{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T00:31:16Z","timestamp":1789777876264,"version":"4.0.1"},"reference-count":73,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2023,6,29]],"date-time":"2023-06-29T00:00:00Z","timestamp":1687996800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000066","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R15ES030556-01A1"],"award-info":[{"award-number":["R15ES030556-01A1"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The molecular mechanisms underlying diet-induced obesity are complex and remain unclear. The activation of the aryl hydrocarbon receptor (AhR), a xenobiotic sensor, by obesogens may contribute to diet-induced obesity through influences on lipid metabolism and insulin resistance acting at various sites, including adipose tissue. Thus, our hypothesis was that conditional AhR depletion, specifically from mature adipose tissue (CadKO), would improve high-fat diet (HFD)-induced metabolic dysfunction. CadKO protects mice from HFD-induced weight gain. CadKO females eat fewer calories, leading to increased energy expenditure (EE) and improved glucose tolerance on HFD. Our exploration of adipose tissue biology suggests that the depletion of AhR from adipocytes provides female mice with an increased capacity for adipogenesis and lipolysis, allowing for the maintenance of a healthy adipocyte phenotype. The HFD-induced leptin rise was reduced in CadKO females, but the hypothalamic leptin receptor (LepR) was increased in the energy regulatory regions of the hypothalamus, suggesting an increased sensitivity to leptin. The estrogen receptor \u03b1 (ER\u03b1) was higher in CadKO female adipose tissue and the hypothalamus. CadKO males displayed a delayed progression of obesity and insulin resistance. In males, CadKO ameliorated proinflammatory adipocytokine secretion (such as TNF\u03b1, IL1\u03b2, IL6) and displayed reduced inflammatory macrophage infiltration into adipose depots. Overall, CadKO improves weight control and systemic glucose homeostasis under HFD challenge but to a more profound extent in females. CadKO facilitates a lean phenotype in females and mediates healthy adipose\u2013hypothalamic crosstalk. In males, adipose-specific AhR depletion delays the development of obesity and insulin resistance through the maintenance of healthy crosstalk between adipocytes and immune cells.<\/jats:p>","DOI":"10.3390\/cells12131748","type":"journal-article","created":{"date-parts":[[2023,6,30]],"date-time":"2023-06-30T00:51:06Z","timestamp":1688086266000},"page":"1748","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Deficiency of Adipose Aryl Hydrocarbon Receptor Protects against Diet-Induced Metabolic Dysfunction through Sexually Dimorphic Mechanisms"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7013-4061","authenticated-orcid":false,"given":"Nazmul","family":"Haque","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, IL 62702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel S.","family":"Ojo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, IL 62702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5688-6429","authenticated-orcid":false,"given":"Stacey L.","family":"Krager","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, IL 62702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8016-6398","authenticated-orcid":false,"given":"Shelley A.","family":"Tischkau","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, IL 62702, USA"},{"name":"Department of Medical Microbiology, Immunology and Cell Biology, Southern Illinois University School of Medicine, Springfield, IL 62702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-1-59745-245-8_1","article-title":"Overview of Adipose Tissue and Its Role in Obesity and Metabolic Disorders","volume":"456","year":"2008","journal-title":"Methods Mol. Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2548","DOI":"10.1210\/jc.2004-0395","article-title":"Adipose Tissue as an Endocrine Organ","volume":"89","author":"Kershaw","year":"2004","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1146\/annurev.physiol.70.120806.095256","article-title":"The integrative role of CNS fuel-sensing mechanisms in energy balance and glucose regu-lation","volume":"70","author":"Sandoval","year":"2008","journal-title":"Annu. Rev. Physiol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Haque, N., and Tischkau, S.A. (2022). Sexual Dimorphism in Adipose-Hypothalamic Crosstalk and the Contribution of Aryl Hydrocarbon Receptor to Regulate Energy Homeostasis. