Adipose tissue endocannabinoid system gene expression: depot differences and effects of diet and exercise

<p>Abstract</p> <p>Background</p> <p>Alterations of endocannabinoid system in adipose tissue play an important role in lipid regulation and metabolic dysfunction associated with obesity. The purpose of this study was to determine whether gene expression levels of cannabinoid type 1 receptor (CB1) and fatty acid amide hydrolase (FAAH) are different in subcutaneous abdominal and gluteal adipose tissue, and whether hypocaloric diet and aerobic exercise influence subcutaneous adipose tissue CB1 and FAAH gene expression in obese women.</p> <p>Methods</p> <p>Thirty overweight or obese, middle-aged women (BMI = 34.3 ± 0.8 kg/m², age = 59 ± 1 years) underwent one of three 20-week weight loss interventions: caloric restriction only (CR, N = 9), caloric restriction plus moderate-intensity aerobic exercise (CRM, 45-50% HRR, N = 13), or caloric restriction plus vigorous-intensity aerobic exercise (CRV, 70-75% HRR, N = 8). Subcutaneous abdominal and gluteal adipose tissue samples were collected before and after the interventions to measure CB1 and FAAH gene expression.</p> <p>Results</p> <p>At baseline, FAAH gene expression was higher in abdominal, compared to gluteal adipose tissue (2.08 ± 0.11 vs. 1.78 ± 0.10, expressed as target gene/β-actin mRNA ratio × 10^-3, P < 0.05). Compared to pre-intervention, CR did not change abdominal, but decreased gluteal CB1 (Δ = -0.82 ± 0.25, P < 0.05) and FAAH (Δ = -0.49 ± 0.14, P < 0.05) gene expression. CRM or CRV alone did not change adipose tissue CB1 and FAAH gene expression. However, combined CRM and CRV (CRM+CRV) decreased abdominal adipose tissue FAAH gene expression (Δ = -0.37 ± 0.18, P < 0.05). The changes in gluteal CB1 and abdominal FAAH gene expression levels in the CR alone and the CRM+CRV group were different (P < 0.05) or tended to be different (P = 0.10).</p> <p>Conclusions</p> <p>There are depot differences in subcutaneous adipose tissue endocannabinoid system gene expression in obese individuals. Aerobic exercise training may preferentially modulate abdominal adipose tissue endocannabinoid-related gene expression during dietary weight loss.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00664729">NCT00664729</a>.</p

Microfluidics for nano-drug delivery systems: From fundamentals to industrialization

In recent years, owing to the miniaturization of the fluidic environment, microfluidic technology offers unique opportunities for the implementation of nano drug delivery systems (NDDSs) production processes. Compared with traditional methods, microfluidics improves the controllability and uniformity of NDDSs. The fast mixing and laminar flow properties achieved in the microchannels can tune the physicochemical properties of NDDSs, including particle size, distribution and morphology, resulting in narrow particle size distribution and high drug-loading capacity. The success of lipid nanoparticles encapsulated mRNA vaccines against coronavirus disease 2019 by microfluidics also confirmed its feasibility for scaling up the preparation of NDDSs via parallelization or numbering-up. In this review, we provide a comprehensive summary of microfluidics-based NDDSs, including the fundamentals of microfluidics, microfluidic synthesis of NDDSs, and their industrialization. The challenges of microfluidics-based NDDSs in the current status and the prospects for future development are also discussed. We believe that this review will provide good guidance for microfluidics-based NDDSs

Effect of exercise training intensity on adipose tissue hormone sensitive lipase gene expression in obese women under weight loss

