Rosiglitazone Reverses Inflammation in Epididymal White Adipose Tissue in Hormone-Sensitive Lipase-Knockout Mice.

Hormone-sensitive lipase (HSL) plays a crucial role in intracellular lipolysis, and loss of HSL leads to diacylglycerol (DAG) accumulation, reduced FA mobilization, and impaired PPARγ signaling. Hsl knockout mice exhibit adipose tissue inflammation, but the underlying mechanisms are still not clear. Here, we investigated if and to what extent HSL loss contributes to endoplasmic reticulum (ER) stress and adipose tissue inflammation in Hsl knockout mice. Furthermore, we were interested in how impaired PPARγ signaling affects the development of inflammation in epididymal white adipose tissue (eWAT) and inguinal white adipose tissue (iWAT) of Hsl knockout mice and if DAG and ceramide accumulation contribute to adipose tissue inflammation and ER stress. Ultrastructural analysis showed a markedly dilated ER in both eWAT and iWAT upon loss of HSL. In addition, Hsl knockout mice exhibited macrophage infiltration and increased F4/80 mRNA expression, a marker of macrophage activation, in eWAT, but not in iWAT. We show that treatment with rosiglitazone, a PPARγ agonist, attenuated macrophage infiltration and ameliorated inflammation of eWAT, but expression of ER stress markers remained unchanged, as did DAG and ceramide levels in eWAT. Taken together, we show that HSL loss promoted ER stress in both eWAT and iWAT of Hsl knockout mice, but inflammation and macrophage infiltration occurred mainly in eWAT. Also, PPARγ activation reversed inflammation but not ER stress and DAG accumulation. These data indicate that neither reduction of DAG levels nor ER stress contribute to the reversal of eWAT inflammation in Hsl knockout mice.

Quality and Vitality of Autologous Fat Grafts Harvested by Different Techniques: A Clinical Comparison Study.

BACKGROUND: Unpredictable outcomes with autologous fat grafting due to reabsorption processes present a major challenge for healthcare providers and patients. A higher number of viable adipocytes is considered to result in a higher volume being retained. Although various adverse factors have been extensively researched, other potential parameters have been less investigated or even neglected. OBJECTIVE: The aim of this study was to investigate the harvesting process of adipose tissue as the primary cause of cell damage and to determine the risk factors associated with low cell survival. METHODS: Thirty-nine male and female subjects undergoing planned elective liposuction or abdominoplasty were enrolled. Forty-seven lipoaspirates harvested by different liposuction techniques were analyzed. RNA isolation and real-time polymerase chain reaction was performed to elucidate differences in the expression of various adipocyte markers. Furthermore, scanning electron microscopy was performed on various samples to determine the cell damage caused by the different techniques. RESULTS: A statistically significant lower expression of peroxisome proliferator-activated receptor γ was detected in subjects with a higher BMI. A trend towards a lower expression of perilipin 1 in lipoaspirates harvested by a super wet + ultrasound technique, compared with dry and super wet techniques, was shown. The lowest level of cell damage determined from scanning electron microscopy images was in lipoaspirates harvested by the super wet + ultrasound technique, and this level was statistically significantly different from those obtained by the 2 other techniques. CONCLUSIONS: Optimization of the outcome in autologous fat grafting may be feasible by targeting and optimizing the harvesting process as a main risk factor for impaired adipocyte viability. Ultrasound-assisted liposuction might be considered a suitable harvesting technique.

The Impact of Prolonged Inflammation on Wound Healing.

The treatment of chronic wounds still challenges modern medicine because of these wounds' heterogenic pathophysiology. Processes such as inflammation, ischemia and bacterial infection play major roles in the progression of a chronic wound. In recent years, preclinical wound models have been used to understand the underlying processes of chronic wound formation. However, the wound models used to investigate chronic wounds often lack translatability from preclinical models to patients, and often do not take exaggerated inflammation into consideration. Therefore, we aimed to investigate prolonged inflammation in a porcine wound model by using resiquimod, a TLR7 and TLR8 agonist. Pigs received full thickness excisional wounds, where resiquimod was applied daily for 6 days, and untreated wounds served as controls. Dressing change, visual documentation and wound scoring were performed daily. Biopsies were collected for histological as well as gene expression analysis. Resiquimod application on full thickness wounds induced a visible inflammation of wounds, resulting in delayed wound healing compared to non-treated control wounds. Gene expression analysis revealed high levels of IL6, MMP1 and CD68 expression after resiquimod application, and histological analysis showed increased immune cell infiltration. By using resiquimod, we were able to show that prolonged inflammation delayed wound healing, which is often observed in chronic wounds in patients. The model we used shows the importance of inflammation in wound healing and gives an insight into the progression of chronic wounds.