose on the baseline excitability of cells in this region. Our findings reveal individual NTS cells are capable of integrating multiple sources of metabolically relevant inputs, highlight the rapid capacity for plasticity in medullary melanocortin circuits, and emphasize the critical importance of physiological recording conditions for electrophysiological studies pertaining to the central control of energy homeostasis.

The purpose of this study was to determine the level of <em>nesfatin</em>-<em>1</em> (NF-<em>1</em>) in the blood serum of healthy volunteers and patients with rheumatoid arthritis (RA) to establish the threshold for normal values of this parameter and to reveal the relationship between the level of NF-<em>1</em> and clinical manifestations of RA. We examined <em>1</em>70 people, of which <em>1</em><em>1</em>0 patients with RA and 60 donors who made up the comparison group. The mean level of serum <em>nesfatin</em>-<em>1</em> in healthy subjects was 3<em>1</em>.6<em>1</em> ± 3.<em>1</em>7 ng/ml (M ± σ). The level of normal values of <em>nesfatin</em>-<em>1</em> in healthy individuals, defined as M ± 2σ, was from 25.27 to 37.95 ng/ml. These studies showed the relationship between the concentration of NF-<em>1</em> and the severity of clinical manifestations of RA. We found that a higher serum level of NF-<em>1</em> was characteristic of patients with a more severe clinical course of the disease. The data obtained indicate that high level of NF-<em>1</em> positively correlates with higher concentrations of C-reactive protein and ESR. This data indirectly proves the proinflammatory effect of NF-<em>1</em> and confirms the hypothesis about the primary role of systemic inflammation in the pathogenesis of RA.

Nucleobindin <em>1</em> (NUCB<em>1</em>; also known as CALNUC or NUC) is a putative DNA- and calcium-binding protein and exhibits significant structural homology with the protein nucleobindin 2 (NUCB2; also known as <em>nesfatin</em>). While NUCB2 has been mapped in detail in the brain and implicated in the hypothalamic control of energy metabolism, no study has to date addressed the presence of NUCB<em>1</em> in the central nervous system. Here we have explored the expression and distribution of NUCB<em>1</em> in the rat brain and spinal cord, using RT-PCR, immunofluorescence and in situ hybridization. NUCB<em>1</em> mRNA and protein was found to be present in all brain regions, extending to the spinal cord and dorsal root ganglia. Double-staining for NUCB<em>1</em> and NeuN, glial fibrillary acidic protein and myelin basic protein revealed that NUCB<em>1</em> is exclusively found in neurons, and not in glial or ependymal cells. Notably, NUCB<em>1</em>-immunoreactivity was observed in all neurons examined, making no distinction between previously identified glutamatergic and GABAergic populations, including those that are known not to stain for NeuN. This included the markedly more restricted population of NUCB2-expressing neurons in the brain. The protein was detected in cell somata and proximal dendrites, but not in axons or terminal structures. Further examination of the subcellular distribution of NUCB<em>1</em> using organelle-specific markers revealed its consistent presence in the Golgi apparatus. These findings identify NUCB<em>1</em> as a novel pan-neuronal marker. Along with the recent demonstration of broad expression of the protein in endocrine cells, the present results suggest that NUCB<em>1</em> may play a role in spatiotemporal calcium handling in signaling cells.

<strong class="sub-title"> Objective: </strong> Acute lung injury (ALI) is the most common complication of sepsis, with rapid onset and high mortality. There is currently no effective treatment for ALI. Therefore, we looked for a good method of treating ALI by studying the effect and mechanism of <em>Nesfatin</em>-<em>1</em> on ALI.

<strong class="sub-title"> Materials and methods: </strong> We used LPS to induce mouse and human alveolar epithelial cell line BEAS-2B to construct an ALI model. Recombinant <em>Nesfatin</em>-<em>1</em> was administered subcutaneously to mice or used to stimulate BEAS-2B cells. We collected mouse bronchoalveolar lavage fluid and mouse lung tissue to detect changes in inflammatory factors and oxidative stress levels. In addition, we examined the expression changes of HMGB<em>1</em> to study the mechanism of <em>Nesfatin</em>-<em>1</em>.

