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Satiety is a central regulator of feeding behavior, energy balance and metabolic health. It arises from the integration of hormonal and neuronal signals that link nutrient intake to appetite control, glucose metabolism and energy storage. These signals originate primarily from the gastrointestinal tract, pancreas, adipose tissue and liver, and converge on the central nervous system to coordinate short- and long-term regulation of food intake.

Disruption of satiety signaling contributes to obesity, diabetes and cardiometabolic disease, making this pathway a major focus of basic and translational research. Recent advances have revealed an increasingly complex endocrine network, extending beyond classical appetite hormones to include stress- and disease-associated regulators that influence feeding behavior and metabolic adaptation.

Key Hormonal Pathways in Satiety Regulation

Satiety control is mediated by multiple interacting hormone classes with distinct temporal and physiological roles. Gut-derived incretins, including glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and glucagon, couple nutrient ingestion to insulin secretion, gastric emptying and appetite suppression. Other gut-hormones, such as oxyntomodulin (OXM), cholecystokinin (CCK) and peptide YY are also important anorexigenic hormones secreted upon food intake. Pancreatic hormones, most notably insulin, act as both metabolic regulators and central satiety signals. Adipose-derived factors such as Leptin and acyl-CoA-binding protein (ACBP) provide long-term feedback on energy stores, while liver-, adipose- and gut-secreted peptides and proteins including asprosin and famsin influence glucose production, feeding behavior and systemic metabolism. Orexigenic hormones such as ghrelin promote hunger during fasting states.

In addition, growth differentiation factor 15 (GDF15) has emerged as a key regulator of appetite suppression in response to metabolic stress, inflammation and disease, acting through central nervous system pathways distinct from classical satiety hormones. Together with emerging regulators such as isthmin, a new insulin-like hormone regulating glucose uptake while suppressing lipid accumulation, these molecules form an integrated endocrine network that dynamically controls appetite, metabolism and energy homeostasis. 

LIT: Exercise-induced appetite suppression: An update on potential mechanisms: S.F. McCarthy, et al.; Physiol. Rep. 12, e70022 (2024) • The gut-brain axis in appetite, satiety, food intake, and eating behavior: Insights from animal models and human studies: G.S. Clarke, et al.; Pharmacol. Res. Perspect. 12, e70027 (2024) • Proteins and Peptides from Food Sources with Effect on Satiety and Their Role as Anti-Obesity Agents: A Narrative Review: A. Ignot-Gutierrez, et al.; Nutrients 16, 3560 (2024)

 

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Incretins and Satiety: Hormonal Signals That Shape Appetite

Incretins (gastric inhibitory polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and glucagon) are gut-derived hormones released after food intake that play a central role in regulating blood glucose and appetite. GIP and GLP-1 are the two primary incretins secreted from the intestine on ingestion of nutrients or glucose to stimulate insulin secretion from pancreatic β-cells. GIP enhances and GLP-1 inhibits postprandial glucagon response. In adipose tissues, only GIP, not GLP-1 facilitates fat deposition. In bone, GIP promotes bone formation while GLP-1 inhibits bone absorption. In the brain, both GIP and GLP-1 are thought to be involved in memory formation and in control of appetite. Glucagon is secreted from pancreatic α-cells and acts in opposition to insulin by promoting gluconeogenesis and glycogenolysis and plays an essential role as regulator of glucose and lipid metabolism. Recently, synthetic long-acting GLP-1 and/or GIP analogs have been shown to improve insulin sensitivity, insulin secretory response and to reduce appetite.

LIT: Exercise-induced appetite suppression: An update on potential mechanisms: S.F. McCarthy, et al.; Physiol. Rep. 12, e70022 (2024) • The gut-brain axis in appetite, satiety, food intake, and eating behavior: Insights from animal models and human studies: G.S. Clarke, et al.; Pharmacol. Res. Perspect. 12, e70027 (2024) • Proteins and Peptides from Food Sources with Effect on Satiety and Their Role as Anti-Obesity Agents: A Narrative Review: A. Ignot-Gutierrez, et al.; Nutrients 16, 3560 (2024)

 

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GDF15 – Exercise-induced Factor Regulating Appetite

Growth and differentiation factor 15 (GDF15; Macrophage Inhibitory Cytokine 1; MIC-1) is a member of transforming growth factor-β (TGF-β) superfamily. GDF15 is a cytokine, secreted from cells undergoing mechanical or chemical stress and it increases during exercice. GDF15 acts through a recently identified receptor expressed in the brain called glial-derived neurotrophic factor (GDNF) receptor α-like (GFRAL) which signals through the "Rearranged during Transfection" (RET) tyrosine kinase receptor. Functions of GDF15 are pleiotropic and include appetite regulation/suppression, actions on metabolism, pregnancy, cell survival, aging, immune response and inflammation. Recombinant GDF15 administered to mice drives weight loss. Inhibition of the GDF15-GFRAL axis with a blocking antibody leads to inhibition of cachexia, preventing weight loss and reversing anorectic behavior.

