Differential changes in appetite hormones post-prandially based on menstrual cycle phase and oral contraceptive use: A preliminary study.

This was a preliminary study that examined whether appetite regulation is altered during the menstrual cycle or with oral contraceptives. Ten naturally cycling females (NON-USERS) and nine tri-phasic oral contraceptive using females (USERS) completed experimental sessions during each menstrual phase (follicular phase: FP; ovulatory phase: OP; luteal phase: LP). Appetite perceptions and blood samples were obtained fasted, 30, 60, and 90 min post-prandial to measure acylated ghrelin, active glucagon-like peptide-1 (GLP-1), and total peptide tyrosine tyrosine (PYY). Changes were considered important if p < 0.100 and the effect size was ≥medium. There appeared to be a three-way (group x phase x time) interaction for acylated ghrelin where concentrations appeared to be greater in USERS versus NON-USERS during the OP 90-min post-prandial and during the LP fasted, and 90-min post-prandial. In USERS, ghrelin appeared to be greater 90-min post-prandial in the OP versus the FP with no other apparent differences between phases. There were no apparent differences between phases in NON-USERS. There appeared to be a three-way interaction for PYY where concentrations appeared to be greater in USERS during the FP 60-min post-prandial and during the OP 30-min post-prandial. In USERS PYY appeared to be greater 60-min post-prandial during the OP versus the LP with no other apparent differences. There were no apparent differences between phases in NON-USERS. There appeared to be no effect of group or phase on GLP-1, or appetite perceptions. These data demonstrate small effects of menstrual cycle phase and oral contraceptive use on the acylated ghrelin and total PYY response to a standardized meal, with no effects on active GLP-1 or perceived appetite, though more work with a large sample size is necessary.

The Influence of Acute and Chronic Exercise on Appetite and Appetite Regulation in Patients with Prediabetes or Type 2 Diabetes Mellitus-A Systematic Review.

This systematic review aims to analyze the effects of acute and chronic exercise on appetite and appetite regulation in patients with abnormal glycemic control. PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials were searched for eligible studies. The included studies had to report assessments of appetite (primary outcome). Levels of appetite-regulating hormones were analyzed as secondary outcomes (considered, if additionally reported). Seven studies with a total number of 211 patients with prediabetes or type 2 diabetes mellitus (T2DM) met the inclusion criteria. Ratings of hunger, satiety, fullness, prospective food consumption, nausea, and desire to eat, as well as levels of (des-)acylated ghrelin, glucagon-like peptide 1, glucose-dependent insulinotropic peptide, pancreatic polypeptide, peptide tyrosine tyrosine, leptin, and spexin were considered. Following acute exercise, the effects on appetite (measured up to one day post-exercise) varied, while there were either no changes or a decrease in appetite ratings following chronic exercise, both compared to control conditions (without exercise). These results were accompanied by inconsistent changes in appetite-regulating hormone levels. The overall risk of bias was low. The present results provide more evidence for an appetite-reducing rather than an appetite-increasing effect of (chronic) exercise on patients with prediabetes or T2DM. PROSPERO ID: CRD42023459322.

Gut hormones and appetite regulation.

PURPOSE OF REVIEW: Various gut hormones interact with the brain through delicate communication, thereby influencing appetite and subsequent changes in body weight. This review summarizes the effects of gut hormones on appetite, with a focus on recent research. RECENT FINDINGS: Ghrelin is known as an orexigenic hormone, whereas glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), cholecystokinin (CCK), postprandial peptide YY (PYY), and oxyntomodulin (OXM) are known as anorexigenic hormones. Recent human studies have revealed that gut hormones act differently in various systems, including adipose tissue, beyond appetite and energy intake, and even involve in high-order thinking. Environmental factors including meal schedule, food contents and quality, type of exercise, and sleep deprivation also play a role in the influence of gut hormone on appetite, weight change, and obesity. Recently published studies have shown that retatrutide, a triple-agonist of GLP-1, GIP, and glucagon receptor, and orforglipron, a GLP-1 receptor partial agonist, are effective in weight loss and improving various metabolic parameters associated with obesity. SUMMARY: Various gut hormones influence appetite, and several drugs targeting these receptors have been reported to exert positive effects on weight loss in humans. Given that diverse dietary and environmental factors affect the actions of gut hormones and appetite, there is a need for integrated and largescale long-term studies in this field.

