Interleukin-15 modulates adipose tissue by altering mitochondrial mass and activity

Area of Science:

• Immunology
• Metabolism
• Mitochondrial Biology

Background:

• Interleukin-15 (IL-15) is an immunomodulatory cytokine known to affect body mass regulation.
• The precise mechanisms by which IL-15 influences body weight, independent of lymphocytes, are not fully understood.
• Mitochondrial function in adipose tissue is a critical component of energy homeostasis and body weight regulation.

Purpose of the Study:

• To investigate the mechanisms underlying IL-15's role in body mass regulation.
• To examine the impact of IL-15 on adipose tissue mitochondrial activity and lipid metabolism.
• To determine if IL-15 affects body weight through alterations in gut microbiota or macronutrient absorption.

Main Methods:

• Metabolic cage studies were conducted in lean IL-15 transgenic (IL-15tg), overweight IL-15 deficient (IL-15-/-), and control C57Bl/6 (B6) mice.
• Intestinal bacterial diversity, macronutrient absorption, and adipose mitochondrial activity were assessed.
• In vitro studies involved treating cultured adipocytes with IL-15.

Main Results:

• Body weight differences were not attributable to variations in activity levels, food intake, or respiratory exchange ratio.
• Gut microbiota profiles did not correlate with body weight differences in germ-free mice or affect macronutrient absorption.
• IL-15 treatment of adipocytes increased mitochondrial membrane potential and decreased lipid deposition; IL-15tg mice exhibited elevated adipose mitochondrial activity and mass.

Conclusions:

• IL-15 plays a significant role in regulating adipose tissue.
• Altered mitochondrial function in adipocytes is a key mechanism linking IL-15 to body mass regulation.
• IL-15's effects on body weight are independent of its influence on gut microbiota and macronutrient absorption.