Strongylocentrotus intermedius Extract Suppresses Adiposity by Inhibiting Adipogenesis and Promoting Adipocyte Browning via AMPK Activation in 3T3-L1 Cells.

The current study aimed to determine whether Strongylocentrotus intermedius (S. intermedius) extract (SIE) exerts anti-obesity potentials employing 3T3-L1 cells as in vitro model. Herein we reported that treatment of SIE for 6 days reduced lipid accretion and TG (triglyceride) content whereas it increased the release of free glycerol. The inhibited lipid accumulation and induced lipolysis were evidenced by the downregulation of lipogenesis proteins, such as fatty acid synthase and lipoprotein lipase, and the upregulation of hormone-sensitive lipase expression. Furthermore, the downregulation of adipogenic transcription factors, including peroxisome proliferator-activated receptor gamma, CCAAT/enhancer-binding protein α, and sterol regulatory element-binding protein 1, highlights that reduced lipid accumulation is supported by lowering adipocyte differentiation. Additionally, treatment activates brown adipocyte phenotype in 3T3-L1 cells by inducing expression of brown adipose tissue-specific proteins, such as uncoupling protein 1 (UCP-1) and peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α). Moreover, SIE induced the phosphorylation of AMP-activated protein kinase (AMPK). The pharmacological approach using AMPK inhibitor revealed that the restraining effect of SIE on adipogenesis and promotion of adipocyte browning were blocked. In GC-MS analysis, SIE was mainly composed of cholest-5-en-3-ol (36.71%) along with saturated and unsaturated fatty acids which have favorable anti-obesity potentials. These results reveal that SIE has the possibility as a lipid-lowering agent for the intervention of obesity.

Chromatin Immunoprecipitation in Adipose Tissue and Adipocytes: How to Proceed and Optimize the Protocol for Transcription Factor DNA Binding.

Chromatin immunoprecipitation (ChIP) coupled to qPCR or sequencing is a crucial experiment to determine direct transcriptional regulation under the control of specific transcriptional factors or co-regulators at loci-specific or pan-genomic levels.Here we provide a reliable method for processing ChIP from adipocytes or frozen adipose tissue collection, isolation of nuclei, cross-linking of protein-DNA complexes, chromatin shearing, immunoprecipitation, and DNA purification. We also discuss critical steps for optimizing the experiment to perform a successful ChIP in lipid-rich cells/tissues.

Loss of RREB1 reduces adipogenesis and improves insulin sensitivity in mouse and human adipocytes.

There are multiple independent genetic signals at the Ras-responsive element binding protein 1 (RREB1) locus associated with type 2 diabetes risk, fasting glucose, ectopic fat, height, and bone mineral density. We have previously shown that loss of RREB1 in pancreatic beta cells reduces insulin content and impairs islet cell development and function. However, RREB1 is a widely expressed transcription factor and the metabolic impact of RREB1 loss in vivo remains unknown. Here, we show that male and female global heterozygous knockout (Rreb1 +/-) mice have reduced body length, weight, and fat mass on high-fat diet. Rreb1+/- mice have sex- and diet-specific decreases in adipose tissue and adipocyte size; male mice on high-fat diet had larger gonadal adipocytes, while males on standard chow and females on high-fat diet had smaller, more insulin sensitive subcutaneous adipocytes. Mouse and human precursor cells lacking RREB1 have decreased adipogenic gene expression and activated transcription of genes associated with osteoblast differentiation, which was associated with Rreb1 +/- mice having increased bone mineral density in vivo. Finally, human carriers of RREB1 T2D protective alleles have smaller adipocytes, consistent with RREB1 loss-of-function reducing diabetes risk.

Comprehensive identification, isolation, and culture of human breast cell types.

