Elephant Seal Blubber Under Multiple Stressors: Persistent Organic Pollutants, Stress Hormones and Hydrostatic Pressure Alter Transcriptome, Lipolysis and Leptin Secretion. - 2026
Elephant Seal Blubber Under Multiple Stressors: Persistent Organic Pollutants, Stress Hormones and Hydrostatic Pressure Alter Transcriptome, Lipolysis and Leptin Secretion.
Pirard, Laura; Khudyakov, Jane I; Martin, Manonet al.
[en] Anthropogenic stressors represent major threats to marine mammals. Yet, their combined effects on health remain poorly understood. To address this, precision-cut adipose tissue slices (PCATS) from weaned northern elephant seal (NES - Mirounga angustirostris) blubber were exposed to three treatments: (i) epinephrine (acute stress), (ii) cortisol, persistent organic pollutants (Aroclor 1254, BDE-47, BDE-99 and 4,4'-DDE) and variations of hydrostatic pressure mimicking NES diving conditions (chronic stress), and (iii) a combination of acute and chronic stressors. Compared to controls, acute, chronic and combined stressors altered the expression of 4854, 1544, and 8930 genes, respectively. Acute stress upregulated the expression of genes associated with inflammation and hypoxia and downregulated genes involved in lipid and xenobiotic metabolism. Chronic stressors activated inflammation, hypoxia and xenobiotic metabolism genes in exposed PCATS. Combined stress exerted the greatest impact on PCATS transcriptome, uniquely altering 4870 genes and regulating genes involved in lipid metabolism, inflammation and hypoxia. Epinephrine also stimulated PCATS lipolysis, while reducing leptin secretion. This study highlights how multiple stressors disrupt blubber metabolic functions, which are crucial for maintaining homeostasis during energy-demanding periods in marine mammals.
Research Center/Unit :
CART - Center for Analytical Research and Technology MolSys - Molecular Systems - ULiège
Disciplines :
Chemistry Aquatic sciences & oceanology
Author, co-author :
Pirard, Laura; Louvain Institute of Biomolecular Science and Technology, UCLouvain, Louvain-la-Neuve1348, Belgium
Khudyakov, Jane I; Department of Biological Sciences, University of the Pacific, Stockton, California95211, United States
Martin, Manon ; Louvain Institute of Biomolecular Science and Technology, UCLouvain, Louvain-la-Neuve1348, Belgium
Vanoost, Louise; Louvain Institute of Biomolecular Science and Technology, UCLouvain, Louvain-la-Neuve1348, Belgium
Warnant, Aurélien; Louvain Institute of Biomolecular Science and Technology, UCLouvain, Louvain-la-Neuve1348, Belgium
Decloux, Delphine; Louvain Institute of Biomolecular Science and Technology, UCLouvain, Louvain-la-Neuve1348, Belgium
Baily, Thomas; Louvain Institute of Biomolecular Science and Technology, UCLouvain, Louvain-la-Neuve1348, Belgium
Crocker, Daniel E; Department of Biology, Sonoma State University, Rohnert Park, California94928, United States
Eppe, Gauthier ; Université de Liège - ULiège > Molecular Systems (MolSys)
Scholl, Georges ; Université de Liège - ULiège > Molecular Systems (MolSys)
Page, Melissa M; Louvain Institute of Biomolecular Science and Technology, UCLouvain, Louvain-la-Neuve1348, Belgium
Rees, Jean-François; Louvain Institute of Biomolecular Science and Technology, UCLouvain, Louvain-la-Neuve1348, Belgium
Smith, Donald R; Microbiology and Environmental Toxicology Department, University of California Santa Cruz, Santa Cruz, California95064, United States
Debier, Cathy; Louvain Institute of Biomolecular Science and Technology, UCLouvain, Louvain-la-Neuve1348, Belgium
Elephant Seal Blubber Under Multiple Stressors: Persistent Organic Pollutants, Stress Hormones and Hydrostatic Pressure Alter Transcriptome, Lipolysis and Leptin Secretion.
Rolland, R. M.; Parks, S. E.; Hunt, K. E.; Castellote, M.; Corkeron, P. J.; Nowacek, D. P.; Wasser, S. K.; Kraus, S. D.; et al. Evidence that ship noise increases stress in right whales. Proc. R. Soc. B2012, 279 (1737), 2363–2368, 10.1098/rspb.2011.2429.
Erbe, C.; Marley, S. A.; Schoeman, R. P.; Smith, J. N.; Trigg, L. E.; Embling, C. B. The Effects of Ship Noise on Marine Mammals─A Review. Front. Mar. Sci.2019, 6, 606, 10.3389/fmars.2019.00606.
Rolland, R. M.; et al. Fecal glucocorticoids and anthropogenic injury and mortality in North Atlantic right whales Eubalaena glacialis. Endanger. Species Res.2017, 34, 417–429, 10.3354/esr00866.
