NK cells in childhood obesity are activated, metabolically stressed, and functionally deficient

Area of Science:

• Immunology
• Pediatric Endocrinology
• Oncology

Background:

• Childhood obesity affects over 50 million children globally.
• Obesity is linked to chronic inflammatory diseases, including type 2 diabetes and cancers.
• Natural killer (NK) cells are crucial for innate immunity, adipose tissue regulation, and antitumor surveillance.

Purpose of the Study:

• To investigate the impact of obesity on NK cell frequency, activation, metabolism, and function in children.
• To compare NK cells from obese children with those from healthy-weight children.

Main Methods:

• Analysis of peripheral NK cell frequencies in a cohort of obese and healthy-weight children.
• Assessment of NK cell activation markers (e.g., PD-1, mTOR), metabolic activity (ECAR, mitochondrial ROS), and functional capacity (proliferation, tumor lysis).
• Correlation analysis between NK cell parameters, body mass index, and insulin resistance.

Main Results:

• Obese children exhibited reduced peripheral NK cell frequencies, inversely correlated with BMI and insulin resistance.
• NK cells from obese children showed increased activation and metabolic stress (elevated PD-1, mTOR, ECAR, ROS).
• Obese children's NK cells displayed a diminished capacity for proliferation and tumor lysis, indicating functional impairment.

Conclusions:

• Childhood obesity leads to a significant reduction and functional decline in NK cells.
• These NK cell alterations suggest compromised antitumor immunity early in the course of obesity.
• Early-life obesity negatively impacts immune surveillance, potentially increasing long-term cancer risk.