Tissues are formed and shaped by cells of many different types and are orchestrated through countless interactions. Deciphering a tissue's biological complexity thus requires studying it at cell-level resolution, where molecular and biochemical features of different cell types can be explored and thoroughly dissected. Unfortunately, the lack of comprehensive methods to identify, isolate, and culture each cell type from many tissues has impeded progress. Here, we present a method for the breadth of cell types composing the human breast. Our goal has long been to understand the essence of each of these different breast cell types, to reveal the underlying biology explaining their intrinsic features, the consequences of interactions, and their contributions to the tissue. This biological exploration has required cell purification, deep-RNA sequencing-and a thorough dissection of the genes and pathways defining each cell type. Whereas the molecular analysis is presented in an adjoining article, we present here an exhaustive cellular dissection of the human breast and explore its cellular composition and histological organization. Moreover, we introduce a novel FACS antibody panel and rigorous gating strategy capable of isolating each of the twelve major breast cell types to purity. Finally, we describe the creation of primary cell models from nearly every breast cell type-some the first of their kind- and submit these as critical tools for studying the dynamic cellular interactions within breast tissues and tumors. Together, this body of work delivers a unique perspective of the breast, revealing insights into its cellular, molecular, and biochemical composition.

The PPIase Activity of CypB Is Essential for the Activation of Both AKT/mTOR and XBP1s Signaling Pathways during the Differentiation of 3T3-L1 Preadipocytes.

In this study, we undertook an extensive investigation to determine how CypB PPIase activity affects preadipocyte differentiation and lipid metabolism. Our findings revealed that inhibition of CypB's PPIase activity suppressed the expression of crucial proteins involved in adipocyte differentiation and induced changes in proteins regulating the cell cycle. Furthermore, we clarified the impact of CypB's PPIase activity on lipid metabolism via the AKT/mTOR signaling pathway. Additionally, we demonstrated the involvement of CypB's PPIase activity in lipid metabolism through the XBP1s pathway. These discoveries offer invaluable insights for devising innovative therapeutic strategies aimed at treating and averting obesity and its related health complications. Targeting CypB's PPIase activity may emerge as a promising avenue for addressing obesity-related conditions. Furthermore, our research opens up opportunities for creating new therapeutic strategies by enhancing our comprehension of the processes involved in cellular endoplasmic reticulum stress.

Genetic Factors Contributing to Interindividual Variability of α-Tocopherol Levels in Subcutaneous Adipose Tissue among Healthy Adult Males.

In humans, α-tocopherol (α-TOC) is mainly stored in adipose tissue, where it participates in preventing damages induced by inflammation and reactive oxygen species. Factors, including genetic ones, that explain adipose tissue α-TOC concentration remain poorly understood. This study, therefore, aimed to characterize the interindividual variability of adipose tissue α-TOC concentration in healthy individuals and to identify single nucleotide polymorphisms (SNPs) associated with it. The study used a randomized cross-over design with 42 healthy adult males. α-TOC concentration was measured in fasting plasma and periumbilical adipose tissue samples, both at fast and 8 h after consumption of three standard meals. Partial least squares (PLS) regression was performed to identify SNPs associated with the interindividual variability of adipose tissue α-TOC concentration. Adipose tissue α-TOC concentration was not associated with fasting plasma concentration (Pearson's r = 0.24, 95% CI: [-0.08, 0.51]). There was a high interindividual variability of adipose tissue α-TOC concentration (CV = 61%). A PLS regression model comprising 10 SNPs in five genes (PPARG, ABCA1, BUD13, CD36, and MGLL) explained 60% (adjusted R2) of the variability of this concentration. The interindividual variability of adipose tissue α-TOC concentration in humans is due, at least partly, to SNPs in genes involved in α-TOC and triglyceride metabolism.

Nuclear Factor-Kappa-B Mediates the Advanced Glycation End Product-Induced Repression of Slc2a4 Gene Expression in 3T3-L1 Adipocytes.