Trumble, S. J.; Norman, S. A.; Crain, D. D.; Mansouri, F.; Winfield, Z. C.; Sabin, R.; Potter, C. W.; Gabriele, C. M.; Usenko, S. Baleen whale cortisol levels reveal a physiological response to 20th century whaling. Nat. Commun.2018, 9, 4587, 10.1038/s41467-018-07044-w.
Agusti, C.; Carbajal, A.; Olvera-Maneu, S.; Domingo, M.; Lopez-Bejar, M. Blubber and serum cortisol concentrations as indicators of the stress response and overall health status in striped dolphins. Comp. Biochem. Physiol.: A Mol. Integr. Physiol.2022, 272, 111268, 10.1016/j.cbpa.2022.111268.
Guo, Y.; et al. Blubber Cortisol-Based Approach to Explore the Endocrine Responses of Indo-Pacific Humpback Dolphins (Sousa chinensis) to Diet Shifts and Contaminant Exposure. Environ. Sci. Technol.2022, 56, 1069–1080, 10.1021/acs.est.1c04550.
Atkinson, S.; Crocker, D.; Houser, D.; Mashburn, K. Stress physiology in marine mammals: how well do they fit the terrestrial model?. J. Comp. Physiol. B2015, 185, 463–486, 10.1007/s00360-015-0901-0.
Hing, S.; Narayan, E. J.; Thompson, R. C. A.; Godfrey, S. S. The relationship between physiological stress and wildlife disease: consequences for health and conservation. Wildlife Res.2016, 43, 51–60, 10.1071/WR15183.
Sonne, C.; Siebert, U.; Gonnsen, K.; Desforges, J. P.; Eulaers, I.; Persson, S.; Roos, A.; Bäcklin, B. M.; Kauhala, K.; Olsen, M. T.; et al. Health effects from contaminant exposure in Baltic Sea birds and marine mammals: A review. Environ. Int.2020, 139, 105725, 10.1016/j.envint.2020.105725.
Debier, C.; Pirard, L.; Verhaegen, M.; Rzucidlo, C.; Tinant, G.; Dewulf, C.; Larondelle, Y.; Smith, D. R.; Rees, J. F.; Crocker, D. E. In vitro Lipolysis and Leptin Production of Elephant Seal Blubber Using Precision-Cut Adipose Tissue Slices. Front. Physiol.2020, 11, 615784, 10.3389/fphys.2020.615784.
Kelesidis, T.; Kelesidis, I.; Chou, S.; Mantzoros, C. S. Narrative Review: The Role of Leptin in Human Physiology: Emerging Clinical Applications. Ann. Int. Med.2010, 152, 93, 10.7326/0003-4819-152-2-201001190-00008.
Coelho, M.; Oliveira, T.; Fernandes, R. State of the art paper Biochemistry of adipose tissue: an endocrine organ. Arch. Med. Sci.2013, 2, 191–200, 10.5114/aoms.2013.33181.
Kershaw, E. E.; Flier, J. S. Adipose Tissue as an Endocrine Organ. J. Clin. Endocrinol. Metab.2004, 89, 2548–2556, 10.1210/jc.2004-0395.
Shan, Q.; Li, H.; Chen, N.; Qu, F.; Guo, J. Understanding the Multiple Effects of PCBs on Lipid Metabolism. Diabetes, Metab. Syndr. Obes.: Targets Ther.2020, 13, 3691, 10.2147/DMSO.S264851.
Nagar, N.; Saxena, H.; Pathak, A.; Mishra, A.; Poluri, K. M. A review on structural mechanisms of protein-persistent organic pollutant (POP) interactions. Chemosphere2023, 332, 138877, 10.1016/j.chemosphere.2023.138877.
Tian, J.; et al. Trophic transfer of polycyclic aromatic hydrocarbons in marine mammals based on isotopic determination. Sci. Total Environ.2023, 875, 162531, 10.1016/j.scitotenv.2023.162531.
Linares, V.; Bellés, M.; Domingo, J. L. Human exposure to PBDE and critical evaluation of health hazards. Arch. Toxicol.2015, 89, 335–356, 10.1007/s00204-015-1457-1.
Guo, W.; Pan, B.; Sakkiah, S.; Yavas, G.; Ge, W.; Zou, W.; Tong, W.; Hong, H.; et al. Persistent Organic Pollutants in Food: Contamination Sources, Health Effects and Detection Methods. Int. J. Environ. Res. Public Health2019, 16 (22), 4361.
Gnegy, M. E. Chapter 14-Catecholamines. In Basic Neurochemistry; Elsevier, 2012; pp. 283–299. 10.1016/B978-0-12-374947-5.00014-6.
