Technical articles
Central–Peripheral Signaling Networks Regulated by Neuropeptides and the Integration of Energy Metabolism
Central–Peripheral Signaling Networks Regulated by Neuropeptides and the Integration of Energy Metabolism
Neuropeptides constitute the central integrative layer of energy homeostasis regulation. The hypothalamus–brainstem network continuously receives signals from the gastrointestinal tract, adipose tissue, pancreas, liver, and circulating nutrient substrates, and in turn reshapes feeding, thermogenesis, glucose homeostasis, and lipid flux through autonomic and neuroendocrine pathways. Accordingly, neuropeptide regulation should be defined as a systemic metabolic network that links central sensing, peripheral execution, and inter-organ information coupling.
Keywords: neuropeptides; central–peripheral signaling network; hypothalamus; brainstem; energy metabolism; feeding regulation; thermogenesis; glucose homeostasis; lipid metabolism; gut–brain axis
I. Research boundaries and system-level positioning of neuropeptide regulation
1.1 Neuropeptide regulation is the central integrative layer for information on energy status
(1) The neuropeptide system undertakes the central decoding of peripheral metabolic information
Under different physiological states such as feeding, fasting, exercise, rest, stress, and sleep, the body continuously generates distinct types of metabolic information, including gastrointestinal satiety signals, energy storage status from adipose tissue, pancreatic secretory status, hepatic substrate output status, and changes in the availability of circulating substrates. The core function of the neuropeptide network is to integrate these signals, which differ in source complexity and time scale, into executable programs for the central nervous system.
(2) The neuropeptide network determines far more than changes in food intake
Functionally, the output of the neuropeptide network extends well beyond increases or decreases in food intake. Its direct targets include feeding motivation, satiety termination, energy expenditure level, sympathetic tone, brown adipose thermogenesis, lipid mobilization, hepatic glucose output, pancreatic hormone secretion, and the switching of metabolic priorities under circadian backgrounds. Thus, neuropeptide regulation is essentially a systemic process of metabolic resource allocation.
1.2 Energy metabolism integration is manifested as multi-organ, multi-level coordination
(1) Energy homeostasis is not merely a simple balance between caloric intake and expenditure
Traditional energy balance emphasizes the quantitative relationship between intake and expenditure. However, under real physiological and pathological conditions, the body must coordinate how substrates are utilized across different organs, how energy is allocated across different time windows, and how efficiently it responds to nutritional fluctuations and environmental stress. The neuropeptide network is one of the major upstream control layers that enables this coordination.
(2) Inter-organ information coupling is a key feature of the neuropeptide system
The gastrointestinal tract provides rapid feedback after feeding events, adipose tissue reflects long-term energy storage background, the pancreas transmits signals related to anabolic metabolism and glucose homeostasis, and the liver serves as a hub for substrate output and metabolic buffering. By integrating these inputs, neuropeptide regulation enables the central nervous system to make comprehensive judgments about energy status across different spatial and temporal scales.
1.3 The neuropeptide network has bidirectional regulatory properties
(1) Peripheral metabolic status can in turn reshape central neuropeptide sensitivity
Factors such as long-term high-fat feeding, chronic inflammation, sleep deprivation, and persistent stress not only alter the function of peripheral metabolic organs, but also reshape how the central nervous system interprets hunger, satiety, and reward signals, thereby changing the activation thresholds and output patterns of neuropeptide pathways.
(2) Central output further remodels peripheral organ function
Through autonomic and neuroendocrine mechanisms, neuropeptide regulation influences peripheral organs such as adipose tissue, liver, and pancreas, thereby translating central judgments into concrete execution programs including lipolysis, thermogenesis, glucose production, hormone secretion, and substrate oxidation. In this way, a continuous central–peripheral closed loop is formed.
II. Structural basis of the central–peripheral neuropeptide signaling network
2.1 The hypothalamus is the core center for energy-state integration
(1) The arcuate nucleus undertakes the primary integration of hunger and satiety signals
The arcuate nucleus is a classic node in the regulation of energy homeostasis. Within this nucleus, NPY/AgRP neurons preferentially encode energy deficiency and feeding drive, whereas POMC/CART neurons preferentially encode satiety and feeding suppression. The functional antagonism between these two neuronal populations constitutes the basic framework of central energy regulation.
