Abstract
Recent studies show that the metabolic effects of fructose may vary depending on the phase of its consumption along with the light/dark cycle. Here, we investigated the metabolic outcomes of fructose consumption by rats during either the light (LPF) or the dark (DPF) phases of the light/dark cycle. This experimental approach was combined with other interventions, including restriction of chow availability to the dark phase, melatonin administration or intracerebroventricular inhibition of adenosine monophosphate-activated protein kinase (AMPK) with Compound C. LPF, but not DPF rats, exhibited increased hypothalamic AMPK phosphorylation, glucose intolerance, reduced urinary 6-sulfatoxymelatonin (6-S-Mel) (a metabolite of melatonin) and increased corticosterone levels. LPF, but not DPF rats, also exhibited increased chow ingestion during the light phase. The mentioned changes were blunted by Compound C. LPF rats subjected to dark phase-restricted feeding still exhibited increased hypothalamic AMPK phosphorylation but failed to develop the endocrine and metabolic changes. Moreover, melatonin administration to LPF rats reduced corticosterone and prevented glucose intolerance. Altogether, the present data suggests that consumption of fructose during the light phase results in out-of-phase feeding due to increased hypothalamic AMPK phosphorylation. This shift in spontaneous chow ingestion is responsible for the reduction of 6-S-Mel and glucose intolerance.
Highlights
Impaired glucose tolerance [1] and insulin resistance [2] can be induced in rodents and humans by excessive fructose consumption.For instance, Sprague–Dawley rats fed a fructose-enriched diet develop impaired glucose tolerance and Nutrients 2017, 9, 332; doi:10.3390/nu9040332 www.mdpi.com/journal/nutrientsNutrients 2017, 9, 332 whole body insulin resistance [3]
We have previously demonstrated that short-term fructose injections in the central nervous system during the light phase leads to an increase in the endogenous glucose production (EGP) by hypothalamic AMP-activated protein kinase (AMPK)
When specified in the results section, one of the three experimental strategies was combined with the fructose treatment: (i) chow availability was restricted to the dark phase (Chow-R rats) during the 8 weeks of treatment; (ii) compound C was administered during the last week of treatment through a cannula placed in the lateral ventricle or (iii) melatonin dissolved in the drinking water was administrated during the dark phase during the 8 weeks of treatment
Summary
Impaired glucose tolerance (defined for humans as 2 h values in the oral glucose tolerance test ranging between 140 mg/dL and 199 mg/dL) [1] and insulin resistance (resistance to insulin-stimulated glucose uptake) [2] can be induced in rodents and humans by excessive fructose consumption.For instance, Sprague–Dawley rats fed a fructose-enriched diet develop impaired glucose tolerance and Nutrients 2017, 9, 332; doi:10.3390/nu9040332 www.mdpi.com/journal/nutrientsNutrients 2017, 9, 332 whole body insulin resistance [3]. Sprague–Dawley rats fed a fructose-enriched diet develop impaired glucose tolerance and Nutrients 2017, 9, 332; doi:10.3390/nu9040332 www.mdpi.com/journal/nutrients. Fructose-enriched diets were found to cause impaired glucose tolerance with concomitant hepatic triglyceride accumulation and insulin resistance [4]. Among the myriad of endocrine changes that putatively underlie these metabolic effects, the consumption of a fructose-enriched diet was shown to reduce nocturnal melatonin production in rats [6]. Surgical ablation of the pineal gland was reported to result in impaired glucose tolerance and insulin resistance with increased nocturnal levels of glycemia and gluconeogenesis [7,8,9]. Exogenous melatonin administration is able to improve the metabolic control in rodents rendered glucose intolerant either by high-fat diets or fructose administration [11,12,13]
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