Timmermans, S.; Souffriau, J.; Libert, C. A general introduction to glucocorticoid biology. Front. Immunol.2019, 10, 1545, 10.3389/fimmu.2019.01545.
Kyrou, I.; Tsigos, C. Stress hormones: physiological stress and regulation of metabolism. Curr. Opin. Pharmacol.2009, 9, 787–793, 10.1016/j.coph.2009.08.007.
Peterson, S. H.; et al. Mercury Bioaccumulation and Cortisol Interact to Influence Endocrine and Immune Biomarkers in a Free-Ranging Marine Mammal. Environ. Sci. Technol.2023, 57, 5678–5692, 10.1021/acs.est.2c08974.
Kashiwabara, L.; Pirard, L.; Debier, C.; Crocker, D. E.; Khudyakov, J. I. Effects of cortisol, epinephrine, and bisphenol contaminants on the transcriptional landscape of marine mammal blubber. Am. J. Physiol. Regul. Integr. Comp. Physiol.2023, 325, R504–R522, 10.1152/ajpregu.00165.2023.
Le Boeuf, B. J.; Naito, Y.; Huntley, A. C.; Asaga, T. Prolonged, continuous, deep diving by northern elephant seals. Can. J. Zool.2011, 67, 2514–2519, 10.1139/z89-355.
Baldelli, A.; et al. Effect of high-pressure on protein structure, refolding, and crystallization. Food Chem. Adv.2024, 5, 100741, 10.1016/j.focha.2024.100741.
Yancey, P. H. Cellular responses in marine animals to hydrostatic pressure. J. Exp. Zool. A Ecol. Integr. Physiol.2020, 333, 398–420, 10.1002/jez.2354.
Louis, C.; Covaci, A.; Crocker, D. E.; Debier, C. Lipophilicity of PCBs and fatty acids determines their mobilisation from blubber of weaned northern elephant seal pups. Sci. Total Environ.2016, 541, 599–602, 10.1016/j.scitotenv.2015.09.094.
Le Boeuf, B. J.; Crocker, D. E.; Costa, D. P.; Blackwell, S. B.; Webb, P. W.; Houser, D. S. Foraging Ecology Of Northern Elephant Seals. Ecol. Monogr.2000, 70, 353–382, 10.1890/0012-9615(2000)070[0353:FEONES]2.0.CO;2.
Robinson, P. W.; et al. Foraging Behavior and Success of a Mesopelagic Predator in the Northeast Pacific Ocean: Insights from a Data-Rich Species, the Northern Elephant Seal. PLoS One2012, 7, e3672810.1371/journal.pone.0036728.
Khudyakov, J. I.; Champagne, C. D.; Meneghetti, L. M.; Crocker, D. E. Blubber transcriptome response to acute stress axis activation involves transient changes in adipogenesis and lipolysis in a fasting-adapted marine mammal. Sci. Rep.2017, 7, 42110, 10.1038/srep42110.
Pirard, L.; et al. Cortisol and epinephrine alter the adipose functions and the mobilization of PCBs in adipose tissue slices from elephant seal. Front Mar Sci.2023, 10, 1290472, 10.3389/fmars.2023.1290472.
Ferrante, M. C.; et al. Polychlorinated biphenyls (PCB 101, PCB 153 and PCB 180) alter leptin signaling and lipid metabolism in differentiated 3T3-L1 adipocytes. Toxicol. Appl. Pharmacol.2014, 279, 401–408, 10.1016/j.taap.2014.06.016.
Kim, J.; et al. 4,4’-Dichlorodiphenyltrichloroethane (DDT) and 4,4’-dichlorodiphenyldichloroethylene (DDE) promote adipogenesis in 3T3-L1 adipocyte cell culture. Pestic. Biochem. Physiol.2016, 131, 40–45, 10.1016/j.pestbp.2016.01.005.
Wu, H.; et al. Polychlorinated biphenyls-153 induces metabolic dysfunction through activation of ROS/NF-κB signaling via downregulation of HNF1b. Redox Biol.2017, 12, 300–310, 10.1016/j.redox.2017.02.026.
Pesta, M.; et al. Trends in gene expression changes during adipogenesis in human adipose derived mesenchymal stem cells under dichlorodiphenyldichloroethylene exposure. Mol. Cell. Toxicol.2018, 14, 369–379, 10.1007/s13273-018-0041-1.
van den Dungen, M. W.; Murk, A. J.; Kok, D. E.; Steegenga, W. T. Persistent organic pollutants alter DNA methylation during human adipocyte differentiation. Toxicol. Vitro2017, 40, 79–87, 10.1016/j.tiv.2016.12.011.
Burkard, M.; Bengtson Nash, S.; Gambaro, G.; Whitworth, D.; Schirmer, K. Lifetime extension of humpback whale skin fibroblasts and their response to lipopolysaccharide (LPS) and a mixture of polychlorinated biphenyls (Aroclor). Cell Biol. Toxicol.2019, 35, 387–398, 10.1007/s10565-018-09457-1.
