Leptin Protein
Description
Introduction to Leptin Protein
Leptin is a 16-kDa protein hormone encoded by the LEP gene, primarily synthesized by adipocytes (fat cells) and gastric mucosa . Discovered in 1994, it regulates long-term energy balance by modulating hunger, satiety, and metabolic activity through interactions with hypothalamic receptors . Circulating leptin levels correlate with adipose tissue mass, serving as a biomarker for energy reserves .
Biosynthesis and Secretion
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Primary Sources: White adipose tissue (constitutive secretion) and gastric mucosa (regulated secretion postprandially) .
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Regulation:
Mechanism of Action
Leptin binds to leptin receptors (LepR), which are class I cytokine receptors .
Receptor Isoforms
| Isoform | Structure | Function |
|---|---|---|
| Ob-Rb | Long intracellular domain | Full signaling via JAK-STAT, MAPK, and PI3K pathways |
| Ob-Ra | Short intracellular domain | Leptin transport across the blood-brain barrier |
Signaling Pathways
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Central (Hypothalamic) Effects:
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Peripheral Effects:
Physiological Roles
Leptin Resistance in Obesity
Obesity induces leptin resistance, characterized by:
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Mechanisms:
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Clinical Implications:
Genetic Associations
Genome-wide studies identify leptin-linked loci:
| SNP | Gene | Effect on Leptin | P-value |
|---|---|---|---|
| rs791600 | LEP | ↓ Leptin levels | 1.1 × 10⁻²³ |
| rs1260326 | GCKR | ↓ Leptin levels | 2.7 × 10⁻¹⁵ |
| rs1121980 | FTO | ↑ Leptin (BMI-dependent) | 7.7 × 10⁻¹⁷ |
Therapeutic Trials
Leptin therapy is effective only in congenital leptin deficiency, not common obesity .
Future Directions
Product Specs
Product Science Overview
Leptin was discovered in 1994 by Jeffrey M. Friedman and his colleagues at Rockefeller University. It is encoded by the obese (ob) gene. Leptin’s primary function is to regulate energy intake and expenditure, including appetite and metabolism. It acts on receptors in the hypothalamus of the brain where it inhibits appetite by counteracting the effects of neuropeptide Y (a potent feeding stimulant secreted by cells in the gut and in the hypothalamus) and anandamide (another potent feeding stimulant that binds to the same receptors as THC, the active ingredient in marijuana). Leptin also promotes the synthesis of α-MSH, an appetite suppressant.
Leptin signals the brain to reduce appetite and increase the amount of energy used. When fat mass decreases, the level of plasma leptin falls, which stimulates appetite and suppresses energy expenditure until fat mass is restored. Conversely, when fat mass increases, so do leptin levels, which suppress appetite until weight is lost. This feedback loop helps to maintain body weight within a relatively narrow range.
Recombinant human leptin is a form of leptin that is produced through recombinant DNA technology. This involves inserting the gene that encodes leptin into bacteria (such as E. coli), which then produce the hormone. The recombinant form is used in research and has potential therapeutic applications.
- Production: Recombinant human leptin is typically produced in E. coli and is a non-glycosylated protein containing 147 amino acids with a molecular mass of approximately 16 kDa .
- Formulation: It is often provided as a lyophilized (freeze-dried) powder and can be reconstituted with sterile water .
- Stability: The lyophilized product is stable at -20°C, and once reconstituted, it should be aliquoted and frozen at -20°C for long-term storage .
Recombinant human leptin retains the biological activity of the native hormone. It can stimulate the proliferation of cells expressing the leptin receptor (OB-R), such as in the BaF3 mouse pro-B cell line transfected with human leptin receptor . The activity is typically measured by the leptin-dependent stimulation of these cells, with an effective dose (ED50) in the range of 0.4-2 ng/mL .
Recombinant human leptin is used in various research applications, including:
- Obesity Research: Studying the role of leptin in body weight regulation and its potential as a therapeutic target for obesity.
- Metabolic Disorders: Investigating leptin’s role in metabolic processes and its potential use in treating metabolic disorders such as diabetes.
- Immune Function: Exploring leptin’s involvement in immune responses, inflammation, and wound healing .
Leptin therapy has been explored for treating conditions such as congenital leptin deficiency, lipodystrophy, and hypothalamic amenorrhea. However, its effectiveness in treating common obesity is limited due to leptin resistance, a condition where the body does not respond adequately to leptin signals.
