Characterization of Fat Used for the Optimization of the Soft Tissue Envelope of the Nose in Rhinoplasty.

Septorhinoplasty (SRP) is one of the most common aesthetic procedures worldwide. A thin or scarred soft tissue envelope, especially in the context of secondary SRP, can lead to unpredictable scarring, shrinkage, and discoloration of the skin. Other than the careful preparation of the soft tissue mantle, no gold standard exists to minimize the above-mentioned risks. Our aim was to create a thin "separation layer" between the nasal bridge (osseous and cartilaginous) and the skin envelope by autologous fat transfer with the addition of platelet-rich fibrin (PRF) to conceal small irregularities, to improve the quality of the skin soft tissue mantle, and to optimize the mobility of the skin. We report 21 patients who underwent SRP on a voluntary basis. All patients had either thin skin and/or revision SRP with scarring. Macroscopic fat harvested from the periumbilical or rib region was minced and purified. PRF was obtained by centrifugation of autologous whole blood samples and mixed with the fat to form a graft, which was then transferred to the nasal dorsum. Postoperative monitoring of graft survival included sonography and magnetic resonance imaging (MRI) of the nose. The harvested adipose tissue was also analyzed in vitro. In the postoperative follow-up after 1 year, survival of the adipose tissue was demonstrated in all patients by both sonography and MRI. The in vitro analysis showed interindividual differences in the quantity, size, and quality of the transplanted adipocytes. Camouflage of the nasal bridge by using adipose tissue was beneficial for the quality of the skin soft tissue mantle and hence represents a good alternative to known methods. Future aims include the ability to assess the quality of adipose tissue to be transplanted based on clinical parameters. Level of evidence: N/A.

Differential effects of lung inflammation on insulin resistance in humans and mice.

BACKGROUND: The rates of obesity, its associated diseases, and allergies are raising at alarming rates in most countries. House dust mites (HDM) are highly allergenic and exposure often associates with an urban sedentary indoor lifestyle, also resulting in obesity. The aim of this study was to investigate the epidemiological association and physiological impact of lung inflammation on obesity and glucose homeostasis. METHODS: Epidemiological data from 2207 adults of the population-based KORA FF4 cohort were used to test associations between asthma and rhinitis with metrics of body weight and insulin sensitivity. To obtain functional insights, C57BL/6J mice were intranasally sensitized and challenged with HDM and simultaneously fed with either low-fat or high-fat diet for 12 weeks followed by a detailed metabolic and biochemical phenotyping of the lung, liver, and adipose tissues. RESULTS: We found a direct association of asthma with insulin resistance but not body weight in humans. In mice, co-development of obesity and HDM-induced lung inflammation attenuated inflammation in lung and perigonadal fat, with little impact on body weight, but small shifts in the composition of gut microbiota. Exposure to HDM improved glucose tolerance, reduced hepatosteatosis, and increased energy expenditure and basal metabolic rate. These effects associate with increased activity of thermogenic adipose tissues independent of uncoupling protein 1. CONCLUSIONS: Asthma associates with insulin resistance in humans, but HDM challenge results in opposing effects on glucose homeostasis in mice due to increased energy expenditure, reduced adipose inflammation, and hepatosteatosis.

Immune Cell Regulation of White Adipose Progenitor Cell Fate.

Adipose tissue is essential for energy storage and endocrine regulation of metabolism. Imbalance in energy intake and expenditure result in obesity causing adipose tissue dysfunction. This alters cellular composition of the stromal cell populations and their function. Moreover, the individual cellular composition of each adipose tissue depot, regulated by environmental factors and genetics, determines the ability of the depots to expand and maintain its endocrine and storage function. Thus, stromal cells modulate adipocyte function and vice versa. In this mini-review we discuss heterogeneity in terms of composition and fate of adipose progenitor subtypes and their interactions with and regulation by different immune cell populations. Immune cells are the most diverse cell populations in adipose tissue and play essential roles in regulating adipose tissue function via interaction with adipocytes but also with adipocyte progenitors. We specifically discuss the role of macrophages, mast cells, innate lymphoid cells and T cells in the regulation of adipocyte progenitor proliferation, differentiation and lineage commitment. Understanding the factors and cellular interactions regulating preadipocyte expansion and fate decision will allow the identification of novel mechanisms and therapeutic strategies to promote healthy adipose tissue expansion without systemic metabolic impairment.

L-Serine Supplementation Blunts Fasting-Induced Weight Regain by Increasing Brown Fat Thermogenesis.