Advanced glycated end products (AGEs) are cytotoxic compounds that are mainly increased in diabetes mellitus (DM), kidney failure, inflammation, and in response to the ingestion of AGE-rich diets. AGEs can also impair glycemic homeostasis by decreasing the expression of the Slc2a4 (solute carrier family 2 member 4) gene and its GLUT4 (solute carrier family 2, facilitated glucose transporter member 4) protein in muscle. However, the mechanisms underlying AGE's effect on adipocytes have not been demonstrated yet. This study investigated the effects of AGEs upon Slc2a4/GLUT4 expression in 3T3-L1 adipocytes, as well as the potential role of NFKB (nuclear factor NF-kappa-B) activity in the effects observed. Adipocytes were cultured in the presence of control albumin (CA) or advanced glycated albumin (GA) at concentrations of 0.4, 3.6, and 5.4 mg/mL for 24 h or 72 h. Slc2a4, Rela, and Nfkb1mRNAs were measured by RT-qPCR, GLUT4, IKKA/B, and p50/p65 NFKB subunits using Western blotting, and p50/p65 binding into the Slc2a4 promoter was analyzed by chromatin immunoprecipitation (ChIP) assay. GA at 0.4 mg/mL increased Slc2a4/GLUT4 expression after 24 h and 72 h (from 50% to 100%), but at 5.4 mg/mL, Slc2a4/GLUT4 expression decreased at 72 h (by 50%). Rela and Nfkb1 expression increased after 24 h at all concentrations, but this effect was not observed at 72 h. Furthermore, 5.4 mg/mL of GA increased the p50/p65 nuclear content and binding into Slc2a4 at 72 h. In summary, this study reveals AGE-induced and NFKB-mediated repression of Slc2a4/GLUT4 expression. This can compromise the adipocyte glucose utilization, contributing not only to the worsening of glycemic control in DM subjects but also the impairment of glycemic homeostasis in non-DM subjects under the high intake of AGE-rich foods.

The Role of Adipocytes Recruited as Part of Tumor Microenvironment in Promoting Colorectal Cancer Metastases.

Adipose tissue dysfunction, which is associated with an increased risk of colorectal cancer (CRC), is a significant factor in the pathophysiology of obesity. Obesity-related inflammation and extracellular matrix (ECM) remodeling promote colorectal cancer metastasis (CRCM) by shaping the tumor microenvironment (TME). When CRC occurs, the metabolic symbiosis of tumor cells recruits adjacent adipocytes into the TME to supply energy. Meanwhile, abundant immune cells, from adipose tissue and blood, are recruited into the TME, which is stimulated by pro-inflammatory factors and triggers a chronic local pro-inflammatory TME. Dysregulated ECM proteins and cell surface adhesion molecules enhance ECM remodeling and further increase contractibility between tumor and stromal cells, which promotes epithelial-mesenchymal transition (EMT). EMT increases tumor migration and invasion into surrounding tissues or vessels and accelerates CRCM. Colorectal symbiotic microbiota also plays an important role in the promotion of CRCM. In this review, we provide adipose tissue and its contributions to CRC, with a special emphasis on the role of adipocytes, macrophages, neutrophils, T cells, ECM, and symbiotic gut microbiota in the progression of CRC and their contributions to the CRC microenvironment. We highlight the interactions between adipocytes and tumor cells, and potential therapeutic approaches to target these interactions.

Adipocytes promote metastasis of breast cancer by attenuating the FOXO1 effects and regulating copper homeostasis.

