Upregulated hepatic lipogenesis from dietary sugars in response to low palmitate feeding supplies brain palmitate.

Palmitic acid (PAM) can be provided in the diet or synthesized via de novo lipogenesis (DNL), primarily, from glucose. Preclinical work on the origin of brain PAM during development is scarce and contrasts results in adults. In this work, we use naturally occurring carbon isotope ratios (13C/12C; δ13C) to uncover the origin of brain PAM at postnatal days 0, 10, 21 and 35, and RNA sequencing to identify the pathways involved in maintaining brain PAM, at day 35, in mice fed diets with low, medium, and high PAM from birth. Here we show that DNL from dietary sugars maintains the majority of brain PAM during development and is augmented in mice fed low PAM. Importantly, the upregulation of hepatic DNL genes, in response to low PAM at day 35, demonstrates the presence of a compensatory mechanism to maintain total brain PAM pools compared to the liver; suggesting the importance of brain PAM regulation.

Analysis of omega-3 and omega-6 polyunsaturated fatty acid metabolism by compound-specific isotope analysis in humans.

Natural variations in the 13C:12C ratio (carbon-13 isotopic abundance [δ13C]) of the food supply have been used to determine the dietary origin and metabolism of fatty acids, especially in the n-3 PUFA biosynthesis pathway. However, n-6 PUFA metabolism following linoleic acid (LNA) intake remains under investigation. Here, we sought to use natural variations in the δ13C signature of dietary oils and fatty fish to analyze n-3 and n-6 PUFA metabolism following dietary changes in LNA and eicosapentaenoic acid (EPA) + DHA in adult humans. Participants with migraine (aged 38.6 ± 2.3 years, 93% female, body mass index of 27.0 ± 1.1 kg/m2) were randomly assigned to one of three dietary groups for 16 weeks: 1) low omega-3, high omega-6 (H6), 2) high omega-3, high omega-6 (H3H6), or 3) high omega-3, low omega-6 (H3). Blood was collected at baseline, 4, 10, and 16 weeks. Plasma PUFA concentrations and δ13C were determined. The H6 intervention exhibited increases in plasma LNA δ13C signature over time; meanwhile, plasma LNA concentrations were unchanged. No changes in plasma arachidonic acid δ13C or concentration were observed. Participants on the H3H6 and H3 interventions demonstrated increases in plasma EPA and DHA concentration over time. Plasma δ13C-EPA increased in total lipids of the H3 group and phospholipids of the H3H6 group compared with baseline. Compound-specific isotope analysis supports a tracer-free technique that can track metabolism of dietary fatty acids in humans, provided that the isotopic signature of the dietary source is sufficiently different from plasma δ13C.

Oleic acid-bound FABP7 drives glioma cell proliferation through regulation of nuclear lipid droplet formation.

Fatty acid-binding protein 7 (FABP7), one of the fatty acid (FA) chaperones involved in the modulation of intracellular FA metabolism, is highly expressed in glioblastoma, and its expression is associated with decreased patients' prognosis. Previously, we demonstrated that FABP7 requires its binding partner to exert its function and that a mutation in the FA-binding site of FABP7 affects tumour biology. Here, we explored the role of FA ligand binding for FABP7 function in tumour proliferation and examined the mechanism of FABP7 and ligand interaction in tumour biology. We discovered that among several FA treatment, oleic acid (OA) boosted cell proliferation of FABP7-expressing cells. In turn, OA increased FABP7 nuclear localization, and the accumulation of FABP7-OA complex in the nucleus induced the formation of nuclear lipid droplet (nLD), as well as an increase in colocalization of nLD with promyelocytic leukaemia (PML) nuclear bodies. Furthermore, OA increased mRNA levels of proliferation-related genes in FABP7-expressing cells through histone acetylation. Interestingly, these OA-boosted functions were abrogated in FABP7-knockout cells and mutant FABP7-overexpressing cells. Thus, our findings suggest that FABP7-OA intracellular interaction may modulate nLD formation and the epigenetic status thereby enhancing transcription of proliferation-regulating genes, ultimately driving tumour cell proliferation.

Baseline omega-3 level is associated with nerve regeneration following 12-months of omega-3 nutrition therapy in patients with type 1 diabetes.

AIM: Omega-3 (n-3) polyunsaturated fatty-acids are essential for the development and maintenance of nerve function, but the relationship of plasma n-3 to the presence of diabetic distal-symmetric-polyneuropathy (DSP) and the effect of n-3 therapy on plasma levels and small nerve fibre morphology in T1D are unknown. METHODS: Participants with T1D (n = 40, 53% female, aged (mean ±â€¯SD) 48 ±â€¯14 years, BMI 28.1 ±â€¯5.8 kg/m2, diabetes duration 27 ±â€¯18 years), 23 of whom had DSP, took seal-oil (10 mL/day; 750 mg eicosapentaenoic acid (EPA), 560 mg docosapentaenoic acid (DPAn-3), and 1020 mg docosahexaenoic acid (DHA)) for 12-months in a single-arm open-label study. The improvement in corneal nerve fibre length (CNFL) (primary outcome) was previously reported. In this secondary analysis, plasma n-3s were measured at baseline, 4, 8 and 12-months. RESULTS: At baseline, participants with DSP had lower DHA than those without (1.73 ±â€¯0.89 vs. 2.27 ±â€¯0.70%, p = 0.049). Twelve-months seal-oil therapy increased mean plasma EPA by 185%, DPA by 29%, DHA by 79% (p < 0.001) and CNFL by 29% (p = 0.001). Change in CNFL was positively associated with higher baseline total n-3 (Spearman's correlation coefficient r = 0.41, p = 0.013), DPA (r = 0.33, p = 0.047) and DHA (r = 0.42, p = 0.012). CONCLUSION: In conclusion, low plasma DHA was associated with prevalent DSP, n-3 therapy increased blood n-3 levels and higher baseline n-3s were associated with greater nerve regeneration.