(2) The paraventricular nucleus and ventromedial nucleus undertake output amplification and state translation
Information integrated in the arcuate nucleus must be further transmitted to downstream nuclei such as the paraventricular nucleus, ventromedial nucleus, and dorsomedial nucleus before it can generate systemic regulation of autonomic activity, behavioral programs, and neuroendocrine axes. Thus, the hypothalamus itself is a hierarchically organized energy information integration network.
2.2 The brainstem is an important interface for visceral afferents and satiety feedback
(1) The nucleus tractus solitarius links vagal afferents with central metabolic control
Information on gastrointestinal distension, gut hormone release, and other visceral states can enter the brainstem nucleus tractus solitarius via vagal afferents, and then ascend from the brainstem to the hypothalamus and related limbic structures. This pathway allows the body to rapidly sense postprandial changes and promptly initiate satiety-related regulation.
(2) The brainstem is not merely a passive relay station
The brainstem itself also participates in satiety termination, autonomic output, and coordination between cardiovascular and metabolic functions. Particularly in short-term feeding suppression, gastrointestinal motility regulation, and acute metabolic adaptation, the brainstem network works in close concert with the hypothalamus.
2.3 The limbic system and arousal network participate in coupling metabolic behavior
(1) Metabolic regulation is not separate from reward, motivation, and arousal states
Feeding behavior is driven not only by energy deficiency but also by reward sensitivity, arousal level, and behavioral motivation. Neuropeptide pathways such as orexin and melanocortin interact with the limbic system, allowing metabolic needs to be translated into concrete behaviors such as food seeking, eating, and activity.
(2) Energy metabolism integration is strongly state-dependent
The same neuropeptide signal may produce different effects under fasting, sleep deprivation, chronic stress, and high nutritional load. This indicates that the neuropeptide network is not a fixed-output system but a dynamic integrative system that is highly sensitive to the organism's overall state.
Table 1. Key nodes and functional positioning in neuropeptide-regulated central–peripheral energy networks
Neuropeptide/signaling axis | Main source or core node | Main functional step | Core functional positioning | Metabolic significance |
NPY/AgRP axis | Arcuate nucleus hunger-related neurons | Feeding initiation, hunger drive, energy conservation | Central amplifier of energy-deficient states | Promotes feeding and suppresses energy expenditure |
POMC/alpha-MSH-MC4R axis | Arcuate nucleus POMC neurons-downstream MC4R network | Satiety establishment, feeding suppression, body weight regulation | Central braking system under energy-replete conditions | Suppresses feeding and promotes weight-reducing outputs |
Orexin axis | Lateral hypothalamus | Arousal, activity, sympathetic mobilization, thermogenesis | Coupling node between behavioral activation and metabolic mobilization | Links wakefulness, thermogenesis, and energy expenditure |
Oxytocin axis | Paraventricular nucleus, supraoptic nucleus, and peripheral projections | Satiety reinforcement, lipid metabolism, peripheral metabolic regulation | Regulatory module for feeding suppression and metabolic improvement | Associated with food intake, adipose tissue inflammation, and glucose homeostasis |
Ghrelin-GHSR axis | Stomach-central hunger signaling pathway | Fasting response, feeding drive, reward sensitivity | Representative ascending peripheral hunger-input axis | Enhances NPY/AgRP activity and biases the system toward feeding |
CCK gut-brain axis | Gastrointestinal tract-vagal afferents-brainstem-hypothalamus | Postprandial satiety, gastric emptying regulation, short-term feeding suppression | Rapid postprandial feedback pathway | Restricts meal size and promotes satiety establishment |
Melatonin circadian axis | Pineal gland-hypothalamic circadian network | Phase synchronization, sleep-metabolism coupling | Circadian metabolic allocation signal | Associated with glucose metabolism, lipid metabolism, and nocturnal energy allocation |
III. Peripheral input signals and their functional translation within the neuropeptide network
3.1 Gastrointestinal signals constitute the first layer of postprandial feedback information flow
(1) Signals such as CCK, GLP-1, and PYY reflect the postprandial satiety background
After feeding, multiple gastrointestinal hormones rapidly convey to the central nervous system the message that nutrients have entered the body. Among these, CCK-related signaling is particularly important for short-term satiety establishment, regulation of gastric emptying, and activation of vagal afferents. These signals help the central nervous system terminate excessive feeding in a timely manner and shift the metabolic state from intake mode to processing mode.