<strong class="sub-title"> Results: </strong> Exogenous <em>Nesfatin</em>-<em>1</em> significantly attenuated LPS-induced ALI and reduced inflammation levels and oxidative stress levels in mouse lung tissue. In cell experiments, <em>Nesfatin</em>-<em>1</em> also reduced inflammation levels and oxidative stress levels in BEAS-2B cells. In addition, <em>Nesfatin</em>-<em>1</em> reduced the expression of HMGB<em>1</em> in mouse lung tissues and BEAS-2B cells, and decreased the activity of p38MAPK and NF-κB signaling pathways in the inflammation-related pathway downstream of HMGB<em>1</em>. However, after overexpression of HMGB<em>1</em>, the therapeutic effect of <em>Nesfatin</em>-<em>1</em> on ALI was attenuated.

<strong class="sub-title"> Conclusions: </strong> <em>Nesfatin</em>-<em>1</em> regulates the expression of HMGB<em>1</em> in alveolar epithelial cells. By reducing the expression of HMGB<em>1</em>, <em>Nesfatin</em>-<em>1</em> can reduce the inflammation-related signaling pathway downstream of HMGB<em>1</em> to reduce the level of inflammation and oxidative stress in alveolar epithelial cells, thereby alleviating ALI.

OBJECTIVE

<em>Nesfatin</em>-<em>1</em>, belonging to adipokine family, serves as an anti-inflammatory mediator. We performed this investigation to evaluate the relation between serum and vitreous <em>nesfatin</em>-<em>1</em> concentrations with diabetic retinopathy (DR).

METHODS

This study was performed in a population of <em>1</em>89 diabetic patients and 48 control subjects. Diabetic patients were then divided into diabetic patients without DR, non-proliferative diabetic retinopathy (NPDR) patients, and proliferative diabetic retinopathy (PDR) patients.

RESULTS

Serum and vitreous <em>nesfatin</em>-<em>1</em> concentrations were significantly lower in the diabetic patients than in the controls. NPDR patients had reduced vitreous <em>nesfatin</em>-<em>1</em> concentrations compared with patients without DR. In addition, there were significantly lower serum and vitreous <em>nesfatin</em>-<em>1</em> concentrations in PDR patients compared with the other three groups. Pearson correlation analysis showed that serum <em>nesfatin</em>-<em>1</em> was negatively correlated with body mass index and fasting plasma glucose in diabetic patients.

CONCLUSIONS

Serum and vitreous <em>nesfatin</em>-<em>1</em> concentrations were negatively correlated with DR.

Metabolic syndrome is associated with a group of conditions abdominal obesity, high triglyceride levels, reduction in low-density lipoprotein, increased blood pressure, and increased fasting blood glucose. Hence, it poses a risk for type 2 diabetes and cardiovascular diseases. The prevalence of metabolic syndrome increases with age. <em>Nesfatin</em>-<em>1</em>, which affects different systems, has recently been discovered as a regulatory peptide molecule. With the discovery of <em>nesfatin</em>-<em>1</em>, it has been reported to inhibit the intake of nutrients and have significant regulatory effects on energy metabolism. As <em>nesfatin</em>-<em>1</em> is present in both central and peripheral tissues, it is thought to have many functions. In addition to its suppressive effect on food intake, <em>nesfatin</em>-<em>1</em> has also been reported to have an effect on the blood glucose level for regulating cardiac functions and affecting obesity by providing weight loss. Considering the effects of <em>nesfatin</em>-<em>1</em>, it may be associated with metabolic syndrome.