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23147679"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1056\/NEJM199602013340503","article-title":"Serum Immunoreactive-Leptin Concentrations in Normal-Weight and Obese Humans","volume":"334","author":"Considine","year":"1996","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/S0140-6736(96)03173-X","article-title":"Decreased cerebrospi-nal-fluid\/serum leptin ratio in obesity: A possible mechanism for leptin resistance","volume":"348","author":"Caro","year":"1996","journal-title":"Lancet"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1038\/s42255-019-0095-y","article-title":"Leptin and the endocrine control of energy balance","volume":"1","author":"Friedman","year":"2019","journal-title":"Nat. Metab."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1038\/nn1455","article-title":"Anatomy and regulation of the central melanocortin system","volume":"8","author":"Cone","year":"2005","journal-title":"Nat. Neurosci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2003","DOI":"10.2337\/diabetes.54.7.2003","article-title":"Autocrine Action of Adiponectin on Human Fat Cells Prevents the Release of Insulin Resistance-Inducing Factors","volume":"54","author":"Sell","year":"2005","journal-title":"Diabetes"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1796","DOI":"10.1172\/JCI200319246","article-title":"Obesity is associated with macro-phage accumulation in adipose tissue","volume":"112","author":"Weisberg","year":"2003","journal-title":"J. Clin. Investig."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1126\/science.7678183","article-title":"Adipose expression of tumor necrosis factor-alpha: Direct role in obesi-ty-linked insulin resistance","volume":"259","author":"Hotamisligil","year":"1993","journal-title":"Science"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.1172\/JCI26498","article-title":"MCP-1 contributes to macrophage infiltration into adi-pose tissue, insulin resistance, and hepatic steatosis in obesity","volume":"116","author":"Kanda","year":"2006","journal-title":"J. Clin. Investig."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/0006-291X(92)91185-S","article-title":"cDNA cloning and structure of mouse putative Ah receptor","volume":"184","author":"Ema","year":"1992","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"8185","DOI":"10.1073\/pnas.89.17.8185","article-title":"Cloning of the Ah-receptor cDNA reveals a distinctive ligand-activated transcrip-tion factor","volume":"89","author":"Burbach","year":"1992","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1080\/1354750032000158420","article-title":"Dioxin\/polychlorinated biphenyl body burden, diabetes and endometriosis: Findings in a population-based study in Belgium","volume":"8","author":"Fierens","year":"2003","journal-title":"Biomarkers"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1097\/00001648-199705000-00005","article-title":"Serum Dioxin and Diabetes Mellitus in Veterans of Operation Ranch Hand","volume":"8","author":"Henriksen","year":"1997","journal-title":"Epidemiology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1638","DOI":"10.2337\/dc06-0543","article-title":"A strong dose-response relation between serum con-centrations of persistent organic pollutants and diabetes: Results from the National Health and Examination Survey 1999\u20132002","volume":"29","author":"Lee","year":"2006","journal-title":"Diabetes Care"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"101234","DOI":"10.1016\/j.diabet.2021.101234","article-title":"Exposure to persistent organic pollutants and the risk of type 2 diabetes: A case-cohort study","volume":"47","author":"Magliano","year":"2021","journal-title":"Diabetes Metab."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1016\/j.chemosphere.2008.12.035","article-title":"Prevalence of diabetes and body burdens of polychlorinated biphenyls, polybrominated diphenyl ethers, and p,p\u2032-diphenyldichloroethene in Great Lakes sport fish consumers","volume":"75","author":"Turyk","year":"2009","journal-title":"Chemosphere"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1574","DOI":"10.2337\/dc07-2449","article-title":"Increased risk of diabetes and polychlorinated biphenyls and dioxins: A 24-year follow-up study of the Yucheng cohort","volume":"31","author":"Wang","year":"2008","journal-title":"Diabetes Care"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.1073\/pnas.0607296104","article-title":"The Aryl hydrocarbon receptor is activated by modified low-density lipoprotein","volume":"104","author":"McMillan","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/0041-008X(84)90337-5","article-title":"Characterization of the wasting syndrome in rats treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin","volume":"73","author":"Seefeld","year":"1984","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3190","DOI":"10.4049\/jimmunol.0903670","article-title":"An Interaction between Kynurenine and the Aryl Hydrocarbon Receptor Can Generate Regulatory T Cells","volume":"185","author":"Mezrich","year":"2010","journal-title":"J. