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Sepsis-like Energy Deficit Is Not Sufficient to Induce Early Muscle Fiber Atrophy and Mitochondrial Dysfunction in a Murine Sepsis Model.

Alexandre PierreClaire BourelRaphael FavoryBenoit BrassartFrederic WalletFrédéric Nicolas DaussinSylvain NormandinMichael HowsamRaphael RomienJeremy LemaireGaelle GrolauxArthur DurandMarie FrimatBruno BastidePhilippe AmouyelEric BoulangerSebastien PreauSteve Lancel
Published in: Biology (2023)
Sepsis-induced myopathy is characterized by muscle fiber atrophy, mitochondrial dysfunction, and worsened outcomes. Whether whole-body energy deficit participates in the early alteration of skeletal muscle metabolism has never been investigated. Three groups were studied: "Sepsis" mice, fed ad libitum with a spontaneous decrease in caloric intake (n = 17), and "Sham" mice fed ad libitum (Sham fed (SF), n = 13) or subjected to pair-feeding (Sham pair fed (SPF), n = 12). Sepsis was induced by the intraperitoneal injection of cecal slurry in resuscitated C57BL6/J mice. The feeding of the SPF mice was restricted according to the food intake of the Sepsis mice. Energy balance was evaluated by indirect calorimetry over 24 h. The tibialis anterior cross-sectional area (TA CSA), mitochondrial function (high-resolution respirometry), and mitochondrial quality control pathways (RTqPCR and Western blot) were assessed 24 h after sepsis induction. The energy balance was positive in the SF group and negative in both the SPF and Sepsis groups. The TA CSA did not differ between the SF and SPF groups, but was reduced by 17% in the Sepsis group compared with the SPF group ( p < 0.05). The complex-I-linked respiration in permeabilized soleus fibers was higher in the SPF group than the SF group ( p < 0.05) and lower in the Sepsis group than the SPF group ( p < 0.01). Pgc1α protein expression increased 3.9-fold in the SPF mice compared with the SF mice ( p < 0.05) and remained unchanged in the Sepsis mice compared with the SPF mice; the Pgc1α mRNA expression decreased in the Sepsis compared with the SPF mice ( p < 0.05). Thus, the sepsis-like energy deficit did not explain the early sepsis-induced muscle fiber atrophy and mitochondrial dysfunction, but led to specific metabolic adaptations not observed in sepsis.
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