<AbstractText>In Parkinson's disease (PD), oxidative stress plays a substantial role in degeneration of dopaminergic neurons at the substantia nigra. Recent reports describe <em>nesfatin</em>-<em>1</em> and glucagon-like peptide-<em>1</em> (GLP-<em>1</em>) as molecules with neuroprotective property that relieve oxidative stress. In this study, we aimed to determine the blood levels of <em>nesfatin</em>-<em>1</em>, GLP-<em>1</em> and oxidative stress status in patients with PD.</AbstractText><AbstractText>Forty patients with PD, followed-up at the Department of Neurology of Mugla Sitki Kocman University Training and Research Hospital, were enrolled, as well as 40 age- and sex-matched participants as a control group. We determined and compared <em>nesfatin</em>-<em>1</em>, GLP-<em>1</em>, total antioxidant status (TAS), and total oxidant status (TOS) levels in patients with PD and control group.</AbstractText><AbstractText>The mean GLP-<em>1</em> and <em>nesfatin</em>-<em>1</em> values of patients with PD were lower than those of the control group, whereas their mean TOS value was higher. The mean TAS values, on the other hand, did not reveal any significant difference between the patient and the control groups.</AbstractText><AbstractText>The lower <em>nesfatin</em>-<em>1</em> and GLP-<em>1</em> levels, in addition to higher TOS levels, in patients with PD compared to those of control group suggest that the neuroprotective effects of these molecules might be related to the oxidative processes. Further studies are required to search for the impact of abovenamed molecules on the treatment option and the likelihood that they may slow down disease progression.</AbstractText>

Obesity and hyper-intestinal permeability are interconnected. This study is designed to evaluate the ability of <i>Mangifera indica</i> seed kernel extract (MESK) in restoring the intestinal barrier and preventing obesity and associated metabolic complications in a high-fat diet-induced obese mouse model. Four groups of Swiss albino mice: (<em>1</em>) normal diet (ND), (2) high-fat diet (HFD), (3) HFD + Orlistat (<em>1</em>00 µg/kg), and (4) HFD + MESK (75 µg/kg), were used to monitor various biochemical parameters associated with metabolic syndrome (glucose, total cholesterol, triglycerides) and body weight in an eight-week-long study. In vivo intestinal permeability was determined by the FITC-dextran method. Interestingly, MESK significantly reduced HFD-induced body weight gain, hepatic lipid accumulation, hepatic fibrosis, hyperglycemia, and dyslipidemia. Additionally, MESK treatment restored the expression of tight junction protein Zonula Occludens-<em>1</em> (ZO-<em>1</em>) and Claudin-<em>1</em> and hence prevented increased intestinal permeability induced by a high-fat diet. Moreover, it also increased the expression of potent satiety molecule <em>Nesfatin</em>-<em>1</em> in the mouse jejunum. Our results, for the first time, establish MESK as a nutraceutical which prevents disruption of the intestinal barrier and thereby intercepts the adverse consequences of compromised intestinal permeability such as obesity, hyperglycemia, dyslipidemia, and systemic inflammation.

<strong class="sub-title"> Keywords: </strong> gut barrier; hepatic fibrosis; metabolic syndrome; nesfatin-<em>1</em>; tight junction.

