Ask the author session

Metabolic dysfunction–associated steatotic liver disease (MASLD) continues to challenge clinicians and researchers worldwide. While much is known about its links to obesity, insulin resistance, and lifestyle factors, a new perspective is emerging—one that shifts our attention to when metabolic dysfunction happens, not just how.

In a recent “Ask the Author” session, Thomas Marjot shares groundbreaking findings from his latest publication in Cell Metabolism, offering a fresh and thought-provoking understanding of Metabolic dysfunction-associated steatotic liver disease.

👉 You can watch the full interview on our website—don’t miss it.

A 24-Hour View of Metabolism

Traditionally, MASLD has been studied as a static condition. But Dr. Marjot and his team took a different approach: they examined metabolic processes across a full 24-hour cycle in patients with MASLD and compared them to overweight controls.

Using advanced metabolic phenotyping techniques—including insulin infusion studies and stable isotope tracing—they were able to map how key metabolic pathways fluctuate between day and night.

The Key Finding: Nighttime Matters Most

The results reveal something striking: MASLD is strongly diurnal, with metabolic dysfunction peaking at night.

During nighttime, patients exhibit:

  • Increased insulin resistance (both hepatic and peripheral)
  • Elevated de novo lipogenesis (fat production in the liver)
  • Higher exposure to circulating fatty acids
  • Reduced insulin availability due to decreased secretion and increased clearance

This creates a “perfect storm” for liver fat accumulation while the body is least equipped to handle it.

Even more compelling, these abnormalities persist even after weight loss and reduction in liver fat, suggesting that nighttime dysfunction is not just a consequence—but a primary driver of the disease.

What Does This Mean for Patients and Clinicians?

These findings could reshape how MASLD is managed in clinical practice:

1. Timing of Medication

Current therapies target metabolic pathways—but rarely consider when drugs are administered. This research suggests that evening dosing may enhance effectiveness by targeting peak dysfunction.

2. Lifestyle Interventions

  • Evening exercise may help counteract poor nighttime muscle metabolism
  • Reducing large evening meals could prevent overwhelming an already compromised metabolic system

3. Rethinking Clinical Measurements

Metabolic markers such as insulin resistance or glucose tolerance may vary significantly depending on the time of day. Incorporating chronobiology into clinical assessments could improve accuracy and interpretation.

Why You Should Watch the Full Session

This blog only scratches the surface of a rich and insightful discussion. In the full video, Dr. Marjot explains:

  • The study design in detail
  • The physiological mechanisms behind nighttime dysfunction
  • The broader implications for research and therapeutic development

👉 Watch the full “Ask the Author” session to hear directly from the expert.

Dive Deeper into the Science

For those interested in the full scientific details, the published paper provides comprehensive insights into:

  • Diurnal changes in lipid and glucose metabolism
  • Molecular pathways involved in MASLD progression
  • Potential therapeutic targets identified through integrated proteomics

👉 Read the full paper to explore the data and methodology behind these findings.

A New Way of Thinking About MASLD

This research challenges a long-standing assumption: that metabolic diseases behave the same way throughout the day. By highlighting the importance of timing, it opens the door to more precise and potentially more effective interventions.

As the field evolves, one thing becomes clear—in MASLD, the night shift may be where the real story unfolds.

👉 Watch the full interview with Dr. Thomas Marjot now here on the Swiss NASH Foundation website.