LIT: GDF15 in Appetite and Exercise: Essential Player or Coincidental Bystander? A.B. Klein, et al.; Endocrinol. 163, bqab242 (2022) • GDF15 is still a mystery hormone: C.M. Sigvardsen, et al.; Trends Endocrinol. Metab. 36, 591 (2025)

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Unique Mouse GDF15 Recombinant Blocking Antibody

AdipoGen Life Sciences' recombinant monoclonal GDF15 antibody (Clone Danae-1-1) is composed of human variable regions (VH and VL) (λ-chain) of immunoglobulin fused to the mouse lgG2b Fc domain. Inhibits the binding of mouse GDF15 to its receptor GFRAL.

High levels of GDF15 cause anorectic effects and cachexia. Various functions have been reported for GDF15, including inhibition of TNF-α production from lipopolysaccharide-stimulated macrophages and the induction of cartilage formation. GDF15 also promotes neuronal survival. GFRAL and GDF15 signaling are implicated in diet-based obesity and insulin resistance. Recently, GDF15 has also been a key player in human aging. It has been linked to aging-related processes, including cellular senescence and the dysfunction of mitochondria, as well as age-related diseases, such as Alzheimer's disease. Blocking of the GDF15-GFRAL binding has some therapeutic implications.

 

Binding Assay: Binding of GDF15 (mouse) to GFRAL (mouse) is inhibited by GDF15, mAb (rec.) (blocking) (Danae-1-1) (preservative free) (Prod. No. AG-27B-0024).

Method: GFRAL (mouse) is coated on an ELISA plate at 1µg/ml. anti-GDF15, mAb (rec.) (blocking) (Danae-1-1) (Prod. No. AG-27B-0024) or an unrelated mAb (recombinant) (Control) were added (starting at 20µg/ml with a twofold serial dilution) together with 30ng/ml of GDF15 (mouse):Fc (silent) InVivoKine™ (Prod. No. AG-40B-0245). After incubation for 1 h at RT, the binding was detected using an anti-Fc human antibody (HRP).

 

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Biologically Active GDF15 and GFRAL Proteins

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Insulin & Isthmin-1: Linking Metabolic Control to Appetite Regulation

Insulin is a central metabolic hormone that not only regulates glucose homeostasis but also plays a critical role in the control of satiety and energy balance. In response to an elevation in plasma glucose and amino acids (after consumption of a meal), insulin is released from the β-cells in the pancreas. When plasma glucose falls (during fasting or exercise), glucagon is secreted by α-cells, which surround the β-cells in the pancreas. In the brain, insulin modulates key appetite-regulating neuronal circuits. By activating anorexigenic pathways and suppressing orexigenic signals, insulin contributes to reduced food intake and the promotion of satiety following meals. Disruption of central insulin signaling has been linked to Types I/II diabetes, obesity, insulin resistance and impaired appetite control. Isthmin-1 (ISM1) is a liver-derived metabolic regulator that improves glucose uptake and insulin sensitivity in peripheral tissues and supports energy homeostasis indirectly by enhancing metabolic efficiency and promoting a balanced energy state.

LIT: Exercise-induced appetite suppression: An update on potential mechanisms: S.F. McCarthy, et al.; Physiol. Rep. 12, e70022 (2024) • The gut-brain axis in appetite, satiety, food intake, and eating behavior: Insights from animal models and human studies: G.S. Clarke, et al.; Pharmacol. Res. Perspect. 12, e70027 (2024) • Proteins and Peptides from Food Sources with Effect on Satiety and Their Role as Anti-Obesity Agents: A Narrative Review: A. Ignot-Gutierrez, et al.; Nutrients 16, 3560 (2024)

 

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Biologically Active GDF15 and GFRAL Proteins

 

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Asprosin

Asprosin is the C-terminal cleavage product of the protein Fibrillin-1. Asprosin is a fasting-induced glucogenic and orexigenic hormone that plays a critical role in the regulation of energy homeostasis. Within the central nervous system, asprosin works by stimulating the orexigenic AgRP+ (Agouti related neuropeptide) neurons via a cAMP-dependent pathway and by inhibiting the anorexigenic POMC+ (proopiomelanocortin) neurons in a GABA- dependent manner, promoting food intake and reducing satiety signals. Elevated circulating asprosin levels have been associated with obesity, insulin resistance and metabolic syndrome, highlighting its relevance
in metabolic disease research.

LIT: Asprosin in health and disease, a new glucose sensor with central and peripheral metabolic effects: M. Farrag, et al.; Front. Endocrinol. 13, 110191 (2023) • Asprosin: its function as a novel endocrine factor in metabolic-related diseases: Y. Zhang, et al.; J. Endocrinol. Invest. 47, 1839 (2024)

 

 

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Biologically Active GDF15 and GFRAL Proteins

 

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Famsin – Linking Metabolic Control to Appetite Regulation

Famsin is an emerging gut-derived hormone that plays an important role in the body’s adaptation to fasting. During periods of food deprivation, circulating famsin levels rise, helping maintain blood glucose by stimulating glucagon release and supporting hepatic glucose production. By acting as part of a gut-pancreas-liver signaling axis, famsin helps to balance energy needs during fasting while interacting with pathways that influence hunger and metabolic regulation.

LIT: Famsin and fasting adaptation: A glucagon connection: S. Li, et al.; Cell Metab. 37, 561 (2025)

 

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Biologically Active GDF15 and GFRAL Proteins

 

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VALIDATED Antibodies for LAG-3 Research

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