Melatonin decreases human adipose tissue insulin sensitivity.

Area of Science:

• Endocrinology
• Metabolism
• Chronobiology

Background:

• Melatonin, a pineal hormone, regulates circadian rhythms and influences various physiological functions.
• Its role in glucose metabolism is debated, with limited evidence on its direct effects on human adipose tissue (AT).

Purpose of the Study:

• To investigate the impact of melatonin on insulin sensitivity in human AT explants.
• To elucidate the molecular mechanisms underlying melatonin's effect on glucose metabolism.

Main Methods:

• Human abdominal AT biopsies (subcutaneous and visceral) from individuals with severe obesity were used.
• Explants were treated with insulin and/or melatonin at different times of day.
• Insulin signaling was assessed via Western blot (pAKT/tAKT ratio), and transcriptomic changes were analyzed using RNAseq.

Main Results:

• Insulin treatment significantly increased insulin signaling (pAKT/tAKT ratio) in AT.
• Melatonin addition decreased insulin signaling in the presence of insulin, an effect significant only in the evening.
• RNAseq revealed melatonin downregulated the insulin signaling pathway in visceral AT during evening conditions.

Conclusions:

• Melatonin diminishes insulin sensitivity in human adipose tissue during the evening.
• This effect could contribute to reduced glucose tolerance associated with evening melatonin supplementation or late-night eating.