Dludla, P. V.; et al. A dose-dependent effect of dimethyl sulfoxide on lipid content, cell viability and oxidative stress in 3T3-L1 adipocytes. Toxicol. Rep.2018, 5, 1014–1020, 10.1016/j.toxrep.2018.10.002.
Lemaire, B.; et al. Precision-cut liver slices to investigate responsiveness of deep-sea fish to contaminants at high pressure. Environ. Sci. Technol.2012, 46, 10310–10316, 10.1021/es301850e.
Hassrick, J. L.; et al. Condition and mass impact oxygen stores and dive duration in adult female northern elephant seals. J. Exp. Biol.2010, 213, 585–592, 10.1242/jeb.037168.
Ortiz, R. M.; Wade, C. E.; Ortiz, C. L. Effects of prolonged fasting on plasma cortisol and TH in postweaned northern elephant seal pups. Am. J. Physiol. Regul. Integr. Comp. Physiol.2001, 280, R790–5, 10.1152/ajpregu.2001.280.3.R790.
Abdi, H. Encyclopedia Of Measurement And Statistics Sage Publications, Inc. 2007 10.4135/9781412952644.
Dagnelie, P. Statistique Theorique Et Appliquee 1. Statistique Descriptive Et Bases De L’inference Statistique; Springer, 2013.
Crocker, D. E.; Champagne, C. D.; Fowler, M. A.; Houser, D. S. Adiposity and fat metabolism in lactating and fasting northern elephant seals. Adv. Nutr.2014, 5, 57–64, 10.3945/an.113.004663.
Fowler, M. A.; Costa, D. P.; Crocker, D. E.; Shen, W.-J.; Kraemer, F. B. Not Hormone-Sensitive Lipase, Is the Primary Lipolytic Enzyme in Fasting Elephant Seals (Mirounga angustirostris). Physiol. Biochem. Zool.2015, 88, 284–294, 10.1086/680079.
Li, Y.; et al. The Molecular Brakes of Adipose Tissue Lipolysis. Front. Physiol.2022, 13, 826314, 10.3389/fphys.2022.826314.
Sun, C.; Mao, S.; Chen, S.; Zhang, W.; Liu, C. PPARs-Orchestrated Metabolic Homeostasis in the Adipose Tissue. Int. J. Mol. Sci.2021, 22, 8974, 10.3390/ijms22168974.
Itabe, H.; Yamaguchi, T.; Nimura, S.; Sasabe, N. Perilipins: a diversity of intracellular lipid droplet proteins. Lipids Health Dis.2017, 16, 83, 10.1186/s12944-017-0473-y.
Murray, R. K. . Harper’s Illustrated-Eighth Edition. 2009.
Peterson, M. G.; et al. Serum POP concentrations are highly predictive of inner blubber concentrations at two extremes of body condition in northern elephant seals. Environ. Pollut.2016, 218, 651–663, 10.1016/j.envpol.2016.07.052.
Lydersen, C.; et al. Blood is a poor substrate for monitoring pollution burdens in phocid seals. Sci. Total Environ.2002, 292, 193–203, 10.1016/S0048-9697(01)01121-4.
De Swart, R. L.; Ross, P. S.; Vos, J. G.; Osterhaus, A. D. M. E. Impaired immunity in harbour seals (Phoca vitulina) exposed to bioaccumulated environmental contaminants: review of a long-term feeding study. Environ. Health Perspect.1996, 104, 823, 10.1289/ehp.96104s4823.
Lelou, E.; et al. The Role of Catecholamines in Pathophysiological Liver Processes. Cells2022, 11, 1021, 10.3390/cells11061021.
Mayati, A.; et al. β2-adrenergic receptor-mediated in vitro regulation of human hepatic drug transporter expression by epinephrine. Eur. J. Pharm. Sci.2017, 106, 302–312, 10.1016/j.ejps.2017.06.010.
Konstandi, M.; et al. Role of adrenoceptor-linked signaling pathways in the regulation of CYP1A1 gene expression. Biochem. Pharmacol.2005, 69, 277–287, 10.1016/j.bcp.2004.09.024.
Esteves, F.; Rueff, J.; Kranendonk, M. The Central Role of Cytochrome P450 in Xenobiotic Metabolism─A Brief Review on a Fascinating Enzyme Family. J. Xenobiot.2021, 11 (3), 94–114, 10.3390/jox11030007.
Jover, R.; Bort, R.; Gómez-Lechón, M. J.; Castell, J. V. Down-regulation of human CYP3A4 by the inflammatory signal interleukin-6: molecular mechanism and transcription factors involved. FASEB J.2002, 16 (13), 1799–1801, 10.1096/fj.02-0195fje.