(2) Gastrointestinal signals exhibit clear pathway specificity
Some gastrointestinal signals act on the central nervous system mainly via humoral routes, whereas others rely more heavily on vagal afferents for rapid feedback. The coexistence of these pathways enables the body to respond quickly to single feeding events while also cumulatively forming judgments about longer-term energy status.
3.2 Stomach-derived hunger signals drive the initiation of orexigenic programs
(1) Ghrelin is a major ascending peripheral signal under fasting conditions
Under fasting or energy-deficient conditions, ghrelin levels rise, enhancing central recognition of hunger and promoting activation of orexigenic pathways such as NPY/AgRP. Its effects are manifested not only as increased food intake but also as enhanced food-seeking motivation and the establishment of an energy-conserving metabolic state.
(2) Orexigenic signals coordinate multi-level metabolic adaptation
Once the central nervous system interprets the organism as being in a state of energy deficiency, increased feeding behavior is accompanied by changes in activity patterns, reorganization of sympathetic output, adjustments in lipid utilization, and downregulation of certain anabolic programs. Thus, orexigenic neuropeptide pathways are essentially a global response system for states of energy shortage.
3.3 Signals from adipose tissue and the pancreas reflect long-term energy storage and anabolic metabolic status
(1) Adipose tissue provides slow-variable information about energy storage
Adipose tissue is not only an energy storage organ but also an important endocrine organ. Its secreted signals reflect the organism's long-term energy reserve status and continuously influence central settings for satiety threshold and feeding demand.
(2) Pancreatic signals connect glucose homeostasis with central regulation
Insulin and related metabolic background information influence not only peripheral glucose utilization but also central recognition of energy sufficiency. By interpreting these signals, the central nervous system determines whether subsequent responses should favor energy storage, maintenance of homeostasis, or mobilization programs.
IV. Core neuropeptide axes and their coordinated roles in energy metabolism
4.1 The NPY/AgRP axis is a classic orexigenic and energy-conserving module
(1) This pathway preferentially reflects energy-deficient states
Under fasting and negative energy balance, the NPY/AgRP pathway becomes more active, enhancing the drive to consume food, delaying satiety termination, and promoting energy allocation patterns that conserve resources.
(2) Its consequences extend across feeding, endocrine, and metabolic expenditure levels
In addition to directly promoting feeding, this pathway can also influence autonomic output, activity patterns, and the background of certain metabolic hormones, making the organism more suitable for survival under resource-limited conditions.
4.2 The POMC/melanocortin axis is an important framework for central anorexigenic and weight-reducing outputs
(1) This pathway represents the braking system under energy-replete conditions
Active peptides derived from POMC neurons can generate anorexigenic and body weight-regulating effects through melanocortin receptor networks. Its function is to limit excessive food intake and shift the organism toward higher energy expenditure.
(2) Its significance extends beyond suppressing food intake alone
The melanocortin system also participates in regulation of metabolic efficiency, support of sympathetic thermogenesis, and control related to the body weight set point, making it particularly important in studies of obesity and hereditary metabolic abnormalities.
4.3 The orexin axis links arousal, activity, and metabolic mobilization
(1) The orexin pathway matches wakefulness with mobilizable energy
The orexin system, located in the lateral hypothalamus, links maintenance of wakefulness with increased activity and sympathetic metabolic mobilization. When the body must generate behavioral output in a waking state, the orexin pathway helps simultaneously enhance thermogenesis and the supply of available energy.
