Regulation of Appetite and Obesity · Journal article
Journal of Endocrinology · September 8, 2026
Encouraging direction, but not yet definitive.
In high-fat diet-fed Leap2-/- mice, 10 weeks of time-restricted feeding reduced body weight, fat mass, and liver weight while improving growth hormone pulsatility, insulin sensitivity, and glucose tolerance without changing total caloric intake. The effect was comparable to that seen in wild-type mice, suggesting that time-restricted feeding benefits metabolic health independently of Leap2 status, though generalization to humans remains uncertain.
Randomized controlled trial in mice. Male Leap2+/+ and Leap2-/- mice aged 10 weeks at enrollment, fed normal diet or high-fat diet in a controlled laboratory setting.. Intervention: Time-restricted feeding for 10 weeks in Leap2-/- high-fat diet mice (n=8).. Compared with: Control feeding (ad libitum or standard protocol) in Leap2-/- high-fat diet mice (n=8).. n = 28.
Body weight significantly increased in Leap2-/- mice on normal diet and was further increased by high-fat diet in both Leap2-/- and wild-type mice, with greater weight gain in Leap2-/- mice. Time-restricted feeding decreased body weight, fat mass, and liver weight in Leap2-/- high-fat diet mice. Time-restricted feeding improved growth hormone pulsatility, insulin sensitivity, and glucose tolerance.
Safety was not reported in the material analysed. Check the source before drawing any conclusion about harm.
This preclinical finding suggests time-restricted feeding may enhance metabolic health through growth hormone and insulin pathways independently of Leap2, potentially supporting investigation of this dietary intervention in humans with obesity or metabolic syndrome. However, results cannot be directly applied to clinical practice without human trials.
A controlled animal study with multiple metabolic endpoints showing that time-restricted feeding improves hormone profiles and energy metabolism in a genetic knockout model, but lacks direct clinical translatability and relies on surrogate outcomes.
As stated by the source record.
Quoted from the source exactly as published.
This preclinical finding suggests time-restricted feeding may enhance metabolic health through growth hormone and insulin pathways independently of Leap2, potentially supporting investigation of this dietary intervention in humans with obesity or metabolic syndrome. However, results cannot be directly applied to clinical practice without human trials.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
Abstract Time-restricted feeding combats obesity by restoring the insulin/growth hormone ratio. Growth hormone and appetite are stimulated by ghrelin but inhibited by Leap2. Whether time-restricted feeding reduces weight gain through Leap2 inhibition is unknown. Ten-week-old male Leap2+/+ and Leap2-/- mice were divided randomly into four groups: Leap2+/+ normal diet (n=6), Leap2+/+ high-fat diet (n=6), Leap2-/- normal diet (n=8), and Leap2-/- high-fat diet (n=8). Body weight was measured weekly. In further experiments, the Leap2-/- high-fat diet mice were randomly assigned to time-restricted feeding or control for 10 weeks. Metabolic parameters were monitored; growth hormone profiles in 6 hours were obtained at week 5, and insulin and glucose tolerance tests were performed at week 8 or 9. Expression of metabolism-related genes was assessed in the liver, white adipose, and brown adipose after 10 weeks. Body weight was significantly increased in Leap2-/- mice with normal diet and further increased in both Leap2-/- and wild-type mice by high-fat diet, with more weight gain in Leap2-/- mice. Time-restricted feeding decreased body weight, fat, and liver weight; improved growth hormone pulsatility, insulin sensitivity, and glucose tolerance; and enhanced lipid metabolism, oxygen consumption, and physical activity during the dark phase, while altering gene expression related to glucose and lipid utilization. It decreased adipocyte size and prevented liver fat accumulation. Although Leap2-/- mice gained more weight during high-fat diet, time-restricted feeding improved growth hormone, insulin, glucose, and lipid metabolism without changing total caloric intake over the 10-week protocol, similar to that observed in wild-type mice.
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