Ellero, S.; et al. Xenobiotic-metabolizing cytochromes P450 in human white adipose tissue: Expression and induction. Drug Metab. Dispos.2010, 38, 679–686, 10.1124/dmd.109.029249.
Godard-Codding, C. A. J.; Fossi, M. C. Field Sampling Techniques and Ecotoxicologic Biomarkers in Cetaceans Marine Mammal Ecotoxicology: Impacts Of Multiple Stressors On Population Health Elsevier 2018 237–25910.1016/B978-0-12-812144-3.00009-7.
Nyman, M.; Raunio, H.; Pelkonen, O. Expression and inducibility of members in the cytochrome P4501 (CYP1) family in ringed and grey seals from polluted and less polluted waters. Environ. Toxicol. Pharmacol.2000, 8, 217–225, 10.1016/S1382-6689(00)00045-4.
Bachman, M. J.; Foltz, K. M.; Lynch, J. M.; West, K. L.; Jensen, B. A. Using cytochrome P4501A1 expression in liver and blubber to understand effects of persistent organic pollutant exposure in stranded Pacific Island cetaceans. Environ. Toxicol. Chem.2015, 34, 1989–1995, 10.1002/etc.3018.
Soulen, B. K.; Divine, L. M.; Venables, B. J.; Roberts, A. P. Persistent organic pollutant exposure and associations with gene expression in northern fur seals (Callorhinus ursinus) from St. Paul Island, Alaska. Mar. Environ. Res.2022, 182, 105789, 10.1016/j.marenvres.2022.105789.
Daskalopoulos, E. P.; Malliou, F.; Rentesi, G.; Marselos, M.; Lang, M. A.; Konstandi, M. Stress is a critical player in CYP3A, CYP2C, and CYP2D regulation: role of adrenergic receptor signaling pathways. Am. J. Physiol. Endocrinol. Metab.2012, 303 (1), E40–E5410.1152/ajpendo.00545.201.
El-Sankary, W.; Plant, N. J.; Gibson, G. G.; Moore, D. J. Regulation of the CYP3A4 Gene by Hydrocortisone and Xenobiotics: Role of the Glucocorticoid and Pregnane X Receptors. Drug Metab. Dispos.2000, 28, 493–496, 10.1016/S0090-9556(24)15091-X.
Burton, L.; et al. Hydrostatic pressure regulates CYP1A2 expression in human hepatocytes via a mechanosensitive aryl hydrocarbon receptor-dependent pathway. Am. J. Physiol. Cell Physiol.2020, 318, C889, 10.1152/ajpcell.00472.2019.
Desforges, J. P.; Hall, A.; McConnell, B.; Rosing-Asvid, A.; Barber, J. L.; Brownlow, A.; De Guise, S.; Eulaers, I.; Jepson, P. D.; Letcher, R. J.; et al. Predicting global killer whale population collapse from PCB pollution. Science1979, 361 (6409), 1373–1376, 10.1126/science.aat1953.
Sivle, L. D.; Kvadsheim, P. H.; Fahlman, A.; Lam, F. P. A.; Tyack, P. L.; Miller, P. J. O.; et al. Changes in dive behavior during naval sonar exposure in killer whales, long-finned pilot whales, and sperm whales. Front. Physiol.2012, 3, 22017, 10.3389/fphys.2012.00400.
Lafontan, M.; Langin, D. Lipolysis and lipid mobilization in human adipose tissue. Prog. Lipid Res.2009, 48, 275–297, 10.1016/j.plipres.2009.05.001.
Fowler, M.; Champagne, C.; Crocker, D. Adiposity and fat metabolism during combined fasting and lactation in elephant seals. J. Exp. Biol.2018, 221, jeb161554, 10.1242/jeb.161554.
Reilly, S. M.; et al. Catecholamines suppress fatty acid re-esterification and increase oxidation in white adipocytes via STAT3. Nat. Metab.2020, 2, 620–634, 10.1038/s42255-020-0217-6.
Lindgren, E. M.; et al. Noradrenaline represses PPAR (peroxisome-proliferator-activated receptor) gamma2 gene expression in brown adipocytes: intracellular signalling and effects on PPARgamma2 and PPARgamma1 protein levels. Biochem. J.2004, 382, 597–606, 10.1042/BJ20031622.
Kim, H. Y.; et al. Polychlorinated biphenyls exposure-induced insulin resistance is mediated by lipid droplet enlargement through Fsp27. Arch. Toxicol.2017, 91, 2353–2363, 10.1007/s00204-016-1889-2.
Yu, C.; Wen, Q.; Ren, Q.; Du, Y.; Xie, X. Polychlorinated biphenyl congener 180 (PCB 180) regulates mitotic clonal expansion and enhances adipogenesis through modulation of C/EBPβ SUMOylat ion in preadipocytes. Food Chem. Toxicol.2021, 152, 112205, 10.1016/j.fct.2021.112205.