AbstractBackgroundHormone sensitive lipase (HSL) is an enzyme that regulates adipose tissue lipolysis and plays an important role in chronic exercise-induced changes in adipose tissue metabolism. The purpose of this study was to determine whether aerobic exercise intensity influences abdominal adipose tissue HSL gene expression in obese women under weight loss.MethodsThirty women (body mass index (BMI) = 33.0 ± 0.7 kg/m2, age = 58 ± 1 years) completed one of three 20-week interventions: caloric restriction alone (CR only, n = 8), CR plus moderate-intensity exercise (CR + moderate-intensity, 45%–50% heart rate reserve (HRR), 3 day/week, n = 9), or CR plus vigorous-intensity exercise (CR + vigorous-intensity, 70%–75% HRR, 3 day/week, n = 13). Each group had a similar prescribed energy deficit comprised of underfeeding alone (2800 kcal/week for CR only) or underfeeding (2400 kcal/week) plus exercise (400 kcal/week). Body composition and maximal aerobic capacity (VO2max) were measured, and subcutaneous abdominal adipose tissue samples were collected before and after the interventions. Adipose tissue HSL gene expression was measured by real time reverse-transcriptase polymerase chain reaction.ResultsAll three interventions reduced body weight, fat mass, percent fat, and waist to a similar degree (all p < 0.01). In addition, all interventions did not change absolute VO2max, but increased relative VO2max (p < 0.05 to p < 0.01). Compared to pre-intervention, neither CR only nor CR + moderate-intensity changed adipose tissue HSL gene expression, but CR + vigorous-intensity significantly increased adipose tissue HSL gene expression (p < 0.01). The changes of HSL gene expression levels in the CR + vigorous-intensity group were significantly different from those in the CR only (p < 0.05) and CR + moderate-intensity (p < 0.01) groups. In the whole cohort, changes in adipose tissue HSL gene expression correlated positively to changes in absolute (r = 0.55, p < 0.01) and relative (r = 0.32, p = 0.09) VO2max.ConclusionThese results support a potential effect of aerobic exercise training intensity on hormone sensitive lipase pathway in adipose tissue metabolism in obese women under weight loss

Study on the Relationship between Combustion Parameters and Cylinder Head Vibration Signal in Time Domain

Combustion-related characteristic parameters, such as the start of combustion (SoC) and the timing of the peak pressure increase rate (PIR), can be used as the feedback signals for the closed-loop control of combustion. A dynamic Finite Element Method (FEM) model was firstly developed to confirm the closely related time period between combustion pressure and vibration. On this basis, a fast processing method was developed to estimate the timings of SoC and the peak PIR in the closely related time period. This method was verified on a twelve-cylinder heavy-duty diesel engine at various engine speed and load. Results showed that the maximum deviation of the two parameters were within 2 °CA and 1.5 °CA, respectively, which suggested that the proposed method had an adequate accuracy

A Proof-of-Concept Inhibitor of Endothelial Lipase Suppresses Triple-Negative Breast Cancer Cells by Hijacking the Mitochondrial Function

Triple-negative breast cancer (TNBC) cells reprogram their metabolism to provide metabolic flexibility for tumor cell growth and survival in the tumor microenvironment. While our previous findings indicated that endothelial lipase (EL/LIPG) is a hallmark of TNBC, the precise mechanism through which LIPG instigates TNBC metabolism remains undefined. Here, we report that the expression of LIPG is associated with long non-coding RNA DANCR and positively correlates with gene signatures of mitochondrial metabolism-oxidative phosphorylation (OXPHOS). DANCR binds to LIPG, enabling tumor cells to maintain LIPG protein stability and OXPHOS. As one mechanism of LIPG in the regulation of tumor cell oxidative metabolism, LIPG mediates histone deacetylase 6 (HDAC6) and histone acetylation, which contribute to changes in IL-6 and fatty acid synthesis gene expression. Finally, aided by a relaxed docking approach, we discovered a new LIPG inhibitor, cynaroside, that effectively suppressed the enzyme activity and DANCR in TNBC cells. Treatment with cynaroside inhibited the OXPHOS phenotype of TNBC cells, which severely impaired tumor formation. Taken together, our study provides mechanistic insights into the LIPG modulation of mitochondrial metabolism in TNBC and a proof-of-concept that targeting LIPG is a promising new therapeutic strategy for the treatment of TNBC