Relationship between time of fructose intake and hypothalamic AMPK rhythm: possible connections of the metabolic outcome with melatonin production

Abstract

The consuption of fructose enriched diets exerts a well recognized effect on glucose homeostasis that is hallmarked by insulin resistance, hepatic steatosis and increased gluconeogesis. The precise mechanism underlying these effects are not completely known but a role for hypothalamic AMPK activation has been demonstrated in the onset of hyperphagia and upregulation of gluconeogenesis. Among several endocrine modulations, fructose was recently described to inhibit nocturnal surge of melatonin. Melatonin is a hormone produced in a circadian fashion that synchronizes the energetic metabolism by increasing insulin sensitivity and decreasing gluconeogenesis. As for melatonin production, AMPK activity varies throughout the light dark/cycle in a circadian fashion with peaking levels during the night. It was recently demonstrated that increasing hypothalamic AMPK activity reduces melatonin production. Interestingly, daytime ingested fructose worsens glucose homeostasis in more dramatic levels than nighttime ingested fructose. The present investigation intends to evaluate if the metabolic alterations induced by daytime ingested fructose are dependent on changes in AMPK rhythm and melatonin production.