<em>Nesfatin</em>-<em>1</em> is produced in the periphery and in the brain where it has been demonstrated to regulate appetite, stress hormone secretion, and cardiovascular function. The anorexigenic action of central <em>nesfatin</em>-<em>1</em> requires recruitment of neurons producing the melanocortins and centrally projecting oxytocin (OT) and corticotropin-releasing hormone (CRH) neurons. We previously have shown that two components of this pathway, the central melanocortin and oxytocin systems, contribute to the hypertensive action of <em>nesfatin</em>-<em>1</em> as well. We hypothesized that the cardiovascular effect of <em>nesfatin</em>-<em>1</em> also was dependent on activation of neurons expressing CRH receptors, and that the order of activation of the melanocortin-CRH-oxytocin circuit was preserved for both the anorexigenic and hypertensive actions of the peptide. Pretreatment of male rats with the CRH-2 receptor antagonist astressin2B abrogated <em>nesfatin</em>-<em>1</em>-induced increases in mean arterial pressure (MAP). Furthermore, the hypertensive action of CRH was blocked by pretreatment with an oxytocin receptor antagonist ornithine vasotocin (OVT), indicating that the hypertensive effect of <em>nesfatin</em>-<em>1</em> may require activation of oxytocinergic (OTergic) neurons in addition to recruitment of CRH neurons. Interestingly, we found that the hypertensive effect of α-melanocyte stimulating hormone (α-MSH) itself was not blocked by either astressin2B or OVT. These data suggest that while α-MSH-producing neurons are part of a core melanocortin-CRH-oxytocin circuit regulating food intake, and a subpopulation of melanocortin neurons activated by <em>nesfatin</em>-<em>1</em> do mediate the hypertensive action of the peptide, α-MSH can signal independently from this circuit to increase MAP.

Heterotopic ossification (HO) is a pathological condition involved in tendinopathy. Adipokines are known to play a key role in HO of tendinopathy. <em>Nesfatin</em>-<em>1</em>, an 82-amino acid adipokine is closely reportedly associated with diabetes mellitus (DM), which, in turn, is closely related to tendinopathy. In the present study, we aimed to investigate the effects of <em>nesfatin</em>-<em>1</em> on the osteogenic differentiation of tendon-derived stem cells (TDSCs) and the pathogenesis of tendinopathy in rats. <i>In vitro</i>, TDSCs were incubated in osteogenic induction medium for <em>1</em>4 days with different <em>nesfatin</em>-<em>1</em> concentration. <i>In vivo</i>, Sprague Dawley rats underwent Achilles tenotomy to evaluate the effect of <em>nesfatin</em>-<em>1</em> on tendinopathy. Our results showed that the expression of <em>nesfatin</em>-<em>1</em> expression in tendinopathy patients was significantly higher than that in healthy subjects. <em>Nesfatin</em>-<em>1</em> affected the cytoskeleton and reduced the migration ability of TDSCs <i>in vitro</i>. Furthermore, <em>nesfatin</em>-<em>1</em> inhibited the expression of <i>Scx</i>, <i>Mkx</i>, and <i>Tnmd</i> and promoted the expression of osteogenic genes, such as <i>COL<em>1</em>a<em>1</em></i>, <i>ALP</i>, and RUNX2; these results suggested that <em>nesfatin</em>-<em>1</em> inhibits cell migration, adversely impacts tendon phenotype, promotes osteogenic differentiation of TDSCs and the pathogenesis of HO in rat tendons. Moreover, we observed that <em>nesfatin</em>-<em>1</em> suppressed autophagy and activated the mammalian target of rapamycin (mTOR) pathway both <i>in vitro</i> and <i>in vivo</i>. The suppression of the mTOR pathway alleviated <em>nesfatin</em>-<em>1</em>-induced HO development in rat tendons. Thus, <em>nesfatin</em>-<em>1</em> promotes the osteogenic differentiation of TDSC and the pathogenesis of HO in rat tendons via the mTOR pathway; these findings highlight a new potential therapeutic target for tendinopathy.

<strong class="sub-title"> Keywords: </strong> mTOR pathway; <em>nesfatin</em>-<em>1</em>; osteogenic tendon differentiation; tendinopathy; tendon-derived stem cells.