Gengricin®: A Nutraceutical Formulation for Appetite Control and Therapeutic Weight Management in Adults Who Are Overweight/Obese.

In the field of nutritional science and metabolic disorders, there is a growing interest in natural bitter compounds capable of interacting with bitter taste receptors (TAS2Rs) useful for obesity management and satiety control. This study aimed to evaluate the effect of a nutraceutical formulation containing a combination of molecules appropriately designed to simultaneously target and stimulate these receptors. Specifically, the effect on CCK release exerted by a multi-component nutraceutical formulation (Cinchona bark, Chicory, and Gentian roots in a 1:1:1 ratio, named Gengricin®) was investigated in a CaCo-2 cell line, in comparison with Cinchona alone. In addition, these nutraceutical formulations were tested through a 3-month randomized controlled trial (RCT) conducted in subjects who were overweight-obese following a hypocaloric diet. Interestingly, the Gengricin® group exhibited a significant greater weight loss and improvement in body composition than the Placebo and Cinchona groups, indicating its effectiveness in promoting weight regulation. Additionally, the Gengricin® group reported higher satiety levels and a significant increase in serum CCK levels, suggesting a physiological basis for the observed effects on appetite control. Overall, these findings highlight the potential of natural nutraceutical strategies based on the combination of bitter compounds in modulating gut hormone release for effective appetite control and weight management.

Low- and high-load resistance training exercise to volitional fatigue generate exercise-induced appetite suppression.

Research on exercise-induced appetite suppression often does not include resistance training (RT) exercise and only compared matched volumes. PURPOSE: To compare the effects of low-load and high-load RT exercise completed to volitional fatigue on appetite-regulation. METHODS: 11 resistance-trained males (24 ± 2 y) completed 3 sessions in a crossover experimental design: 1) control (CTRL); 2) RT exercise at 30% 1-repetition maximum (RM); and 3) RT exercise at 90% 1-RM. RT sessions consisted of 3 sets of 5 exercises completed to volitional fatigue. Acylated ghrelin, active glucagon-like peptide-1 (GLP-1), active peptide tyrosine (PYY), lactate, and subjective appetite perceptions were measured pre-exercise, 0-, 60-, and 120-min post-exercise. Energy intake was recorded the day before, of, and after each session. RESULTS: Lactate was elevated following both 30% (0-, 60-, 120-min post-exercise) and 90% (0-, 60-min post-exercise; P < 0.001, d > 3.92) versus CTRL, with 30% greater than 90% (0-min post-exercise; P = 0.011, d = 1.14). Acylated ghrelin was suppressed by 30% (P < 0.007, d > 1.22) and 90% (P < 0.028, d > 0.096) post-exercise versus CTRL, and 30% suppressed concentrations versus 90% (60-min post-exercise; P = 0.032, d = 0.95). There was no effect on PYY (P > 0.171, ηp2 <0.149) though GLP-1 was greater at 60-min post-exercise in 90% (P = 0.052, d = 0.86) versus CTRL. Overall appetite was suppressed 0-min post-exercise following 30% and 90% versus CTRL (P < 0.013, d > 1.10) with no other differences (P > 0.279, d < 0.56). There were no differences in energy intake (P > 0.101, ηp2 <0.319). CONCLUSIONS: RT at low- and high-loads to volitional fatigue induced appetite suppression coinciding with changes in acylated ghrelin though limited effects on anorexigenic hormones or free-living energy intake were present.

Sex-Specific Appetite Regulation of Lipocalin-2 in High-Fat-Diet-Induced Obese Mice.

