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- Title
Altered Hepatic Gluconeogenesis and Energy Metabolism During Carbohydrate Restriction in Humans.
- Authors
Browning, Jeffrey D.; Davis, Jeanie; Burgess, Shawn C.
- Abstract
Carbohydrate restriction is now a common weight loss approach. This diet modifies hepatic metabolism in humans by increasing ketosis and shifting the source of hepatic glucose production from glycogenolysis to gluconeogenesis. However, it is not known whether elevated gluconeogenesis during carbohydrate restriction originates from increased PEPCK flux or from glycerol derived from lipolysis. Moreover, the manner in which associated pathways, such as the tricarboxylic acid (TCA) cycle and gluconeogenesis, adapt to accommodate altered hepatic fat oxidation during this diet is largely unknown. To gain a better understanding of hepatic energy production and its relationship to gluconeogenesis during carbohydrate restriction in humans, we used ²H and [sup 13]C tracers combined with nuclear magnetic resonance spectroscopy to measure endogenous glucose production, glycogenolysis (GLY), gluconeogenesis from PEP (GNG[sub PEP]), gluconeogenesis from glycerol (GNG[sub glycerol]), pyruvate cycling, and hepatic TCA cycle flux. Human subjects were studied after an overnight fast, following two weeks on either a carbohydrate-restricted diet (20 g/d CHO) or Western-style calorie-restricted diet (-800 kcal/d). Compared to control subjects, carbohydrate restriction resulted in a 2-fold decrease in the percent of glucose derived from GLY and a corresponding increase ill GNG[sub PEP]. Surprisingly, there was no difference in GNG[sub glycerol] between groups, although both groups demonstrated a 2-fold higher contribution than previous measurements in normal subjects. Carbohydrate restriction stimulated an increase in PEPCK flux without an appreciable change in hepatic pyruvate cycling. Interestingly, the rate of substrate oxidation in the hepatic TCA cycle strongly correlated with the absolute rate of GNG[sub PEP] in both the control and carbohydrate restricted groups; however, this correlation was shifted significantly during carbohydrate restriction as a function of circulating ketone levels, indicating a relationship with β-oxidation. We conclude that carbohydrate restriction modifies hepatic glucose production by increased reliance on gluconeogenesis from PEP and that this is facilitated in part by increased PEPCK flux driven by altered hepatic energetics. ADA-Funded Research
- Publication
Diabetes, 2007, Vol 56, pA391
- ISSN
0012-1797
- Publication type
Academic Journal