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Key points Obesity during pregnancy and childbirth is associated with labour dystocia leading to instrumental or operative delivery, but the underlying pathophysiological mechanisms remain unclear and insufficient uterine contractility has been suggested., This study examined whether reduced myometrial mitochondrial capacity or quantity could contribute as a pathophysiological mechanism to labour dystocia., Data did not support reduced myometrial mitochondrial capacity or quantity in the myometrium at term in obese women, but a reduced myocyte density with increased triglyceride content was demonstrated, which could lead to poorer uterine contractility., These results add to the understanding of systemic effects of obesity, placing also the myometrium at term as an affected non-adipose tissue., Abstract Obesity is known to increase the risk of labour dystocia and insufficient energy supply, due to reduced mitochondrial capacity or quantity, could be a possible mechanism leading to reduced efficiency of uterine contractility during labour. In the present study of 36 women having an elective Caesarean section at term, obesity did not change mitochondrial phenotype in the myometrial myocyte obtained from uterine biopsies taken at delivery. Respiration rates in isolated mitochondria were unaffected by obesity. No indication of reduced content, investigated by quantification of the complexes of the respiratory chain, or altered regulation, examined by myometrial mRNA levels of genes related to mitochondrial biogenesis and inflammation, was detected. Yet we found increased myometrial triglyceride content in the obese group (2.39 ± 0.26 vs. 1.56 ± 0.20 m m, P = 0.024), while protein content and citrate synthase activity per gram wet weight myometrium were significantly lower in the obese (109.2 ± 7.2 vs. 139.4 ± 5.6 mg g−1, P = 0.002, and 24.8 ± 1.0 vs. 29.6 ± 1.4 U g−1 wet wt, P = 0.008, respectively). These differences were substantiated by our histological findings where staining for nuclei, cytoplasm, glycogen and collagen supported the idea of a smaller muscle content in the myometrium in obese women. In conclusion no indication of myometrial mitochondrial dysfunction in the isolated state was found, but the observed increase of lipid content might play a role in the pathophysiological mechanisms behind labour dystocia in obese women. [ABSTRACT FROM AUTHOR]

J&3x00F8;rgensen W, Gam C, Andersen JL, Schjerling P, Scheibye- Knudsen M, Mortensen OH, Grunnet N, Nielsen MO, Quistorff B. Changed mitochondrial function by pre- and/or postpartum diet alterations in sheep. Am J Physiol Endocrinol Metab 297: E1349-El357, 2009. First published October 13, 2009; doi:10.1152/ajpendo.00505.2009.—In a sheep model, we investigated diet effects on skeletal muscle mitochondria to look for fetal programming. During pregnancy, ewes were fed normally (N) or were 50% food restricted (L) during the last trimester, and lambs born to these ewes received a normal (N) or a high-fat diet (H) for the first 6 mo of life. We examined mitochondrial function in permeabilized muscle fibers from the lambs at 6 mo of age (adolescence) and after 24 mo of age (adulthood). The postpartum H diet for the lambs induced an ∼30% increase (P < 0.05) of mitochondrial V02max and an ∼50% increase (P < 0.05) of the respiratory coupling ratio (RCR) combined with lower levels of UCP3 and PGC- I a mRNA levels (P < 0.05). These effects proved to be reversible by a normal diet from 6 to 24 mo of age. However, at 24 mo, a long-term effect of the maternal gestational diet restriction (fetal programming) became evident as a lower "02n,ax (-40%, P < 0.05), a lower state 4 respiration (∼40%, P < 0.05), and lower RCR (∼15%, P < 0.05). Both PGC-1α and UCP3 mRNA levels were increased (P < 0.05). Two analyzed muscles were affected differently, and muscle rich in type I fibers was more susceptible to fetal programming. We conclude that fetal programming, seen as a reduced VO2max in adulthood, results from gestational undernutrition. Postnatal high-fat diet results in a pronounced RCR and VO2max increase in adolescence. However, these effects are reversible by diet correction and are not maintained in adulthood. [ABSTRACT FROM AUTHOR]

We hypothesized that the peroxisome proliferator-activated receptor-γ coactivator-1 (PGC-1) family of transcriptional coactivators (PGC-1α, PGC-1β, and PRC) is differentially regulated by training once daily vs. training twice daily every second day and that this difference might be observed in the acute response to endurance exercise. Furthermore, we hypothesized that expression levels of the PGC-1 family differ with muscular fiber-type composition. Thus, before and after 10 wk of knee extensor endurance training, training one leg once daily and the other leg twice daily every second day, keeping the total amount of training for the legs equal, skeletal muscle mRNA expression levels of PGC-1α, PGC-1β, and PRC were determined in young healthy men (n = 7) in response to 3 h of acute exercise. No significant difference was found between the two legs, suggesting that regulation of the PGC-1 family is independent of training protocol. Training decreased PGC-1β in both legs, whereas PGC-1α was increased, but not significantly, in the leg training once daily. PRC did not change with training. Both PGC-1α and PRC were increased by acute exercise both before and after endurance training, whereas PGC-1β did not change. The mRNA levels of the PGC-1 family were examined in different types of human skeletal muscle (triceps, soleus, and vastus lateralis; n = 7). Only the expression level of PGC-1β differed and correlated inversely with percentage of type I fibers. In conclusion, there was no difference between training protocols on the acute exercise and training response of the PGC-1 family. However, training caused a decrease in PGC-1β mRNA levels. [ABSTRACT FROM AUTHOR]

Peroxisome proliferator-activated receptor-γ coactivator-1α and -1β (PGC-1α and PGC-1β) were overexpressed by adenovirus-mediated gene transfer in cultures of primary rat skeletal muscle cells derived from neonatal myoblasts. Effects on muscle fiber type transition and metabolism were studied from days 5 to 22 of culture. PGC-1α and PGC-1β overexpression caused a three- to fourfold increase in mRNA level, a doubling of enzymatic activity of citrate synthase, a slight increase in short-chain acyl-CoA dehydrogenase mRNA, a doubling of the mRNA level, and a 30–50% increase in enzymatic activity of glyceraldehyde-3-phosphate dehydrogenase. Lactate dehydrogenase or creatine kinase activity was unchanged. PGC-1α enhanced glycogen buildup twofold at 5 or 25 mM glucose, whereas PGC-1β caused a decrease. Both PGC-1α and PGC-1β overexpression caused a faster maturation of myotubes, as seen by mRNA downregulation of the immature embryonal and perinatal myosin heavy-chain (MHC) isoforms. PGC-1α or PGC-1β overexpression enhanced mRNA of the slow oxidative-associated MHC isoform MHCIb and downregulated mRNA levels of the fast glycolytic-associated MHC isoforms MHCIIX and MHCIIB. Only PGC-1β overexpression caused an increase in mRNA of the intermediary fast oxidative-associated MHC isoform MHCIIA. PGC-1α or PGC-1β overexpression upregulated GLUT4 mRNA and downregulated myocyte enhancer factor 2C transcription factor mRNA; only PGC-1α overexpression caused an increase in the mRNA expression of TRB3, a negative regulator of insulin signaling. These results show that both PGC-1α and PGC-1β are involved in the regulation of skeletal muscle fiber transition and metabolism and that they have both overlapping and differing effects. [ABSTRACT FROM AUTHOR]