May, P.; et al. In Vitro Cocktail Effects of PCB-DL (PCB118) and Bulky PCB (PCB153) with BaP on Adipogenesis and on Expression of Genes Involved in the Establishment of a Pro-Inflammatory State. Int. J. Mol. Sci.2018, 19, 841, 10.3390/ijms19030841.
Mullerova, D.; et al. Polychlorinated Biphenyl 153 in Lipid Medium Modulates Differentiation of Human Adipocytes. Physiol. Res.2017, 66, 653–662, 10.33549/physiolres.933280.
González-Casanova, J. E.; Pertuz-Cruz, S. L.; Caicedo-Ortega, N. H.; Rojas-Gomez, D. M. Adipogenesis Regulation and Endocrine Disruptors: Emerging Insights in Obesity. Biomed. Res. Int.2020, 2020 (1), 7453786, 10.1155/2020/7453786.
Armstrong, L. E.; Akinbo, S.; Slitt, A. L. 2,2′,4,4′,5-Pentabromodiphenyl ether induces lipid accumulation throughout differentiation in 3T3-L1 and human preadipocytes in vitro. J. Biochem. Mol. Toxicol.2020, 34 (34), e2248510.1002/jbt.22485.
Bavaresco, A.; Mazzeo, P.; Lazzara, M.; Barbot, M. Adipose tissue in cortisol excess: What Cushing’s syndrome can teach us?. Biochem. Pharmacol.2024, 223, 116137, 10.1016/j.bcp.2024.116137.
Behan-Bush, R. M.; et al. Toxicity Impacts on Human Adipose Mesenchymal Stem/Stromal Cells Acutely Exposed to Aroclor and Non-Aroclor Mixtures of Polychlorinated Biphenyl. Environ. Sci. Technol.2023, 57, 1731–1742, 10.1021/acs.est.2c07281.
Bottner, A.; et al. Increased Body Fat Mass and Suppression of Circulating Leptin Levels in Response to Hypersecretion of Epinephrine in Phenylethanolamine-N-Methyltransferase (PNMT)-Overexpressing Mice. Endocrinology2000, 141, 4239–4246, 10.1210/endo.141.11.7755.
Than, A.; et al. The crosstalks between adipokines and catecholamines. Mol. Cell. Endocrinol.2011, 332, 261–270, 10.1016/j.mce.2010.11.002.
Tsubai, T.; et al. Insulin elevates leptin secretion and mRNA levels via cyclic AMP in 3T3-L1 adipocytes deprived of glucose. Heliyon2016, 2, e0019410.1016/j.heliyon.2016.e00194.
Deck, C. A.; Honeycutt, J. L.; Cheung, E.; Reynolds, H. M.; Borski, R. J. Assessing the Functional Role of Leptin in Energy Homeostasis and the Stress Response in Vertebrates. Front. Endocrinol.2017, 8, 63, 10.3389/fendo.2017.00063.
Caron, A.; Lee, S.; Elmquist, J. K.; Gautron, L. Leptin and brain–adipose crosstalks. Nat. Rev. Neurosci.2018, 19 (3), 153–165, 10.1038/nrn.2018.7.
Mashburn, K. L.; Atkinson, S. Variability in leptin and adrenal response in juvenile Steller sea lions (Eumetopias jubatus) to adrenocorticotropic hormone (ACTH) in different seasons. Gen. Comp. Endrocrinol.2008, 155, 352–358, 10.1016/j.ygcen.2007.05.030.
Deyarmin, J. S.; McCormley, M. C.; Champagne, C. D.; Stephan, A. P.; Busqueta, L. P.; Crocker, D. E.; Houser, D. S.; Khudyakov, J. I. Blubber transcriptome responses to repeated ACTH administration in a marine mammal. Sci. Rep.2019, 9 (1), 2718, 10.1038/s41598-019-39089-2.
Linsky, J. M. J.; Dunlop, R. A.; Noad, M. J.; McMichael, L. A. Blubber gene expression and cortisol concentrations reveal changing physiological stress in a Southern ocean sentinel species. Mar. Environ. Res.2024, 199, 106596, 10.1016/j.marenvres.2024.106596.
Mangum, L. H.; Howell, G. E.; Chambers, J. E. Exposure to p,p’-DDE enhances differentiation of 3T3-L1 preadipocytes in a model of sub-optimal differentiation. Toxicol. Lett.2015, 238, 65–71, 10.1016/j.toxlet.2015.07.009.
González-Casanova, J. E.; Pertuz-Cruz, S. L.; Caicedo-Ortega, N. H.; Rojas-Gomez, D. M. Adipogenesis Regulation and Endocrine Disruptors: Emerging Insights in Obesity. Biomed. Res. Int.2020, 7453786, 10.1155/2020/7453786.
