Adipose Tissue Biology Research Articles

Hypoxia signaling in the adipose tissue.

Obesity per se is rapidly emerging all over the planet and further accounts for many other life-threatening conditions, such as diabetes, cardiovascular diseases, and cancers. Decreased oxygen supply or increased relative oxygen consumption in the adipose tissue results in adipose tissue hypoxia, which is a hallmark of obesity. This review aims to provide an up-to-date overview of the hypoxia signaling in the adipose tissue. First, we summarize literature evidence to demonstrate that hypoxia is regularly observed during adipose tissue remodeling in human and rodent models of obesity. Next, we discuss how hypoxia-inducible factors (HIFs) are regulated and how adipose tissues behave in response to hypoxia. Then, the differential roles of adipose HIF-1α and HIF-2α in adipose tissue biology and obesity pathology are highlighted. Finally, the review emphasizes the importance of modulating adipose hypoxia as a therapeutic avenue to assist adipose tissues in functionally adapting to hypoxic conditions, ultimately promoting adipose health and improving outcomes due to obesity.

Meflin/ISLR is a marker of adipose stem and progenitor cells in mice and humans that suppresses white adipose tissue remodeling and fibrosis.

Identifying specific markers of adipose stem and progenitor cells (ASPCs) in vivo is crucial for understanding the biology of white adipose tissues (WAT). PDGFRα-positive perivascular stromal cells represent the best candidates for ASPCs. This cell lineage differentiates into myofibroblasts that contribute to the impairment of WAT function. However, ASPC marker protein(s) that are functionally crucial for maintaining WAT homeostasis are unknown. We previously identified Meflin as a marker of mesenchymal stem cells (MSCs) in bone marrow and tissue-resident perivascular fibroblasts in various tissues. We also demonstrated that Meflin maintains the undifferentiated status of MSCs/fibroblasts. Here, we show that Meflin is expressed in WAT ASPCs. A lineage-tracing experiment showed that Meflin+ ASPCs proliferate in the WAT of obese mice induced by a high-fat diet (HFD), while some of them differentiate into myofibroblasts or mature adipocytes. Meflin knockout mice fed an HFD exhibited a significant fibrotic response as well as increases in adipocyte cell size and the number of crown-like structures in WAT, accompanied by impaired glucose tolerance. These data suggested that Meflin expressed by ASPCs may have a role in reducing disease progression associated with WAT dysfunction.

Characterization and analysis of extracellular vesicle-derived miRNAs from different adipose tissues in mice

Adipose tissue is traditionally classified into two main types based on their functions: brown adipose tissue (BAT) and white adipose tissue (WAT). Each type plays a distinct role in the body's energy metabolism. Additionally, a third type, beige adipose tissue, can develop within subcutaneous WAT (including inguinal WAT, iWAT) in response to specific stimuli and exhibits characteristics of both BAT and WAT. Extracellular vesicles (EVs) are crucial for intercellular communication, carrying a diverse array of biomolecules such as proteins, lipids, and nucleic acids. While the functional diversity and endocrine roles of adipose tissues are well-documented, a comparative analysis of the functions of EVs released by different adipose tissues from mice housed at room temperature has not been thoroughly explored. MicroRNAs (miRNAs), which are highly enriched in small extracellular vesicles (sEVs), offer a promising avenue for investigating the complex functions and unique roles of various adipose tissues. In this study, we isolated sEVs from different adipose tissues under basal conditions and performed a comprehensive analysis of their miRNA content. By comparing miRNA profiles across different adipose tissues, we aim to elucidate the potential roles of sEV-derived miRNAs in mediating intercellular communication and the distinct physiological functions of adipose tissues. Understanding the molecular features of miRNAs in adipose tissue EVs could reveal new aspects of adipose tissue biology and lay the groundwork for further research into their physiological significance.

Key Players in the Complex Pathophysiology of Obesity: A Cross-Talk Between the Obesogenic Genes and Unraveling the Metabolic Pathway of Action of Capsaicin and Orange Peel.