<em>Nesfatin</em>-<em>1</em> (Nesf-<em>1</em>) is an anorexigenic peptide involved in the regulation of homeostatic feeding. Nesf-<em>1</em> is expressed in the central nervous system and other organs, including pancreas, where it promotes the release of insulin from β-cells. This raises the possibility that Nesf-<em>1</em> dysfunction could be involved in metabolic disorders, particularly in type 2 diabetes mellitus (T2D). Recently, it has been discovered that dolphins can be a natural animal model that fully replicates human T2D, due to its prolonged glucose tolerance curve and maintenance of a state of hyperglycemia similar to human T2D during fasting. This correspondence suggests that dolphins may be a suitable model for investigating physiological and pathological metabolic disorders. Here, we have characterized Nesf-<em>1</em> distribution in the pancreas of the common bottlenose dolphin (<i>Tursiops truncatus</i>) and measured plasmatic levels of Nesf-<em>1</em> and glucose during fasting and post-prandial states. The <i>Mediterranean Marine Mammal Tissue Bank</i> (MMMTB) of the University of Padova provided us with pancreas samples, derived from four animals, and plasma samples, collected before and after the main meal. Interestingly, our results showed that Nesf-<em>1</em>-immunoreactive cells were distributed in Langerhans islets, co-localized with glucagon in α-cells. Similar to humans, dolphin plasma Nesf-<em>1</em> concentration doesn't show a statistically significant difference when comparing fasting and post-prandial states. On the other hand, blood glucose levels were significantly higher before than after the main meal. Our data provide a comparative analysis for further studies on the involvement of Nesf-<em>1</em> in mammalian metabolic disorders.

Resveratrol (RES) is a polyphenolic compound, and our previous results have demonstrated its neuroprotective effect in a series of animal models. The aim of this study was to investigate its potential effect on a nonalcoholic fatty liver disease (NAFLD) rat model. The parameters of liver function and glucose and lipid metabolism were measured. Behavior performance was observed via the open field test (OFT), the sucrose preference test (SPT), the elevated plus maze (EPM), the forced swimming test (FST), and the Morris water maze (MWM). The protein expression levels of Copine 6, p-catenin, catenin, p-glycogen synthase kinase-3beta (GSK3β), GSK3β, and cyclin D<em>1</em> in the hippocampus and prefrontal cortex (PFC) were detected using Western blotting. The results showed that RES could reverse <em>nesfatin</em>-<em>1</em>-related impairment of liver function and glucolipid metabolism, as indicated by the decreased plasma concentrations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin (IBIL), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), glucose, insulin, and <em>nesfatin</em>-<em>1</em>; increase the plasma level of high-density lipoprotein cholesterol (HDL-C); and reduce hepatocyte steatosis in NAFLD rats. Although there was no significant difference among groups with regard to performance in the OFT, EPM, and FST tasks, RES-treated NAFLD rats showed an increased sucrose preference index in the SPT and improved learning and memory ability in the MWM task. Furthermore, the imbalanced protein expression levels of Copine 6, p-catenin, and p-GSK3β in the hippocampus and PFC of NAFLD rats were also restored to normal by treatment with RES. These results suggested that four consecutive weeks of RES treatment not only ameliorated glucolipid metabolic impairment and liver dysfunction in the NAFLD rat model but also mitigated the attendant behavioral and cognitive impairments. In addition to the mediating role of <em>nesfatin</em>-<em>1</em>, the mechanism underlying the therapeutic effect of RES on NAFLD might be associated with its ability to regulate the imbalanced expression level of Copine 6 and the Wnt signaling pathway in the hippocampus and PFC.