BACKGROUND: Obesity and the forkhead box O1(FOXO1) affect the survival of breast cancer patients, but the underlying mechanism remains unclear. We aimed to investigate the role of FOXO1 in obesity-associated-breast cancer. METHODS: We screened 383 breast disease patients from the first affiliated hospital with Nanjing Medical University in 2020. We performed wound healing, transwell, matrigel assays to assess the metastatic ability of cancer cells. We adopted mRNAs sequencing to select the differentially expressed transcripts in breast cancer. We applied immunohistochemistry, western blot, tissue microarrays to assess the level of FOXO1 and epithelial-mesenchymal transition (EMT) pathways. We conducted bioinformatic analysis to investigate interactions between FOXO1 and miR-135b. We used fluorescence in situ hybridization, RT-qPCR to confirm the characteristics of circCNIH4. We conducted luciferase reporter assay, rescue experiments to investigate interactions between circCNIH4 and miR-135b. RESULTS: Obesity was positively correlated with the incidence and progression of breast cancer. Adipocytes enhanced the migration of breast cancer and attenuated the effects of FOXO1. MiR-135b was a binding gene of FOXO1 and was regulated by circCNIH4. CircCNIH4 exhibited antitumor activity in vitro and in vivo. CONCLUSION: Adipocytes might accelerate the progression of breast cancer by modulating FOXO1/miR-135b/ circCNIH4 /EMT axis and regulating copper homeostasis.

The association of initial and changes in serum A-FABP level with the development and improvement of pre-sarcopenia.

CONTEXT: Several cross-sectional studies have reported the association between serum adipocyte fatty acid binding protein (A-FABP) level and pre-sarcopenia. However, data on the impacts of serum A-FABP level and its changes over time on the development and improvement of pre-sarcopenia are scarce. METHODS: This longitudinal cohort study included 1496 adults (41.2% men; median age, 58 [53-63] years) in 2013-2014 and was followed up to 2015-2016. Participants underwent serum A-FABP level measurements at baseline and follow-up visit. Visceral fat area (VFA) was measured using magnetic resonance imaging. Skeletal muscle mass (SMM) was estimated by bioelectrical impedance analysis and converted to skeletal muscle index (SMI). Pre-sarcopenia was defined as SMI < 1 standard deviation of the sex-specific mean for the young reference group. RESULTS: During an average follow-up period of 2.1 years, baseline serum A-FABP level was positively associated with the incidence of pre-sarcopenia (standardized by weight: risk ratio [RR] 3.22, 95% confidence interval [CI] 1.96-5.38; standardized by VFA: RR 2.11, 95%CI 1.29-3.51) and negatively associated with the improvement of pre-sarcopenia (standardized by weight: RR 0.66, 95%CI 0.45-0.97; standardized by VFA: RR 0.71, 95%CI 0.54-0.94), regardless of whether SMM was standardized by weight or VFA. Moreover, changes in serum A-FABP level provided additional information on the incidence and improvement of pre-sarcopenia, independent of baseline serum A-FABP level (all P < 0.05). CONCLUSIONS: Baseline serum A-FABP level and its changes were positively associated with the incidence, and negatively associated with the improvement of pre-sarcopenia.

Anatomy, Histology, and Embryonic Origin of Adipose Tissue: Insights to Understand Adipose Tissue Homofunctionality in Regeneration and Therapies.

Preadipocytes are formed during the 14th and 16th weeks of gestation. White adipose tissue, in particular, is generated in specific areas and thereby assembles after birth, rapidly increasing following the propagation of adipoblasts, which are considered the preadipocyte cell precursors. The second trimester of gestation is a fundamental phase of adipogenesis, and in the third trimester, adipocytes, albeit small may be present within the main deposition areas. In the course of late gestation, adipose tissue develops in the foetus and promotes the synthesis of large amounts of uncoupling protein 1, in similar quantities relative to differentiated brown adipose tissue. In mammals, differentiation occurs in two functionally different types of adipose cells: white adipose cells resulting from lipid storage and brown adipose cells from increased metabolic energy consumption. During skeletogenesis, synovial joints develop through the condensation of mesenchymal cells, which forms an insertional layer of flattened cells that umlaut skeletal elements, by sharing the same origin in the development of synovium. Peri-articular fat pads possess structural similarity with body subcutaneous white adipose tissue; however, they exhibit a distinct metabolic function due to the micro-environmental cues in which they are embedded. Fat pads are an important component of the synovial joint and play a key role in the maintenance of joint homeostasis. They are also implicated in pathological states such as osteoarthritis.In this paper we explore the therapeutic potential of adipocyte tissue mesenchymal precursor-based stem cell therapy linking it back to the anatomic origin of adipose tissue.

