OBJECTIVES Determine if simvastatin impairs exercise training adaptations. BACKGROUND Statins are commonly prescribed in combination with therapeutic lifestyle changes, including exercise, to reduce cardiovascular disease risk in patients with the metabolic syndrome. Statin use has been linked to skeletal muscle myopathy and impaired mitochondrial function, but it is unclear whether statin use alters adaptations to exercise training. METHODS We examined the effects of simvastatin on changes in cardiorespiratory fitness and skeletal muscle mitochondrial content in response to aerobic exercise training. Sedentary overweight or obese adults with at least 2 metabolic syndrome risk factors (defined according to National Cholesterol Education Panel Adult Treatment Panel III criteria) were randomized to 12 weeks of aerobic exercise training or to exercise in combination with simvastatin (40 mg per day). The primary outcomes were cardiorespiratory fitness and skeletal muscle (vastus lateralis) mitochondrial content (citrate synthase enzyme activity). RESULTS Thirty-seven participants (exercise plus statins; n=18; exercise only; n=19) completed the study. Cardiorespiratory fitness increased by 10% (P<0.05) in response to exercise training alone, but was blunted by the addition of simvastatin resulting in only a 1.5% increase (P<0.005 for group by time interaction). Similarly, skeletal muscle citrate synthase activity increased by 13% in the exercise only group (P <0.05), but decreased by 4.5% in the simvastatin plus exercise group (P<0.05 for group by time interaction). CONCLUSION Simvastatin attenuates increases in cardiorespiratory fitness and skeletal muscle mitochondrial content when combined with exercise training in overweight or obese patients at risk of the metabolic syndrome.

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These findings provide evidence for the significant influence of body composition on oocyte transcript abundance in women undergoing hormonal induction to retrieve oocytes. They further identify the potential for maternal diet to influence oocyte gene expression. The preconception period is, therefore, an important window of opportunity to consider for lifestyle interventions.

Nonalcoholic fatty liver disease (NAFLD) is strongly linked to obesity, insulin resistance, and abnormal hepatic lipid metabolism; however, the precise regulation of these processes remains poorly understood. Here we examined genes and proteins involved in hepatic oxidation and lipogenesis in 14-week-old leptin-deficient Ob/Ob mice, a commonly studied model of obesity and hepatic steatosis. Obese Ob/Ob mice had increased fasting glucose, insulin, and calculated HOMA-IR as compared with lean wild-type (WT) mice. Ob/Ob mice also had greater liver weights, hepatic triglyceride (TG) content, and markers of de novo lipogenesis, including increased hepatic gene expression and protein content of acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), and stearoyl-CoA desaturase-1 (SCD-1), as well as elevated gene expression of PPARγ and SREBP-1c compared with WT mice. While hepatic mRNA levels for PGC-1α, PPARα, and TFAM were elevated in Ob/Ob mice, measures of mitochondrial function (β-HAD activity and complete (to CO2) and total mitochondrial palmitate oxidation) and mitochondrial OXPHOS protein subunits I, III, and V content were significantly reduced compared with WT animals. In summary, reduced hepatic mitochondrial content and function and an upregulation in de novo lipogenesis contribute to obesity-associated NAFLD in the leptin-deficient Ob/Ob mouse.

Maternal body composition, gestational weight gain (GWG) and diet quality influence offspring obesity risk. While the gut microbiome is thought to play a crucial role, it is understudied in pregnancy. Using a longitudinal pregnancy cohort, maternal anthropometrics, body composition, fecal microbiome and dietary intake were assessed at 12, 24 and 36 weeks of gestation. Fecal samples (n = 101, 98 and 107, at each trimester, respectively) were utilized for microbiome analysis via 16S rRNA amplicon sequencing. Data analysis included alpha- and beta-diversity measures and assessment of compositional changes using MaAsLin2. Correlation analyses of serum metabolic and anthropometric markers were performed against bacterial abundance and predicted functional pathways. α-diversity was unaltered by pregnancy stage or maternal obesity status. Actinobacteria, Lachnospiraceae, Akkermansia, Bifidobacterium, Streptococcus and Anaerotuncus abundances were associated with gestation stage. Maternal obesity status was associated with increased abundance of Lachnospiraceae, Bilophila, Dialister and Roseburia. Maternal BMI, fat mass, triglyceride and insulin levels were positively associated with Bilophila. Correlations of bacterial abundance with diet intake showed that Ruminococcus and Paraprevotella were associated with total fat and unsaturated fatty acid intake, while Collinsella and Anaerostipes were associated with protein intake. While causal relationships remain unclear, collectively, these findings indicate pregnancy- and maternal obesity-dependent interactions between dietary factors and the maternal gut microbiome.