Saturated fatty acids such as palmitic acid promote inflammation and insulin resistance in peripheral tissues, contrasting with the protective action of polyunsaturated fatty acids such ...docosahexaenoic acid. Palmitic acid effects have been in part attributed to its potential action through Toll-like receptor 4. Beside, resistin, an adipokine, also promotes inflammation and insulin resistance via TLR4. In the brain, palmitic acid and resistin trigger neuroinflammation and insulin resistance, but their link at the neuronal level is unknown. Using human SH-SY5Yneuroblastoma cell line we show that palmitic acid treatment impaired insulin-dependent Akt and Erk phosphorylation whereas DHA preserved insulin action. Palmitic acid up-regulated TLR4 as well as pro-inflammatory cytokines IL6 and TNFα contrasting with DHA effect. Similarly to palmitic acid, resistin treatment induced the up-regulation of IL6 and TNFα as well as NFκB activation. Importantly, palmitic acid potentiated the resistin-dependent NFkB activation whereas DHA abolished it. The recruitment of TLR4 to membrane lipid rafts was increased by palmitic acid treatment; this is concomitant with the augmentation of resistin-induced TLR4/MYD88/TIRAP complex formation mandatory for TLR4 signaling. In conclusion, palmitic acid increased TLR4 expression promoting resistin signaling through TLR4 up-regulation and its recruitment to membrane lipid rafts.
•MicroRNA 200a is up-regulated in the hypothalamus of ob/ob mice.•Leptin treatment reduces miR-200a in the hypothalamus of ob/ob mice.•Silencing of hypothalamic miR-200a restores liver ...insulin-sensitivity.
Early in life, leptin plays a crucial role in hypothalamic neural organization. Leptin, most likely, controls neural gene expression conferring then specific phenotype regarding energy homeostasis. MicroRNAs are new regulators for several physiological functions, including the regulation of metabolism. However, the impact of leptin on hypothalamic microRNA patterns remains unknown. Here, we demonstrate that miR-200a, miR-200b and miR-429 are up-regulated in the hypothalamus of genetically obese and leptin deficient ob/ob mice. Leptin treatment down-regulates these miRNAs in ob/ob hypothalamus. The hypothalamic silencing of miR-200a increased the expression level of leptin receptor and insulin receptor substrate 2, reduced body weight gain, and restored liver insulin responsiveness. In addition, the overexpression of pre-miR-200a in a human neuroblastoma cell line impaired insulin and leptin signaling. These findings link the alteration of leptin and insulin signaling to the up-regulation of hypothalamic miR-200a which could be a new target for treatment of obesity.
Background: Isolated gastrocnemius tightness (IGT) is a prevalent condition linked to various foot pathologies. In a previous quantitative gait analysis study, we identified an increase in knee ...flexion during the midstance phase in IGT patients compared with controls. Although stretching and eccentric exercises (the Stanish protocol) are commonly used for IGT management, their impact on gait parameters remains poorly understood. This study aimed to assess the influence of a Stanish protocol on gait parameters in bilateral IGT subjects. Methods: We enrolled 10 asymptomatic bilateral IGT subjects and 10 controls. Quantitative gait analysis and dynamic baropodometry were carried out on each subject. A Stanish protocol was applied for 4 weeks (five sessions/week) by the IGT group, followed by a similar gait analysis. The ankle and knee range of motion and foot pressure distribution were assessed during the midstance phase of the gait. Results: An increase in knee flexion was initially present in the IGT group compared with controls (8.9 +/− 4.6 vs. 3.4 +/− 2.3 degrees, p < 0.001). There was no difference in the ankle range of motion and foot pressures between the groups at that time. Significant reductions in knee flexion during gait were observed in the IGT subjects after the Stanish protocol (8.9 +/− 4.6 to 3.7 +/− 2.3 degrees, p < 0.001) with a normalization of this parameter (3.4 +/− 2.3 in controls vs. 3.7 +/− 2.3 degrees in IGT, p = 0.72). There was no change in ankle range of motion and foot pressure after the Stanish protocol. Conclusions: Our findings support the effectiveness of the Stanish protocol in reducing knee flexion and normalizing gait in IGT subjects. This protocol not only offers a noninvasive approach for IGT-related issues management but could also enable prophylactic care in asymptomatic cases.
the purpose of this study was to assess the orthopaedic surgeons' perceptions and attitudes on COVID-19 related changes in their practice.
an online survey was shared with orthopaedic surgeons ...practicing in different countries.
this study showed that orthopaedic surgery plan management was adapted to respond more effectively to the COVID-19 pandemic while maintaining the continuity of health care and ensuring protection of medical staff and patients. Among the introduced measures, elective surgery was postponed to free-up beds for suspected or COVID-19 positive patients requiring hospitalization. Additionally, the number of outpatient visits was considerably decreased and non-urgent visits were postponed to reduce the flow of patients in and out of hospitals and therefore minimize the risk of contamination. Interestingly, data revealed the willingness of orthopaedic surgeons to take care of COVID-19 positive patients and support their colleagues in intensive care units, if needed.
orthopaedic surgery departments have adapted their programs to face the unprecedented challenges due to the COVID-19 pandemic. Quick measures were taken to reduce the risk of contamination in patients, medical staff and to allow hospitals to free up beds for treatment of patients with positive or suspected COVID-19.
•Deep learning-based human pose estimation methods for marker-less motion capture.•The performance of pose estimation methods is dependent on the training dataset.•A well-adapted human pose dataset ...for clinical gait study is collected.
