Identification of a regulatory pathway inhibiting adipogenesis via RSPO2

Healthy adipose tissue remodeling depends on the balance between de novo adipogenesis from adipogenic progenitor cells and the hypertrophy of adipocytes. De novo adipogenesis has been shown to promote healthy adipose tissue expansion, which confers protection from obesity-associated insulin resistance. Here, we define the role and trajectory of different adipogenic precursor subpopulations and further delineate the mechanism and cellular trajectory of adipogenesis, using single-cell RNA-sequencing datasets of murine adipogenic precursors. We identify Rspo2 as a functional regulator of adipogenesis, which is secreted by a subset of CD142+ cells to inhibit maturation of early progenitors through the receptor Lgr4. Increased circulating RSPO2 in mice leads to adipose tissue hypertrophy and insulin resistance and increased RSPO2 levels in male obese individuals correlate with impaired glucose homeostasis. Taken together, these findings identify a complex cellular crosstalk that inhibits adipogenesis and impairs adipose tissue homeostasis.

Latissimus dorsi muscle flap transfer through endoscopic approach combined with the implant after tissue expansion for breast reconstruction of mastectomy patients

Background Implant-based breast reconstruction is easy to be performed but has flaws that an unnatural appearance might be presented when no sufficient coverage existing. While autologous tissue reconstruction also has disadvantages like donor site scar and skin patch effect. There is a demand for a new method to obtain natural and aesthetic appearance while surmounting drawbacks of conventional breast reconstruction surgery. Methods A retrospective review of thirty-one patients undergoing tissue expander (TE)/implant two-stage breast reconstruction with latissimus dorsi muscle flap (LDMF) transfer through endoscopic approach in Peking University Third Hospital from April 2016 to August 2020 was performed. The LDMF harvest time, drain time, and complications were reviewed. The 3D volume was obtained to assess the volume symmetry of bilateral breasts. The BREAST-Q reconstruction module was used to evaluate the satisfaction. Results The mean endoscopic LDMF harvest time was 90.4 min. In the mean follow-up of 11.2 months, there were no severe capsular contracture happened. The reconstructed side achieved good volume symmetry to the contralateral side (P = 0.256). Based on the evaluation of the BREAST-Q scores, the outcome of Satisfaction with Breasts was excellent or good in 87.1% of the cases. Conclusions The novel type of two-stage breast reconstruction protocol, which includes tissue expansion followed by implant insertion with endoscopy-assisted LDMF transfer, could effectively reduce visible scars, avoid the patch effect, while require short time for LDMF harvest and present low incidence of complications. It is a promising method for breast reconstruction because it achieves good outcomes in the mastectomy patients.

Choosing the Optimal Tissue Expander Size: A Single Center Randomized Clinical Trial on Chinese Microtia Patients’ Normal Ears Using 3D Scanning

The tissue expansion technique is the most suitable procedure for Chinese patients with microtia. However, it is difficult to determine whether the expanded flap is sufficient, and there are no clear or objective guidelines for determining the volume of the expander for different sizes of auricles. One hundred patients with unilateral microtia who visited our department in 2021 were randomly selected for auricular data collection using 3D scanning. The auricle length, width, projection, perimeter, and surface area were measured. Eight different volumes of expanders underwent CT and the surface areas of these expanders were measured. The surface areas of the auricles and expanders were compared and the correlation between them was explored. The average auricle parameters were calculated. The scatter plot showed a linear relationship between auricle length and auricle surface area (R2 = 0.9913), which demonstrated that the auricle area was approximately equal to the auricle length multiplied by 76.921. Additionally, the surface area of the expanders was measured and made into a table for selection against the surface area of the auricles. Using our equation, the auricle surface could be estimated by simply measuring the non-defective auricle length; therefore, the suitable volume of the expander could be determined.

Adipose-Specific PPARα Knockout Mice Have Increased Lipogenesis by PASK–SREBP1 Signaling and a Polarity Shift to Inflammatory Macrophages in White Adipose Tissue

The nuclear receptor PPARα is associated with reducing adiposity, especially in the liver, where it transactivates genes for β-oxidation. Contrarily, the function of PPARα in extrahepatic tissues is less known. Therefore, we established the first adipose-specific PPARα knockout (PparaFatKO) mice to determine the signaling position of PPARα in adipose tissue expansion that occurs during the development of obesity. To assess the function of PPARα in adiposity, female and male mice were placed on a high-fat diet (HFD) or normal chow for 30 weeks. Only the male PparaFatKO animals had significantly more adiposity in the inguinal white adipose tissue (iWAT) and brown adipose tissue (BAT) with HFD, compared to control littermates. No changes in adiposity were observed in female mice compared to control littermates. In the males, the loss of PPARα signaling in adipocytes caused significantly higher cholesterol esters, activation of the transcription factor sterol regulatory element-binding protein-1 (SREBP-1), and a shift in macrophage polarity from M2 to M1 macrophages. We found that the loss of adipocyte PPARα caused significantly higher expression of the Per-Arnt-Sim kinase (PASK), a kinase that activates SREBP-1. The hyperactivity of the PASK–SREBP-1 axis significantly increased the lipogenesis proteins fatty acid synthase (FAS) and stearoyl-Coenzyme A desaturase 1 (SCD1) and raised the expression of genes for cholesterol metabolism (Scarb1, Abcg1, and Abca1). The loss of adipocyte PPARα increased Nos2 in the males, an M1 macrophage marker indicating that the population of macrophages had changed to proinflammatory. Our results demonstrate the first adipose-specific actions for PPARα in protecting against lipogenesis, inflammation, and cholesterol ester accumulation that leads to adipocyte tissue expansion in obesity.