"Controlled Slip" Energy Harvesting While Walking.

Rapid development in wearable electronics and systems continues to impose challenges on portable energy storage sustained over time, and thus human energy harvesting is a potentially attractive means of sustainable, long-term energy. We introduce a novel 'controlled slip' energy harvesting approach for capturing energy during human locomotion. While slip is normally considered undesirable, controlled slip holds potential to enable a significant amount of energy harvesting during each step of human gait. Custom-designed 'controlled slip' energy harvesting shoes were fabricated by mounting a sliding plate and a generator with a one-way bearing to the sole of standard walking shoes, which induces controlled forward slip during early stance while energy is harvested. Fourteen healthy subjects performed treadmill walking trials with the 'controlled slip' energy harvesting shoes which generated average electrical power of 1.15-1.44 W at walking speeds of 2.9-4.3 km/h. Interestingly, without prompting, subjects chose to walk with the 'controlled slip' energy harvesting shoes in either one of two distinct ways: landing with the heel first (heel strikers) or landing with the toe first (toe strikers). While heel strikers and toe strikers exhibited similar electrical power output and hip flexion angle at initial foot contact, heel strikers had higher peak ankle power and lower knee flexion angle at initial foot contact than toe strikers. 'Controlled slip' energy harvesting could potentially generate electrical power for a broad spectrum of wearable devices.

Soft Wearable Skin-Stretch Device for Haptic Feedback Using Twisted and Coiled Polymer Actuators.

Soft and integrated design can enable wearable haptic devices to augment natural human taction. This paper proposes a novel, soft, haptic finger-worn wearable device based on compliant and adhesive silicone skin and lightweight twisted and coiled polymer (TCP) actuators using ultra high molecular weight polyethylene (UHMWPE) fibers to provide lateral skin stretch sensations. Recently, silicone elastomers have been used in wearable sensors and in haptic applications for their high compliance or adhesion. TCP actuators have also demonstrated high power to weight ratios, large stroke length, simple mechanism, and inherent softness. Lateral skin stretch is sensitive to small motions and has been used for intuitive proprioceptive feedback applications. We combined these characteristics to design and manufacture a wearable, functional haptic prototype. Prototype performance was evaluated using an optical tracking system, a force gauge test bench, and compared to vibrotactile haptic feedback in a experiment with 14 healthy participants. Results showed that participant mean reaction times were comparable to those of a vibrotactile feedback system, though task completion times were longer. This paper is the first to employ TCP actuators for haptic stimulation and could serve as a foundation for future applications involving soft wearable haptics in gaming, health, and virtual reality.

Wearable lower limb haptic feedback device for retraining Foot Progression Angle and Step Width.

Technological developments in the last decade have enabled the integration of sensors and actuators into wearable devices for gait interventions to slow the progression of knee osteoarthritis. Wearable haptic gait retraining is one area which has seen promising results for informing modifications of gait parameters for reducing knee adduction moments (KAM) during walking. Two gait parameters which can be easily adjusted to influence KAM include foot progression angle (FPA) and step width (SW). The purpose of this study was to: (1) determine whether a custom haptic ankle bracelet using binary vibrotactile and tactile apparent movement feedback could retrain ten healthy subjects to walk with a modified FPA and SW within a short training session with 80% accuracy; and (2) whether there was a difference between the number of steps required to complete the retraining task based on the two feedback schemes being tested. Retraining multiple gait parameters using a single device was a novel aspect of this work and we found that nine out of ten subjects were able to retrain their gait using the ankle bracelet in both feedback schemes to within 2° and 39mm of target FPA and SW respectively. We also found no difference in the number steps required for completion between the two schemes (p>0.05). Future research will investigate the device performance with patients with knee osteoarthritis and the effective change in KAM by modifying a combination of FPA and SW.

Lower Extremity Lateral Skin Stretch Perception for Haptic Feedback.

Tactile feedback in recent decades has allowed humans to receive information through technology beyond traditional visual and auditory senses. Lateral skin stretch has the potential to be a mode of tactile feedback, reliably enabling the perception of directional cues through the use of a single actuator. Experiments were conducted to explore sensitivity to skin stretch on nine locations on the human lower leg. Thirty-two stimuli were presented to subjects, exploring effects of displacement (from 0.2-2.0 mm) and speed (from 0.5-4.0 mm/s) on the perception of left and right directions. Higher accuracy came from stimuli having higher displacements and speeds. Three of the locations: soleus, calcaneal tendon (upper), and fibularis longus (lower) all had a mean accuracy of at least 85 percent and are suitable locations for a skin stretch tactile feedback device.