(2) Its function emphasizes the integration of behavior and metabolism
Unlike pathways dedicated primarily to feeding regulation, the orexin pathway is more concerned with synchronizing behavioral state and metabolic state, indicating that the neuropeptide network functions as a whole-body state management system in energy metabolism.
4.4 The oxytocin axis participates in satiety reinforcement and metabolic improvement
(1) Oxytocin is not limited to reproductive regulation
In the field of energy metabolism, the oxytocin axis can participate in feeding suppression, adipose tissue metabolic remodeling, and improvement of glucose homeostasis. Its effects indicate that some neuropeptides possess both behavioral regulatory and metabolic intervention properties.
(2) Oxytocin-related effects reflect central–peripheral coupling
Oxytocin can influence satiety and feeding at the central level while also regulating peripheral adipose tissue, pancreatic function, and inflammatory background. It is therefore particularly suitable as a representative neuropeptide for studying metabolic integration.
4.5 CCK-related signaling is an important component of the gut–brain satiety axis
(1) CCK-8 is more suitable as a representative short-term satiety signal after feeding
CCK-8 can be used to simulate the postprandial ascending gastrointestinal signal process and to study vagal afferent activation, brainstem nucleus tractus solitarius integration, and subsequent hypothalamic satiety pathway changes. It is particularly important for dissecting rapid postprandial feeding suppression and gastrointestinal feedback regulation.
V. Integrated mechanisms by which the neuropeptide network regulates feeding, thermogenesis, and substrate allocation
5.1 Feeding initiation and termination are direct phenotypes of neuropeptide balance
(1) Hunger drive is dominated by orexigenic pathways
When energy-deficiency signals predominate, orexigenic signals such as ghrelin and NPY/AgRP increase food-seeking drive and food intake tendency while weakening the organism's interpretation of satiety signals.
(2) Satiety establishment depends on coordinated braking by multiple pathways
In the postprandial state, CCK, GLP-1, PYY, and central melanocortin-related pathways jointly participate in feeding termination. Different pathways are weighted differently across time scales, thereby forming a satiety control mode that combines rapid, sustained, and state-dependent regulation.
5.2 Thermoregulation is an important energy-expenditure endpoint of neuropeptide output
(1) Neuropeptide pathways can connect to brown adipose thermogenesis via the sympathetic system
When the central nervous system determines that the organism needs to increase energy expenditure, it can enhance brown adipose tissue thermogenic programs through the autonomic nervous system and promote the shift of white adipose tissue toward a mobilized state. This process means that neuropeptide regulation extends beyond behavior and directly enters the organ-level execution layer of metabolism.
(2) Thermogenesis is not an isolated event
Body temperature regulation, activity level, arousal state, and substrate supply capacity are interrelated. Orexin, melanocortin, and other related neuropeptide axes jointly determine whether a high-expenditure state can be stably established.
5.3 Glucose homeostasis and lipid flux are also under upstream control of neuropeptides
(1) Central regulation of peripheral organs affects glucose and lipid fate
The neuropeptide network can influence hepatic glucose output, insulin secretion, adipose tissue lipolysis, and fatty acid oxidation patterns, so that similar feeding phenotypes may underlie very different outcomes in glucose tolerance and lipid homeostasis.
(2) Substrate allocation reflects the true integrative capacity of the neuropeptide network
The key to energy metabolism integration is not whether a single index rises or falls, but how substrates such as glucose, fatty acids, and amino acids are re-ranked and redistributed among different organs. The neuropeptide system is the central organizer of this process.
VI. Functional shifts of the neuropeptide network in metabolic disease
6.1 Obesity reflects distorted interpretation of central–peripheral information
(1) Persistent nutritional excess can alter central efficacy of satiety signals
Under high-fat diets and long-term positive energy balance, central sensitivity to satiety- and energy storage-related signals may decline, leading to an upward shift in satiety threshold, weakened feeding suppression, and sustained reinforcement of feeding behavior.
(2) Obesity is not the result of a single organ
Obesity simultaneously involves abnormal hypothalamic signal interpretation, adipose tissue inflammation, increased hepatic metabolic burden, elevated pancreatic secretory pressure, and altered behavioral patterns. It therefore needs to be understood at the level of the central–peripheral network.
