Ectopic lipid deposition impairs muscle anabolic response especially during aging. We hypothesized that the anabolic efficiency of dietary protein in skeletal muscle might be affected within the context of a high-fat diet. The objective of the study was to investigate muscle protein synthesis in response to two levels of protein intake combined to two levels of fat intake.


Two groups of sixty adult and forty-nine old male Wistar rats were randomly divided into four groups: isocaloric standard diet (12% protein, 14% lipid, as STD12); isocaloric standard (high-protein) diet (25% protein, 14% lipid, STD25); hypercaloric high-fat (normal-protein) diet (12% protein, 45% lipid, HFD12); and hypercaloric high-fat (high-protein) diet (25% protein, 45% lipid, HFD25). The nutritional intervention lasted 10 weeks. The fractional synthesis (FSR) and absolute synthesis rates (ASR) of mixed muscle proteins were calculated using isotopically labeled C13-valine incorporation in tibialis anterior (TA). Muscle lipid content was assessed using chromatography method.


Rats in the high-fat diet groups self-limited their food intake, so that energy intake was not different among the groups. Regardless of dietary intervention, TA weight was lower in old groups compared to their adult counterparts (all p values < 0.01). FSR was lower in old rats fed the HFD25 compared to the old STD12 group (diet effect: p=0.02), whereas FSR in old groups was higher than adult groups (age effect, all p values < 0.05). When considering the ASR, no differences emerged between groups except for a tendency towards higher ASR values in the old HFD12 group than the STD25 group (diet effect: p=0.09). Only old rats in the HFD12 group exhibited increased intramuscular triacylglycerols in TA (age effect : p=0.02 ; diet effect : HFD12 vs. STD 12: 2.04±1.74 vs. 0.83±0.49ug/g, p=0.02).A negative relationship was observed between intramuscular lipid infiltration and TA muscle protein content (r=-0.263, p=0.028).


Aging is characterized by a reduced muscle weight despite an increased FSR, suggesting specific alterations in the nutritional regulation of muscle protein turnover. In isocaloric conditions, higher protein intake modulates muscle lipid infiltration but does not improve age-related anabolic resistance in high-fat diet old rats.