<em>Nesfatin</em>-<em>1</em> is an 82 amino acid peptide that has been involved in a wide variety of physiological functions in both mammals and fish. This study aimed to elucidate the role of <em>nesfatin</em>-<em>1</em> on rainbow trout food intake, and its putative effects on glucose and fatty acid sensing systems. Intracerebroventricular administration of 25 ng/g <em>nesfatin</em>-<em>1</em> resulted in a significant inhibition of appetite, likely mediated by the activation of central POMC and CART. <em>Nesfatin</em>-<em>1</em> stimulated the glucosensing machinery (changes in sglt<em>1</em>, g6pase, gsase, and gnat3 mRNA expression) in the hindbrain and hypothalamus. Central fatty acid sensing mechanisms were unaltered by <em>nesfatin</em>-<em>1</em>, but this peptide altered the expression of mRNAs encoding factors regulating lipid metabolism (fat/cd36, acly, mcd, fas, lpl, pparα, and pparγ), suggesting that <em>nesfatin</em>-<em>1</em> promotes lipid accumulation in neurons. In the liver, intracerebroventricular <em>nesfatin</em>-<em>1</em> treatment resulted in decreased capacity for glucose use and lipogenesis, and increased the potential of fatty acid oxidation. Altogether, the present results demonstrate that <em>nesfatin</em>-<em>1</em> is involved in the homeostatic regulation of food intake and metabolism in fish.

<em>Nesfatin</em>-<em>1</em>, a newly identified energy-regulating peptide, is widely expressed in the central and peripheral tissues, and has a variety of physiological activities. A large number of recent studies have shown that <em>nesfatin</em>-<em>1</em> exhibits antioxidant, anti-inflammatory, and anti-apoptotic properties and is involved in the occurrence and progression of various diseases. This review summarizes current data focusing on the therapeutic effects of <em>nesfatin</em>-<em>1</em> under different pathophysiological conditions and the mechanisms underlying its antioxidant, anti-inflammatory, and anti-apoptotic activities.

<strong class="sub-title"> Keywords: </strong> anorexigenic; anti-apoptotic; anti-inflammatory; antioxidant; <em>nesfatin</em>-<em>1</em>.

OBJECTIVE

To investigate changes in body mass index (BMI) and <em>nesfatin</em>-<em>1</em> levels in patients with morbid obesity who had undergone laparoscopic sleeve gastrectomy (LSG).

METHODS

Blood samples were collected from, and the BMI calculated of 30 morbidly obese patients pre-surgery and at 3 and 6 months post-surgery. Nesfatin-<em>1</em> hormone levels were measured using enzyme-linked immunosorbent assay (ELISA). Descriptive statistical analysis of the data was performed using Kruskal-Wallis variance analysis, one-way ANOVA, and the Bonferroni-Dunn test. The correlations between continuous variables not displaying normal distribution and those displaying normal distributions were analyzed using the Spearman correlation test and the Pearson correlation test, respectively.

RESULTS

The mean age of the 30 patients was 4<em>1</em>.23 ± <em>1</em>0.37 years. The mean BMI values (kg/m2) were 49.30 ± 7.92, 39,48 ± 7.32, and 34.39 ± 7.56 presurgery, three months post-surgery, and six months post-surgery, respectively (p < 0.00<em>1</em>). Mean <em>nesfatin</em>-<em>1</em> levels (ng/ml) were 22.80 ± <em>1</em>4.<em>1</em>6, 60.23 ± 52.92, and 96.99 ± 40.20 presurgery, three months post-surgery, and six months post-surgery, respectively (p < 0.00<em>1</em>). The postoperative months 3 and 6 BMI values were significantly lower than the preoperative BMI value and the postoperative month 6 BMI value was significantly lower than the postoperative month 3 BMI value (p < 0.00<em>1</em>). The postoperative months 3 and 6 <em>nesfatin</em>-<em>1</em> levels were significantly higher than the preoperative <em>nesfatin</em>-<em>1</em> levels. A negative correlation was found between age and preoperative <em>nesfatin</em>-<em>1</em> values (p = 0.00<em>1</em>, r = -0.0557).

CONCLUSIONS

Observation of significant increases in <em>nesfatin</em>-<em>1</em> hormone levels in morbidly obese patients who had undergone LSG indicate that <em>nesfatin</em>-<em>1</em> has important anorexigenic effects post-surgery and may be an important component of future obesity treatments.

