Elevated maternal non-esterified fatty acid concentrations during late gestation are associated with altered skeletal muscle development and mitochondrial dynamics related-markers in calves

Background Late gestation represents an important developmental window for fetal skeletal muscle formation, which is associated with postnatal body growth, metabolic health and mobility in offspring. Although elevated circulating non-esterified fatty acids (NEFA) in dairy cows have been extensively studied in relation to milk production, their associations with fetal and neonatal skeletal muscle development remain unclear. Methods Sixty healthy Holstein cows with similar body weight, parity and calving dates were enrolled in this study after dry-off, and retrospectively assigned to low NEFA ( n = 30, 263 ± 8.8 μmol/L) and high NEFA group ( n = 30, 379 ± 9.1 μmol/L) according to serum NEFA concentrations at 1, 3, 5, and 7 weeks after dry-off. Skeletal muscle was collected from calves at birth and at one month of age to assess the impacts on offspring muscle mass, fiber morphology and metabolic functions. C2C12 myoblasts were also used to assess the NEFA addition on myogenesis in vitro. Results Cows with high NEFA (within the physiological prepartum range) in the dry period had no effect on calf birth weight ( P = 0.15), but exhibited reduced biceps femoris ( P = 0.05) and semitendinosus muscle mass ( P < 0.01). Moreover, calves in the high-NEFA group shifted the muscle fiber composition, characterized by a lower proportion of fast-twitch fibers ( P < 0.01) and a higher proportion of slow-twitch fibers ( P = 0.01). The protein abundance of mitochondrial fission-related markers dynamin-related protein 1 (DRP1) and mitochondrial fission protein 1 (FIS1), as well as stimulator of interferon genes (STING)-associated inflammatory markers, was increased in skeletal muscle tissue of calves born to high-NEFA cows ( P < 0.01). These alterations were persistently observed at one month of age. In vitro, NEFA supplementation reduced myogenic differentiation and fast-twitch myofiber formation ( P < 0.01), while increasing the expression of mitochondrial dynamics-related genes and inflammatory markers ( P < 0.01). Conclusion Overall, this study reveals that the calves born to mothers with elevated NEFA during the dry period are associated with altered skeletal muscle development and changes in the expression of mitochondrial dynamics- and inflammation-related markers.