Food-derived polyphenols and some alkaloids have reported bioactivities related to the prevention of systemic metabolic disorders such as obesity, glucose intolerance, and dyslipidemia. For food-derived components to exert their functions in vivo, it is essential to interact with biological factors such as proteins, lipids, and nucleic acids. However, it is still unclear whether bioactive components in foods express functions related to their target factors. In this review, I introduce the target proteins in which food-derived components express functions in cells.

A comparative transcriptomic analysis in adipose stem and progenitor cells (ASPCs) between obese and lean mice might facilitate the identification of novel adipogenic genes. Here, we compare transcriptomic differences in the ASPCs of subcutaneous adipose tissue (SAT) between the mice fed on a high-fat-diet (HFD) and the chow diet (CD)-fed mice by analyzing three independent single-cell RNA sequencing datasets. Six differential genes, including three up-regulated genes Aspn, Rrbp1, Fbln2 and three down-regulated genes Htra1, Plpp3, Efemp1, are identified and confirmed in HFD-fed mice. Further, the expression of these genes is found to be significantly diminished in the differentiated 3T3-L1 cells. Treatment with luteolin, a dietary flavonoid known to inhibit 3T3-L1 adipogenesis, reverses the decreased expression of Aspn, Htra1 and Efemp1. Furthermore, knockdown of Aspn, Htra1 and Efemp1 significantly facilitates 3T3-L1 adipogenesis. Together, these genes not only are differential in ASPCs between obese and lean mice, but also are the adipogenic inhibitory genes that can be up-regulated by luteolin treatment.

Adaptive thermogenesis comprises shivering thermogenesis dependent on skeletal muscles and non-shivering thermogenesis (NST) mediated by uncoupling protein 1 (UCP1). Although the thermogenic function of UCP1 was adopted early in some placental mammals, positive selection predominantly occurred in the ancestral branches of small-bodied species. Some previous studies have revealed that rodents living in northern or high mountain regions adapt to cold environments by increasing NST, whereas those living in tropical and subtropical regions that are not exposed to cold stress express low concentrations of UCP1, indicating that UCP1 may have evolved to adapt to ambient temperatures. In this study, we explored the evolution of UCP1 and its significance to temperature adaptation by performing detailed evolutionary and statistical analyses on 64 rodents with known genomes. As a result, a total of 71 UCP1 gene sequences were obtained, including 47 intact genes, 22 partial genes, and 2 pseudogenes. Further, 47 intact genes and 3 previously published intact UCP1 genes were incorporated into evolutionary analyses, and correlation analyses between evolutionary rate and ambient temperatures (including average annual temperature, maximum temperature, and minimum temperature) of the rodent survives were conducted. The results show that UCP1 is under purifying selection (ω = 0.11), and among rodents with intact UCP1 sequences, Urocitellus parryii and Dicrostonyx groenlandicus-the two species with the lowest ambient temperatures among the rodents used here-have higher evolutionary rates than others. In the statistical analyses, in addition to ambient temperatures, body weight and weight at birth were also taken into account since weight was previously proposed to be linked to UCP1 evolution. The results showed that after controlling for the phylogenetic effect, the maximum temperature was significantly negatively correlated with the evolutionary rate of UCP1, whereas weight did not have a relationship with UCP1 evolutionary rate. Consequently, it is suggested that ambient temperature can drive the evolution of rodent UCP1, thereby enhancing NST adaptation to cold stress.

This study aims to explore the relationship between body adipose tissue characteristics and clinical outcomes in cancer patients receiving immune checkpoint inhibitor (ICI) therapy.

We conducted an extensive literature search across three major online databases-Embase, PubMed, and the Cochrane Library-to identify studies examining the link between body adipose tissue and treatment outcomes in cancer patients undergoing ICI therapy, from the inception of each database until February 20, 2024. The quality of the included studies was evaluated using the Newcastle-Ottawa Scale. The primary outcomes analyzed were hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), as well as odds ratios (ORs) for disease control rate (DCR). Pooled estimates and 95% confidence intervals (CIs) were calculated.

A total of 23 studies were included, encompassing 2741 cancer patients. The analysis revealed that patients with higher levels of visceral adipose tissue (VAT) exhibited significantly improved OS (HR: 0.72, 95% CI: 0.59-0.89, p < 0.001) and PFS (HR: 0.80, 95% CI: 0.67-0.96, p = 0.015), along with a higher DCR (OR: 1.81, 95% CI: 1.26-2.60, p = 0.001), compared to those with lower VAT levels. Additionally, increased subcutaneous adipose tissue (SAT) levels were associated with significantly better OS (HR: 0.69, 95% CI: 0.58-0.82, p < 0.001) and PFS (HR: 0.82, 95% CI: 0.68-1.00, p = 0.049), and a higher DCR (OR: 1.99, 95% CI: 1.15-3.44, p = 0.014). Elevated total adipose tissue (TAT) levels were also linked to longer OS (HR: 0.73, 95% CI: 0.55-0.97, p = 0.028). However, a higher visceral-to-subcutaneous adipose tissue ratio (VSR) was associated with a shorter OS (HR: 1.43, 95% CI: 1.09-1.87, p = 0.010). No significant relationship was found between TAT (HR: 0.81, 95% CI: 0.54-1.23, p = 0.332) and VSR (HR: 1.20, 95% CI: 0.95-1.51, p = 0.131) with PFS in ICI-treated patients.