The Plasma Levels of Protein Adiponectin (AdipoQ) and Meteorin-Like (Metrnl) in Newly Diagnosed Type 2 Diabetes Mellitus.

Purpose: This study aimed to measure the concentrations of the Adiponectin and Meteorin - Like (Metrnl) in newly diagnosed type 2 diabetes patients. Patients and Methods: A comparative cross-sectional study contained two groups: Group 1 (86 newly diagnosed diabetes mellitus type 2 patients) and group 2 (71 healthy persons). The plasma concentrations of Adiponectin and Metrnl were measured by Enzyme Link Immunosorbent Assay (ELISA). Results: The plasma level of Adiponectin of the newly diagnosed diabetes mellitus type 2 group and the healthy group were 1219.82 ng/mL (1132.43-2772.50) and 1187.25 ng/mL (1160.66-3807.50) respectively. The plasma level of Metrnl of two groups were 757.60 pg/mL (564.15-994.00) and 697.60 pg/mL (538.50-986.10) respectively. There were no significant difference between two groups. Metrnl had no correlation with glucose, HbA1c, lipid profile, BMI. Adiponectin had correlation with Metrnl and HDL-cholesterol. Adiponectin had no correlation to glucose, HbA1c, LDL-cholesterol, total cholesterol, triglyceride, BMI. People with the lower Adiponectin concentration had the higher risk of diabetes (OR=6.52; 95% CI: 2.43 -17.55). Conclusion: Adiponectin and Metrnl were not significantly different in newly diagnosed type 2 diabetes and healthy people. The lower concentration of Adiponectin might increase the risk of type 2 diabetes.

Piperlongumine inhibits the early stage of adipogenesis in 3T3-L1 cells.

Piperlongumine (PLM), a natural compound isolated from long peppers, has been reported to possess multiple pharmacological roles, including anti-tumor and anti-diabetic. However, the pharmacological role of PLM on adipogenesis is still unknown. In this study, we found that PLM strongly inhibited 3T3-L1 adipocyte differentiation. This inhibition was determined by the accumulation of lipid droplets and intracellular triglycerides. In addition, PLM downregulated both the mRNA and protein expression of adipogenic transcription factors, including CCAAT-enhancer binding proteins ß (C/EBPß), C/EBPα, and peroxisome proliferator-activated receptor γ (PPARγ). Based on the time-course experiment, we found that the inhibitory effect of PLM on adipogenesis was mainly involved in the early stage of adipogenesis. Studying these differential effects could uncover new mechanisms for regulating adipogenesis and new chemicals for treating obesity.

A novel long noncoding RNA AK029592 contributes to thermogenic adipocyte differentiation.

Exploration of factors originating from brown adipose tissue that govern the thermogenic adipocyte differentiation is imperative for comprehending the regulatory framework underlying brown fat biogenesis and for devising therapeutic approaches for metabolic disorders associated with obesity. Prior evidence has illuminated the pivotal role of long noncoding RNAs (lncRNAs) in orchestrating thermogenesis within adipose tissue. Here, we aimed to explore and identify the critical lncRNA that could promote thermogenic adipocyte differentiation and to provide a novel strategy to treat obesity-related metabolic diseases in the future. In this study, through amalgamation with our previous lncRNA microarray data from small extracellular vesicles derived from BAT (sEV-BAT), we have identified sEV-BAT-enriched lncRNA AK029592 as a critical constituent of the thermogenic program, which actively fostered beige adipocyte differentiation and enhanced the thermogenic capacities of adipose tissue. Moreover, lncRNA AK029592 could sponge miR-199a-5p in adipocytes to stimulate thermogenic gene expression. Consequently, we concluded lncRNA AK029592 as a crucial lncRNA component of the thermogenic program that regulated beige adipocyte differentiation and white adipose tissue browning, thereby providing a novel therapeutic target and strategy in combating obesity and related metabolic diseases.

