Why (and how) being sick often reduces appetite

Amazing stuff!

"Key points

• Many people experience appetite loss when they’re sick.
• Researchers found that mice in similar states displayed a strong aversion to protein-rich food in particular.
• The aversion was linked to ammonia production and a gut-to-brain communication circuit.
• The findings could inform more effective post-illness diets and treatments for anorexia or cancer cachexia.

...

uncovered a gut-to-brain signaling pathway in mice that restricts appetite—specifically for protein—during recovery. ...

Many people experience appetite loss when they’re sick, and with less food intake, their bodies begin breaking down molecules like protein for energy. This is known as a catabolic state and it’s where the researchers started their work.

They offered mice that were in a catabolic state one of three diets that each had the same amounts of calories and micronutrients but different macronutrients: protein, carbohydrates, or fat. The mice given the high-carbohydrate and high-fat diets ate expected amounts, but those given the protein-rich diet ate much less than mice not in a catabolic state.

Through various experimental approaches, Jaschke and colleagues found that mice recovering from catabolic states displayed an exceptionally strong aversion to protein-rich food. ..."

From the highlights and abstract:

"Highlights

• Mice voluntarily restrict dietary protein during recovery from catabolic insults

• Three amino acids (Q, K, and T) are necessary and sufficient for protein aversion

• Gut EC sense dietary ammoniagenesis in a TRPA1-dependent manner

• TRPA1-dependent serotonin release is transduced from the gut to the brain

Summary

Dietary needs are dynamic, with optimal ranges for nutrients varying over time and across physiological states. How optimal nutrient set points are established and why they are adjusted remains largely unknown.

In our efforts to understand the physiology of recovery, we made the surprising observation that mice restrict protein intake at the expense of caloric supply. We identified three amino acids—glutamine (Q), lysine (K), and threonine (T)—within dietary protein, which are necessary and sufficient for protein aversion during recovery from catabolic states.

The anorexigenic effects of QKT are driven by ammoniagenesis in the gut, sensed by enterochromaffin cells in a TRPA1-dependent fashion and transduced to brainstem neurons via serotonin signaling, inducing anorexia. We propose that this mechanism serves as a first-line defense against ammonia toxicity.

In summary, we identified a set of adaptive food preferences during recovery (“recovery behavior”), with implications for understanding diseases of pathologic recovery and the development of therapeutic interventions deployed to enhance recovery."

Gut-to-Brain Signaling Restricts Post-Illness Protein Appetite | Yale School of Medicine

Gut-to-brain signaling restricts dietary protein intake during recovery from catabolic states (no public access)

Graphical abstract