This study highlights the prognostic relevance of VAT and SAT in predicting treatment response and survival outcomes in cancer patients receiving ICIs. These findings suggest that assessments of VAT and SAT should be incorporated into prognostic evaluations for this patient population.

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.

Bone tissue engineering (BTE) has long sought to elucidate the key factors controlling human/humanized bone formation for regenerative medicine and disease modeling applications, yet with no definitive answers due to the high number and co-dependency of parameters. This study aims to clarify the relative impacts of in vitro biomimetic 'preculture composition' and 'preculture duration' before in vivo implantation as key criteria for the optimization of BTE design. These parameters are directly related to in vitro osteogenic differentiation (OD) and mineralization and are being investigated across different osteoprogenitor-loaded biomaterials, specifically fibrous calcium phosphate-polycaprolactone (CaP-mPCL) scaffolds and gelatin methacryloyl (GelMA) hydrogels. The results show that OD and mineralization levels prior to implantation, enhanced by a mineralization medium supplement to the osteogenic medium (OM), significantly improve ectopic BTE outcomes, regardless of the biomaterial type. Specifically, preculture conditions are pivotal in achieving more faithful mimicry of human bone structure, cellular and extracellular matrix composition and organization, and provide control over bone marrow composition. This work emphasizes the potential of using biomimetic culture compositions, specifically the addition of a mineralization medium as a cost-effective and straightforward approach to enhance BTE outcomes, facilitating rapid development of bone models with superior quality and resemblance to native bone.

Time-restricted feeding (TRF), an intermittent fasting approach involving a shortened eating window within 24 h, has gained popularity as a weight management approach. This review addresses how TRF may favor fat redistribution and the function of the adipose organ. TRF trials (mainly 16:8 model, with a duration of 5-48 weeks) reported a significant weight loss (1.2-10.2%, ~ 1.4-9.4 kg), with a considerable decrease in total fat mass (1.6-21%, ~ 0.5-7 kg) and visceral adipose compartment (VAC, 11-27%) in overweight and obese subjects. Experimental TRF in normal-fed and obesogenic-diet-fed mice and rats (with a fasting duration ranging between 9 and 21 h within 1-17 weeks) reported a significant reduction in body weight (~ 7-40%), total fat mass (~ 17-71%), and intrahepatic fat (~ 25-72%). TRF also improves VAC and subcutaneous adipose compartment (SAC) function by decreasing adipocyte size, macrophage infiltration, M1-macrophage polarity, and downregulating inflammatory genes. In conclusion, beyond its effect on body weight loss, total fat mass, and intrahepatic fat accumulation, TRF favors adipose organ fat redistribution in overweight and obese subjects by decreasing VAC and improving the function of VAC and SAC.

The expression of uncoupling protein 1 (UCP1), which regulates energy expenditure, is limited to brown/beige adipocytes in most mammals; however, it is also detected in the skeletal muscles of cattle. We previously observed a positive relationship between Ucp1 and fast-twitch myosin heavy chain (Myh) expression in bovine skeletal muscles. In the present study, we explored the regulatory expression of Ucp1 in bovine myogenic cells using cell culture. Vitamin C and high-dose capsaicin, which induce the formation of fast-twitch myotubes in murine myogenic cells, did not stimulate myogenesis in bovine myosatellite cells. Treatment with 4-phenylbutyric acid (PBA), a histone deacetylase inhibitor that enhances histone acetylation, upregulates the expression of all myogenic regulatory factors (MRFs), except Myog, in bovine myogenic cells. Consistent with this, PBA increased the expression levels of acetylated lysine 27 of histone 3 (H3K27), the fast-twitch component MYH1/2, and Ucp1 in bovine myogenic cells. SB203580, an inhibitor of p38 MAP kinase, blocked PBA-induced myogenesis and Ucp1 upregulation. PBA is a butyric acid-related molecule, and cattle produce large amounts of volatile fatty acids (VFAs), including acetic acid, propionic acid, and butyric acid, through ruminal fermentation. Propionic acid treatment stimulated H3K27 acetylation, myogenesis, and Ucp1 induction. Thus, the upregulation of muscular Ucp1 may be related to myogenic stimulation through the modulation of histone acetylation status in cattle; we propose that the cattle-specific expression of muscular UCP1 results from VFA production through ruminal fermentation.

Epidemiology studies have demonstrated a clear association between obesity and the development of several distinct malignancies, with excessive visceral adiposity being an increasingly prevalent feature in patients with cancer presenting for therapeutic intervention. Clinical trials and meta-analyses have helped to inform effective and safe dosing of traditional systemically administered anticancer agents in adult patients with cancer and obesity, but there remains much debate not only regarding the effect of obesity on the more novel targeted molecular and immune-based therapies, but also about how obesity is best defined and measured clinically. Low muscle mass is associated with poor outcomes in cancer, and body composition studies using biochemical and imaging modalities are helping to fully delineate the importance of both obesity and sarcopenia in clinical outcomes; such studies might also go some way to explaining how obesity can paradoxically be associated with favourable clinical outcomes in certain cancers. As the cancer survivorship period increases and the duration of anticancer treatment lengthens, this Review highlights the challenges facing appropriate treatment selection and emphasizes how a multidisciplinary approach is warranted to manage weight and skeletal muscle loss during and after cancer treatment.