6.2 Insulin resistance and fatty liver reflect abnormalities in organ-level allocation programs
(1) Erroneous central judgment can drive persistence of peripheral abnormalities
If the central nervous system continues to interpret the organism as one that "needs to keep ingesting" or "cannot effectively establish satiety," it can further drive abnormal hepatic glucose output, lipid accumulation, and increased pancreatic burden, thereby amplifying the phenotype of metabolic disease.
(2) Similar body weight may correspond to different neuropeptide backgrounds
Even among individuals with similar body weight, marked differences may exist in glucose tolerance, degree of fatty liver, and activity-related metabolic patterns because of differences in the basal status of neuropeptide pathways.
6.3 Circadian disruption weakens the temporal coordination capacity of the neuropeptide network
(1) Sleep–wake imbalance reorganizes the time windows of energy metabolism
When sleep deprivation, circadian misalignment, or chronic stress is present, the timing of neuropeptide regulation over feeding, activity, and thermogenesis is disrupted, thereby reducing metabolic efficiency and increasing the risk of body weight abnormalities.
(2) Circadian problems compound metabolic problems
Once central temporal coordination is impaired, the metabolic task switching of peripheral organs also loses synchrony, leading to abnormal feeding timing, reduced insulin sensitivity, and impaired lipid handling.
VII. Core pathways and evaluation systems that should be emphasized in research design
7.1 Major research pathways
(1) Hunger–satiety integration pathways
Focus should be placed on the interactions among ghrelin, NPY/AgRP, POMC/melanocortin, and satiety signals such as CCK, GLP-1, and PYY, in order to analyze changes in the threshold for feeding initiation and the strength of satiety termination.
(2) Neuropeptide–autonomic nervous system–thermogenesis pathways
Focus should be placed on how pathways such as orexin, melanocortin, and oxytocin regulate brown adipose thermogenesis, lipid mobilization, and body temperature maintenance through sympathetic output.
(3) Neuropeptide–glucose homeostasis pathways
Emphasis should be placed on how changes in central signaling influence pancreatic secretion, hepatic glucose output, glucose tolerance, and insulin sensitivity, thereby establishing causal links between feeding regulation and glucose metabolic regulation.
(4) Circadian–arousal–metabolism coupling pathways
Research should focus on how the neuropeptide network works together with the circadian system, sleep architecture, and activity patterns to determine energy expenditure and the timing of substrate utilization.
7.2 Key evaluation indices
(1) Central-level indices
① Changes in the expression of NPY, AgRP, POMC, CART, and related molecules in key regions such as the arcuate nucleus, paraventricular nucleus, and brainstem.
② Changes in the expression of GHSR, MC4R, OXTR, CCK-related receptors, and other key receptors.
③ Readouts related to neuronal activation, such as c-Fos and pCREB.
④ Hypothalamic inflammation, glial responses, and stress-related molecular changes.
⑤ Neuropeptide release, receptor sensitivity, and changes in related downstream signaling pathways.
(2) Peripheral-level indices
① Food intake, feeding phase, satiety duration, and gastric emptying rate.
② Fasting blood glucose, postprandial blood glucose, glucose tolerance, and insulin sensitivity.
③ Brown adipose thermogenic markers, white adipose lipolysis levels, and indices related to energy expenditure.
④ Changes in plasma neuropeptide or related hormone levels.
⑤ Hepatic lipid burden, expression of gluconeogenesis-related enzymes, and inflammatory status of adipose tissue.
(3) Whole-organism phenotypic indices
① Changes in body weight, fat mass, and lean mass.
② Oxygen consumption, respiratory exchange ratio, and substrate oxidation patterns.
③ Changes in body temperature, activity level, and sleep structure.
④ Adaptation capacity under fasting, feeding, high-fat load, and stress conditions.
⑤ Integrated phenotypes of obesity, fatty liver, insulin resistance, and metabolic inflammation.
