Studying the interaction between immune and metabolic responses

It’s no secret that modern high-calorie diets aren’t terribly compatible with the innate metabolic and immune responses that kept our species going for thousands of years—when people had to walk miles every day to find meager supplies of food and were on the constant lookout for lion attacks. The metabolic system and the immune system had to work together to fight pathogens, process food for energy and shut off when there was a more immediate threat in the environment.

Uncovering how these ancestral metabolic and innate immune systems work together helps us understand how these systems go awry in our modern world, leading to metabolic syndrome and associated conditions like type 2 diabetes, heart disease and obesity.

New research from the Texas A&M College of Medicine contributes one additional small piece of that puzzle. The researchers found that there is a role for a type of innate immune transcription factor, called NFkB, in controlling fat metabolism during metabolic adaptation to fasting, according to research published recently in the journal Developmental Cell. Essentially, they discovered one way that the immune system affects metabolism of fat in the body.

While the study was done using Drosophila (tiny fruit flies) there may be implications for how the human body functions as well.

“This kind of research allows us to go back in time, so to speak, and understand why these pathways are integrated,” said Jason Karpac, PhD, assistant professor in the College of Medicine and lead author of the study.

During fasting, when the body doesn’t have new sources of energy coming in, NFkB helps control the break down existing fats into their constituent fatty acids to provide energy and help the animal survive. Specifically, NFkB limits the function of a metabolic transcription factor, Foxo. It is the interaction of these two transcription factors that regulate lipid metabolism during metabolic adaptation. This is an example of the coordination of innate immune and metabolic responses.

“These old primitive responses must have co-evolved together, so studying the integration of innate immune and metabolic systems can help us see why they’re critical and why they might be causing disease in humans,” Karpac said. “My lab and others are beginning to establish how these systems work together, which holds promise for discovering both novel disease mechanisms and pharmaceutical targets aimed at treating the underlying metabolic imbalances that lead to obesity and other problems.”