Given the fast-increasing prevalence of obesity and its comorbidities, it would be critical to improve our understanding of the cell-type level differences between the two key human adipose tissue depots, subcutaneous (SAT) and visceral adipose tissue (VAT), in their depot-specific contributions to cardiometabolic health. We integrated cell-type level RNA- and ATAC-seq data from human SAT and VAT biopsies and cell-lines to comprehensively elucidate transcriptomic, epigenetic, and genetic differences between the two fat depots. We identify cell-type marker genes for tissue specificity and functional enrichment, and show through genome-wide association study (GWAS) and partitioned polygenic risk score (PRS) enrichment analyses that the marker genes upregulated in SAT adipocytes have more prominent roles in abdominal obesity than those of VAT. We also identify SREBF1 , a master transcription factor (TF) of fatty acid synthesis and adipogenesis, as specifically upregulated in SAT adipocytes and present in numerous SAT functional pathways. By integrating multi-omics data from an independent human cohort, we further show that the risk allele carrier status of seven abdominal obesity GWAS variants in the cis region of SREBF1 affects the adipocyte expression of 146 SAT adipocyte marker genes in trans . We replicate this finding independently in the UK Biobank by showing that the partitioned abdominal obesity PRSs of the trans gene sets differ by the regional SREBF1 risk allele carrier status. In summary, we discover the master TF, SREBF1 , driving the SAT adipocyte expression profiles of more than a hundred of adipocyte marker genes in trans , a finding that indicates that human trans genes can be identified by integrating single cell omics with biobank data.

Abnormal adipose tissue formation is associated with metabolic disorders such as obesity, diabetes, and liver and cardiovascular diseases. Thus, identifying the novel factors that control adipogenesis is crucial for understanding these conditions and developing targeted treatments. In this study, we identified the melanosome-related factor MLPH as a novel adipogenic factor. MLPH was induced during the adipogenesis of 3T3-L1 cells and human mesenchymal stem cells. Although MLPH did not affect lipid metabolism, such as lipogenesis or lipolysis, adipogenesis was severely impaired by MLPH depletion. We observed that MLPH prevented excess reactive oxygen species (ROS) accumulation and lipid peroxidation during adipogenesis and in mature adipocytes. In addition, increased MLPH expression was observed under cirrhotic conditions in liver cancer cells and its overexpression also reduced ROS and lipid peroxidation. Our findings demonstrate that MLPH is a novel adipogenic factor that maintains redox homeostasis by preventing lipid peroxidation and ROS accumulation, which could lead to metabolic diseases.

Brown and beige adipocytes can be activated by β-adrenergic agonist via cAMP-dependent signaling. Performing RNA-sequencing analysis in human cervical area-derived adipocytes, we found that dibutyryl-cAMP, which can mimic in vivo stimulation of browning and thermogenesis, enhanced the expression of browning and batokine genes and upregulated several signaling pathway genes linked to thermogenesis. We observed that the expression of inhibitor of DNA binding and cell differentiation (ID) 1 and particularly ID3 was strongly induced by the adrenergic stimulation. The degradation of ID1 and ID3 elicited by the ID antagonist AGX51 during thermogenic activation prevented the induction of proton leak respiration that reflects thermogenesis and abrogated cAMP analogue-stimulated upregulation of thermogenic genes and mitochondrial complex I, II, and IV subunits, independently of the proximal cAMP-PKA signaling pathway. The presented data suggests that ID proteins contribute to efficient thermogenic response of adipocytes during adrenergic stimulation.

Lipodystrophy and obesity are associated with insulin resistance and metabolic syndrome accompanied by fat tissue dysregulation. Here, we show that serine protease inhibitor A1 (SerpinA1) expression in the liver is increased during recovery from lipodystrophy caused by the adipocyte-specific loss of insulin signaling in mice. SerpinA1 induces the proliferation of white and brown preadipocytes and increases the expression of uncoupling protein 1 (UCP1) to promote mitochondrial activation in mature white and brown adipocytes. Liver-specific SerpinA1 transgenic mice exhibit increased browning of adipose tissues, leading to increased energy expenditure, reduced adiposity and improved glucose tolerance. Conversely, SerpinA1 knockout mice exhibit decreased adipocyte mitochondrial function, impaired thermogenesis, obesity, and systemic insulin resistance. SerpinA1 forms a complex with the Eph receptor B2 and regulates its downstream signaling in adipocytes. These results demonstrate that SerpinA1 is an important hepatokine that improves obesity, energy expenditure and glucose metabolism by promoting preadipocyte proliferation and activating mitochondrial UCP1 expression in adipocytes.

The liver, a crucial organ for metabolic processes, has a generally uniform histological structure across amphibian taxa. However, ontogenetic changes, particularly those related to biphasic life cycle and metamorphosis, are less documented. Here, we explored and described the liver histology of an emerging model organism, the Balkan crested newt (Triturus ivanbureschi) at three ontogenetic stages: larval, juvenile (just after metamorphosis) and adult. At the larval stage, the liver is characterized by hepatocytes containing large lipid droplets, poorly developed basement membranes in the blood vessels, and a lack of melanin-rich macrophage centers. Juveniles show transitional characteristics between larvae and adults. Lipid droplets in hepatocytes are abundant, but also, at the juvenile stage the well-developed basement membrane of blood vessels and melanomacrophages are present, as in adults. The presence of lipid droplets in hepatocytes during larval and juvenile stages suggests the liver's role in fat storage and energy provision during development and growth. Melanomacrophages, which synthesize melanin, perform phagocytosis, and neutralize free radicals, have been found in juveniles (after metamorphosis) and increase with age. The biphasic life cycle and liver histology transition in Triturus newts provide an insight in changes in liver histology and make them a suitable model for studying fat deposition regulation and the evolution of the immune system in terrestrial vertebrates.

