Title

Skeletal muscle protein utilization and intracellular signaling events in physically active adults: The impact of an acute energy deficit and leucine intake

Date of Completion

January 2008

Keywords

Chemistry, Biochemistry|Health Sciences, Nutrition

Degree

Ph.D.

Abstract

Skeletal muscle protein utilization is affected by energy balance. However, no studies have characterized the effect of energy deprivation on direct measures of skeletal muscle protein utilization. ^ Purpose. This investigation characterized the effect of an acute energy deficit on skeletal muscle protein turnover (SMPTO) with specific regard for protein synthesis and associated intracellular signaling proteins (ISPs) in physically active adults. ^ Methods. Eleven men (21 y, 76 kg, 176 cm, 15% body fat, VO2peak=57 mL·kg-1·min-1) and seven women (21y, 65 kg, 166 cm, 29% body fat, VO2peak=46 mL·kg -1·min-1) participated in a 20-d, two-phase diet intervention study (WM: weight maintenance; and ED: energy deficient: ∼80% of estimated energy requirements), at two levels of leucine intake (HIGH vs. LOW). SMPTO and ISPs were measured on day 10 of their respective WM and ED diet interventions (1.5 g·kg-1·d-1 protein, dietary fat approximating 30% of total calories). Mixed muscle fractional synthetic rate (FSR) was determined using primed, constant infusions of [ 2H5]-phenylalanine. ISPs specific to FSR were quantified using Western blotting techniques. Resting energy expenditure (REE) and nitrogen balance (NBAL) were estimated using indirect calorimetry and a micro-Kjeldahl apparatus, respectively. Plasma substrates, as well as hormones, were also determined during WM and ED diet interventions. ^ Results. Subjects lost approximately 1 kg body weight during ED (P < 0.0001), with no influence on REE, and NBAL. Leucine intake was greater (P < 0.05) for HIGH (9.3 ± 0.4 g/d) vs. LOW (7.8 ± 0.5 g/d); however, no differences were noted in plasma leucine concentrations. Total amino acids (1938 ± 47 vs. 1811 ± 47 μM) and non-essential amino acids (1014 ± 36 vs. 884 ± 28 μM) decreased ( P < 0.01) in response to ED. Average plasma glucose was lower (P < 0.001) for ED compared to WM (90.1 ± 1 vs. 86.7 ± 1 mg/dL). FFA and lactate were not influenced by energy deprivation. Insulin concentrations tended to be lower for ED (11.8 ± 0.5) compared to WM (12.7 ± 0.7 μIU/mL) ( P = 0.08). Plasma cortisol was not affected by energy status. FSR was reduced ∼32% (P < 0.05) for ED (0.056 ± 0.01%/h) compared to WM (0.083 ± 0.007%/h). Akt and 4E-BP1 phosphorylation was lower (P < 0.05) at 300-min and 120-min, respectively for ED compared to WM. AMPK activation was not affected by energy status. ISP phosphorylation was not affected by leucine intake. ^ Conclusion. These findings show that FSR and related protein synthetic ISPs are downregulated in response to an acute, moderate energy deficit in healthy, physically active adults. ^