How obesity affects adipocyte turnover.

Cellular turnover is fundamental for tissue homeostasis and integrity. Adipocyte turnover, accounting for 4% of the total cellular mass turnover in humans, is essential for adipose tissue homeostasis during metabolic stress. In obesity, an altered adipose tissue microenvironment promotes adipocyte death. To clear dead adipocytes, macrophages are recruited and form a distinctive structure known as crown-like structure; subsequently, new adipocytes are generated from adipose stem and progenitor cells in the adipogenic niche to replace dead adipocytes. Accumulating evidence indicates that adipocyte death, clearance, and adipogenesis are sophisticatedly orchestrated during adipocyte turnover. In this Review, we summarize our current understandings of each step in adipocyte turnover, discussing its key players and regulatory mechanisms.

Identification of adipocyte infiltration-related gene subtypes for predicting colorectal cancer prognosis and responses of immunotherapy/chemotherapy.

Colorectal cancer (CRC) is a prevalent and aggressive malignancy characterized by a complex tumor microenvironment (TME). Given the variations in the level of adipocyte infiltration in TME, the prognosis may differ among CRC patients. Thus, there is an urgent need to establish a reliable method for identifying adipocyte subtypes in CRC in order to elucidate the impact of adipocyte infiltration on CRC treatment and prognosis. Herein, 144 adipocyte-infiltration-related genes (AIRGs) were identified as predictive markers for the immune-associated features and prognosis of CRC patients. Based on the 144 genes, the unsupervised clustering algorithm identified two distinct clusters of CRC patients with variations in molecular and signaling pathways, clinicopathological characteristics and responses to CRC chemotherapy and immunotherapy. Furthermore, an AIRG prognostic signature was constructed and validated in independent datasets. Overall, this study developed a prognostic signature based on AIRGs in CRC, which may contribute to the development of personalized treatment strategies and enhance prognostic prediction for CRC patients.

Anatomical location, sex, and age modulate adipocyte progenitor populations in perivascular adipose tissues.

Perivascular adipose tissue (PVAT) regulates vascular function due to its capacity to synthesize vasoactive products and its mechanical properties. PVATs most abundant cells are adipocytes, and their populations are maintained by the maturation of adipocyte progenitor cells (APC), which may play a pivotal role in the pathogenesis of cardiovascular diseases. However, the distribution of APC within PVAT depots, their potential variation in spatial location, and the influence of sex and age on their abundance remain unknown. We hypothesize that APC abundance in PVAT is affected by location, age, sex and that APC subtypes have specific spatial distributions. PVAT from thoracic and abdominal aorta, and mesenteric arteries, and AT from interscapular, gonadal, and subcutaneous depots from 13-week and 30-week-old females and males Pdgfrα-CreERT2 x LSL-tdTomato mice (n = 28) were analyzed. Abdominal aorta PVAT had fewer progenitors than mesenteric PVAT and gonadal AT. Aging reduced the abundance of APC in the thoracic aorta but increased their numbers in mesenteric PVAT. Females had more APC than males in mesenteric PVAT and gonadal AT depots. APC exhibited unique spatial distribution in the aorta and mesenteric PVAT where they localized neighboring vasa vasorum and arteries. APC subtypes (APC1, APC2, APC3, diff APC) were identified in all PVAT depots. Thoracic aorta PVAT APC3 were located in the adventitia while diff APC were in the parenchyma. This study identified variability in APC populations based on depot, age, and sex. The distinctive spatial distribution and the presence of diverse APC subtypes suggest that they may contribute differently to cardiovascular diseases-induced PVAT remodeling.

Relationship between the Cell Death-Inducing DNA Fragmentation Factor 45-Like Effector Protein Family and the Risk of Dyslipidemia.

