Gibbs Rachel L, Swanson Rebecca M, Beard Joslyn K, Hicks Zena M, Most Micah S, Beer Haley N, Grijalva Pablo C, Clement Shawna M, Marks-Nelson Eileen S, Schmidt Ty B, Petersen Jessica L, Yates Dustin T
Stress Physiology Laboratory, Department of Animal Science, University of Nebraska-Lincoln, Lincoln, NE, United States.
Front Physiol. 2023 Sep 6;14:1252508. doi: 10.3389/fphys.2023.1252508. eCollection 2023.
Intrauterine growth restriction () is associated with reduced β2 adrenergic sensitivity, which contributes to poor postnatal muscle growth. The objective of this study was to determine if stimulating β2 adrenergic activity postnatal would rescue deficits in muscle growth, body composition, and indicators of metabolic homeostasis in IUGR offspring. Time-mated ewes were housed at 40°C from day 40 to 95 of gestation to produce IUGR lambs. From birth, IUGR lambs received daily IM injections of 0.8 μg/kg clenbuterol HCl (; = 11) or saline placebo (; = 12). Placebo-injected controls ( = 13) were born to pair-fed thermoneutral ewes. Biometrics were assessed weekly and body composition was estimated by ultrasound and bioelectrical impedance analysis (). Lambs were necropsied at 60 days of age. Bodyweights were lighter ( ≤ 0.05) for IUGR and IUGR+CLEN lambs than for controls at birth, day 30, and day 60. Average daily gain was less ( ≤ 0.05) for IUGR lambs than controls and was intermediate for IUGR+CLEN lambs. At day 58, BIA-estimated whole-body fat-free mass and ultrasound-estimated loin eye area were less ( ≤ 0.05) for IUGR but not IUGR+CLEN lambs than for controls. At necropsy, loin eye area and muscles were smaller ( ≤ 0.05) for IUGR but not IUGR+CLEN lambs than for controls. protein content was less ( ≤ 0.05) and fat-to-protein ratio was greater ( ≤ 0.05) for IUGR but not IUGR+CLEN lambs than for controls. from IUGR lambs had less ( ≤ 0.05) β2 adrenoreceptor content, fewer ( ≤ 0.05) proliferating myoblasts, tended to have fewer ( = 0.08) differentiated myoblasts, and had smaller ( ≤ 0.05) muscle fibers than controls. Proliferating myoblasts and fiber size were recovered ( ≤ 0.05) in IUGR+CLEN lambs compared to IUGR lambs, but β2 adrenoreceptor content and differentiated myoblasts were not recovered. lipid droplets were smaller ( ≤ 0.05) in size for IUGR lambs than for controls and were further reduced ( ≤ 0.05) in size for IUGR+CLEN lambs. These findings show that clenbuterol improved IUGR deficits in muscle growth and some metabolic parameters even without recovering the deficit in β2 adrenoreceptor content. We conclude that IUGR muscle remained responsive to β2 adrenergic stimulation postnatal, which may be a strategic target for improving muscle growth and body composition in IUGR-born offspring.
宫内生长受限（IUGR）与β2肾上腺素能敏感性降低有关，这会导致出生后肌肉生长不良。本研究的目的是确定出生后刺激β2肾上腺素能活性是否能挽救IUGR后代在肌肉生长、身体组成和代谢稳态指标方面的缺陷。将同期发情的母羊在妊娠第40天至95天饲养在40°C环境中以生产IUGR羔羊。从出生开始，IUGR羔羊每天接受0.8μg/kg盐酸克伦特罗肌肉注射（n = 11）或生理盐水安慰剂（n = 12）。注射安慰剂的对照组（n = 13）由配对饲养于热中性环境的母羊所生。每周评估生物特征，并通过超声和生物电阻抗分析（BIA）估计身体组成。羔羊在60日龄时进行剖检。在出生时、第30天和第60天，IUGR和IUGR+CLEN羔羊的体重均低于对照组（P≤0.05）。IUGR羔羊的平均日增重低于对照组（P≤0.05），IUGR+CLEN羔羊的平均日增重介于两者之间。在第58天，BIA估计的全身去脂体重和超声估计的腰大肌面积，IUGR羔羊低于对照组（P≤0.05），而IUGR+CLEN羔羊与对照组无差异。剖检时，IUGR羔羊的腰大肌面积和肌肉体积小于对照组（P≤0.05），而IUGR+CLEN羔羊与对照组无差异。IUGR羔羊的肌肉蛋白含量较低（P≤0.05），脂肪与蛋白比例较高（P≤0.05），而IUGR+CLEN羔羊与对照组无差异。IUGR羔羊的肌肉β2肾上腺素能受体含量较少（P≤0.05），增殖的成肌细胞较少（P≤0.05），分化的成肌细胞数量有减少趋势（P = 0.08），且肌纤维小于对照组（P≤0.05）。与IUGR羔羊相比，IUGR+CLEN羔羊的增殖成肌细胞数量和肌纤维大小恢复（P≤0.05），但β2肾上腺素能受体含量和分化的成肌细胞数量未恢复。IUGR羔羊的脂滴尺寸小于对照组（P≤0.05），IUGR+CLEN羔羊的脂滴尺寸进一步减小（P≤0.05）。这些发现表明，即使未恢复β2肾上腺素能受体含量的缺陷，克伦特罗也能改善IUGR在肌肉生长和一些代谢参数方面的缺陷。我们得出结论，IUGR肌肉在出生后仍对β2肾上腺素能刺激有反应，这可能是改善IUGR出生后代肌肉生长和身体组成的一个策略性靶点。