Obesity is a widespread prevailing health concern with multifactorial causes. Among the various defined molecular targets associated with obesity, peroxisome proliferator activated receptor gamma, leptin, ghrelin, and adiponectin play crucial roles in fundamental processes including energy balance, adipose tissue biology, and metabolic health, making them particularly significant in the study of obesity.Capsaicin and orange peel exhibit promising anti-obesity properties through their thermogenic, metabolic, and anti-inflammatory effects. Potential pathways for therapeutic approaches in the management of obesity are provided by these targets. The lipid-lowering and anti-obesity benefits of specific plant species have been highlighted in Asian medicine. Due to the potential anti-obesity qualities, capsaicin, which is derived from chilli peppers, and orange peel extract has been focused in this review. Capsaicin causes apoptosis in preadipocytes and adipocytes and suppresses adipogenesis. Citrus fruits area significant source of bioactive substances, primarily flavonoids. Due to their ability to reduce adipocyte development and cellular lipid content, citrus polyphenols are helpful in the control of obesity. This extensive analysis offers insights into new treatment approaches for the prevention and management of obesity and metabolic syndrome by examining the interactions of molecular variables in obesity as well as the possible anti-obesity advantages of capsaicin and orange peel extract.

A Closer Look into White Adipose Tissue Biology and the Molecular Regulation of Stem Cell Commitment and Differentiation.

White adipose tissue (WAT) makes up about 20-25% of total body mass in healthy individuals and is crucial for regulating various metabolic processes, including energy metabolism, endocrine function, immunity, and reproduction. In adipose tissue research, "adipogenesis" is commonly used to refer to the process of adipocyte formation, spanning from stem cell commitment to the development of mature, functional adipocytes. Although, this term should encompass a wide range of processes beyond commitment and differentiation, to also include other stages of adipose tissue development such as hypertrophy, hyperplasia, angiogenesis, macrophage infiltration, polarization, etc.… collectively, referred to herein as the adipogenic cycle. The term "differentiation", conversely, should only be used to refer to the process by which committed stem cells progress through distinct phases of subsequent differentiation. Recognizing this distinction is essential for accurately interpreting research findings on the mechanisms and stages of adipose tissue development and function. In this review, we focus on the molecular regulation of white adipose tissue development, from commitment to terminal differentiation, and examine key functional aspects of WAT that are crucial for normal physiology and systemic metabolic homeostasis.

Effect of Obesity on Aquaporin5 Expression in Human Placental and Uterus Tissues.

Background: Obesity and overweight are also becoming more prevalent among women of childbearing age and pregnant women. In maternal obesity, the activation of metabolic, inflammatory, and oxidative stress pathways is proven, which appears to be a key step in the pathological changes observed in placental and uterine function. Several recent studies have evidenced that aquaporins (AQPs) are critical players in adipose tissue biology and are involved in the onset of obesity. Methods: Our studies aimed to investigate the changes in placental volume and vascularization and measure the AQP5 expression and total antioxidant capacity (TAC) in the placenta and uterus tissues in obese and typical-weight mothers. We also aim to measure the AQP5 plasma concentration. Results: We found AQP5 dominance in the uterus and plasma at 34 weeks of normal pregnancy. The placental volume increased and the vascularization decreased in obese mothers compared to the control. The AQP5 expression increased in the uterus of the obese group and did not change in the placenta. The TAC decreased in the plasma of overweight mothers. Conclusions: We hypothesize that increased AQP5 expression prolongs the length of pregnancy and inhibits the onset of contractions. Based on our findings, we can develop diagnostic tests and provide new targets for tocolytic drug development.

B-1 lymphocytes in adipose tissue as innate modulators of inflammation linked to cardiometabolic disease.

Fat is stored in distinct depots with unique features in both mice and humans and B cells reside in all adipose depots. We have shown that B cells modulate cardiometabolic disease through activities in two of these key adipose depots: visceral adipose tissue (VAT) and perivascular adipose tissue (PVAT). VAT refers to the adipose tissue surrounding organs, within the abdomen and thorax, and is comprised predominantly of white adipocytes. This depot has been implicated in mediating obesity-related dysmetabolism. PVAT refers to adipose tissue surrounding major arteries. It had long been thought to exist to provide protection and insulation for the vessel, yet recent work demonstrates an important role for PVAT in harboring immune cells, promoting their function and regulating the biology of the underlying vessel. The role of B-2 cells and adaptive immunity in adipose tissue biology has been nicely reviewed elsewhere. Given that, the predominance of B-1 cells in adipose tissue at homeostasis, and the emerging role of B-1 cells in a variety of disease states, we will focus this review on how B-1 cells function in VAT and PVAT depots to promote homeostasis and limit inflammation linked to cardiometabolic disease and factors that regulate this function.

