Related Experiment Videos
Leptin modulates NK cell function and MAPK signaling in obesity
Arthur Gomes de Andrade1, Ana Rachel Vasconcelos de Lima2, Aline Cavalcanti de Queiroz2
1Immunology Laboratory of Infectious Diseases, Department of Cellular and Molecular Biology, Federal University of Paraiba, João Pessoa, Paraíba 58051-900, Brazil.
Immunology Letters
|August 10, 2026
Summary
Obesity impairs natural killer (NK) cell function, with leptin having different effects based on weight and sex. This study reveals how metabolic and sex factors alter NK cell responses in obesity.
Area of Science:
- Immunology
- Metabolic Health
- Endocrinology
Background:
- Obesity is linked to chronic inflammation and immune dysregulation.
- Natural killer (NK) cells are sensitive to metabolic signals, and their function is often impaired in obesity.
- Leptin, a hormone associated with obesity, plays a role in immune homeostasis.
Purpose of the Study:
- To investigate the impact of leptin on NK cell frequency, activation, and function in normal-weight and obese adults.
- To explore the intracellular signaling pathways affected by leptin in NK cells from individuals with varying weight status.
- To examine sex-based differences in leptin's modulation of NK cell responses.
Main Methods:
- Comparative analysis of NK cell frequency, activation markers (CD16, NKp46), and effector functions (granzyme B, IFN-γ) in normal-weight and obese adults.
- Leptin stimulation assays to assess dose-dependent effects on NK cell responses.
- Intracellular signaling analysis, including phosphorylation of ERK1/2, p38, and mTOR, in response to leptin.
- Sex-stratified analyses to identify gender-specific modulations.
Main Results:
- Obesity was associated with reduced NK cell frequency and expression of activating receptors (CD16, NKp46).
- Leptin impaired NK cell effector functions (granzyme B, IFN-γ production) in obese individuals, with high leptin concentrations having a suppressive effect.
- Leptin stimulation revealed reduced ERK1/2 and p38 phosphorylation in obese individuals' NK cells, correlating with impaired function.
- mTOR phosphorylation was intrinsically lower in obese individuals' NK cells, irrespective of leptin.
- Sex differences were observed, with lean men showing higher mTOR and granzyme B under high leptin, and men exhibiting more pronounced leptin-mediated IFN-γ suppression.
Conclusions:
- Leptin exerts context-dependent effects on NK cells, influenced by metabolic status and sex.
- Impaired NK cell signaling and function in obesity are partly mediated by leptin's divergent actions.
- These findings highlight the complex interplay between metabolism, sex hormones, and immune cell function in obesity-related immune dysregulation.