The overdevelopment of adipose tissues, accompanied by excess lipid accumulation and energy storage, leads to adipose deposition and obesity. With the increasing incidence of obesity in recent years, obesity is becoming a major risk factor for human health, causing various relevant diseases (including hypertension, diabetes, osteoarthritis and cancers). Therefore, it is of significance to antagonize obesity to reduce the risk of obesity-related diseases. Excess lipid accumulation in adipose tissues is mediated by adipocyte hypertrophy (expansion of pre-existing adipocytes) or hyperplasia (increase of newly-formed adipocytes). It is necessary to prevent excessive accumulation of adipose tissues by controlling adipose development. Adipogenesis is exquisitely regulated by many factors in vivo and in vitro, including hormones, cytokines, gender and dietary components. The present review has concluded a comprehensive understanding of adipose development including its origin, classification, distribution, function, differentiation and molecular mechanisms underlying adipogenesis, which may provide potential therapeutic strategies for harnessing obesity without impairing adipose tissue function.

In regenerating tissues, synthesis and remodeling of membranes rely on lipid turnover and transport. Our study addresses lipid adaptations in intestinal regeneration of Drosophila melanogaster and limb regeneration of Ambystoma mexicanum. We found changes in lipid profiles at different locations: transport, storage organs and regenerating tissues. We demonstrate that attenuating insulin signaling, exclusively in fat storage, inhibits the regeneration-specific response in both the fat storage and the regenerating tissue in Drosophila. Furthermore, in uninjured axolotls we found sex-specific lipid profiles in both storage and circulation, while in regenerating animals these differences subside. The regenerating limb presents a unique sterol profile, albeit with no sex differences. We postulate that regeneration triggers a systemic response, where organs storing lipids play a significant role in the regulation of systemic lipid traffic. Second, that this response may be an active and well-regulated mechanism, as observed when homeostatic sex-differences disappear in regenerating salamanders.

HDAC11, as a rising star in the histone deacetylase (HDAC) family, has attracted widespread interest in the biomedical field in recent years specially owing to its high defatty-acylase activity compared its innate deacetylase activity. Numerous studies have provided evidence indicating the crucial involvement of HDAC11 in cancers, immune responses, and metabolic processes. Several potent and selective HDAC11 inhibitors have been discovered and identified, which is crucial for exploring the function of HDAC11 and its potential therapeutic applications. Herein, we present a critical overview of the current advances in the biological function of HDAC11 and its inhibitors. We initially discuss the physiological functions of HDAC11 and its pathological roles in relevant diseases. Subsequently, our main focus centers on the design strategy and development process of HDAC11 inhibitors. Additionally, we address significant challenges and outline future directions in this field. This perspective may provide guidance for the further development of HDAC11 inhibitors and their prospects in disease treatment.

Dermal white adipose tissue (DWAT) is a distinctive adipose depot located within the lower dermis of the skin. Its significance as an ancillary fat in skin homoeostasis has recently received increased attention. New research has revealed that DWAT responses to skin pathology and physiology changes, impacting skin development, hair cycling, defense mechanisms, and fibrotic conditions. In this review, we explore the developmental process of DWAT and the adipose commitment timing of hypodermal. We explore the development process of DWAT and its pivotal role in regulating the hair cycle. We conclude the antibacterial activity and reversible dedifferentiation of dermal adipocytes in response to skin defense. Furthermore, we underscore the potentially crucial yet underestimated anti-fibrotic functions of DWAT-derived adipokines and adipocyte-myofibroblast transition.

Adipose tissue is composed of adipocytes, stromal vascular fraction, nerves, surrounding immune cells, and the extracellular matrix. Under various physiological or pathological conditions, adipose tissue shifts cellular composition, lipid storage, and organelle dynamics to respond to the stress; this remodeling is called "adipose tissue plasticity". Adipose tissue plasticity includes changes in the size, species, number, lipid storage capacity, and differentiation function of adipocytes, as well as alterations in the distribution and cellular composition of adipose tissue. This plasticity has a major role in growth, obesity, organismal protection, and internal environmental homeostasis. Moreover, certain thresholds exist for this plasticity with significant individualized differences. Here, we comprehensively elaborate on the specific connotation of adipose tissue plasticity and the relationship between this plasticity and the development of many diseases. Meanwhile, we summarize possible strategies for treating obesity in response to adipose tissue plasticity, intending to provide new insights into the dynamic changes in adipose tissue and contribute new ideas to relevant clinical problems.

Obesity is increasing globally and is closely associated with a range of metabolic disorders, including metabolic associated fatty liver disease, diabetes, and cardiovascular diseases. An effective strategy to combat obesity involves stimulating brown and beige adipocyte thermogenesis, which significantly enhances energy expenditure. Recent research has underscored the vital role of PRDM16 in the development and functionality of thermogenic adipocytes. Consequently, PRDM16 has been identified as a potential therapeutic target for obesity and its related metabolic disorders. This review comprehensively examines various studies that focus on combating obesity by directly targeting PRDM16 in adipose tissue.