INTRODUCTION: Lipocalin 2 (Lcn2) is a key factor in appetite suppression. However, the effect of Lcn2 on appetite in terms of sex differences has not been thoroughly studied. METHODS: Young (3-month-old) whole-body Lcn2 knockout (Lcn2-/-) mice were fed a normal diet (ND) or high-fat diet (HFD) for 8 weeks to investigate obesity, food intake, serum metabolism, hepatic lipid metabolism, and regulation of gastrointestinal hormones. RESULTS: Lcn2 deficiency significantly increased the body weight and food intake of male mice when fed ND instead of HFD and females when fed HFD but not ND. Compared to wild-type (WT) male mice, the adiponectin level and phosphorylated form of adenosine 5'-monophosphate-activated protein kinase (AMPK) in the hypothalamus were both increased in ND-fed Lcn2-/- male mice but decreased in HFD-fed Lcn2-/- male mice. However, in female mice, adiponectin and its energy metabolism pathway were not altered. Instead, estradiol was found to be substantially higher in ND-fed Lcn2-/- female mice and substantially lower in HFD-fed Lcn2-/- female mice compared with WT female mice. Estradiol alteration also caused similar changes in ERα in the hypothalamus, leading to changes in the PI3K/AKT energy metabolism pathway. It suggested that the increased appetite caused by Lcn2 deficiency in male mice may be due to increased adiponectin expression and promotion of AMPK phosphorylation, while in female mice it may be related to the decrease of circulating estradiol and the inhibition of the hypothalamic ERα/PI3K/AKT energy metabolism pathway. CONCLUSION: Lcn2 plays in a highly sex-specific manner in the regulation of appetite in young mice.

Sequential appetite suppression by oral and visceral feedback to the brainstem.

The termination of a meal is controlled by dedicated neural circuits in the caudal brainstem. A key challenge is to understand how these circuits transform the sensory signals generated during feeding into dynamic control of behaviour. The caudal nucleus of the solitary tract (cNTS) is the first site in the brain where many meal-related signals are sensed and integrated1-4, but how the cNTS processes ingestive feedback during behaviour is unknown. Here we describe how prolactin-releasing hormone (PRLH) and GCG neurons, two principal cNTS cell types that promote non-aversive satiety, are regulated during ingestion. PRLH neurons showed sustained activation by visceral feedback when nutrients were infused into the stomach, but these sustained responses were substantially reduced during oral consumption. Instead, PRLH neurons shifted to a phasic activity pattern that was time-locked to ingestion and linked to the taste of food. Optogenetic manipulations revealed that PRLH neurons control the duration of seconds-timescale feeding bursts, revealing a mechanism by which orosensory signals feed back to restrain the pace of ingestion. By contrast, GCG neurons were activated by mechanical feedback from the gut, tracked the amount of food consumed and promoted satiety that lasted for tens of minutes. These findings reveal that sequential negative feedback signals from the mouth and gut engage distinct circuits in the caudal brainstem, which in turn control elements of feeding behaviour operating on short and long timescales.

Obesity as a Neuroendocrine Disorder.

Obesity is one of the most prevalent diseases in the world. Based on hundreds of clinical and basic investigations, its etiopathogenesis goes beyond the simple imbalance between energy intake and expenditure. The center of the regulation of appetite and satiety lies in the nuclei of the hypothalamus where peripheral signals derived from adipose tissue (e.g., leptin), the gastrointestinal tract, the pancreas, and other brain structures, arrive. These signals are part of the homeostatic control system (eating to survive). Additionally, a hedonic or reward system (eating for pleasure) is integrated into the regulation of appetite. This reward system consists of a dopaminergic circuit that affects eating-related behaviors influencing food preferences, food desires, gratification when eating, and impulse control to avoid compulsions. These systems are not separate. Indeed, many of the hormones that participate in the homeostatic system also participate in the regulation of the hedonic system. In addition, factors such as genetic and epigenetic changes, certain environmental and sociocultural elements, the microbiota, and neuronal proinflammatory effects of high-energy diets also contribute to the development of obesity. Therefore, obesity can be considered a complex neuroendocrine disease, and all of the aforementioned components should be considered for the management of obesity.

