Piezo channels contribute to the regulation of myelination in Schwann cells.

Peripheral nerves and Schwann cells have to sustain constant mechanical constraints, caused by developmental growth as well as stretches associated with movements of the limbs and mechanical compressions from daily activities. In Schwann cells, signaling molecules sensitive to stiffness or stretch of the extracellular matrix, such as YAP/TAZ, have been shown to be critical for Schwann cell development and peripheral nerve regeneration. YAP/TAZ have also been suggested to contribute to tumorigenesis, neuropathic pain, and inherited disorders. Yet, the role of mechanosensitive ion channels in myelinating Schwann cells is vastly unexplored. Here we comprehensively assessed the expression of mechanosensitive ion channels in Schwann cells and identified that PIEZO1 and PIEZO2 are among the most abundant mechanosensitive ion channels expressed by Schwann cells. Using classic genetic ablation studies, we show that PIEZO1 is a transient inhibitor of radial and longitudinal myelination in Schwann cells. Contrastingly, we show that PIEZO2 may be required for myelin formation, as the absence of PIEZO2 in Schwann cells delays myelin formation. We found an epistatic relationship between PIEZO1 and PIEZO2, at both the morphological and molecular levels. Finally, we show that PIEZO1 channels affect the regulation of YAP/TAZ activation in Schwann cells. Overall, we present here the first demonstration that PIEZO1 and PIEZO2 contribute to mechanosensation in Schwann cells as well myelin development in the peripheral nervous system.

Conjugated linoleic acid supplementation alters the 6-mo change in fat oxidation during sleep.

BACKGROUND: Conjugated linoleic acid (CLA) is a family of positional and geometric isomers with 2 conjugated double bonds formed from linoleic acid and linolenic acid. CLA has a wide range of biological effects, including body fat reduction. OBJECTIVE: The aim of our study was to determine CLA's effects on energy expenditure, macronutrient utilization, and dietary fat oxidation in overweight adults after 6 mo of supplementation. DESIGN: We recruited 23 subjects from our main CLA efficacy study who were receiving either 4 g/d of 78% active CLA isomers (3.2 g/d: 39.2% cis-9,trans-11 and 38.5% trans-10,cis-12) or 4 g/d of safflower oil. Energy expenditure and substrate utilization were measured before and after 6 mo of CLA supplementation by using whole-room indirect calorimetry. Dietary fat oxidation was measured by using stable isotope-labeled oleate and palmitate. RESULTS: Our substudy detected a difference in the change in fat utilization between the CLA (4 +/- 8 g) and placebo (-7 +/- 11 g) groups during sleep after 6 mo of supplementation. In addition, the percentage of energy from protein was reduced during sleep in the CLA group (CLA: -3.3 +/- 2.6%; placebo: 0.3 +/- 5.7%). We also detected a difference in the change in energy expenditure during sleep (CLA: 0 +/- 38 kcal; placebo: -43 +/- 90 kcal). We did not detect a change in labeled dietary fat oxidation after 6 mo of CLA supplementation given with a breakfast meal. CONCLUSION: Mixed isomer CLA supplementation, but not placebo, positively altered fat oxidation and energy expenditure during sleep.

Bioelectrical impedance vs. four-compartment model to assess body fat change in overweight adults.

OBJECTIVE: The Tanita TBF-305 body fat analyzer is marketed for home and clinical use and is based on the principles of leg-to-leg bioelectrical impedance analysis (BIA). Few studies have investigated the ability of leg-to-leg BIA to detect change in percentage fat mass (%FM) over time. Our objective was to determine the ability of leg-to-leg BIA vs. the four-compartment (4C) model to detect small changes in %FM in overweight adults. RESEARCH METHODS AND PROCEDURES: Thirty-eight overweight adults (BMI, 25.0 to 29.9 kg/m2; age, 18 to 44 years; 31 women) participated in a 6-month, randomized, double-blind, placebo-controlled study of a nutritional supplement. Body composition was measured at 0 and 6 months using the Tanita TBF-305 body fat analyzer [using equations derived by the manufacturer (%FM(T-Man)) and by Jebb et al. (%FM(T-Jebb))] and the 4C model (%FM(4C)). RESULTS: Subjects in the experimental group lost 0.9%FM(4C) (p = 0.03), a loss that did not reach significance using leg-to-leg BIA (0.6%FM(T-Man), p = 0.151; 0.6%FM(T-Jebb), p = 0.144). We observed large standard deviations (SDs) in the mean difference in %FM between the 4C model and the Tanita(Manufacturer) (2.5%) and Tanita(Jebb) (2.2%). Ten subjects fell outside +/-1 SD of the mean differences at 0 and 6 months; those individuals were younger and shorter than those within +/-1 SD. DISCUSSION: Leg-to-leg BIA performed reasonably well in predicting decreases in %FM in this group of overweight adults but resulted in wide SDs vs. %FM(4C) in individuals. Cross-sectional determinations of %FM of overweight individuals using leg-to-leg BIA should be interpreted with caution.

The financial reality of overeating.

OBJECTIVE: Obesity has been linked to frequency of meals eaten outside the home and the associated large portion sizes. These large portions, which have been shown to promote overeating, are often offered for a small additional cost which may appear economical to the consumer. The aim of this study was to calculate additional costs from medical, gasoline, and increased caloric needs that result from weight gain attributable to overeating and thus provide consumers with added incentive not to upsize their meal, or overeat in general. METHODS: The effects and costs of overeating were estimated for men and women with a BMI of 22.5, 27.5, and 32.5 by conducting a Pubmed search for relevant literature combined with US statistics obtained from open Federal and other websites. RESULTS: Among fast food restaurants, the average upsized meal increases energy content of the meal from 927 to 1324 kcal at an added cost of Dollar 0.67. Because the regular meal is already 37% of a 2500 kcal diet, the extra energy of upsizing is likely to be in excess of need and thus potentially stored as 36 grams of added adipose tissue. This hypothesized weight gain predicts an average increase auto fuel cost by Dollar 0.05 for both men and women, maintenance food cost by Dollar 0.36 and Dollar 0.35 for men and women, respectively, and health care cost from Dollar 0.82 to Dollar 6.64. CONCLUSIONS: These calculated costs exceed the value of upsized meals and may provide motivation to some consumers not to upsize their meals. The same rationale can be applied to other environments notorious for encouraging overeating. Thus, this information could be presented to individuals along with other more well publicized health risks and consequences during weight control counseling.