Traditional Chinese medical literature contains numerous records of many traditional Chinese herbal medicines that exhibit efficacy in enhancing resistance to cold, yet there is a lack of scientific explanation. Lycium barbarum is among the herbal medicines that are explicitly documented to enhance resistance to cold in the "Ben Cao Gang Mu (Compendium of Materia Medica)". Herein, we investigated L. barbarum polysaccharide (LBP)-induced browning of inguinal white adipose tissue (iWAT), energy expenditure and thermogenic function in a long-term (4 months) treatment mouse model. LBP supplementation resulted in a significant reduction in weight and adipocyte size in iWAT, along with increased gut microbiota diversity. Specifically, the levels of Lachnospiraceae, Ruminococcaceae and Bacteroidaceae (short-chain fatty acid-producing bacteria) were elevated, leading to a higher level of short-chain fatty acids (SCFAs) in the caecal content. These effects subsequently triggered the release of glucagon-like peptide-1 (GLP-1) and activated the CREB/PGC1α signaling pathway in iWAT, thereby increasing energy expenditure and enhancing thermogenic function. The antibiotic treatment experiments confirmed that the LBP-mediated gut microbiota participated in the process of iWAT browning. In summary, our findings provide the first scientific explanation and mechanistic insights into the cold resistance of L. barbarum and identify potentially safe natural product supplements for individuals in alpine areas.

Cell identities are defined by intrinsic transcriptional networks and spatio-temporal environmental factors. Here, we explored multiple factors that contribute to the identity of adipose stem cells, including anatomic location, microvascular neighborhood, and sex. Our data suggest that adipose stem cells serve a dual role as adipocyte precursors and fibroblast-like cells that shape the adipose tissue's extracellular matrix in an organotypic manner. We further find that adipose stem cells display sexual dimorphism regarding genes involved in estrogen signaling, homeobox transcription factor expression and the renin-angiotensin-aldosterone system. These differences could be attributed to sex hormone effects, developmental origin, or both. Finally, our data demonstrate that adipose stem cells are distinct from mural cells, and that the state of commitment to adipogenic differentiation is linked to their anatomic position in the microvascular niche. Our work supports the importance of sex and microvascular function in adipose tissue physiology.

Extensive research has shown that PR domain 16 (PRDM16) plays a critical role in adipose tissue metabolism, including processes such as browning and thermogenesis of adipocytes, beigeing of adipocytes, and adipogenic differentiation of myoblasts. These functions have been associated with diseases such as obesity and diabetes. Additionally, PRDM16 has been correlated with various other conditions, including migraines, heterochromatin abnormalities, metabolic syndrome, cardiomyopathy, sarcopenia, nonsyndromic cleft lip, and essential hypertension, among others. However, there is currently no systematic or comprehensive conclusion regarding the mechanism of PRDM16 in human tumours, including haematologic and solid tumours. The aim of this review is to provide an overview of the research progress on PRDM16 in haematologic and solid tumours by incorporating recent literature findings. Furthermore, we explore the prospects of PRDM16 in the precise diagnosis and treatment of human haematologic and solid tumours.

This study aimed to assess the fatty acid (FA) composition of abdominal subcutaneous and visceral adipose tissue (ASAT and VAT, respectively) in the UK Biobank imaging cohort (N = 33,823) using magnetic resonance imaging (MRI).

We measured the fractions of saturated, monounsaturated, and polyunsaturated FA (fSFA, fMUFA, and fPUFA, respectively) in ASAT and VAT from multiecho MRI scans. We selected a subcohort of participants who followed a vegan and an omnivore diet (N = 36) to validate the effect of diet on adipose tissue. In the wider imaging cohort, we examined the relationships between adipose tissue FA composition and various traits related to disease and body size.

We measured adipose tissue FA composition for over 33,000 participants, revealing higher fSFA and fPUFA and lower fMUFA in VAT (p < 0.00016). fMUFA and fPUFA were higher in ASAT and lower in VAT for women (p < 0.00016). Vegan participants exhibited lower fSFA in both ASAT and VAT (p < 0.00016). VAT fSFA and fMUFA showed significant associations with disease, as well as anthropometric variables.

This extensive analysis revealed the relationships between adipose tissue FA composition and a range of factors in a diverse population, highlighting the importance of studying body adipose tissue beyond its quantity.

Living organisms store their energy in different forms of fats including lipid droplets, triacylglycerols, and steryl esters. In mammals and some non-mammal species, the energy is stored in adipose tissue which is the innervated specialized connective tissue that incorporates a variety of cell types such as macrophages, fibroblasts, pericytes, endothelial cells, adipocytes, blood cells, and several kinds of immune cells. Adipose tissue is so complex that the scope of its function is not only limited to energy storage, it also encompasses to thermogenesis, mechanical support, and immune defense. Since defects and complications in adipose tissue are heavily related to certain chronic diseases such as obesity, cardiovascular diseases, type 2 diabetes, insulin resistance, and cholesterol metabolism defects, it is important to further study adipose tissue to enlighten further mechanisms behind those diseases to develop possible therapeutic approaches. Adipose organoids are accepted as very promising tools for studying fat tissue development and its underlying molecular mechanisms, due to their high recapitulation of the adipose tissue in vitro. These organoids can be either derived using stromal vascular fractions or pluripotent stem cells. Due to their great vascularization capacity and previously reported incontrovertible regulatory role in insulin sensitivity and blood glucose levels, adipose organoids hold great potential to become an excellent candidate for the source of stem cell therapy. In this review, adipose tissue types and their corresponding developmental stages and functions, the importance of adipose organoids, and the potential they hold will be discussed in detail.