According to the research, obesity is associated with hyperlipidemia, hypertension, and type 2 diabetes mellitus, which are grouped as metabolic syndrome. Notably, under the obese status, the adipocyte could accumulate excessive lipid as lipid droplets (LDs), leading the dysfunctional fat mass. Recently, emerging evidence has shown that the cell death-inducing DNA fragmentation factor 45-like effector protein (CIDE) family played an important role in regulating lipid metabolism. In addition, diverse CIDE proteins were also confirmed to influence the intracellular lipid metabolism, such as within adipocyte, hepatocyte, and macrophage. Nevertheless, the results which showed the regulatory influence of CIDE proteins are significantly contradictory from in vitro experiments and in vivo clinical studies. Similarly, recent studies have changed the perception of these proteins, redefining them as regulators of lipid droplet dynamics and fat metabolism, which contribute to a healthy metabolic phenotype in humans. However, the underlying mechanisms by which the diverse CIDE proteins alter lipid metabolism are not elucidated. In the current review, the understandings of CIDE proteins in lipid catabolism were well-summarized. On the other hand, the relatively mechanisms were also proposed for the further understandings of the CIDE protein family.

Circulating plasma fibronectin affects tissue insulin sensitivity, adipocyte differentiation, and transcriptional landscape of adipose tissue in mice.

Plasma fibronectin (pFN) is a hepatocyte-derived circulating extracellular matrix protein that affects cell morphology, adipogenesis, and insulin signaling of adipocytes in vitro. In this study, we show pFN accrual to adipose tissue and its contribution to tissue homeostasis in mice. Hepatocyte-specific conditional Fn1 knockout mice (Fn1-/-ALB) show a decrease in adipose tissue FN levels and enhanced insulin sensitivity of subcutaneous (inguinal), visceral (epididymal) adipose tissue on a normal diet. Diet-induced obesity model of the Fn1-/-ALB mouse showed normal weight gain and whole-body fat mass, and normal adipose tissue depot volumes and unaltered circulating leptin and adiponectin levels. However, Fn1-/-ALB adipose depots showed significant alterations in adipocyte size and gene expression profiles. The inguinal adipose tissue on a normal diet, which had alterations in fatty acid metabolism and thermogenesis suggesting browning. The presence of increased beige adipocyte markers Ucp1 and Prdm16 supported this. In the inguinal fat, the obesogenic diet resulted in downregulation of the browning markers and changes in gene expression reflecting development, morphogenesis, and mesenchymal stem cell maintenance. Epididymal adipose tissue showed alterations in developmental and stem cell gene expression on both diets. The data suggests a role for pFN in adipose tissue insulin sensitivity and cell profiles.

Jaboticaba Peel Extract Attenuates Ovariectomy-Induced Bone Loss by Preserving Osteoblast Activity.

Therapies to prevent osteoporosis are relevant since it is one of the most common non-communicable human diseases in the world and the most prevalent bone disorder in adults. Since jaboticaba peel extract (JPE) added to the culture medium enhanced the osteogenic potential of mesenchymal stem cells (MSCs) derived from osteoporotic rats, we hypothesized that JPE prevents the development of ovariectomy-induced osteoporosis. Ovariectomized rats were treated with either JPE (30 mg/kg of body weight) or its vehicle for 90 days, starting 7 days after the ovariectomy. Then, the femurs were subjected to microcomputed tomography and histological analyses, and the osteoblast and adipocyte differentiation of MSCs was evaluated. JPE attenuated ovariectomy-induced bone loss, as evidenced by higher bone volume/total volume and trabecular number, along with lower trabecular separation and bone marrow adiposity. These protective effects of JPE on bone tissue are due to its ability to prevent the imbalance between osteoblast and adipocyte differentiation of MSCs, since, compared with MSCs derived from ovariectomized rats treated with vehicle, MSCs treated with JPE exhibited higher gene and protein expression of osteogenic markers and extracellular matrix mineralization, as well as lower gene expression of adipogenic markers. These data highlight the potential therapeutic use of JPE to prevent osteoporosis.