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.

Autologous Fat Grafting in Reconstructive Breast Surgery: Clinically Relevant Factors Affecting the Graft Take.

BACKGROUND: Autologous fat grafting is an effective tool for soft tissue augmentation in reconstructive breast surgery. Despite the major advantages of this minimally invasive approach, the unpredictability of graft survival presents challenges. OBJECTIVES: No clear consensus on the optimal technique has yet been published and well-defined prospective studies investigating impairing factors are lacking. This aim of this study was to generate valuable fundamental data. METHODS: Ten female patients undergoing elective autologous fat grafting after nipple-sparing mastectomy were enrolled. Punch biopsies and lipoaspirates were collected from the harvest site for histologic, gene expression, and scanning electron microscopic analysis. Noninvasive Lipometer measurements determining the subcutaneous adipose tissue thickness at the graft site were used to calculate the respective take rate. Patient- and surgery-related data were acquired and correlated with the take rate. RESULTS: A statistically relevant correlation between the take rate and the existing mean subcutaneous adipose tissue thickness at the grafted breast prior to surgery was observed. An approximate correlation was identified regarding the number of previous grafting sessions, body weight, and BMI. No statistically significant correlation was demonstrated for age, harvest site, or the mean adipocyte size. A lower level of cell damage was observed in scanning electron microscopic samples of washed lipoaspirates; and a strong indirect correlation with the expression of the adipocyte markers FABP4 and PLIN1 was apparent. CONCLUSIONS: Factors correlating to the take rate were identified. Future studies investigating the clinical relevance of each impairing factor are essential to contribute to the optimization of this valuable method.

The effect of spermidine on autoimmunity and beta cell function in NOD mice.

Spermidine is a natural polyamine which was shown to prolong lifespan of organisms and to improve cardiac and cognitive function. Spermidine was also reported to reduce inflammation and modulate T-cells. Autophagy is one of the mechanisms that spermidine exerts its effect. Autophagy is vital for ß-cell homeostasis and autophagy deficiency was reported to lead to exacerbated diabetes in mice. The effect of spermidine in type 1 diabetes pathogenesis remains to be elucidated. Therefore, we examined the effect of spermidine treatment in non-obese diabetic (NOD) mice, a mouse model for type 1 diabetes. NOD mice were given untreated or spermidine-treated water ad libitum from 4 weeks of age until diabetes onset or 35 weeks of age. We found that treatment with 10 mM spermidine led to higher diabetes incidence in NOD mice despite unchanged pancreatic insulitis. Spermidine modulated tissue polyamine levels and elevated signs of autophagy in pancreas. Spermidine led to increased proportion of pro-inflammatory T-cells in pancreatic lymph nodes (pLN) in diabetic mice. Spermidine elevated the proportion of regulatory T-cells in early onset mice, whereas it reduced the proportion of regulatory T-cells in late onset mice. In summary spermidine treatment led to higher diabetes incidence and elevated proportion of T-cells in pLN.