Caloric restriction and intermittent fasting alter hepatic lipid droplet proteome and diacylglycerol species and prevent diabetes in NZO mice
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Caloric restriction and intermittent fasting alter hepatic lipid droplet proteome and diacylglycerol species and prevent diabetes in NZO mice. / Baumeier, Christian; Kaiser, Daniel; Heeren, Jörg; Scheja, Ludger; John, Clara; Weise, Christoph; Eravci, Murat; Lagerpusch, Merit; Schulze, Gunnar; Joost, Hans-Georg; Schwenk, Robert Wolfgang; Schürmann, Annette.
in: Biochim Biophys Acta, Jahrgang 1851, Nr. 5, 05.2015, S. 566-76.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Caloric restriction and intermittent fasting alter hepatic lipid droplet proteome and diacylglycerol species and prevent diabetes in NZO mice
AU - Baumeier, Christian
AU - Kaiser, Daniel
AU - Heeren, Jörg
AU - Scheja, Ludger
AU - John, Clara
AU - Weise, Christoph
AU - Eravci, Murat
AU - Lagerpusch, Merit
AU - Schulze, Gunnar
AU - Joost, Hans-Georg
AU - Schwenk, Robert Wolfgang
AU - Schürmann, Annette
N1 - Copyright © 2015. Published by Elsevier B.V.
PY - 2015/5
Y1 - 2015/5
N2 - Caloric restriction and intermittent fasting are known to improve glucose homeostasis and insulin resistance in several species including humans. The aim of this study was to unravel potential mechanisms by which these interventions improve insulin sensitivity and protect from type 2 diabetes. Diabetes-susceptible New Zealand Obese mice were either 10% calorie restricted (CR) or fasted every other day (IF), and compared to ad libitum (AL) fed control mice. AL mice showed a diabetes prevalence of 43%, whereas mice under CR and IF were completely protected against hyperglycemia. Proteomic analysis of hepatic lipid droplets revealed significantly higher levels of PSMD9 (co-activator Bridge-1), MIF (macrophage migration inhibitor factor), TCEB2 (transcription elongation factor B (SIII), polypeptide 2), ACY1 (aminoacylase 1) and FABP5 (fatty acid binding protein 5), and a marked reduction of GSTA3 (glutathione S-transferase alpha 3) in samples of CR and IF mice. In addition, accumulation of diacylglycerols (DAGs) was significantly reduced in livers of IF mice (P=0.045) while CR mice showed a similar tendency (P=0.062). In particular, 9 DAG species were significantly reduced in response to IF, of which DAG-40:4 and DAG-40:7 also showed significant effects after CR. This was associated with a decreased PKCε activation and might explain the improved insulin sensitivity. In conclusion, our data indicate that protection against diabetes upon caloric restriction and intermittent fasting associates with a modulation of lipid droplet protein composition and reduction of intracellular DAG species.
AB - Caloric restriction and intermittent fasting are known to improve glucose homeostasis and insulin resistance in several species including humans. The aim of this study was to unravel potential mechanisms by which these interventions improve insulin sensitivity and protect from type 2 diabetes. Diabetes-susceptible New Zealand Obese mice were either 10% calorie restricted (CR) or fasted every other day (IF), and compared to ad libitum (AL) fed control mice. AL mice showed a diabetes prevalence of 43%, whereas mice under CR and IF were completely protected against hyperglycemia. Proteomic analysis of hepatic lipid droplets revealed significantly higher levels of PSMD9 (co-activator Bridge-1), MIF (macrophage migration inhibitor factor), TCEB2 (transcription elongation factor B (SIII), polypeptide 2), ACY1 (aminoacylase 1) and FABP5 (fatty acid binding protein 5), and a marked reduction of GSTA3 (glutathione S-transferase alpha 3) in samples of CR and IF mice. In addition, accumulation of diacylglycerols (DAGs) was significantly reduced in livers of IF mice (P=0.045) while CR mice showed a similar tendency (P=0.062). In particular, 9 DAG species were significantly reduced in response to IF, of which DAG-40:4 and DAG-40:7 also showed significant effects after CR. This was associated with a decreased PKCε activation and might explain the improved insulin sensitivity. In conclusion, our data indicate that protection against diabetes upon caloric restriction and intermittent fasting associates with a modulation of lipid droplet protein composition and reduction of intracellular DAG species.
KW - Animals
KW - Blood Glucose
KW - Caloric Restriction
KW - Diabetes Mellitus, Type 2
KW - Diglycerides
KW - Disease Models, Animal
KW - Fasting
KW - Fatty Acids
KW - Food Deprivation
KW - Insulin
KW - Insulin Resistance
KW - Lipid Droplets
KW - Liver
KW - Male
KW - Mice, Obese
KW - Muscle, Skeletal
KW - Obesity
KW - Oxidation-Reduction
KW - Protein Kinase C-epsilon
KW - Proteome
KW - Time Factors
U2 - 10.1016/j.bbalip.2015.01.013
DO - 10.1016/j.bbalip.2015.01.013
M3 - SCORING: Journal article
C2 - 25645620
VL - 1851
SP - 566
EP - 576
JO - Biochim Biophys Acta
JF - Biochim Biophys Acta
SN - 0006-3002
IS - 5
ER -