Weight regain after fasting, often exceeding the pre-fasting weight, is a common phenomenon and big problem for the treatment of obesity. Thus, novel interventions maintaining reduced body weight are critically important to prevent metabolic disease. Here we investigate the metabolic effects of dietary L-serine supplementation, known to modulate various organ functions. C57BL/6N-Rj male mice were supplemented with or without 1% L-serine in their drinking water and fed with a chow or high-fat diet. Mice were fed either ad libitum or subjected to repeated overnight fasting. Body weight, body composition, glucose tolerance and energy metabolism were assessed. This was combined with a detailed analysis of the liver and adipose tissues, including the use of primary brown adipocytes to study mitochondrial respiration and protein expression. We find that L-serine supplementation has little impact on systemic metabolism in ad libitum-fed mice. Conversely, L-serine supplementation blunted fasting-induced body weight regain, especially in diet-induced obese mice. This reduction in body weight regain is likely due to the increased energy expenditure, based on elevated brown adipose tissue activity. Thus, L-serine supplementation during and after weight-loss could reduce weight regain and thereby help tackle one of the major problems of current obesity therapies.

Asc-1 regulates white versus beige adipocyte fate in a subcutaneous stromal cell population.

Adipose tissue expansion, as seen in obesity, is often metabolically detrimental causing insulin resistance and the metabolic syndrome. However, white adipose tissue expansion at early ages is essential to establish a functional metabolism. To understand the differences between adolescent and adult adipose tissue expansion, we studied the cellular composition of the stromal vascular fraction of subcutaneous adipose tissue of two and eight weeks old mice using single cell RNA sequencing. We identified a subset of adolescent preadipocytes expressing the mature white adipocyte marker Asc-1 that showed a low ability to differentiate into beige adipocytes compared to Asc-1 negative cells in vitro. Loss of Asc-1 in subcutaneous preadipocytes resulted in spontaneous differentiation of beige adipocytes in vitro and in vivo. Mechanistically, this was mediated by a function of the amino acid transporter ASC-1 specifically in proliferating preadipocytes involving the intracellular accumulation of the ASC-1 cargo D-serine.

Identification and characterization of distinct brown adipocyte subtypes in C57BL/6J mice.

Brown adipose tissue (BAT) plays an important role in the regulation of body weight and glucose homeostasis. Although increasing evidence supports white adipose tissue heterogeneity, little is known about heterogeneity within murine BAT. Recently, UCP1 high and low expressing brown adipocytes were identified, but a developmental origin of these subtypes has not been studied. To obtain more insights into brown preadipocyte heterogeneity, we use single-cell RNA sequencing of the BAT stromal vascular fraction of C57/BL6 mice and characterize brown preadipocyte and adipocyte clonal cell lines. Statistical analysis of gene expression profiles from brown preadipocyte and adipocyte clones identify markers distinguishing brown adipocyte subtypes. We confirm the presence of distinct brown adipocyte populations in vivo using the markers EIF5, TCF25, and BIN1. We also demonstrate that loss of Bin1 enhances UCP1 expression and mitochondrial respiration, suggesting that BIN1 marks dormant brown adipocytes. The existence of multiple brown adipocyte subtypes suggests distinct functional properties of BAT depending on its cellular composition, with potentially distinct functions in thermogenesis and the regulation of whole body energy homeostasis.

Thermally-induced formation of taste-active 2,5-diketopiperazines from short-chain peptide precursors in cocoa.

2,5-diketopiperazines (DKPs) are cyclic dipeptides responsible for the specific bitter taste of cocoa formed during roasting. The 2,5-diketopiperazine and peptide composition of four different cocoa bean samples from different origins were studied using LC-MS techniques. 34 diketopiperazines were identified, of which 10 are newly reported in cocoa. Their formation was followed during two different roasting time-series using a zero-order and an alternative Prout-Tompkins solid-state kinetic models. The activation energies of diketopiperazine formation showed a distribution close to normal with individual values depending on the nature of the substituents. The relative concentrations of the DKPs were correlated with their putative peptide precursors in unroasted cocoa bean samples. The results showed a significant positive correlation, indicating that oligopeptides formed in cocoa bean fermentation are taste-precursors for bitter tasting diketopiperazines. Unexpectedly, for most diketopiperazines, a single major peptide precursor could be suggested.

Pregnancy-associated breast cancer: the risky status quo and new concepts of predictive medicine.

The paper is motivated by severe concerns regarding currently applied care of the pregnancy-associated breast cancer (PABC) characterised by particularly poor outcomes of the disease. Psychological and ethical aspects play a crucial role in PABC: the highest priority not to damage the foetus significantly complicates any treatment generally, and it is quite usual that patients disclaim undergoing any breast cancer treatment during pregnancy. Although, due to global demographic trends, PABC is far from appearing rarely now, severe societal and economic consequences of the disease are still neglected by currently applied reactive medical approach. These actualities require creating new strategies which should be better adapted to the needs of the society at large by advancing the PABC care based on predictive diagnostic approaches specifically in premenopausal women, innovative screening programmes focused on young female populations, targeted prevention in high-risk groups, and optimised treatment concepts. The article summarises the facts and provides recommendations to advance the field-related research and medical services specifically dedicated to the PABC care.