Sexual dimorphism and the multi-omic response to exercise training in rat subcutaneous white adipose tissue

Subcutaneous white adipose tissue (scWAT) is a dynamic storage and secretory organ that regulates systemic homeostasis, yet the impact of endurance exercise training (ExT) and sex on its molecular landscape is not fully established. Utilizing an integrative multi-omics approach, and leveraging data generated by the Molecular Transducers of Physical Activity Consortium (MoTrPAC), we show profound sexual dimorphism in the scWAT of sedentary rats and in the dynamic response of this tissue to ExT. Specifically, the scWAT of sedentary females displays -omic signatures related to insulin signaling and adipogenesis, whereas the scWAT of sedentary males is enriched in terms related to aerobic metabolism. These sex-specific -omic signatures are preserved or amplified with ExT. Integration of multi-omic analyses with phenotypic measures identifies molecular hubs predicted to drive sexually distinct responses to training. Overall, this study underscores the powerful impact of sex on adipose tissue biology and provides a rich resource to investigate the scWAT response to ExT.

Cardiometabolic characteristics of people with metabolically healthy and unhealthy obesity

There is considerable heterogeneity in the cardiometabolic abnormalities associated with obesity. We evaluated multi-organ system metabolic function in 20 adults with metabolically healthy obesity (MHO; normal fasting glucose and triglycerides, oral glucose tolerance, intrahepatic triglyceride content, and whole-body insulin sensitivity), 20 adults with metabolically unhealthy obesity (MUO; prediabetes, hepatic steatosis, and whole-body insulin resistance), and 15 adults who were metabolically healthy lean. Compared with MUO, people with MHO had (1) altered skeletal muscle biology (decreased ceramide content and increased expression of genes involved in BCAA catabolism and mitochondrial structure/function); (2) altered adipose tissue biology (decreased expression of genes involved in inflammation and extracellular matrix remodeling and increased expression of genes involved in lipogenesis); (3) lower 24-h plasma glucose, insulin, non-esterified fatty acids, and triglycerides; (4) higher plasma adiponectin and lower plasma PAI-1 concentrations; and (5) decreased oxidative stress. These findings provide a framework of potential mechanisms responsible for MHO and the metabolic heterogeneity of obesity. This study was registered at ClinicalTrials.gov (NCT02706262).

The Impact of Excessive Fructose Intake on Adipose Tissue and the Development of Childhood Obesity.

Worldwide, childhood obesity cases continue to rise, and its prevalence is known to increase the risk of non-communicable diseases typically found in adults, such as cardiovascular disease and type 2 diabetes mellitus. Thus, comprehending its multiple causes to build healthier approaches and revert this scenario is urgent. Obesity development is strongly associated with high fructose intake since the excessive consumption of this highly lipogenic sugar leads to white fat accumulation and causes white adipose tissue (WAT) inflammation, oxidative stress, and dysregulated adipokine release. Unfortunately, the global consumption of fructose has increased dramatically in recent years, which is associated with the fact that fructose is not always evident to consumers, as it is commonly added as a sweetener in food and sugar-sweetened beverages (SSB). Therefore, here, we discuss the impact of excessive fructose intake on adipose tissue biology, its contribution to childhood obesity, and current strategies for reducing high fructose and/or free sugar intake. To achieve such reductions, we conclude that it is important that the population has access to reliable information about food ingredients via food labels. Consumers also need scientific education to understand potential health risks to themselves and their children.

Dysfunction of the Brown Adipose Organ in HFD-Obese Rats and Effect of Tart Cherry Supplementation.

Obesity has a great impact on adipose tissue biology, based on its function as a master regulator of energy balance. Brown adipose tissue (BAT) undergoes remodeling, and its activity declines in obese subjects due to a whitening process. The anti-obesity properties of fruit extracts have been reported. The effects of tart cherry against oxidative stress, inflammation, and the whitening process in the BAT of obese rats were investigated. Intrascapular BAT (iBAT) alterations and effects of Prunus cerasus L. were debated in rats fed for 17 weeks with a high-fat diet (DIO), in DIO supplemented with seed powder (DS), and with seed powder plus the juice (DJS) of tart cherry compared to CHOW rats fed with a normo-caloric diet. iBAT histologic observations revealed a whitening process in DIO rats that was reduced in the DS and DJS groups. A modulation of uncoupling protein-1 (UCP-1) protein and gene expression specifically were detected in the obese phenotype. An upregulation of UCP-1 and related thermogenic genes after tart cherry intake was detected compared to the DIO group. Metabolic adjustment, endoplasmic reticulum stress, protein carbonylation, and the inflammatory microenvironment in the iBAT were reported in DIO rats. The analysis demonstrated an iBAT modulation that tart cherry promoted. In addition to our previous results, these data confirm the protective impact of tart cherry consumption on obesity.

