Affinity kinetics of leptin-reactive immunoglobulins are associated with plasma leptin and markers of obesity and diabetes

Houda Bouhajja (1) , Noura Bougacha-Elleuch (2) , Nicolas Lucas (3) , Romain Legrand (3) , Rim Marrakchi (4) , Srini Kaveri (5) , Kamel Jamoussi (6) , Hammadi Ayadi (7) , Mohamed Abid (1) , Mouna Mnif-Feki (1) , Sergueï O. Fetissov (8, 9, 10)

1 Hedi Chaker Hospital [Sfax]
2 Université de Sfax
3 TargEDys Rouen
4 Biochemistry Laboratory, Hedi Chaker Hospital, Sfax, Tunisia.
5 CRC - Centre de Recherche des Cordeliers
6 Biochemistry Laboratory, Hedi Chaker Hospital, Sfax, Tunisia.
7 CBS - Centre de Biotechnologie de Sfax
8 IRIB - Institute for Research and Innovation in Biomedicine
9 UNIROUEN - Université de Rouen Normandie
10 ADEN - Nutrition, inflammation et dysfonctionnement de l'axe intestin-cerveau

Obese subjects display elevated plasma levels of leptin reflecting the phenomenon of leptin resistance. Here, we aimed to determine whether leptin-reactive immunoglobulins (Ig) are present in obese and type 2 diabetes (T2D) patients and whether their plasma levels and affinity kinetics may correlate with obesity and diabetes markers. We show that leptin levels are increased in obese patients with and without T2D. Although mean plasma levels of leptin-reactive IgG were similar between study groups, IgG in obese non-diabetic patients had increased dissociation rate and lower affinity (increased dissociation equilibrium constant value; KD). In controls and diabetic patients, the association rates of leptin IgG correlated negatively with obesity and diabetes markers, respectively. In contrast, KD values correlated positively with plasma leptin levels and obesity traits in our cohort, and with diabetes markers in both the total cohort and in the obese T2D group. Taken together, our data reveal that leptin-reactive IgG are present in healthy subjects, obese, and diabetic patients but display altered affinity kinetics in obesity. Increased IgG binding to leptin in healthy subjects associated with lower body mass index (BMI) suggests an enhancing role of IgG in leptin signaling. Accordingly, a decreased affinity of IgG for leptin, found in obese patients, can be relevant to leptin resistance.

Domaines: Alimentation et Nutrition

Houda Bouhajja, Noura Bougacha-Elleuch, Nicolas Lucas, Romain Legrand, Rim Marrakchi, et al.. Affinity kinetics of leptin-reactive immunoglobulins are associated with plasma leptin and markers of obesity and diabetes. Nutrition & Diabetes, 2018, 8 (1), ⟨10.1038/s41387-018-0044-y⟩. ⟨hal-02315360⟩