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.

Brown adipose tissue (BAT) is mammals' primary non-shivering thermogenesis organ, and the molecular mechanisms regulating BAT growth and adipogenesis are largely unknown. The Hippo-YAP pathway has been well-known for controlling organ size, and Vestigial like 4 (VGLL4) is a transcriptional regulator that modulates the Hippo-YAP pathway by competing against YAP for binding to TEAD proteins. In this study, we dissected the function of VGLL4 in regulating BAT development. We generated a conventional Vgll4 mutant mouse line, in which the two Tondu (TDU) domains of VGLL4 were disrupted. We found that deletion of the TDU domains of VGLL4 resulted in perinatal lethality and paucity of the interscapular BAT. Histological and magnetic resonance imaging studies confirmed that the adipogenesis of BAT was impaired in Vgll4 mutants. Adeno-associated virus (AAV) mediated, brown adipocyte-specific overexpression of VGLL4 increased BAT volume and protected the adult male mice from acute cold stress. Genomic studies suggest that VGLL4/TEAD1 complex directly regulates the myogenic and adipogenic gene expression programs of BAT. In conclusion, our data identify VGLL4 as a previously unrecognized adipogenesis factor that regulates classical BAT development.

Obesity is a chronic disease caused primarily by the imbalance between the amount of calories supplied to the body and energy expenditure. Not only does it deteriorate the quality of life, but most importantly it increases the risk of cardiovascular diseases and the development of type 2 diabetes mellitus, leading to reduced life expectancy. In this review, we would like to present the molecular pathomechanisms underlying obesity, which constitute the target points for the action of anti-obesity medications. These include the central nervous system, brain-gut-microbiome axis, gastrointestinal motility, and energy expenditure. A significant part of this article is dedicated to incretin-based drugs such as GLP-1 receptor agonists (e.g., liraglutide and semaglutide), as well as the brand new dual GLP-1 and GIP receptor agonist tirzepatide, all of which have become "block-buster" drugs due to their effectiveness in reducing body weight and beneficial effects on the patient's metabolic profile. Finally, this review article highlights newly designed molecules with the potential for future obesity management that are the subject of ongoing clinical trials.

Recent research into laminopathic lipodystrophies-rare genetic disorders caused by mutations in the LMNA gene-has greatly expanded our knowledge of their complex pathology and metabolic implications. These disorders, including Hutchinson-Gilford progeria syndrome (HGPS), Mandibuloacral Dysplasia (MAD), and Familial Partial Lipodystrophy (FPLD), serve as crucial models for studying accelerated aging and metabolic dysfunction, enhancing our understanding of the cellular and molecular mechanisms involved. Research on laminopathies has highlighted how LMNA mutations disrupt adipose tissue function and metabolic regulation, leading to altered fat distribution and metabolic pathway dysfunctions. Such insights improve our understanding of the pathophysiological interactions between genetic anomalies and metabolic processes. This review merges current knowledge on the phenotypic classifications of these diseases and their associated metabolic complications, such as insulin resistance, hypertriglyceridemia, hepatic steatosis, and metabolic syndrome, all of which elevate the risk of cardiovascular disease, stroke, and diabetes. Additionally, a range of published therapeutic strategies, including gene editing, antisense oligonucleotides, and novel pharmacological interventions aimed at addressing defective adipocyte differentiation and lipid metabolism, will be explored. These therapies target the core dysfunctional lamin A protein, aiming to mitigate symptoms and provide a foundation for addressing similar metabolic and genetic disorders.

Lymphedema occurs as a result of lymphatic vessel damage or obstruction, leading to the lymphatic fluid stasis, which triggers inflammation, tissue fibrosis, and adipose tissue deposition with adipocyte hypertrophy. The treatment of lymphedema is divided into conservative and surgical approaches. Among surgical treatments, methods like lymphaticovenular anastomosis and vascularized lymph node transfer are gaining attention as they focus on restoring lymphatic flow, constituting a physiologic treatment approach. Lymphatic endothelial cells form the structure of lymphatic vessels. These cells possess button-like junctions that facilitate the influx of fluid and leukocytes. Approximately 10% of interstitial fluid is connected to venous return through lymphatic capillaries. Damage to lymphatic vessels leads to lymphatic fluid stasis, resulting in the clinical condition of lymphedema through three mechanisms: Inflammation involving CD4+ T cells as the principal contributing factor, along with the effects of immune cells on the VEGF-C/VEGFR axis, consequently resulting in abnormal lymphangiogenesis; adipocyte hypertrophy and adipose tissue deposition regulated by the interaction of CCAAT/enhancer-binding protein α and peroxisome proliferator-activated receptor-γ; and tissue fibrosis initiated by the overactivity of Th2 cells, leading to the secretion of profibrotic cytokines such as IL-4, IL-13, and the growth factor TGF-β1. Surgical treatments aimed at reconstructing the lymphatic system help facilitate lymphatic fluid drainage, but their effectiveness in treating already damaged lymphatic vessels is limited. Therefore, reviewing the pathophysiology and molecular mechanisms of lymphedema is crucial to complement surgical treatments and explore novel therapeutic approaches.