High Intensity Interval Training can Ameliorate Hypothalamic Appetite Regulation in Male Rats with Type 2 Diabetes: The Role of Leptin.

Disruption of leptin (LEP) signaling in the hypothalamus caused by type 2 diabetes (T2D) can impair appetite regulation. The aim of this study was to investigate whether the improvement in appetite regulation induced by high-intensity interval training (HIIT) in rats with T2D can be mediated by LEP signaling. In this study, 20 male Wister rats were randomly assigned to one of four groups: CO (non-type 2 diabetes control), T2D (type 2 diabetes), EX (non-type 2 diabetes exercise), and T2D + EX (type 2 diabetes + exercise).To induce T2D, a combination of a high-fat diet for 2 months and a single dose of streptozotocin (35 mg/kg) was administered. Rats in the EX and T2D + EX groups performed 4-10 intervals of treadmill running at 80-100% of their maximum velocity (Vmax). Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), serum levels of insulin (INS) and LEP (LEPS) as well as hypothalamic expression of LEP receptors (LEP-R), Janus kinase 2 (JAK-2), signal transducer and activator of transcription 3 (STAT-3), neuropeptide Y (NPY), agouti-related protein (AGRP), pro-opiomelanocortin cocaine (POMC), amphetamine-related transcript (CART), suppressor of cytokine signaling (SOCS3), forkhead box protein O1 (FOXO1) were assessed. ANOVA and Tukey post hoc tests were used to compare the results between the groups. The levels of LEPS and INS, as well as the levels of LEP-R, JAK-2, STAT-3, POMC, and CART in the hypothalamus were found to be higher in the T2D + EX group compared to the T2D group. On the other hand, the levels of HOMA-IR, NPY, AGRP, SOCS3, and FOXO1 were lower in the T2D + EX group compared to the T2D group (P < 0.0001). The findings of this study suggest that HIIT may improve appetite regulation in rats with T2D, and LEP signaling may play a crucial role in this improvement. Graphical abstract (leptin signaling in the hypothalamus), Leptin (LEP), Leptin receptor (LEP-R), Janus kinase 2 (JAK2), Signal transducer and activator of transcription 3 (STAT3), expressing Neuropeptide Y (NPY), Agouti-related protein (AGRP), anorexigenic neurons (expressing pro-opiomelanocortin cocaine (POMC), Amphetamine-related transcript (CART), suppressor of cytokine signaling (SOCS3), forkhead box protein O1 (FOXO1).

Serotonergic regulation of appetite and sodium appetite.

Serotonin is a neurotransmitter that is synthesized and released from the brainstem raphe nuclei to affect many brain functions. It is well known that the activity of raphe serotonergic neurons is changed in response to the changes in feeding status to regulate appetite via the serotonin receptors. Likewise, changes in volume status are known to alter the activity of raphe serotonergic neurons and drugs targeting serotonin receptors were shown to affect sodium appetite. Therefore, the central serotonin system appears to regulate ingestion of both food and salt, although neural mechanisms that induce appetite in response to hunger and sodium appetite in response to volume depletion are largely distinct from each other. In this review, we discuss our current knowledge regarding the regulation of ingestion - appetite and sodium appetite - by the central serotonin system.

Interleukin-6 is not involved in appetite regulation following moderate-intensity exercise in males with normal weight and obesity.

