Abstract
Maternal obesity (MO) has harmful effects on both fetal development and subsequent offspring health. We previously demonstrated that MO enhances collagen accumulation in fetal skeletal muscle, but its impact on mature offspring muscle collagen accumulation is unknown. Ewes were fed either a control diet (Con, fed 100% of NRC nutrient recommendations) or obesogenic diet (OB, fed 150% of NRC nutrient recommendations) from 60 days before conception to birth. All ewes received the Con diet during lactation. Male offspring were euthanized at 2.5 years (mean) and the left Longissimus dorsi (LD) muscle and semitendinosus (ST) muscle were sampled. Collagen concentration increased by 37.8±19.0% (P<0.05) in LD and 31.2±16.0% (P<0.05) in ST muscle of OB compared to Con offspring muscle. Mature collagen cross-linking (pyridinoline concentration) was increased for 22.3±7.4% and 36.3±9.9% (P<0.05) in LD and ST muscle of OB group respectively. Expression of lysyl oxidase, lysyl hydroxylase-2b (LH2b) and prolyl 4-hydroxylase (P4HA) was higher in OB LD and ST muscle. In addition, the expression of metalloproteinases (MMPs) was lower but tissue inhibitor of metalloproteinases (TIMPs) was higher in OB offspring muscle, indicating reduced collagen remodeling. MO enhanced collagen content and cross-linking in offspring muscle, which might be partially due to reduced collagen remodeling. Our observation that the collagen content and cross-linking are enhanced in MO offspring muscle is significant, because fibrosis is known to impair muscle functions and is a hallmark of muscle aging.
Highlights
Obesity is an increasingly critical problem and impacts general health worldwide in epidemic proportions
We have recently established an obese sheep model to study fetal development and developmental programming resulting from pre-pregnancy obesity and high energy diet in a paradigm that resembles the situation in obese women who become pregnant [17]
Excessive fibrogenesis during fetal skeletal muscle development, if it persists into adult life, may have important negative physiological consequences for offspring health
Summary
Obesity is an increasingly critical problem and impacts general health worldwide in epidemic proportions. We have developed a pregnant ewe model of MO and overnutrition in which females become obese prior to conception and remain obese throughout pregnancy [5,6] Using this model, when offspring from obese mothers were subjected to a bout of ad libitum feeding as adults, they exhibited decreased insulin sensitivity and increased adiposity compared to offspring from control mothers fed only to requirements [7]. Our earlier study in the fetuses of MO ewes revealed enhanced transforming growth factor b (TGF-b) signaling and collagen accumulation in fetal muscle associated with an inflammatory response in skeletal and cardiac muscle born to obese mothers [6,10]. The results presented here show that MO induced accumulation and enhanced cross-linking, which should be due to the inhibited remodeling of collagen in offspring skeletal muscle
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