Aaseth, J.; Javorac, D.; Djordjevic, A.B.; Bulat, Z.; Skalny, A.V.; Zaitseva, I.P.; Aschner, M.; Tinkov, A.A. The Role of Persistent Organic Pollutants in Obesity: A Review of Laboratory and Epidemiological Studies. Toxics2022, 10, 65, 10.3390/toxics10020065.
Louis, C.; et al. Mobilisation of lipophilic pollutants from blubber in northern elephant seal pups (Mirounga angustirostris) during the post-weaning fast. Environ. Res.2014, 132, 438–448, 10.1016/j.envres.2014.04.016.
Kershaw, J. L.; Sherrill, M.; Davison, N. J.; Brownlow, A.; Hall, A. J. Evaluating morphometric and metabolic markers of body condition in a small cetacean, the harbor porpoise (Phocoena phocoena). Ecol. Evol.2017, 7, 3494–3506, 10.1002/ece3.2891.
Musovic, S.; Olofsson, C. S. Adrenergic stimulation of adiponectin secretion in visceral mouse adipocytes is blunted in high-fat diet induced obesity. Sci. Rep.2019, 9 (1), 10680, 10.1038/s41598-019-47113-8.
Arsenescu, V.; Arsenescu, R. I.; King, V.; Swanson, H.; Cassis, L. A. Polychlorinated biphenyl-77 induces adipocyte differentiation and proinflammatory adipokines and promotes obesity and atherosclerosis. Environ. Health Perspect.2008, 116, 761–768, 10.1289/ehp.10554.
Wen, Q.; et al. The brominated flame retardant PBDE 99 promotes adipogenesis via regulating mitotic clonal expansion and PPARγ expression. Sci. Total Environ.2019, 670, 67–77, 10.1016/j.scitotenv.2019.03.201.
Howell, G.; Mangum, L. Exposure to bioaccumulative organochlorine compounds alters adipogenesis, fatty acid uptake, and adipokine production in NIH3T3-L1 cells. Toxicol. Vitro2011, 25, 394–402, 10.1016/j.tiv.2010.10.015.
Keller, P.; Keller, C.; Robinson, L. E.; Pedersen, B. K. Epinephrine infusion increases adipose interleukin-6 gene expression and systemic levels in humans. Clinical Trial2004, 97, 1309–1312, 10.1152/japplphysiol.00284.2004.
Frost, R. A.; Nystrom, G. J.; Lang, C. H. Epinephrine stimulates IL-6 expression in skeletal muscle and C2C12 myoblasts: role of c-Jun NH2-terminal kinase and histone deacetylase activity. Am. J. Physiol. Endocrinol.Metab.2004, 286, 809–817, 10.1152/ajpendo.00560.2003.
Mattingly, A. J.; Laitano, O.; Clanton, T. L. Epinephrine stimulates CXCL1 IL-1α, IL-6 secretion in isolated mouse limb muscle. Physiol. Rep.2017, 5, e1351910.14814/phy2.13519.
Sakers, A.; De Siqueira, M. K.; Seale, P.; Villanueva, C. J. Adipose-tissue plasticity in health and disease. Cell2022, 185, 419–446, 10.1016/j.cell.2021.12.016.
Zhou, J.; Yan, J.; Liang, H.; Jiang, J. Epinephrine Enhances the Response of Macrophages under LPS Stimulation. BioMed. Res. Int.2014, 2014, 254686, 10.1155/2014/254686.
Alotiby, A. Immunology of Stress: A Review Article. J. Clin. Med.2024, 13, 6394, 10.3390/jcm13216394.
Rolle-Kampczyk, U.; et al. Accumulation of distinct persistent organic pollutants is associated with adipose tissue inflammation. Sci. Total Environ.2020, 748, 142458, 10.1016/j.scitotenv.2020.142458.
Gourronc, F. A.; Robertson, L. W.; Klingelhutz, A. J. A delayed proinflammatory response of human preadipocytes to PCB126 is dependent on the aryl hydrocarbon receptor. Environ. Sci. Pollut. Res.2018, 25, 16481–16492, 10.1007/s11356-017-9676-z.
Pereira-Fernandes, A.; Dirinck, E.; Dirtu, A.C.; Malarvannan, G.; Covaci, A.; Van Gaal, L.; Vanparys, C.; Jorens, P.G.; Blust, R. Expression of obesity markers and Persistent Organic Pollutants levels in adipose tissue of obese patients: reinforcing the obesogen hypothesis?. PLoS One2014, 9, e8481610.1371/journal.pone.0084816.
Khairy, M.; et al. Bioaccumulation of PCBs, OCPs and PBDEs in Marine Mammals From West Antarctica. Front. Mar. Sci.2021, 8, 768715, 10.3389/fmars.2021.768715.