Table 2. Pathways, targets, and common evaluation indices in studies of neuropeptide-regulated central–peripheral energy networks
Research direction | Major pathways | Key targets | Common evaluation indices |
Hunger-satiety regulation | Ghrelin-GHSR, NPY/AgRP, POMC/MC4R, CCK axis | GHSR, NPY, AgRP, POMC, MC4R, CCKAR | Food intake, satiety duration, gastric emptying, arcuate nucleus gene expression |
Thermogenesis and energy expenditure | Orexin/melanocortin-sympathetic-BAT axis | OX1R/OX2R, MC4R, UCP1 | Oxygen consumption, body temperature, BAT markers, sympathetic activity |
Oxytocin metabolic regulation | OXT-OXTR-adipose/pancreatic/central integration axis | OXTR, adipose thermogenesis- and inflammation-related molecules | Food intake, fat mass, glucose tolerance, adipose tissue phenotype |
Glucose homeostasis | Central-pancreas-liver regulatory axis | Insulin, hepatic gluconeogenesis-related targets, AMPK | Fasting blood glucose, GTT, ITT, hepatic glucose output |
Nutrient sensing and substrate switching | AMPK, mTOR, coupling of fatty acid oxidation and glycolysis | AMPK, mTOR, CPT1, hexokinase | RER, ATP, fatty acid oxidation and glycolysis readouts |
Circadian metabolic integration | Orexin/melatonin-sleep-metabolism axis | OX1R/OX2R, MT1/MT2 | Sleep structure, feeding phase, body temperature, and activity rhythms |
VIII. Common products used in studies of neuropeptide-regulated central–peripheral networks
Name | CAS No. | Experimental Step | Key Use | Notes for Use |
Oxytocin | Oxytocin axis and anorexigenic studies | Used to evaluate the regulatory effects of the OXT-OXTR pathway on food intake, adipose tissue metabolism, and glucose homeostasis | Suitable for use together with food intake, body weight, fat mass, glucose tolerance, and adipose tissue phenotype analyses | |
Carbetocin | Oxytocin receptor activation studies | Used to establish more stable OXTR agonist conditions and analyze the sustained effects of oxytocin signaling on satiety and peripheral metabolism | Suitable for use together with chronic dosing, body weight changes, and adipose tissue remodeling experiments | |
Atosiban | Oxytocin receptor antagonism studies | Used to block OXTR/vasopressin-related receptor signaling and verify the causal contribution of the oxytocin axis to anorexigenic effects and metabolic improvement | Suitable for paired design with Oxytocin or Carbetocin for pathway discrimination | |
Ghrelin | Hunger signal activation studies | Used to simulate peripheral orexigenic input under fasting conditions and analyze GHSR-related hunger drive and central responses | Suitable for use together with feeding initiation time, NPY/AgRP expression, and reward behavior analyses | |
Orexin A | Orexin axis and arousal-metabolism coupling studies | Used to evaluate the role of the orexin pathway in arousal, activity, sympathetic output, and thermogenic regulation | Suitable for use together with body temperature, energy expenditure, activity level, and sleep structure analyses | |
Orexin B | Orexin receptor subtype discrimination studies | Used to compare the differences in the effects of distinct orexin ligands on arousal, feeding, and autonomic regulation | Suitable for use together with Orexin A and receptor antagonists for subtype preference analysis | |
SB-334867 | OX1R mechanism validation studies | Used to block OX1R-related signaling and analyze orexin-mediated effects on feeding, arousal, and energy expenditure | More suitable for receptor-specific validation following upstream orexin stimulation | |
Exendin-4 | Gut-brain satiety and glucose metabolism studies | Used to simulate GLP-1-related signaling and analyze effects on feeding suppression and improved glucose homeostasis | Suitable for use together with postprandial feeding, insulin secretion, and glucose tolerance analyses | |
Setmelanotide | Melanocortin pathway studies | Used to evaluate the role of MC4R-related pathways in feeding suppression, body weight control, and metabolic remodeling | More suitable for validation in melanocortin dysfunction or obesity-related models | |
Melanotan II | Melanocortin receptor agonism studies | Used to enhance melanocortin receptor signaling and evaluate MC3R/MC4R-related anorexigenic and weight-reducing effects | Suitable for combined design with genetic obesity models and receptor blockade experiments | |
