Abstract #T229

# T229
Caloric restriction reduces protein accretion in skeletal muscle by attenuating IGF-I signaling in young calves.
Yue Lu1, Jennifer S. Bradley1, Sarah R. McCoski1, John M. Gonzalez2, Adam J. Geiger1, R. Michael Akers1, Alan D. Ealy1, Sally E. Johnson*1, 1Virginia Polytechnic Institute and State University, Blacksburg, VA, 2Kansas State University, Manhattan, KS.

Caloric restriction decreases skeletal muscle mass in mammals, principally due to a reduction in fiber size. This study examined the consequences of reduced caloric intake on the metabolic properties of skeletal muscles in young Holstein heifer calves. Newborn heifers were assigned to a control (CON, n = 5; 28% CP, 25% fat) or caloric restricted (CR, n = 5; 20% CP, 20% fat) milk replacer diet from birth to 8 wks of age. Grain (25% CP, 4% fat) was pair-fed beginning at wk 5. Diets supported ADG of 771 g/d and 220 g/d for CON and CR calves, respectively. Heifers were euthanized at 8 wks and the LM was collected for muscle morphometry, gene expression and metabolic signal transduction measurements. The effect of diet was exained using by Student t-test with α = 0.05. Results revealed that CR heifers had smaller (P < 0.05) LM fiber cross-sectional area and a greater percentage of oxidative type I and IIA fibers. The oxidative fiber type of the CR LM was not associated with elevated expression of PGC1α, a mitochondria biogenesis factor. Reverse transcription-qPCR revealed PGC1α mRNA levels were 40% lower in CR than CON LM. Western blot analysis detected reduced (P < 0.05) amounts of PGC1α4, a PGC1a splice variant, in CR LM. The PGC1α4 target gene, IGF-I, was 40% lower (P < 0.05) in CR than CON. Downstream mediators of autocrine IGF-I signaling are attenuated in CR by comparison to CON. The amount of phosphorylated AKT was lower (P < 0.05) in CR than CON. However, activated components of the AKT/mTOR signaling axis, p70 S6 kinase, ERK1/2 and 4E-BP1, were equivalent or unaffected (P > 0.05) by CR. Activation of the energy sensor, AMP kinase, was not detected in either CON or CR lysates indicating that a block to mTOR-controlled protein synthesis is absent. Protein lysates from CR LM contained less (P < 0.05) total and phosphorylated, inactive GSK3β than CON LM. Elevated GSK3β activity is associated with inhibition of protein synthesis as well as induction of atrogin. Reverse transcription-qPCR demonstrated no differences (P < 0.05) in atrogin expression levels between CON and CR. These results indicate that CR suppresses a hypertrophic PGC1α4/IGF-I/AKT pathway in young heifer calves through an undiscovered mechanism.

Key Words: skeletal muscle, metabolism, IGF-I