Endothelial cells play an important role in the metabolism of adipose tissue (AT). This study aimed to analyze the changes that adipose tissue in AT endothelial cells undergo during the development of obesity, using single-nucleus RNA sequence (snRNA-seq). Mouse paraepididymal AT cells were subjected to snRNA-seq with the 10X Genomics platform. The cell types were then clustered using t-distributed stochastic neighbor embedding and unbiased computational informatics analyses. Protein-protein interactions network was established using the STRING database and visualized using Cytoscape. The dataset was subjected to differential gene enrichment analysis. In total, 21,333 cells acquired from 24 mouse paraepididymal AT samples were analyzed using snRNA-seq. This study identified 18 distinct clusters and annotated macrophages, fibroblasts, epithelial cells, T cells, endothelial cells, stem cells, neutrophil cells, and neutrophil cell types based on representative markers. Cluster 12 was defined as endothelial cells. The proportion of endothelial cells decreased with the development of obesity. Inflammatory factors, such as Vegfa and Prdm16 were upregulated in the medium obesity group but downregulated in the obesity group. Genes, such as Prox1, Erg, Flt4, Kdr, Flt1, and Pecam1 promoted the proliferation of AT endothelial cells and maintained the internal environment of AT. This study established a reference model and general framework for studying the mechanisms, biomarkers, and therapeutic targets of endothelial cell dysfunction-related diseases at the single-cell level.

Bone marrow adipose tissue (BMAT) is a metabolically and clinically relevant fat depot that exists within bone. Two subtypes of BMAT, regulated and constitutive, reside in hematopoietic-rich red marrow and fatty yellow marrow, respectively, and exhibit distinct characteristics compared to peripheral fat such as white and brown adipose tissues. Bone marrow adipocytes (BMAds) are evolutionally preserved in most vertebrates, start development after birth and expand throughout life, and originate from unique progenitor populations that control bone formation and hematopoiesis. Mature BMAds also interact closely with other cellular components of the bone marrow niche, serving as a nearby energy reservoir to support the skeletal system, a signaling hub that contributes to both local and systemic homeostasis, and a final fuel reserve for survival during starvation. Though BMAT and bone are often inversely correlated, more BMAT does not always mean less bone, and the prevention of BMAT expansion as a strategy to prevent bone loss remains questionable. BMAT adipogenesis and lipid metabolism are regulated by the nervous systems and a variety of circulating hormones. This contributes to the plasticity of BMAT, including BMAT expansion in common physiological or pathological conditions, and BMAT catabolism under certain extreme circumstances, which are often associated with malnutrition and/or systemic inflammation. Altogether, this article provides a comprehensive overview of the local and systemic functions of BMAT and discusses the regulation and plasticity of this unique adipose tissue depot in health and disease. © 2024 American Physiological Society. Compr Physiol 14:5521-5579, 2024.

Adipose tissues in the hypodermis, the crucial stem cell reservoir in the skin and the endocrine organ for the maintenance of skin homeostasis undergo significant changes during skin aging. Dermal white adipose tissue (dWAT) has recently been recognized as an important organ for both non-metabolic and metabolic health in skin regeneration and rejuvenation. Defective differentiation, adipogenesis, improper adipocytokine production, and immunological dissonance dysfunction in dWAT lead to age-associated clinical changes. Here, we review age-related alterations in dWAT across levels, emphasizing the mechanisms underlying the regulation of aging. We also discuss the pathogenic changes involved in age-related fat dysfunction and the unfavorable consequences of accelerated skin aging, such as chronic inflammaging, immunosenescence, delayed wound healing, and fibrosis. Research has shown that adipose aging is an early initiation event and a potential target for extending longevity. We believe that adipose tissues play an essential role in aging and form a potential therapeutic target for the treatment of age-related skin diseases. Further research is needed to improve our understanding of this phenomenon.

Mesenchymal stem cells, due to their multipotent ability, are considered one of the best candidates to be used in regenerative medicine. To date, the most used source is represented by the bone marrow, despite the limited number of cells and the painful/invasive procedure for collection. Therefore, the scientific community has investigated many alternative sources for the collection of mesenchymal stem cells, with the adipose tissue representing the best option, given the abundance of mesenchymal stem cells and the easy access. Although adipose mesenchymal stem cells have recently been investigated for their multipotency, the molecular mechanisms underlying their adipogenic potential are still unclear. In this scenario, this communication is aimed at defining the role of miRNAs in adipogenic potential of adipose-derived mesenchymal stem cells via real-time PCR. Even if preliminary, our data show that cell culture conditions affect the expression of specific miRNA involved in the adipogenic potential of mesenchymal stem cells. The in vitro/in vivo validation of these results could pave the way for novel therapeutic strategies in the field of regenerative medicine. In conclusion, our research highlights how specific cell culture conditions can modulate the adipogenic potential of adipose mesenchymal stem cells through the regulation of specific miRNAs.

