title: High-Fat Diet and Palmitate Alter the Rhythmic Secretion of Glucagon-Like Peptide-1 by the Rodent L-cell.
abstract: Secretion of the incretin hormone, glucagon-like peptide-1 (GLP-1), by the intestinal L-cell is rhythmically regulated by an independent molecular clock. However, the impact of factors known to affect the activity of similar cell-autonomous clocks, such as circulating glucocorticoids and high-fat feeding, on GLP-1 secretory patterns remains to be elucidated. Herein the role of the endogenous corticosterone rhythm on the pattern of GLP-1 and insulin nutrient-induced responses was examined in corticosterone pellet-implanted rats. Moreover, the impact of nutrient excess on the time-dependent secretion of both hormones was assessed in rats fed a high-fat, high-sucrose diet. Finally, the effects of the saturated fatty acid, palmitate, on the L-cell molecular clock and GLP-1 secretion were investigated in vitro using murine GLUTag L-cells. Diurnal variations in GLP-1 and insulin nutrient-induced responses were maintained in animals lacking an endogenous corticosterone rhythm, suggesting that glucocorticoids are not the predominant entrainment factor for L-cell rhythmic activity. In addition to hyperglycemia, hyperinsulinemia, insulin resistance, and disorganization of feeding behavior, high-fat high-sucrose-fed rats showed a total abrogation of the diurnal variation in GLP-1 and insulin nutrient-induced responses, with comparable levels of both hormones at the normal peak (5:00 pm) and trough (5:00 am) of their daily pattern. Finally, palmitate incubation induced profound derangements in the rhythmic expression of circadian oscillators in GLUTag L-cells and severely impaired the secretory activity of these cells. Collectively our findings demonstrate that obesogenic diets disrupt the rhythmic activity of the L-cell, partially through a direct effect of specific nutritional components.
authors.affiliation: Departments of Physiology (M.G.-L., W.K.W., A.M., P.L.B.) and Medicine (P.L.B.), University of Toronto, Toronto, Ontario, Canada M5S 1A8.
authors.forename: Manuel
authors.initials: M
authors.lastname: Gil-Lozano
authors.affiliation: Departments of Physiology (M.G.-L., W.K.W., A.M., P.L.B.) and Medicine (P.L.B.), University of Toronto, Toronto, Ontario, Canada M5S 1A8.
authors.forename: W Kelly
authors.initials: WK
authors.lastname: Wu
authors.affiliation: Departments of Physiology (M.G.-L., W.K.W., A.M., P.L.B.) and Medicine (P.L.B.), University of Toronto, Toronto, Ontario, Canada M5S 1A8.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Martchenko
authors.affiliation: Departments of Physiology (M.G.-L., W.K.W., A.M., P.L.B.) and Medicine (P.L.B.), University of Toronto, Toronto, Ontario, Canada M5S 1A8.
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Brubaker
mesh_terms: D000818:Animals; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology; D003345:Corticosterone / Q000378:metabolism; D059305:Diet, High-Fat; D004041:Dietary Fats / Q000494:pharmacology*; D019858:Enteroendocrine Cells / Q000187:drug effects* / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D005951:Glucose Tolerance Test; D007328:Insulin / Q000378:metabolism; D008297:Male; D019308:Palmitic Acid / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D055571:Secretory Pathway / Q000187:drug effects
chemical_list: D004041:Dietary Fats; D007328:Insulin; D019308:Palmitic Acid; D052216:Glucagon-Like Peptide 1; D003345:Corticosterone