Lehnert, K.; Ronnenberg, K.; Weijs, L.; Covaci, A.; Das, K.; Hellwig, V.; Siebert, U. Xenobiotic and Immune-Relevant Molecular Biomarkers in Harbor Seals as Proxies for Pollutant Burden and Effects. Arch. Environ. Contam. Toxicol.2015, 70 (1), 106–120, 10.1007/s00244-015-0202-3.
Desforges, J. P. Immunotoxic Effects Of Environmental Pollutants In Marine Mammals. Environ. Int.2015, 86, 126–139, 10.1016/j.envint.2015.10.007.
Schaap, I.; Buedenbender, L.; Johann, S.; Hollert, H.; Dogruer, G. Impact of chemical pollution on threatened marine mammals: A systematic review. J. Hazard. Mater.2023, 459, 132203, 10.1016/j.jhazmat.2023.132203.
He, A.; Dean, J. M.; Lodhi, I. J. Peroxisomes as Cellular Adaptors to Metabolic and Environmental Stress. Trends Cell Biol.2021, 31, 656, 10.1016/j.tcb.2021.02.005.
Netzer, N.; Gatterer, H.; Faulhaber, M.; Burtscher, M.; Pramsohler, S.; Pesta, D.; et al. Hypoxia, Oxidative Stress and Fat. Biomolecules2015, 5 (2), 1143–1150.
Allen, K. N.; Vázquez-Medina, J. P. Natural Tolerance to Ischemia and Hypoxemia in Diving Mammals: A Review. Front. Physiol.2019, 10, 1199, 10.3389/fphys.2019.01199.
Hindle, A. G. Diving deep: understanding the genetic components of hypoxia tolerance in marine mammals. J. Appl. Physiol.2020, 128, 1439–1446, 10.1152/japplphysiol.00846.2019.
Karacaoglu, E.; Bayram, I.; Çeliköz, B.; Zienowicz, R. J. Does sustained epinephrine release trigger a hypoxia-neovascularization cascade?. Plast. Reconstr. Surg.2007, 119, 858–864, 10.1097/01.prs.0000252004.78314.56.
Cetin-Atalay, R.; Meliton, A.Y.; Sun, K.A.; Woods, P.S.; Peng, Y.J.; Fang, Y.; Hamanaka, R.B.; Prabhakar, N.R.; Mutlu, G.M. Intermittent Hypoxia Attenuates and Reverses Epinephrine-Induced Changes in Gene Expression in Endothelial Cells FASEB J. 2022 36 10.1096/fasebj.2022.36.S1.R4588.
Myre, M.; Imbeault, P. Persistent organic pollutants meet adipose tissue hypoxia: Does cross-talk contribute to inflammation during obesity?. Obesity Rev.2014, 15, 19–28, 10.1111/obr.12086.
El Amine, Z.; Mauger, J.F.; Imbeault, P. Human Preadipocytes Differentiated under Hypoxia following PCB126 Exposure during Proliferation: Effects on Differentiation, Glucose Uptake and Adipokine Profile. Cells2023, 12, 2326, 10.3390/cells12182326.
Vorrink, S. U.; Domann, F. E. Regulatory crosstalk and interference between the xenobiotic and hypoxia sensing pathways at the AhR-ARNT-HIF1α signaling node. Chem. Biol. Interact.2014, 218, 82–88, 10.1016/j.cbi.2014.05.001.
Vanderhaeghen, T.; Beyaert, R.; Libert, C. Bidirectional Crosstalk Between Hypoxia Inducible Factors and Glucocorticoid Signalling in Health and Disease. Front. Immunol.2021, 12, 684085, 10.3389/fimmu.2021.684085.
Kirkpatrick, A. W.; et al. Age group differences in blubber fatty acid profiles in northern elephant seals (Mirounga angustirostris). Front. Mar. Sci.2022, 9, 942711, 10.3389/fmars.2022.942711.
Lauria, M. Z.; et al. Discovery of Fluorotelomer Sulfones in the Blubber of Greenland Killer Whales (Orcinus orca). Environ. Sci. Technol. Lett.2025, 12, 1218–1224, 10.1021/acs.estlett.5c00516.
Reiter, E. B.; Escher, B. I.; Siebert, U.; Jahnke, A. Activation of the xenobiotic metabolism and oxidative stress response by mixtures of organic pollutants extracted with in-tissue passive sampling from liver, kidney, brain and blubber of marine mammals. Environ. Int.2022, 165, 107337, 10.1016/j.envint.2022.107337.
Routti, H.; et al. Environmental Chemicals Modulate Polar Bear (Ursus maritimus) Peroxisome Proliferator-Activated Receptor Gamma (PPARG) and Adipogenesis in Vitro. Environ. Sci. Technol.2016, 50, 10708–10720, 10.1021/acs.est.6b03020.