OBJECTIVE: In obesogenic states and after exercise, interleukin (IL)-6 elevations are established, and IL-6 is speculated to be an appetite-regulating mechanism. This study examined the role of IL-6 on exercise-induced appetite regulation in sedentary normal weight (NW) males and those with obesity (OB). METHODS: Nine NW participants and eight participants with OB completed one non-exercise control (CTRL) and one moderate-intensity continuous training (MICT; 60 minutes, 65% V̇O2max ) session. IL-6, acylated ghrelin, active peptide tyrosine-tyrosine3-36 , active glucagon-like peptide-1, and overall appetite perceptions were measured fasted, pre exercise, and 30, 90, and 150 minutes post exercise. RESULTS: Fasted IL-6 concentrations were elevated in OB (p = 0.005, η p 2 = 0.419); however, increases following exercise were similar between groups (p = 0.934, η p 2 = 0.000). Acylated ghrelin was lower in OB versus NW (p < 0.017, d > 0.84), and OB did not respond to MICT (p > 0.512, d < 0.44) although NW had a decrease versus CTRL (p < 0.034, d > 0.61). IL-6 did not moderate/mediate acylated ghrelin release after exercise (p > 0.251). There were no observable effects of MICT on tyrosine-tyrosine3-36 , glucagon-like peptide-1, or overall appetite (p > 0.334, η p 2 < 0.062). CONCLUSIONS: These results suggest that IL-6 is not involved in exercise-induced appetite suppression. Despite blunted appetite-regulatory peptide responses to MICT in participants with OB, NW participants exhibited decreased acylated ghrelin; however, no differences in appetite perceptions existed between CTRL and MICT or NW and OB.

The metabolic interplay between dietary carbohydrate and exercise and its role in acute appetite regulation in males: a randomized controlled study.

An understanding of the metabolic determinants of postexercise appetite regulation would facilitate development of adjunctive therapeutics to suppress compensatory eating behaviours and improve the efficacy of exercise as a weight-loss treatment. Metabolic responses to acute exercise are, however, dependent on pre-exercise nutritional practices, including carbohydrate intake. We therefore aimed to determine the interactive effects of dietary carbohydrate and exercise on plasma hormonal and metabolite responses and explore mediators of exercise-induced changes in appetite regulation across nutritional states. In this randomized crossover study, participants completed four 120 min visits: (i) control (water) followed by rest; (ii) control followed by exercise (30 min at ∼75% of maximal oxygen uptake); (iii) carbohydrate (75 g maltodextrin) followed by rest; and (iv) carbohydrate followed by exercise. An ad libitum meal was provided at the end of each 120 min visit, with blood sample collection and appetite assessment performed at predefined intervals. We found that dietary carbohydrate and exercise exerted independent effects on the hormones glucagon-like peptide 1 (carbohydrate, 16.8 pmol/L; exercise, 7.4 pmol/L), ghrelin (carbohydrate, -48.8 pmol/L; exercise: -22.7 pmol/L) and glucagon (carbohydrate, 9.8 ng/L; exercise, 8.2 ng/L) that were linked to the generation of distinct plasma 1 H nuclear magnetic resonance metabolic phenotypes. These metabolic responses were associated with changes in appetite and energy intake, and plasma acetate and succinate were subsequently identified as potential novel mediators of exercise-induced appetite and energy intake responses. In summary, dietary carbohydrate and exercise independently influence gastrointestinal hormones associated with appetite regulation. Future work is warranted to probe the mechanistic importance of plasma acetate and succinate in postexercise appetite regulation. KEY POINTS: Carbohydrate and exercise independently influence key appetite-regulating hormones. Temporal changes in postexercise appetite are linked to acetate, lactate and peptide YY. Postexercise energy intake is associated with glucagon-like peptide 1 and succinate levels.

Alpha-Melanocyte-Stimulating Hormone-Mediated Appetite Regulation in the Central Nervous System.

