Meeting Abstract

36.4  Friday, Jan. 4  Direct measurement of starvation-induced shifts in endogenous fuel oxidation in mice MCCUE, M.D.; St. Mary’s Univ mmccue1@stmarytx.edu

Fasting animals typically switch from one metabolic substrate to another in the order of carbohydrates, lipids, and then proteins. The timing of these physiological transitions are traditionally estimated using indirect measures of substrate oxidation including, changes in respiratory exchange ratios (RER), blood metabolites, or enzyme activity. Here I describe how different nutrient pools in the body can be chronically ¹³C labeled and how fasting-induced physiological shifts in substrate oxidation can be directly quantified using ¹³CO₂-breath testing. Weanling mice were raised to adulthood on diets supplemented with one of three artificially enriched isotope tracers (i.e., ¹³C-1-L-leucine, ¹³C-1-palmitic acid, or ¹³C-1-D-glucose). The adult mice were then fasted for 72 hours during which VO₂, VCO₂, δ¹³CO₂, and blood metabolites (i.e., glucose, ketone bodies, and triacylglycerides) were continually measured. The fasting mice exhibited predicted reductions in body mass, activity, BMR, and RER. Although RERs rapidly decreased between 6h-8h, they remained constant thereafter, precluding meaningful interpretations of changes in fuel oxidation. Breath testing revealed a clear, transient peak in ¹³CO₂ production in the ¹³C-glucose mice occurred between 8h-18h, during the transition of Phase I to Phase II. By 6h endogenous lipid oxidation increased from 6% of the energy budget to over half of the energy used by mice. The amount of energy derived from protein oxidation dropped sharply during the first 10h (i.e. protein sparing) and eventually reached a point where protein oxidation accounted for as little as 9% of the energy expenditure. By the end of the 72-hour experiment protein oxidation accounted for at least 24% of the total energy expenditure. This experiment supports the idea that direct measurements of substrate oxidation complement traditional,indirect approaches to studying fasting physiology.