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"6103","DOI":"10.1038\/s41598-018-24213-5","article-title":"Serotonin is an endogenous regulator of intesti-nal CYP1A1 via AhR","volume":"8","author":"Manzella","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1006\/bbrc.1998.9100","article-title":"Depletion of Arylhydrocarbon Receptor during Adipose Differentiation in 3T3-L1 Cells","volume":"249","author":"Shimba","year":"1998","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1248\/bpb.26.1266","article-title":"Transcriptional Regulation of the AhR Gene during Adipose Differentiation","volume":"26","author":"Shimba","year":"2003","journal-title":"Biol. Pharm. Bull."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1289\/ehp.1205421","article-title":"Coplanar polychlorinated biphenyls impair glu-cose homeostasis in lean C57BL\/6 mice and mitigate beneficial effects of weight loss on glucose homeostasis in obese mice","volume":"121","author":"Baker","year":"2013","journal-title":"Environ. Health Perspect."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"111809","DOI":"10.1016\/j.mce.2022.111809","article-title":"Aryl hydrocarbon receptor affects circa-dian-regulated lipolysis through an E-Box-dependent mechanism","volume":"559","author":"Khazaal","year":"2023","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1038\/ijo.2015.63","article-title":"Aryl hydrocarbon receptor deficiency pro-tects mice from diet-induced adiposity and metabolic disorders through increased energy expenditure","volume":"39","author":"Xu","year":"2015","journal-title":"Int. J. Obes. (Lond.)"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1289\/ehp.1205003","article-title":"Obesity Is Mediated by Differential Aryl Hydrocarbon Receptor Signaling in Mice Fed a Western Diet","volume":"120","author":"Trask","year":"2012","journal-title":"Environ. Health Perspect."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.taap.2016.03.011","article-title":"Inhibition of the aryl hydrocar-bon receptor prevents Western diet-induced obesity. Model for AHR activation by kynurenine via oxidized-LDL, TLR2\/4, TGF\u03b2, and IDO1","volume":"300","author":"Moyer","year":"2016","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"7004","DOI":"10.1074\/jbc.M115.693655","article-title":"Aryl Hydrocarbon Receptor Plays Protective Roles against High Fat Diet (HFD)-induced Hepatic Steatosis and the Subsequent Lipotoxicity via Direct Transcriptional Regulation of Socs3 Gene Expression","volume":"291","author":"Wada","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Girer, N.G., Carter, D., Bhattarai, N., Mustafa, M., Denner, L., Porter, C., and Elferink, C.J. (2019). Inducible Loss of the Aryl Hydrocarbon Re-ceptor Activates Perigonadal White Fat Respiration and Brown Fat Thermogenesis via Fibroblast Growth Factor 21. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20040950"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"17858","DOI":"10.1073\/pnas.0504757102","article-title":"Aryl hydrocarbon receptor-dependent liver development and hepatotoxicity are mediated by different cell types","volume":"102","author":"Walisser","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1177\/0748730417696786","article-title":"Aryl Hydrocarbon Receptor Deficiency Alters Circa-dian and Metabolic Rhythmicity","volume":"32","author":"Jaeger","year":"2017","journal-title":"J. Biol. Rhythms."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3489","DOI":"10.1038\/s41467-022-31126-5","article-title":"Adipocyte-derived kynurenine promotes obesity and insulin resistance by activating the AhR\/STAT3\/IL-6 signaling","volume":"13","author":"Huang","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_37","first-page":"E316","article-title":"Sexually dimorphic responses to fat loss after caloric restriction or surgical lipectomy","volume":"293","author":"Shi","year":"2007","journal-title":"Am. J. Physiol. Metab."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.mce.2014.11.029","article-title":"The sexual dimorphism of obesity","volume":"402","author":"Palmer","year":"2015","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/2042-6410-3-13","article-title":"Sex differences in human adipose tissues\u2014The biology of pear shape","volume":"3","author":"Karastergiou","year":"2012","journal-title":"Biol. Sex Differ."