Mechanism of Action
LepR Receptor Binding and BBB Penetration
Full-length leptin/" class="wiki-internal-link">leptin activates the long-form leptin receptor (LepRb) in the hypothalamus to suppress appetite and increase energy expenditure. Leptin resistance in obesity is partly caused by impaired leptin transport across the blood-brain barrier (BBB). The 116-130 fragment, due to its small size, may use alternative BBB transport mechanisms, potentially bypassing the saturable transport system that limits full leptin.
Hypothalamic Signaling
Leptin fragment 116-130 activates JAK2-STAT3 signaling downstream of LepRb, suppressing NPY/AgRP neurons (orexigenic) and activating POMC/CART neurons (anorexigenic) in the arcuate nucleus. Its hypothalamic activity per mol is lower than full-length leptin but improved CNS delivery may compensate.
Research Summary
Weight Loss in Obese Rodents
PreclinicalIn diet-induced obese (DIO) and ob/ob mice, leptin fragment 116-130 administered subcutaneously reduces food intake and body weight comparably to full-length leptin at equivalent molar doses. Importantly, some studies show activity in leptin-resistant DIO animals where full leptin is ineffective, supporting the BBB penetration hypothesis.
Metabolic Parameters
PreclinicalChronic administration in rodent models improves fasting glucose, insulin sensitivity, and reduces hepatic steatosis. Adipose tissue lipolysis increases. These effects mirror full leptin's metabolic actions at similar CNS leptin receptor engagement.
Calculate your Leptin Fragment (116-130) dose Vial strength, BAC water, exact syringe draw in IU. Free, no signup. Open Calc →
Research Protocols
| Goal | Dose | Frequency | Route |
|---|---|---|---|
| Appetite suppression (obese rodent) | 0.1-1 mg/kg SC | Daily | Subcutaneous |
| Weight loss (DIO mouse) | 0.5 mg/kg IP | Daily x 14 days | Intraperitoneal |
| BBB penetration assessment | Radiolabeled fragment | Single dose | IV + brain quantification |
No human clinical data. All protocols are rodent research. Leptin fragment 116-130 is not available as a clinical compound.
Interactions
Safety Profile
No human safety data. Full-length leptin has been tested in clinical trials for lipodystrophy (metreleptin is FDA-approved) and obesity, showing generally good tolerability but limited efficacy in common obesity due to leptin resistance. Fragment 116-130 has no human data. Theoretical concerns include immune responses to a self-derived fragment sequence and potential off-target receptor activation.
References
- [1]Grasso P, et al. Intranasal administration of leptin(116-130) inhibits food intake and produces weight loss in lean, obese, and leptin-resistant mice. Exp Biol Med. 2011;236(5):474-478.
- [2]Zhang F, et al. Crystal structure of the obese protein leptin-E100. Nature. 1997;387(6629):206-209.
- [3]Banks WA, et al. Leptin enters the brain by a saturable system independent of insulin. Peptides. 1996;17(2):305-311.