<em>Nesfatin</em>-<em>1</em> is a peptide derived from nucleobindin-2 and involved in the regulation of food intake and hyperglycemia. <em>Nesfatin</em>-<em>1</em> is a recently described anorexigenic peptide, which may be involved in weight loss, malnutrition, and the regulation of appetite. <em>Nesfatin</em>-<em>1</em> has an effect on the regulation of glucose homeostasis as well as that of food intake. The aim of this article is to bring a different perspective to the readers on the effects of <em>nesfatin</em>-<em>1</em> on food intake and hyperglycemia. The central injection of <em>nesfatin</em>-<em>1</em> may produce anorexigenic effects. The circulating level of <em>nesfatin</em>-<em>1</em> is thought to be regulated by nutritional status. Long-term changes in body weight can affect <em>nesfatin</em>-<em>1</em> levels. In overweight and obese individuals, <em>nesfatin</em>-<em>1</em> levels may increase. <em>Nesfatin</em>-<em>1</em> is synthesized in the hypothalamic appetite control regions. <em>Nesfatin</em>-<em>1</em> levels may decrease in individuals with diabetes but may increase in those with impaired glucose tolerance. <em>Nesfatin</em>-<em>1</em> may have a reducing effect on glucose levels. In addition, an increase in glucose levels may lead to an increase in the release of <em>nesfatin</em>-<em>1</em> from pancreatic cells. Injection of <em>nesfatin</em>-<em>1</em> can prevent hepatic glucose formation and stimulate glucose uptake. Reduction of hypothalamic <em>nesfatin</em>-<em>1</em> levels increases hepatic glucose flow and decreases glucose uptake from peripheral tissues. In the light of all this information, <em>nesfatin</em>-<em>1</em> may be considered to be an important regulator in the metabolic process. <em>Nesfatin</em>-<em>1</em> appears to be able to contribute to the treatment of obesity and diabetes because of its anorexigenic and antihyperglycemic effects. Key teaching points <em>Nesfatin</em>-<em>1</em> is a anorexigenic peptide. <em>Nesfatin</em>-<em>1</em> is derived from Nucleobindin-2. Nucleobindin-2 mRNA is produced in different areas of the brain. <em>Nesfatin</em>-<em>1</em> is an inhibitory factor on appetite and a regulator of energy balance that reduces the increase in body weight.

<em>Nesfatin</em>-<em>1</em> is a novel anorexigenic peptide that regulates feeding behavior and gastrointestinal function. This study aimed to explore the effects of <em>nesfatin</em>-<em>1</em> on gastric distension (GD)-sensitive neurons in the basomedial amygdala (BMA) and the potential mechanism for <em>nesfatin</em>-<em>1</em> to regulate gastric motility through the arcuate nucleus (Arc). The projection of nerve fiber and expression of <em>nesfatin</em>-<em>1</em> were observed by retrograde tracing and fluo-immunohistochemistry staining. Single-unit discharges in the BMA were recorded extracellularly, and gastric motility in conscious rats was monitored. Results showed that the <em>nesfatin</em>-<em>1</em>/ fluorogold-double labeled neurons were observed in the Arc. <em>Nesfatin</em>-<em>1</em> could excite the GD-excitatory neurons and inhibit the GD-inhibitory neurons in the BMA. Gastric motility and gastric emptying were significantly reduced by <em>nesfatin</em>-<em>1</em> administration to the BMA in a dose-dependent manner. The effects of <em>nesfatin</em>-<em>1</em> could be partially blocked by melanocortin 3/4 receptors antagonist, SHU9<em>1</em><em>1</em>9. Electrical stimulation of the Arc significantly excited the response of GD neurons to <em>nesfatin</em>-<em>1</em> and promoted gastric motility. Nevertheless, these effects could be mitigated by pretreatment with anti-NUCB2/<em>nesfatin</em>-<em>1</em> antibody. It is suggested that <em>nesfatin</em>-<em>1</em> in the BMA plays an important role in decreasing gastric motility and the Arc may be involved in this regulation process.