Mixed lactate and caffeine compound increases satellite cell activity and anabolic signals for muscle hypertrophy

J Appl Physiol (1985). 2015 Mar 15;118(6):742-9. doi: 10.1152/japplphysiol.00054.2014. Epub 2015 Jan 8.


We examined whether a mixed lactate and caffeine compound (LC) could effectively elicit proliferation and differentiation of satellite cells or activate anabolic signals in skeletal muscles. We cultured C2C12 cells with either lactate or LC for 6 h. We found that lactate significantly increased myogenin and follistatin protein levels and phosphorylation of P70S6K while decreasing the levels of myostatin relative to the control. LC significantly increased protein levels of Pax7, MyoD, and Ki67 in addition to myogenin, relative to control. LC also significantly increased follistatin expression relative to control and stimulated phosphorylation of mTOR and P70S6K. In an in vivo study, male F344/DuCrlCrlj rats were assigned to control (Sed, n = 10), exercise (Ex, n = 12), and LC supplementation (LCEx, n = 13) groups. LC was orally administered daily. The LCEx and Ex groups were exercised on a treadmill, running for 30 min at low intensity every other day for 4 wk. The LCEx group experienced a significant increase in the mass of the gastrocnemius (GA) and tibialis anterior (TA) relative to both the Sed and Ex groups. Furthermore, the LCEx group showed a significant increase in the total DNA content of TA compared with the Sed group. The LCEx group experienced a significant increase in myogenin and follistatin expression of GA relative to the Ex group. These results suggest that administration of LC can effectively increase muscle mass concomitant with elevated numbers of myonuclei, even with low-intensity exercise training, via activated satellite cells and anabolic signals.

Keywords: follistatin; low-intensity exercise; mTOR; sarcopenia; skeletal muscle cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caffeine / pharmacology*
  • Cell Differentiation / drug effects
  • Cell Line
  • Cell Proliferation / drug effects
  • Follistatin / metabolism
  • Hypertrophy / drug therapy*
  • Hypertrophy / metabolism
  • Hypertrophy / physiopathology*
  • Lactic Acid / pharmacology*
  • Male
  • Mice
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / physiopathology
  • Muscular Diseases / drug therapy*
  • Muscular Diseases / metabolism
  • Muscular Diseases / physiopathology*
  • MyoD Protein / metabolism
  • Myogenin / metabolism
  • Physical Conditioning, Animal / methods
  • Rats
  • Rats, Inbred F344
  • Ribosomal Protein S6 Kinases, 70-kDa / metabolism
  • Running / physiology
  • Satellite Cells, Skeletal Muscle / drug effects*
  • Satellite Cells, Skeletal Muscle / metabolism
  • Satellite Cells, Skeletal Muscle / physiology*


  • Follistatin
  • MyoD Protein
  • Myogenin
  • Lactic Acid
  • Caffeine
  • Ribosomal Protein S6 Kinases, 70-kDa

Supplementary concepts

  • Myostatin-related muscle hypertrophy