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1210\/er.2015-1137","article-title":"Sex and Gender Differences in Risk, Pathophysiology and Complications of Type 2 Diabetes Mellitus","volume":"37","author":"Harreiter","year":"2016","journal-title":"Endocr. Rev."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1016\/j.molmet.2015.08.004","article-title":"Impact of tamoxifen on adipocyte lineage trac-ing: Inducer of adipogenesis and prolonged nuclear translocation of Cre recombinase","volume":"4","author":"Ye","year":"2015","journal-title":"Mol. Metab."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.nutres.2017.06.002","article-title":"Obesity and fatty liver are prevented by inhibition of the aryl hydrocarbon receptor in both female and male mice","volume":"44","author":"Moyer","year":"2017","journal-title":"Nutr. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1289\/ehp.1408594","article-title":"Effects of Adipocyte Aryl Hydrocarbon Receptor Deficiency on PCB-Induced Disruption of Glucose Homeostasis in Lean and Obese Mice","volume":"123","author":"Baker","year":"2015","journal-title":"Environ. Health Perspect."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Gourronc, F.A., Markan, K.R., Kulhankova, K., Zhu, Z., Sheehy, R., Quelle, D.E., Zingman, L.V., Kurago, Z.B., Ankrum, J.A., and Klingelhutz, A.J. (2020). Pdgfr\u03b1-Cre mediated knockout of the aryl hydrocarbon receptor protects mice from high-fat diet induced obesity and hepatic steatosis. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0236741"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"E1420","DOI":"10.1152\/ajpendo.00362.2009","article-title":"Long-term Fenretinide treatment prevents high-fat di-et-induced obesity, insulin resistance, and hepatic steatosis","volume":"297","author":"Preitner","year":"2009","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"R1025","DOI":"10.1152\/ajpregu.1992.262.6.R1025","article-title":"Dietary obesity in nine inbred mouse strains","volume":"262","author":"West","year":"1992","journal-title":"Am. J. Physiol. Integr. Comp. Physiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1038\/s41598-017-19104-0","article-title":"Testosterone boosts physical activity in male mice via dopaminergic pathways","volume":"8","author":"Laurent","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1644","DOI":"10.3389\/fimmu.2020.01644","article-title":"Increased AHR Transcripts Correlate With Pro-inflammatory T-Helper Lymphocytes Polarization in Both Metabolically Healthy Obesity and Type 2 Diabetic Patients","volume":"11","author":"Zhao","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1093\/toxsci\/56.2.431","article-title":"Exposure to 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) Is Associated with Hyperinsulinemia and Insulin Resistance","volume":"56","author":"Cranmer","year":"2000","journal-title":"Toxicol. Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"152831","DOI":"10.1016\/j.tox.2021.152831","article-title":"The aryl hydrocarbon receptor activates ceramide biosynthesis in mice contributing to hepatic lipogenesis","volume":"458","author":"Liu","year":"2021","journal-title":"Toxicology"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"18504","DOI":"10.1074\/jbc.RA119.009282","article-title":"Aryl hydrocarbon receptor (AhR) regulates adipocyte differentiation by assembling CRL4B ubiquitin ligase to target PPAR\u03b3 for proteasomal degradation","volume":"294","author":"Dou","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e016","DOI":"10.1621\/nrs.04016","article-title":"Estrogen receptor and aryl hydrocarbon receptor signaling pathways","volume":"4","author":"Matthews","year":"2006","journal-title":"Nucl. Recept. Signal."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"12729","DOI":"10.1073\/pnas.97.23.12729","article-title":"Increased adipose tissue in male and female estrogen re-ceptor-alpha knockout mice","volume":"97","author":"Heine","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/0303-7207(92)90120-U","article-title":"Effects of in vivo estrogen treatment on adipose tissue metab-olism and nuclear estrogen receptor binding in isolated rat adipocytes","volume":"85","author":"Pedersen","year":"1992","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1289\/ehp.10554","article-title":"Polychlorinated biphenyl-77 induces adipocyte differentia-tion and proinflammatory adipokines and promotes obesity and atherosclerosis","volume":"116","author":"Arsenescu","year":"2008","journal-title":"Environ. Health Perspect."