Interrupting T cell memory ameliorates exaggerated metabolic response to weight cycling

Area of Science:

• Immunology
• Metabolic disease
• Obesity research

Background:

• Weight cycling, common in humans, exacerbates cardiometabolic disease and disrupts glucose homeostasis.
• Obesity and weight regain induce adipose tissue inflammation and metabolic dysfunction.
• Immune cells, like memory T cells, persist in adipose tissue after weight loss, contributing to inflammation upon weight regain.

Purpose of the Study:

• To investigate the role of immune memory in metabolic dysfunction associated with weight cycling.
• To explore the therapeutic potential of targeting the CD70-CD27 axis for weight cycling-induced metabolic consequences.

Main Methods:

• Blocking the CD70-CD27 axis in animal models undergoing weight cycling.
• Assessing changes in adipose tissue immune cell populations, including memory T cells and T cell clonality.
• Evaluating metabolic responses, specifically glucose tolerance, in mice with impaired immune memory formation.

Main Results:

• Blocking the CD70-CD27 axis reduced memory T cells and T cell clonality in adipose tissue post-weight cycling.
• Mice unable to form obesogenic immune memory were protected from worsened glucose tolerance during weight cycling.
• These findings highlight the immune system's 'memory' of obesity contributing to weight cycling's adverse effects.

Conclusions:

• Targeting the CD70-CD27 axis represents a novel immunomodulatory strategy to mitigate the metabolic consequences of weight cycling.
• This approach offers a potential therapeutic avenue, particularly relevant with the rise of weight loss drugs promoting weight cycling.