Leptin
Description
Leptin is a hormone predominantly made by adipose cells and enterocytes in the small intestine that helps regulate energy balance by inhibiting hunger, which in turn diminishes fat storage in adipocytes; leptin acts on the neurons in certain brain areas such as the hypothalamus, hippocampus, and brain stem to regulate food intake, thermogenesis, energy expenditure, and homeostasis of glucose/lipid metabolism. A role for leptin in pregnancy was suggested by the findings that plasma levels during gestation are greater than in nongravid individuals and that leptin is synthesized within the fetoplacental unit, and observational studies have established that leptin production is dysregulated in several pathologic stages of pregnancy in association with alterations of fetal growth (Hauguel-de Mouzon, Lepercq et al. 2006). The adiponectin/leptin ratio has been suggested as a marker of adipose tissue dysfunction since it correlates with insulin resistance better than adiponectin or leptin alone, and is decreased with increasing number of metabolic risk factors proposed as predictive markers for the metabolic syndrome and stroke (Fruhbeck, Catalan et al. 2018). We have not been able to find reagents that recognize MAR leptin.
Alignment
Protein alignment for human, rhesus macaque and marmoset leptin:
Protein alignment for marmoset, owl monkey, and squirrel monkey leptin:
References
- Fruhbeck, G., V. Catalan, A. Rodriguez and J. Gomez-Ambrosi (2018). "Adiponectin-leptin ratio: A promising index to estimate adipose tissue dysfunction. Relation with obesity-associated cardiometabolic risk." Adipocyte 7(1): 57-62.
- Hauguel-de Mouzon, S., J. Lepercq and P. Catalano (2006). "The known and unknown of leptin in pregnancy." Am J Obstet Gynecol 194(6): 1537-1545.
Status
The recombinant MAR leptin molecule was produced in HEK293 cells as a tagged molecule, and it was used to immunize mice. Serological evaluation of the immunized mice resulted in weak antibody responses against Twin-tagged MAR Leptin. Fusion of mouse spleen cells with myeloma cells did not result in the generation of clones.
In summary, the previous approach for generating anti-MAR Leptin mAbs was unsuccessful. We will repeat the mouse immunization with the most immunogenic MAR Leptin variant, at a higher dose, and with a different adjuvant.