RNA splicing dysregulation and the involvement of specific splicing factors are emerging as common factors in both obesity and metabolic disorders. The study provides compelling evidence that the absence of the splicing factor SRSF1 in mature adipocytes results in whitening of brown adipocyte tissue (BAT) and impaired thermogenesis, along with the inhibition of white adipose tissue browning in mice. Combining single-nucleus RNA sequencing with transmission electron microscopy, it is observed that the transformation of BAT cell types is associated with dysfunctional mitochondria, and SRSF1 deficiency leads to degenerated and fragmented mitochondria within BAT. The results demonstrate that SRSF1 effectively binds to constitutive exon 6 of Ndufs3 pre-mRNA and promotes its inclusion. Conversely, the deficiency of SRSF1 results in impaired splicing of Ndufs3, leading to reduced levels of functional proteins that are essential for mitochondrial complex I assembly and activity. Consequently, this deficiency disrupts mitochondrial integrity, ultimately compromising the thermogenic capacity of BAT. These findings illuminate a novel role for SRSF1 in influencing mitochondrial function and BAT thermogenesis through its regulation of Ndufs3 splicing within BAT.

Nutritional, endocrine, and neurological signals converge in multiple brain centres to control feeding behaviour and food intake as part of the allostatic regulation of energy balance. Among the several neuroendocrine systems involved, the leptin, glucocorticoid, and glucagon-like peptide 1 (GLP1) systems have been extensively researched. Leptin is at the top hierarchical level since its complete absence is sufficient to trigger severe hyperphagia. Glucocorticoids are key regulators of the energy balance adaptation to stress and their sustained excess leads to excessive adiposity and metabolic perturbations. GLP1 participates in metabolic adaptation to food intake, regulating insulin secretion and satiety by parallel central and peripheral signalling systems. Herein, we review the brain and peripheral targets of these three hormone systems that integrate to regulate food intake, feeding behaviour, and metabolic homeostasis. We examine the functional relationships between leptin, glucocorticoids, and GLP1 at the central and peripheral levels, including the cross-regulation of their circulating levels and their cooperative or antagonistic actions at different brain centres. The pathophysiological roles of these neuroendocrine systems in dysregulated intake are explored in the two extremes of body adiposity - obesity and lipodystrophy - and eating behaviour disorders.

Genome-wide association studies (GWAS) have identified coronary artery disease (CAD) susceptibility locus on chromosome 3q22.3. This locus contains a cluster of several genes that includes muscle rat sarcoma virus (MRAS). Common MRAS variants are also associated with CAD causing risk factors such as hypertension, dyslipidemia, obesity, and type II diabetes. The MRAS gene is an oncogene that encodes a membrane-bound small GTPase. It is involved in a variety of signaling pathways, regulating cell differentiation and cell survival (mitogen-activated protein kinase [MAPK]/extracellular signal-regulated kinase and phosphatidylinositol 3-kinase) as well as acute phase response signaling (tumor necrosis factor [TNF] and interleukin 6 [IL6] signaling). In this review, we will summarize the role of genetic MRAS variants in the etiology of CAD and its comorbidities with the focus on tissue distribution of MRAS isoforms, cell type/tissue specificity, and mode of action of single nucleotide variants in MRAS associated complex traits. Finally, we postulate that CAD risk variants in the MRAS locus are specific to smooth muscle cells and lead to higher levels of MRAS, particularly in arterial and cardiac tissue, resulting in MAPK-dependent tissue hypertrophy or hyperplasia.

A pair of coumarin-based polycyclic meroterpenoid enantiomers (+)/(-)-gerbeloid A [(+)-1a and (-)-1b] were isolated from the medicinal plant Gerbera piloselloides, which have a unique caged oxatricyclo [4.2.2.03,8] decene scaffold. Their planar and three-dimensional structures were exhaustively characterized by comprehensive spectroscopic data and X-ray diffraction analysis. Guided by the hypothetical biosynthetic pathway, the biomimetic synthesis of racemic 1 was achieved using 4-hydroxy-5-methylcoumarin and citral as the starting material via oxa-6π electrocyclization and intramolecular [2 + 2] photocycloaddition. Subsequently, the results of the biological activity assay demonstrated that both (+)-1a and (-)-1b exhibited potent lipid-lowering effects in 3T3-L1 adipocytes and the high-fat diet zebrafish model. Notably, the lipid-lowering activity of (+)-1a is better than that of (-)-1b at the same concentration, and molecular mechanism study has shown that (+)-1a and (-)-1b impairs adipocyte differentiation and stimulate lipolysis by regulating C/EBPα/PPARγ signaling and Perilipin signaling in vitro and in vivo. Our findings provide a promising drug model molecule for the treatment of obesity.

The energy-burning capability of beige adipose tissue is a potential therapeutic tool for reducing obesity and metabolic disease, but this capacity is decreased by aging. Here, we evaluate the impact of aging on the profile and activity of adipocyte stem and progenitor cells (ASPCs) and adipocytes during the beiging process in mice. We found that aging increases the expression of Cd9 and other fibro-inflammatory genes in fibroblastic ASPCs and blocks their differentiation into beige adipocytes. Fibroblastic ASPC populations from young and aged mice were equally competent for beige differentiation in vitro, suggesting that environmental factors suppress adipogenesis in vivo. Examination of adipocytes by single nucleus RNA-sequencing identified compositional and transcriptional differences in adipocyte populations with aging and cold exposure. Notably, cold exposure induced an adipocyte population expressing high levels of de novo lipogenesis (DNL) genes, and this response was severely blunted in aged animals. We further identified Npr3, which encodes the natriuretic peptide clearance receptor, as a marker gene for a subset of white adipocytes and an aging-upregulated gene in adipocytes. In summary, this study indicates that aging blocks beige adipogenesis and dysregulates adipocyte responses to cold exposure and provides a resource for identifying cold and aging-regulated pathways in adipose tissue.