PDGFRβ + cell HIF2α is dispensable for white adipose tissue metabolic remodeling and hepatic lipid accumulation in obese mice

BackgroundObesity is associated with extensive white adipose tissue (WAT) expansion and remodeling. Healthy WAT expansion contributes to the maintenance of energy balance in the liver, thereby ameliorating obesity-related hepatic steatosis. Tissue-resident mesenchymal stromal cell populations, including PDGFRβ + perivascular cells, are increasingly recognized pivotal as determinants of the manner in which WAT expands. However, the full array of regulatory factors controlling WAT stromal cell functions remains to be fully elucidated. Hypoxia-inducible factors (HIFs) are critical regulators in WAT stromal cell populations such as adipocyte precursor cells (APCs). It is revealed that HIF1α activation within PDGFRβ + stromal cells results in the suppression of de novo adipogenesis and the promotion of a pro-fibrogenic cellular program in obese animals. However, the role of HIF2α in PDGFRβ + cells remains undetermined in vivo.MethodsNew genetic models were employed in which HIF1α (encoded by the Hif1a gene) and HIF2α (encoded by the Epas1 gene) are selectively inactivated in PDGFRβ + cells in an inducible manner using tamoxifen (TAM). With these models, both in vitro and in vivo functional analysis of PDGFRβ + cells lacking HIF proteins were performed. Additionally, comprehensive metabolic phenotyping in diet-induced mouse models were performed to investigate the roles of PDGFRβ + cell HIF proteins in WAT remodeling, liver energy balance and systemic metabolism.ResultsUnlike HIF1α inactivation, the new findings in this study suggest that inducible ablation of HIF2α in PDGFRβ + cells does not cause apparent effects on WAT expansion induced by obesogenic diet. The adipogenic ability of PDGFRβ + APCs is not significantly altered by genetic HIF2α ablation. Moreover, no difference of key parameters associated with healthy WAT remodeling such as improvements of WAT insulin sensitivity, reduction in metabolic inflammation, as well as changes in liver fat accumulation or systemic glucose metabolism, is detected in PDGFRβ + cell Epas1-deficient mice.ConclusionThe new findings in this study support that, in contrast to HIF1α, PDGFRβ + cell HIF2α appears dispensable for WAT metabolic remodeling and the resulting effects on liver metabolic homeostasis in diet-induced obesity, underscoring the isoform-specific roles of HIFα proteins in the regulation of adipose tissue biology.

Genetic Investigation of the Trail Mechanism in Diabetic and Non-diabetic Obese Patients.

Obesity is an important healthcare issue caused by abnormally increased adipose tissue because of energy-intake overcoming energy expenditure. Disturbances in the physiological function of adipose tissue mediate the development of diabetes. It is a metabolic disease that results from decreased insulin-levels and/or changes in the insulin action mechanism. Tumor Necrosis Factor-Associated Apoptosis-Inducing Ligand(TRAIL), which is a member of the Tumor Necrosis Factor(TNF)-family with an important role in adipose tissue biology, is included in many studies with its ability to induce apoptosis in cancer cells, but the number of human-studies conducted on the gene related to its protective-role against diabetes and obesity at this level is insufficient. Our study was carried out as a case and control and included three groups (80 diabetic obese, 80 non-diabetic obese, and 80 healthy individuals as the control group). The Real-Time-PZR(RT-qPZR), and DNA Sanger-Sequencing Methods were used for gene expression and gene squences. As a result of the analyses, TRAIL gene expression level was found to be higher in the controls than in the diabetic-obese and non-diabetic-obese group. This change in TRAIL gene expression suggests that TRAIL maybe a protective factor against diabetes. The presence of rs781673405, rs143353036, rs1244378045, rs767450259, rs759369504, rs750556128, and rs369143448 mutations, which was determined with the Sequencing-Method, was shown for the first time in the present study. In addition, it is the first study in which human TRAIL gene-expression and sequencing were performed together. We believe that these data will make an important contribution to the literature.

Obesity, Dietary Fats, and Gastrointestinal Cancer Risk-Potential Mechanisms Relating to Lipid Metabolism and Inflammation.