The deep learning-based human pose estimation methods, which can estimate joint centers position, have achieved promising results on the publicly available human pose datasets (e.g., Human3.6 M). However, these datasets may be less efficient for gait study, particularly for clinical applications, because of the limited number of subjects, their homogeneity (all asymptomatic adults), and the errors introduced by marker placement on subjects’ regular clothing.
How a new human pose dataset, adapted for gait study, could contribute to the advancement and evaluation of marker-less motion capture systems?
A marker-less system, based on deep learning-based pose estimation methods, was proposed. A new dataset (ENSAM dataset) was collected. Twenty-two asymptomatic adults, one adult with scoliosis, one adult with spondylolisthesis, and seven children with bone disease performed ten walking trials, while being recorded both by the proposed marker-less system and a reference system – combining a marker-based motion capture system and a medical imaging system (EOS). The dataset was split into training and test sets. The pose estimation method, already trained on the Human3.6 M dataset, was evaluated on the ENSAM test set, then reevaluated after further training on the ENSAM training set. The joints coordinates were evaluated, using Bland-Altman bias and 95 % confidence interval, and joint position error (the Euclidean distance between the estimated joint centers and the corresponding reference values).
The Bland-Altman 95 % confidence intervals were substantially improved after finetuning the pose estimation method on the ENSAM training set (e.g., from 106.9 mm to 17.4 mm for the hip joint). With the new dataset and approach, the mean joint position error varied from 6.2 mm for ankles to 21.1 mm for shoulders.
The proposed marker-less system achieved promising results in terms of joint position errors. Future studies are necessary to assess the system in terms of gait parameters.
Adiponectin, an insulin-sensitizing hormone, and resistin, known to promote insulin resistance, constitute a potential link between obesity and type 2 diabetes. In addition, fibroblast growth factor ...(FGF)21 has effects similar to those of adiponectin in regulating glucose and lipid metabolism and insulin sensitivity. However, the interplay between adiponectin, FGF21, and resistin signaling pathways during the onset of insulin resistance is unknown. Here, we investigated whether central resistin promotes insulin resistance through the impairment of adiponectin and FGF21 signaling. We show that chronic intracerebroventricular resistin infusion downregulated both hypothalamic and hepatic APPL1, a key protein in adiponectin signaling, associated with decreased Akt-APPL1 interaction and an increased Akt association with its endogenous inhibitor tribbles homolog 3. Resistin treatment also decreased plasma adiponectin levels and reduced both hypothalamic and peripheral expression of adiponectin receptors. Additionally, we report that intracerebroventricular resistin increased plasma FGF21 levels and downregulated its receptor components in the hypothalamus and peripheral tissues, promoting FGF21 resistance. Interestingly, we also show that resistin effects were abolished in TLR4 knockout mice and in neuronal cells expressing TLR4 siRNAs. Our study reveals a novel mechanism of insulin resistance onset orchestrated by a central resistin-TLR4 pathway that impairs adiponectin signaling and promotes FGF21 resistance.
Antiproliferative BTG/Tob proteins interact directly with the CAF1 deadenylase subunit of the CCR4-NOT complex. This binding requires the presence of two conserved motifs, boxA and boxB, ...characteristic of the BTG/Tob APRO domain. Consistently, these proteins were shown to stimulate mRNA deadenylation and decay in several instances. Two members of the family, BTG1 and BTG2, were reported further to associate with the protein arginine methyltransferase PRMT1 through a motif, boxC, conserved only in this subset of proteins. We recently demonstrated that BTG1 and BTG2 also contact the first RRM domain of the cytoplasmic poly(A) binding protein PABPC1. To decipher the mode of interaction of BTG1 and BTG2 with partners, we performed nuclear magnetic resonance experiments as well as mutational and biochemical analyses. Our data demonstrate that, in the context of an APRO domain, the boxC motif is necessary and sufficient to allow interaction with PABPC1 but, unexpectedly, that it is not required for BTG2 association with PRMT1. We show further that the presence of a boxC motif in an APRO domain endows it with the ability to stimulate deadenylation in cellulo and in vitro. Overall, our results identify the molecular interface allowing BTG1 and BTG2 to activate deadenylation, a process recently shown to be necessary for maintaining T-cell quiescence.
The beneficial effect of polyunsaturated omega-3 fatty acid (w-3 FA) consumption regarding cardiovascular diseases, insulin resistance and inflammation has been widely reported. Fish oil is ...considered as the main source of commercialized w-3 FAs, and other alternative sources have been reported such as linseed or microalgae. However, despite numerous reports, the underlying mechanisms of action of w-3 FAs on insulin resistance are still not clearly established, especially those from microalgae. Here, we report that Odontella aurita, a microalga rich in w-3 FAs eicosapentaenoic acid, prevents high fat diet-induced insulin resistance and inflammation in the liver of Wistar rats. Indeed, a high fat diet (HFD) increased plasma insulin levels associated with the impairment of insulin receptor signaling and the up-regulation of toll-like receptor 4 (TLR4) expressions. Importantly, Odontella aurita-enriched HFD (HFOA) reduces body weight and plasma insulin levels and maintains normal insulin receptor expression and responsiveness. Furthermore, HFOA decreased TLR4 expression, JNK/p38 phosphorylation and pro-inflammatory factors. In conclusion, we demonstrate for the first time, to our knowledge, that diet supplementation with whole Ondontella aurita overcomes HFD-induced insulin resistance through the inhibition of TLR4/JNK/p38 MAP kinase signaling pathways.
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