Understanding the complex action mechanism of appetite regulation peptides can significantly impact therapeutic options in the treatment of obesity and other metabolic diseases. Hypothalamic alpha-melanocyte-stimulating hormone (α-MSH) is an anorexigenic peptide, closely related to the occurrence of obesity, playing a central role in food intake and energy expenditure. In the central nervous system, α-MSH is cleaved from proopiomelanocortin and then released into different hypothalamic regions to act on melanocortin 3/4 receptor-expressing neurons, lowering food intake, and raising energy expenditure via appetite suppression and sympathetic nervous system. Furthermore, it can increase the transmission of some anorexigenic hormones (e.g., dopamine) and interact with other orexigenic factors (e.g., agouti-related protein, neuropeptide Y) to influence food reward rather than merely feeding behavior. Therefore, α-MSH is a critical node of the hypothalamus in transmitting appetite suppression signals and is a key component of the central appetite-regulating circuits. Herein, we describe the role of α-MSH in appetite suppression in terms of specific receptors, effector neurons, sites of action, and the interaction with other appetite-relative peptides, respectively. We focus on the role of α-MSH in obesity. The status of research on α-MSH-related drugs is also discussed. With the intention of illuminating a new approach for targeting α-MSH in the hypothalamus as a strategy to manage obesity, we hope to further understand the direct or indirect mechanisms by which α-MSH exerts its appetite-regulating effects.

The impact of acute exercise on appetite control: Current insights and future perspectives.

The interaction of exercise with appetite control and energy intake has been widely studied due to the ability of exercise-related energy expenditure to influence energy and substrate balance. Many empirical studies have explored appetite and energy intake responses to acute (single) exercise bouts involving a variety of protocols in diverse populations revealing several consistent trends. The balance of evidence suggests that acute moderate-to-vigorous intensity land-based exercise suppresses subjective appetite feelings and the orexigenic hormone acylated ghrelin and elevates the anorexigenic hormones peptide YY and glucagon-like peptide-1. These perturbations are transient and hormone concentrations usually return to resting values in the hours after exercise without evoking compensatory increases in appetite or energy intake on the same day. This evidence counters the popular assertion that exercise transiently increases appetite and may prompt greater energy intake at subsequent meals. The indifference of the appetite control system to acute exercise-induced energy deficits contrasts with the immediate increases in appetite and energy intake provoked by equivalent diet-induced energy deficits. There is, however, considerable inter-individual variability in subjective appetite and hormonal responses to acute exercise with some individuals experiencing greater exercise-induced appetite suppression than others. Current evidence supports the promotion of exercise as a strategy for inducing a short-term energy deficit but the relevance of this for long-term appetite regulation and the control of body mass remains uncertain.

A gut-brain axis mediates sodium appetite via gastrointestinal peptide regulation on a medulla-hypothalamic circuit.

Salt homeostasis is orchestrated by both neural circuits and peripheral endocrine factors. The colon is one of the primary sites for electrolyte absorption, while its potential role in modulating sodium intake remains unclear. Here, we revealed that a gastrointestinal hormone, secretin, is released from colon endocrine cells under body sodium deficiency and is indispensable for inducing salt appetite. As the neural substrate, circulating secretin activates specific receptors in the nucleus of the solitary tracts, which further activates the downstream paraventricular nucleus of the hypothalamus, resulting in enhanced sodium intake. These results demonstrated a previously unrecognized gut-brain pathway for the timely regulation of sodium homeostasis.

Hormonal Gut-Brain Signaling for the Treatment of Obesity.

The brain, particularly the hypothalamus and brainstem, monitors and integrates circulating metabolic signals, including gut hormones. Gut-brain communication is also mediated by the vagus nerve, which transmits various gut-derived signals. Recent advances in our understanding of molecular gut-brain communication promote the development of next-generation anti-obesity medications that can safely achieve substantial and lasting weight loss comparable to metabolic surgery. Herein, we comprehensively review the current knowledge about the central regulation of energy homeostasis, gut hormones involved in the regulation of food intake, and clinical data on how these hormones have been applied to the development of anti-obesity drugs. Insight into and understanding of the gut-brain axis may provide new therapeutic perspectives for the treatment of obesity and diabetes.

Effects of acute resistance exercise with different loads on appetite, appetite hormones and autonomic nervous system responses in healthy young men.