Obesity is a major driving factor in the incidence, progression, and poor treatment response in gastrointestinal cancers. Herein, we conducted a comprehensive analysis of the impact of obesity and its resulting metabolic perturbations across four gastrointestinal cancer types, namely, oesophageal, gastric, liver, and colorectal cancer. Importantly, not all obese phenotypes are equal. Obese adipose tissue heterogeneity depends on the location, structure, cellular profile (including resident immune cell populations), and dietary fatty acid intake. We discuss whether adipose heterogeneity impacts the tumorigenic environment. Dietary fat quality, in particular saturated fatty acids, promotes a hypertrophic, pro-inflammatory adipose profile, in contrast to monounsaturated fatty acids, resulting in a hyperplastic, less inflammatory adipose phenotype. The purpose of this review is to examine the impact of obesity, including dietary fat quality, on adipose tissue biology and oncogenesis, specifically focusing on lipid metabolism and inflammatory mechanisms. This is achieved with a particular focus on gastrointestinal cancers as exemplar models of obesity-associated cancers.

Metabolic flux analysis in adipose tissue reprogramming.

Obesity is a growing epidemic in the United States and worldwide and is associated with insulin resistance and cardiovascular disease, among other comorbidities. Understanding of the pathology that links overnutrition to these disease processes is ongoing. Adipose tissue is a heterogeneous organ comprised of multiple different cell types and it is likely that dysregulated metabolism within these cell populations disrupts both inter- and intracellular interactions and is a key driver of human disease. In recent years, metabolic flux analysis, which offers a precise quantification of metabolic pathway fluxes in biological systems, has emerged as a candidate strategy for uncovering the metabolic changes that stoke these disease processes. In this mini review, we discuss metabolic flux analysis as an experimental tool, with a specific emphasis on mass spectrometry with isotope tracing as this is the technique most frequently used for metabolic flux analysis in adipocytes. Furthermore, we examine existing literature that uses metabolic flux analysis to further our understanding of adipose tissue biology. Our group has a specific interest in understanding the role of white adipose tissue inflammation in the progression of cardiometabolic disease, as we know that in obesity the accumulation of pro-inflammatory adipose tissue macrophages is associated with significant morbidity, so we use this as a paradigm throughout our review for framing the application of these experimental techniques. However, there are many other biological applications to which they can be applied to further understanding of not only adipose tissue biology but also systemic homeostasis.

Vitamin D and obesity.

An inverse association between vitamin D status and obesity has been reported across diverse populations and age groups in humans. In animal model of diet-induced obesity, dysregulation of vitamin D metabolism has been observed. However, the causal relationship between vitamin D status and obesity is not conclusive. Several explanations, such as volumetric dilution, sequestration of vitamin D into adipose tissue, and limited sunlight exposure, have been suggested as the underlying mechanisms linking poor vitamin D status and obesity. Vitamin D can modulate adipose tissue biology, spanning from adipocyte differentiation to adipocyte apoptosis and energy metabolism, indicating its potential impact on adiposity. In this chapter, we will review the prevalence of vitamin D deficiency and determinants of vitamin D deficiency among different populations, as well as changes in vitamin D metabolism associated with obesity. Additionally, we will review vitamin D's regulation of adipogenesis and lipogenesis at the cellular level in order to gain a deeper understanding of the underlying mechanisms linking vitamin D levels and obesity.

LncRNA U90926 is dispensable for the development of obesity-associated phenotypes invivo.

Obesity is a global health problem characterized by excessive fat accumulation, driven by adipogenesis and lipid accumulation. Long non-coding RNAs (lncRNAs) have recently been implicated in regulating adipogenesis and adipose tissue function. Mouse lncRNA U90926 was previously identified as a repressor of invitro adipogenesis in 3T3-L1 preadipocytes. Consequently, we hypothesized that, invivo, U90926 may repress adipogenesis, and hence its deletion would increase weight gain and adiposity. We tested the hypothesis by applying U90926-deficient (U9-KO) mice to a high-throughput phenotyping pipeline. Compared with WT, U9-KO mice showed no major differences across a wide range of behavioral, neurological, and other physiological parameters. In mice fed a standard diet, we have found no differences in obesity-related phenotypes, including weight gain, fat mass, and plasma concentrations of glucose, insulin, triglycerides, and free fatty acids, in U9-KO mice compared to WT. U90926 deficiency lacked a major effect on white adipose tissue morphology and gene expression profile. Furthermore, in mice fed a high-fat diet, we found increased expression of U90926 in adipose tissue stromal vascular cell fraction, yet observed no effect of U90926 deficiency on weight gain, fat mass, adipogenesis marker expression, and immune cell infiltration into the adipose tissue. These data suggest that the U90926 lacks an essential role in obesity-related phenotypes and adipose tissue biology invivo.