Estrogen Impairs Adipose Tissue Expansion and Cardiometabolic Profile in Obese-Diabetic Female Rats

It has been reported that 17β-estradiol (E2) can exert beneficial effects against the development of obesity, providing women with a healthier metabolic profile and conferring cardiovascular protection. However, a growing body of evidence questions this role in the context of obesity and diabetes. We focus on the adipose tissue–heart axis to address the question of whether E2 can have metabolically detrimental effects in an obese-diabetic rat model. Female Zucker Diabetic Fatty rats were used: LEAN, fa/+; SHAM, sham-operated fa/fa; OVA, ovariectomized fa/fa, and OVA+E2, ovariectomized and E2 treated fa/fa. The secretory expression profile, tissue expansion parameters and composition of visceral adipose tissue, as well as systemic and cardiac parameters related to insulin resistance, fibrosis, and inflammation were analyzed. Ovariectomy induced an attenuation of both diabetic condition and metabolic dysfunction of adipose tissue and cardiac muscle in fa/fa rats, suggesting that E2, in the context of diabetes and obesity, loses its cardioprotective role and could even contribute to greater metabolic alterations. Adipose tissue from OVA rats showed a healthier hyperplastic expansion pattern, which could help maintain tissue function, increase adiponectin expression, and decrease pro-inflammatory adipokines. These findings should be taken into account when considering hormone replacement therapy for obese-diabetic women.

Reconstruction of Scalp Anterior Hairline with Tissue Expansion and Skin Flap

<b><i>Introduction:</i></b> Cutaneous defects involving the frontal region and anterior hairline of the scalp can result from congenital or acquired conditions. The negative esthetic impact can cause disturbances in the psychic and social sphere of the patient, causing problems in interpersonal relationships and in the body image itself. The use of skin expanders is usually effective in this region due to the bone base providing support and stability for its use. <b><i>Case Report:</i></b> We describe the case of a 64-year-old woman submitted to reconstruction of the anterior hairline of the scalp due to scar sequelae after coronal rhytidoplasty followed by pustular erosive dermatosis. We used tissue expansion (50 mL of saline per week until it reached 300 mL) and advancement flap. <b><i>Discussion/Conclusion:</i></b> Scalp reconstruction also includes vascularized soft tissue coverage, acceptable cosmetic appearance, and minimal morbidity for the donor area. The correction of scalp scars must obey 2 basic principles: tissue similarity and natural capillary pattern (direction, angle, capillary growth, and proper capillary line design). Tissue expansion and skin flap techniques can successfully correct defects in extensive scarring alopecia such as in the presented case.

Imaging Three-Dimensional Brain Organoid Architecture from Meso- to Nanoscale across Development

Organoids are human stem cell-derived three-dimensional cultures offering a new avenue to model human development and disease. Brain organoids allow studying various aspects of human brain development in the finest details in vitro in a tissue-like context. However, spatial relationships of subcellular structures such as synaptic contacts between distant neurons are hardly accessible by conventional light microscopy. This limitation can be overcome by systems that quickly image the entire organoid in three dimensions and in super-resolution. To that end we have developed a setup combining tissue expansion and light sheet fluorescence microscopy for imaging and quantifying diverse spatial parameters during organoid development. This technique enables zooming from a mesoscopic perspective into super-resolution within a single imaging session, thus revealing cellular and subcellular structural details in three spatial dimensions, including unequivocal delineation of mitotic cleavage planes as well as the alignment of pre- and postsynaptic proteins. We expect light sheet fluorescence expansion microscopy (LSFEM) to facilitate qualitative and quantitative assessment of organoids in developmental and disease-related studies.Summary statementThe combination of light sheet fluorescence and expansion microscopy enables imaging of mature human brain organoids in toto and down to synaptic resolution

Sex differences in white adipose tissue expansion: emerging molecular mechanisms

The escalating prevalence of individuals becoming overweight and obese is a rapidly rising global health problem, placing an enormous burden on health and economic systems worldwide. Whilst obesity has well described lifestyle drivers, there is also a significant and poorly understood component that is regulated by genetics. Furthermore, there is clear evidence for sexual dimorphism in obesity, where overall risk, degree, subtype and potential complications arising from obesity all differ between males and females. The molecular mechanisms that dictate these sex differences remain mostly uncharacterised. Many studies have demonstrated that this dimorphism is unable to be solely explained by changes in hormones and their nuclear receptors alone, and instead manifests from coordinated and highly regulated gene networks, both during development and throughout life. As we acquire more knowledge in this area from approaches such as large-scale genomic association studies, the more we appreciate the true complexity and heterogeneity of obesity. Nevertheless, over the past two decades, researchers have made enormous progress in this field, and some consistent and robust mechanisms continue to be established. In this review, we will discuss some of the proposed mechanisms underlying sexual dimorphism in obesity, and discuss some of the key regulators that influence this phenomenon.