CCK-8 | Gut-brain satiety signaling studies | Used to simulate postprandial ascending CCK signaling and analyze vagal afferents, brainstem nucleus tractus solitarius, and hypothalamic satiety integration | Suitable for use together with short-term feeding suppression, gastric emptying, vagal-related activation, and c-Fos readouts | |
Desulfated CCK-8 | Mechanistic control and receptor selectivity studies | Used to distinguish the contribution of CCK sulfation to effects mediated by different receptors and to verify the structural dependence of the principal effects of CCK-8 | More suitable for paired use with CCK-8 as a structure-function control molecule | |
Devazepide | CCK1R antagonism studies | Used to block CCK1R-mediated peripheral satiety and gastrointestinal feedback effects and to verify the role of the CCK gut-brain axis in short-term anorexigenic responses | Suitable for use together with CCK-8 for analyses of vagal afferent involvement and receptor dependence | |
AICAR | AMPK nutrient-sensing studies | Used to activate the AMPK pathway and observe changes in central energy sensing and peripheral oxidative metabolism | Suitable for use together with energy expenditure, fatty acid oxidation, and pAMPK detection | |
Dorsomorphin | AMPK pathway inhibition studies | Used to inhibit AMPK signaling and verify the necessity of energy-sensing pathways in neuropeptide regulation | Suitable for paired use with AICAR in studies of central nutrient sensing and substrate switching | |
Rapamycin | mTOR nutrient sufficiency signaling studies | Used to inhibit the mTOR pathway and evaluate the influence of amino acid sensing and protein synthesis-related signaling on feeding and metabolic integration | Suitable for use together with L-Leucine or fasting-refeeding models | |
L-Leucine | Amino acid sensing and mTOR studies | Used to simulate amino acid input under nutrient-replete conditions and analyze central nutrient sensing and anorexigenic responses | Suitable for use together with mTOR activation, food intake changes, and protein synthesis-related indices | |
Etomoxir | Fatty acid oxidation blockade studies | Used to inhibit CPT1-related mitochondrial entry of fatty acids and evaluate the contribution of fatty acid oxidation to neuropeptide effects | Suitable for use together with oxygen consumption, ketone bodies, ATP levels, and mitochondrial function readouts | |
Oleic acid | Lipid signaling and hypothalamic lipid-sensing studies | Used to analyze the effects of unsaturated fatty acids on feeding, inflammation, and metabolic regulation | Can be paired with palmitic acid to compare protective and deleterious lipid effects | |
Palmitic acid | Lipotoxicity and neuroinflammation models | Used to establish high-fat load and lipotoxicity conditions and analyze hypothalamic inflammation and blunting of satiety signaling | Suitable for use together with glial activation, ER stress, and metabolic inflammation readouts | |
2-Deoxy-D-glucose | Glucose sensing and glycolysis restriction studies | Used to simulate reduced glucose availability and analyze central responses to acute energy deficit | Suitable for use together with AMPK activation, feeding responses, and ATP level detection | |
Forskolin | cAMP pathway amplification studies | Used to activate adenylate cyclase, increase cAMP levels, and analyze downstream GPCR signaling changes | Suitable for mechanistic studies involving melanocortin, oxytocin, and other GPCR-related pathways | |
Melatonin | Circadian-metabolism coupling studies | Used to evaluate the effects of circadian signals on feeding phase, glucose-lipid metabolism, and oxidative stress status | Suitable for use together with sleep structure, body temperature rhythms, and glucose metabolism studies |
The core of neuropeptide regulation lies in converting peripheral metabolic states into central programs for organ-level allocation. Its functions encompass feeding, thermogenesis, glucose homeostasis, lipid mobilization, and circadian coordination, and it effectively constitutes the system-level control layer of energy metabolism integration. Establishing a research framework centered on "peripheral input-central integration-peripheral execution-feedback remodeling" will facilitate a more accurate analysis of the mechanistic basis of obesity, insulin resistance, fatty liver, and circadian disruption.
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