Although the effect of continuous aerobic exercise on the appetite has been widely explored, the influence of resistance exercise (RE) with different variables, including training loads, training volume, and inter-set rest, on appetite responses requires further investigation. This study examined the importance of training load in RE-induced appetite regulation, with the total training volume and inter-set rest equalized. In total, 11 healthy young men (age = 23 ± 2 years, body mass index = 22 ± 2 kg/m2) were included. Participants completed 3 trials, namely moderate-load RE (MOD; 4 sets of 8 repetitions at 85% 8RM), low-load RE (LOW; 4 sets of 15 repetitions at 45% 8RM), and a control (CON; no exercise), in a randomized, crossover design. Subjective appetite ratings; concentrations of ghrelin, peptide YY (PYY), and lactate; and the autonomic nervous system activity were evaluated before exercise and 1 h after exercise. The hunger and predicted food consumption ratings, and ghrelin concentrations immediately after exercise were significantly lower in the MOD and LOW trials (p < 0.05 vs. CON). The PYY and lactate concentrations immediately after exercise were significantly higher in the MOD and LOW trials (p < 0.05 vs. CON). Heart rate variability recovery was slower in the MOD trial. These findings suggest that both moderate-load and low-load RE at equal training volumes and inter-set rest induce similar responses on hunger suppression and orexigenic signals, except for the slower recovery of autonomic modulation after moderate-load RE. Our results suggest that when individuals aim to potentiate appetite suppression after a bout of RE, both moderate- and low-load RE could be applied.

Brain Related Gut Peptides - A Review.

Gut peptides are small peptides secreted by gut endocrine cells that can modulate the roles and functions of different organs through signaling. Gut peptides can also majorly impact the body's energy homeostasis by regulating appetite and energy metabolism. The gut-brain axis (GBA) is bidirectional communication between the central nervous system (CNS) and the peripheral enteric nervous system. The regulation of appetite acts by hypothalamic neuronal activity. The complex interaction of hedonic and homeostatic factors implicates appetite regulation. In the CNS, the hypothalamus and brainstem have a dominating role in appetite regulation. The arcuate nucleus (ARC) of the hypothalamus plays a vital role in energy homeostasis, while other nuclei also play a role in appetite regulation. The gut conveys peripheral information about energy balance to the brain via gut peptides and receptors for the digestion of food. The varied gut peptides have different actions on appetite regulation.

Possible role of transcription factors (BSX, NKX2.1, IRX3 and SIRT1) in the regulation of appetite in goldfish (Carassius auratus).

The homeobox genes play important roles in the embryonic development of animals. Recent evidence suggests they might also regulate feeding and act as transcription factors of appetite regulators. Examples of these genes are a brain-specific homeobox transcription factor (BSX), NK2 homeobox 1 (NKX2.1) and the Iroquois homeobox 3 (IRX3). Sirtuin1 (SIRT1) acts as a transcription factor for nutrient (e.g. lipid, glucose) homeostasis and responds to stress and nutrient availability, and has been shown to interact with appetite regulators. Very little is known about the role of these genes in the regulation of feeding and nutrient homeostasis in fish. In this study, we assessed the roles of BSX, NKX2.1, IRX3 and SIRT1 in the central regulation of feeding in goldfish by examining their mRNA brain distribution, assessing the effects of fasting on their brain expression and assessing the effects of peripheral injections of cholecystokinin (CCK, a brain-gut peptide), on their brain expression. All genes showed a widespread distribution in the brain, with high levels in the hypothalamus. In both hypothalamus and telencephalon, fasting induced increases in BSX, IRX3 and NKX2.1 expressions but had no effect on SIRT1 expression levels. CCK injections increased hypothalamic expression levels of IRX3 and SIRT1, and telencephalic expression levels of NKX2.1 and SIRT1, with no effect on either hypothalamic BSX or NKX2.1 expression levels or telencephalon BSX or IRX3 expression levels. Our results suggest that, in goldfish as in mammals, central BSX, NKX2.1, IRX3 and SIRT1 are present in regions of the brain regulating feeding, are sensitive to nutrient status and interact with appetite-regulating peptides.