Proceedings of The Physiological Society
University of Oxford (2011) Proc Physiol Soc 23, C51
Adaptive metabolic response of whole body and skeletal muscle to periodic high sugar availability in lean sedentary individuals
H. Kubis1, F. Sartor1, M. Jackson1, C. Squillace1, D. Ayer2
1. Bangor University, Bangor, United Kingdom. 2. Huntsman Cancer Institute, University of Utah, Utah, United States.
Hyperglycemia is a contributing factor for metabolic alterations seen in type 2 diabetes mellitus (T2DM). Skeletal muscle in T2DM displays reduced oxidative capacity with an elevation in glycolytic and lipogenic enzyme expression. Recently it was shown that transcription factors MondoA and MondoB mediate responses to elevated glucose availability in various cell types in vitro. Up-regulation of glycolytic and lipogenic gene expression in skeletal muscle was shown to be related to MondoA. While there is growing evidence about the regulatory impact of high glucose availability on metabolism in type 2 diabetes, less is known about the contribution of nutrition based periodic high glucose availability, like chronic ingestion of sugar sweetened beverages, in healthy sedentary individuals. Therefore we recruited sedentary healthy lean subjects without former history of chronic soft-drink consumption. They consumed sugar sweetened beverages (~2g sugar/kg body weight per day) on top of their usual diet for 4 weeks. Pre and post intervention fasting glucose, insulin and blood lipids were measured. Additionally muscle biopsies from quadriceps femoris were taken (under 1% lignocaine injection anaesthesia) for RT-PCR based metabolic gene expression measurements and Western Blot analysis of MondoA. Moreover, indirect calorimetry, DEXA scan and a diet diary has been performed. Post intervention indirect calorimetry showed a significant increase in RER (Pre=0.75 ± 0.09, Post=0.87 ± 0.08) revealing a reduction in fatty acid oxidation and increase in carbohydrate metabolism, DEXA analysis revealed a gain in fat mass (Pre=15.2 ± 5.1kg, Post=16.2 ± 4.7kg). Fasting glucose was significantly increased (Pre= 4.83 ± 0.43 mmol/L, Post= 5.13 ± 0.38 mmol/L), while insulin levels (Pre= 4.95± 1.90 mU/L, Post= 6.40 ± 1.62 mU/L) and HOMA2 derived insulin resistance (Pre= 0.68 ± 0.19, Post= 0.84 ± 0.20) showed trends. Blood lipids did not alter post intervention. Muscle biopsy analysis revealed a significant increase in lipogenic ACC mRNA (Pre= 0.99±0.52AU, Post= 1.21±0.78AU) and glycolytic GAPDH mRNA (Pre= 1.00±0.74AU, Post= 1.94±1.52AU) expression, as well as a significant reduction of PGC1alpha mRNA (Pre= 0.96±0.44AU, Post= 0.79 ±0.53). Additionally, protein levels of MondoA (Pre= 1.00 ± 1.08 AU, Post= 2.58 ± 2.46 AU) showed a trend towards elevation post intervention. In conclusion 4 weeks sugar sweetened beverage consumption could shift substrate metabolism towards use of carbohydrate, increased fasting blood glucose and mediated alterations of metabolic gene expression in muscle towards increased glycolytic and lipogenic activity. In conclusion, we suggest that periodical high glucose availability, induced by repetitive soft-drink consumption, may contribute to alterations in metabolism known to be symptomatic for T2DM individuals even before the development of obesity.
Where applicable, experiments conform with Society ethical requirements