Isolation of Murine Adipose-Derived Stromal/Stem Cells Using an Explant Culture Method.

Adipose tissue provides a valuable cell source for tissue engineering, regenerative medicine, and adipose tissue biology studies. The most widely used adipose-derived stromal/stem cells (ASCs) isolation protocol involves enzymatic digestion with collagenase. However, the yield of the method often proves to bepoor if not impossiblefor collection of sufficient stromal vascular fraction (SVF) for expansion when the sample size is small, for instance whenonly newborn mice are available for cell culture. Here, we describe an efficient protocol for the isolation and expansion of ASCs using explant cultureas an alternative. Briefly, adipose tissue was minced after removing excess liquid. Then, the minced tissue was placed in culture dishes or flasks. The cells will migrate out of tissue and adhere to the culture surface after one or more days.

Overview of G-protein coupled receptors (GPCRs) in adipose tissues and their regulatory roles in the pathophysiology of human diseases

Despite the advancement of allopathic medicine, G-protein coupled receptors (GPCRs) are investigated as ideal drug targets for a range of chronic diseases including cancers, obesity, type II diabetes mellitus, non-alcoholic fatty liver, cardiovascular diseases, and neurodegeneration. During the past decades, scientists have been directly focused on the deep understanding of GPCR signaling pathways involved in the regulation of energy homeostasis and glucose metabolism which can hopefully direct towards the synthesis of novel drug compounds. Regulation of energy homeostasis is always aligned with the GPCRs associated with adipose tissues in which obesity is identified as one of the major diseases. However, evidence has not been provided on Food and Drug Administration (FDA) approved therapeutics for obesity that can directly affect the metabolism of adipose tissues yet. With the aid of these findings related to adipose tissue biology, further expansion and metabolic activation of white adipose tissues, brown adipose tissues, and beige adipose tissues will be potential target therapy for a variety of human diseases in the future. Therefore, the present review primarily focuses on the GPCRs present in adipose tissues and their regulatory roles in the pathophysiology of human diseases.

Cortisol and epinephrine alter the adipose functions and the mobilization of PCBs in adipose tissue slices from elephant seal

Marine mammals are exposed to increasing intensities of anthropogenic stressors such as acoustic disturbance and contaminants. Correlative studies have suggested concerning shifts in behavioral and physiological status of stress-exposed individuals, which could alter the health and survival of marine mammal populations. However, functional studies of the effects of multiple stressors on marine mammals are lacking. To fill in this gap, we recently developed an ex vivo approach of precision-cut adipose tissue slices (PCATS) to study the impact of stressors on the function of an essential endocrine organ: the adipose tissue. In the present study, we investigated the impact of hormones associated with the stress response on adipose tissue from northern elephant seals (Mirounga angustirostris). Blubber biopsies were collected from 17 weaned northern elephant seal pups, separated into inner and outer layers, dissected into PCATS, and cultured for 48 hours. To mimic prolonged and short-term exposure to physiological stress, PCATS were treated with 2 µM cortisol (CORT) for the entire 48 hours or 100 nM epinephrine (EPI) for the last 12 hours of culture, respectively. Hormones were applied individually or in combination. CORT and EPI exhibited an interacting, blubber layer-dependent, effect on adipose tissue biology, as quantified by gene expression in PCATS, and release of glycerol, free fatty acids, leptin and polychlorinated biphenyls into culture media. EPI stimulated a higher rate of lipolysis than CORT in PCATS from both blubber layers. The combination of CORT and EPI upregulated the expression of adipose triglyceride lipase in inner blubber PCATS and downregulated hormone-sensitive lipase in outer blubber-derived PCATS. Expression of the leptin gene and secretion of the leptin adipokine were both decreased by EPI, while addition of CORT attenuated this effect in inner blubber PCATS only. CORT also increased the expression of the antioxidant enzyme glutathione peroxidase 3 in PCATS from both blubber layers. Polychlorinated biphenyls exhibited selective and limited mobilization from PCATS treated with stress hormones, highlighting the lipophilic properties of these toxic compounds. This study showed that physiological stress can impact several essential functions of marine mammal blubber, such as lipolysis and adipokine production.