An altered metabolism during ovarian cancer progression allows for increased macromolecular synthesis and unrestrained growth. However, the metabolic phenotype of cancer stem or tumor-initiating cells, small tumor cell populations that are able to recapitulate the original tumor, has not been well characterized. In the present study, we compared the metabolic phenotype of the stem cell enriched cell variant, MOSE-LFFLv (TIC), derived from mouse ovarian surface epithelial (MOSE) cells, to their parental (MOSE-L) and benign precursor (MOSE-E) cells. TICs exhibit a decrease in glucose and fatty acid oxidation with a concomitant increase in lactate secretion. In contrast to MOSE-L cells, TICs can increase their rate of glycolysis to overcome the inhibition of ATP synthase by oligomycin and can increase their oxygen consumption rate to maintain proton motive force when uncoupled, similar to the benign MOSE-E cells. TICs have an increased survival rate under limiting conditions as well as an increased survival rate when treated with AICAR, but exhibit a higher sensitivity to metformin than MOSE-E and MOSE-L cells. Together, our data show that TICs have a distinct metabolic profile that may render them flexible to adapt to the specific conditions of their microenvironment. By better understanding their metabolic phenotype and external environmental conditions that support their survival, treatment interventions can be designed to extend current therapy regimens to eradicate TICs.

Tumor cells often exhibit an altered metabolic phenotype. However, it is unclear as to when this switch takes place in ovarian cancer, and the potential for these changes to serve as therapeutic targets in clinical prevention and intervention trials. We used our recently developed and characterized mouse ovarian surface epithelial (MOSE) cancer progression model to study metabolic changes in distinct disease stages. As ovarian cancer progresses, complete oxidation of glucose and fatty acids were significantly decreased, concurrent with increases in lactate excretion and 3H-deoxyglucose uptake by the late-stage cancer cells, shifting the cells towards a more glycolytic phenotype. These changes were accompanied by decreases in TCA flux but an increase in citrate synthase activity, providing substrates for de novo fatty acid and cholesterol synthesis. Also, uncoupled maximal respiration rates in mitochondria decreased as cancer progressed. Treatment of the MOSE cells with 1.5μM sphingosine, a bioactive sphingolipid metabolite, decreased citrate synthase activity, increased TCA flux, decreased cholesterol synthesis and glycolysis. Together, our data confirm metabolic changes during ovarian cancer progression, indicate a stage specificity of these changes, and suggest that multiple events in cellular metabolism are targeted by exogenous sphingosine which may be critical for future prevention trials.

Objective We have previously demonstrated that activation of toll-like receptor 4 (TLR4) in skeletal muscle results in an increased reliance on glucose as an energy source and a concomitant decrease in fatty acid oxidation under basal conditions. Herein, we examined the effects of lipopolysaccharide (LPS), the primary ligand for TLR4, on mitochondrial oxygen consumption in skeletal muscle cell culture and isolated mitochondria. Materials/ methods Skeletal muscle cell cultures were exposed to LPS and oxygen consumption was assessed using a Seahorse Bioscience extracellular flux analyzer. Mice were also exposed to LPS and oxygen consumption was assessed in mitochondria isolated from skeletal muscle. Results Acute LPS exposure resulted in significant reductions in cyanide 4-(trifluoromethoxy) phenylhydrazone (FCCP)-stimulated maximal respiration (state 3u) and increased oligomycin induced state 4 (state 4O) respiration in C2C12 and human primary myotubes. These findings were observed in conjunction with increased mRNA of uncoupling protein 3 (UCP3), superoxide dismutase 2 (SOD2), and pyruvate dehydrogenase activity. The LPS-mediated changes in substrate oxidation and maximal mitochondrial respiration were prevented in the presence of the antioxidants N-acetylcysteine and catalase, suggesting a potential role of reactive oxygen species in mediating these effects. Mitochondria isolated from red gastrocnemius and quadriceps femoris muscle from mice injected with LPS also demonstrated reduced respiratory control ratio (RCR), and ADP- and FCCP-stimulated respiration. Conclusion LPS exposure in skeletal muscle alters mitochondrial oxygen consumption and substrate preference, which is absent when antioxidants are present.

For K-12 students, obesity has been linked to student educational achievements. The study objective was to determine whether academic performance in university students is correlated with BMI. Students from two consecutive academic years (Jan–May 2013 and Jan–May 2014) were given an optional class survey in May, as extra credit. Of the 452 students that completed the survey, 204 females and 75 males (N = 279; 73% female and 27% male) consented to participate in the study. The number of correct answers to problem-solving questions (PSQs) and the overall final grade for the class were compared to the calculated BMI using linear regression with a Pearson's R correlation and unpaired t-tests. BMI was significantly negatively correlated with student's final grades (P = 0.001 Pearson's r = − 0.190) and PSQs were positively correlated with final grades (P < 0.001; Pearson's r = 0.357). Our findings show a correlation between healthy body weight and improved academic performance. Further, the data suggest that future research in the area of body weight, diet, and exercise and any correlations of these with academic performance in college students are warranted.

ObjectiveThe purpose of this investigation was to understand the metabolic adaptations to a short-term (5 days), isocaloric, high fat diet (HFD) in healthy, young males.MethodsTwo studies were undertaken with 12 subjects. Study 1 investigated the effect of the HFD on skeletal muscle substrate metabolism and insulin sensitivity. Study 2 assessed the metabolic and transcriptional response in skeletal muscle to the transition from a fasted-to-fed state using a high fat meal challenge prior to and following 5 days of HFD.ResultsStudy 1 showed no effect of a HFD on skeletal muscle metabolism or insulin sensitivity in fasting samples. Study 2 showed that a HFD elicits significant increases in fasting serum endotoxin, and disrupts the normal postprandial excursions of serum endotoxin, and metabolic and transcriptional responses in skeletal muscle. These effects following 5 days of HFD were accompanied by an altered fasting and postprandial response in the ratio of phosphorylated to total p38 protein. These changes all occurred in the absence of alterations in insulin sensitivity.ConclusionsOur findings provide evidence for early biological adaptations to high fat feeding that proceed and possibly lead to insulin resistance.