Unchanged mitochondrial phenotype, but accumulation of lipids in the myometrium in obese pregnant women.

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 mm, 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.

Gestational Protein Restriction in Wistar Rats; Effect of Taurine Supplementation on Properties of Newborn Skeletal Muscle.

Taurine ameliorates changes occurring in newborn skeletal muscle as a result of gestational protein restriction in C57BL/6 mice, but taurine supplementation effects may be exaggerated in C57BL/6 mice due to their inherent excessive taurinuria.We examined if maternal taurine supplementation could ameliorate changes in gene expression levels, properties of mitochondria, myogenesis, and nutrient transport and sensing, in male newborn skeletal muscle caused by a maternal low protein (LP) diet in Wistar rats.LP diet resulted in an 11% non-significant decrease in birth weight, which was not rescued by taurine supplementation (LP-Tau). LP-Tau offspring had significantly lower birth weight compared to controls. Gene expression profiling revealed 895 significantly changed genes, mainly an LP-induced down-regulation of genes involved in protein translation. Taurine fully or partially rescued 32% of these changes, but with no distinct pattern as to which genes were rescued.Skeletal muscle taurine content in LP-Tau offspring was increased, but no changes in mRNA levels of the taurine synthesis pathway were observed. Taurine transporter mRNA levels, but not protein levels, were increased by LP diet.Nutrient sensing signaling pathways were largely unaffected in LP or LP-Tau groups, although taurine supplementation caused a decrease in total Akt and AMPK protein levels. PAT4 amino acid transporter mRNA was increased by LP, and normalized by taurine supplementation.In conclusion, gestational protein restriction in rats decreased genes involved in protein translation in newborn skeletal muscle and led to changes in nutrient transporters. Taurine partly rescued these changes, hence underscoring the importance of taurine in development.

The effect of long-term taurine supplementation and fructose feeding on glucose and lipid homeostasis in Wistar rats.

The nonprotein amino acid taurine has been shown to counteract the negative effects of a high-fructose diet in rats with regard to insulin resistance and dyslipidemia. Here we examined the long-term (26 weeks) effects of oral taurine supplementation (2% in the drinking water) in fructose-fed Wistar rats.The combination of fructose and taurine caused a significant increase in fasting glucose compared to the control diet without changing hepatic phosphoenol pyruvate carboxykinase mRNA levels. The combination of fructose and taurine also improved glucose tolerance compared to control. Neither a high-fructose diet nor taurine supplementation induced significant changes in body weight, body fat or total calorie intake, fasting insulin levels, HOMA-IR, or insulin-induced Akt phosphorylation in skeletal muscle.Fructose alone caused a decrease in liver triglyceride content, with taurine supplementation preventing this. There was no effect of long-term fructose diet and/or taurine supplementation on plasma triglycerides, plasma nonesterified fatty acids, as well as plasma HDL, LDL, and total cholesterol.In conclusion, the study suggests that long-term taurine supplementation improves glucose tolerance and normalize hepatic triglyceride content following long-term fructose feeding. However, as the combination of taurine and fructose also increased fasting glucose levels, the beneficial effect of taurine supplementation towards amelioration of glucose intolerance and insulin resistance may be questionable.

Diabetes, myometrium, and mitochondria in pregnant women at term.

AIMS: Poor myometrial contractility has been demonstrated in women at term with diabetes and decreased muscular mitochondrial content and/or function has been extensively implicated in the progression of type 2 diabetes. Alterations of the uterine mitochondrial phenotype in pregnant women with diabetes have yet to be investigated as a causal link to decreased myometrial contractility. METHODS: Observational study of 18 women with diabetes (type 2 and gestational) scheduled for an elective Caesarean section at term with matching controls. A uterine biopsy and fasting blood samples were taken on the day of delivery. RESULTS: Respiration rates in isolated mitochondria and myometrial mRNA levels of genes related to mitochondrial biogenesis were unaffected by diabetes. Mitochondrial quantity examined by quantification of the complexes of the respiratory chain and histology did not indicate alterations in mitochondrial quantity. Citrate syntase activity was higher (0.31 ± 0.02 vs. 0.24 ± 0.02 U/mg protein, P = 0.008), whereas protein content was lower in women with diabetes compared with the control group (94.6 ± 6.9 vs. 118.6 ± 7.4 mg/g wet wt, P = 0.027). Histological examinations did not support any structural alterations in the myometrium or its mitochondria. CONCLUSION: No indication of decreased mitochondrial function, content, morphology, or localization in the myometrium at term in women with diabetes compared with controls was observed. The increase in citrate syntase activity in the myometrium could be explained by the lower protein content in the myometrium, which we suggest is due to alterations in tissue or cellular composition.