Nighttime may be an important window for treatment and lifestyle decisions in fatty liver disease. Digest
Metabolic dysfunction-associated steatotic liver disease (MASLD) involves fat accumulation in the liver, but less is known about whether the underlying metabolic defects vary across the day. Researchers tested whether day–night differences in how the body handles sugar and fat could help explain why fat builds up in the liver.
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The study included 24 overweight adults: 12 with MASLD and 12 controls without MASLD. Participants did not have diabetes, and each completed separate daytime and nighttime testing visits after 12 hours of fasting. Researchers measured insulin sensitivity using the gold-standard hyperinsulinemic–euglycemic clamp and also assessed sugar production and use as well as fat metabolism. Insulin is a hormone that, in insulin-sensitive individuals, effectively helps move sugar (glucose) from the blood into cells and reduces the body's own sugar production. Insulin resistance impairs this process, resulting in higher blood sugar and increased fat release into the bloodstream.
- Controls showed lower de novo lipogenesis (the liver's production of new fat from non-fat sources) at night, while MASLD participants kept this pathway elevated.
- In MASLD, but not in controls, the liver produced more glucose at night than during the day under low-dose insulin infusion.
- The body cleared less sugar from the blood at night in both groups, while MASLD participants consistently had about 40% to 60% lower glucose clearance than controls overall, indicating reduced uptake into skeletal muscle.
- During low-dose insulin infusion, MASLD participants showed a greater nighttime rise in free fatty acids in the blood than controls, and this was linked to higher liver fat levels measured by an ultrasound-based test.
- At night, insulin levels were lower only in MASLD, even though participants received the same insulin infusion as during their daytime test. This was not a sign of better insulin sensitivity: the body was still responding poorly to insulin, while its own insulin secretion dropped by more than 66% and insulin was removed from the blood faster.
- Eleven MASLD patients participated in a 12-week lifestyle and weight-loss program. They lost about 6.3% of their body weight and showed improvements in body composition, liver markers, and liver fat. Even so, many nighttime metabolic differences persisted.
Rather than pointing to a single defect, the findings suggest a nighttime imbalance in how the body handles fuel in MASLD. Normally, insulin helps coordinate how the liver, muscles, and body fat manage sugar and fat during fasting. That coordination appeared weaker at night in MASLD. The researchers also analyzed proteins in the blood and in small samples of fat and muscle tissue to look for underlying biological signals. These patterns pointed to differences in how the body processes fat for energy and how muscles use fuel. However, this was just an additional exploratory analysis that does not prove that these processes are causing the observed effects.
Overall, the results indicate that nighttime may be an important window for treatment in MASLD, including when people eat, exercise, or take medications, with large evening meals potentially placing greater metabolic stress. Further studies need to confirm the results and are also needed to test whether changing the timing of these lifestyle behaviors improves outcomes. In Q&A #76, I explain how choline and creatine may help protect against fatty liver disease.