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1093\/toxsci\/kfq052","article-title":"2,3,7,8-Tetrachlorodibenzo-p-Dioxin Impairs an Insulin Signaling Pathway through the Induction of Tumor Necrosis Factor-\u03b1 in Adipocytes","volume":"115","author":"Nishiumi","year":"2010","journal-title":"Toxicol. Sci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1289\/ehp.1104282","article-title":"Inflammatory Pathway Genes Belong to Major Targets of Persistent Organic Pollutants in Adipose Cells","volume":"120","author":"Kim","year":"2012","journal-title":"Environ. Health Perspect."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"105300","DOI":"10.1016\/j.neuint.2022.105300","article-title":"Arcuate nucleus of the hypothalamus contributes to the hypophagic effect and plasma metabolic changes induced by vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide","volume":"155","author":"Martins","year":"2022","journal-title":"Neurochem. Int."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/0006-8993(89)90062-0","article-title":"Central implants of diluted estradiol: Independent effects on ingestive and reproductive behaviors of ovariectomized rats","volume":"491","author":"Butera","year":"1989","journal-title":"Brain Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/0031-9384(86)90404-X","article-title":"Central vs. peripheral effects of estrogen on food intake and lipoprotein lipase activity in ovariecto-mized rats","volume":"37","author":"Palmer","year":"1986","journal-title":"Physiol. Behav."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/j.cmet.2011.08.009","article-title":"Distinct Hypothalamic Neurons Mediate Estrogenic Effects on Energy Homeostasis and Reproduction","volume":"14","author":"Xu","year":"2011","journal-title":"Cell Metab."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.cmet.2006.05.002","article-title":"Role of adiponectin in human skeletal muscle bioenergetics","volume":"4","author":"Civitarese","year":"2006","journal-title":"Cell Metab."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2562","DOI":"10.2337\/db05-1322","article-title":"Adiponectin increases fatty acid oxidation in skeletal mus-cle cells by sequential activation of AMP-activated protein kinase, p38 mitogen-activated protein kinase, and peroxisome pro-liferator-activated receptor alpha","volume":"55","author":"Yoon","year":"2006","journal-title":"Diabetes"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1038\/nm788","article-title":"Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase","volume":"8","author":"Yamauchi","year":"2002","journal-title":"Nat. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"682","DOI":"10.2337\/diabetes.52.3.682","article-title":"Differential Sensitivity to Central Leptin and Insulin in Male and Female Rats","volume":"52","author":"Clegg","year":"2003","journal-title":"Diabetes"},{"key":"ref_66","first-page":"3424","article-title":"Effects of gender, body composition, and menopause on plasma concentrations of leptin","volume":"81","author":"Rosenbaum","year":"1996","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_67","first-page":"579","article-title":"Sexual Dimorphism in Plasma Leptin Concentration1","volume":"82","author":"Saad","year":"1997","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1002\/oby.21133","article-title":"Shaping fat distribution: New insights into the molecular determinants of depot- and sex-dependent adipose biology","volume":"23","author":"Fried","year":"2015","journal-title":"Obesity"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Fujii, H., Kawada, N., and Japan Study Group of NAFLD (JSG-NAFLD) (2020). The Role of Insulin Resistance and Diabetes in Nonalcoholic Fatty Liver Disease. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21113863"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"5629","DOI":"10.1074\/jbc.M008553200","article-title":"Liporegulation in diet-induced obesity. The an-tisteatotic role of hyperleptinemia","volume":"276","author":"Lee","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"8067","DOI":"10.1021\/acs.est.5b01389","article-title":"Metabolomics Reveals that Aryl Hydrocarbon Re-ceptor Activation by Environmental Chemicals Induces Systemic Metabolic Dysfunction in Mice","volume":"49","author":"Zhang","year":"2015","journal-title":"Environ. Sci. Technol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1007\/s10238-012-0227-0","article-title":"Adiponectin: A key playmaker adipocytokine in non-alcoholic fatty liver disease","volume":"14","author":"Gatselis","year":"2013","journal-title":"Clin. Exp. Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1053\/j.gastro.2010.03.033","article-title":"A novel role for the dioxin receptor in fatty acid me-tabolism and hepatic steatosis","volume":"139","author":"Lee","year":"2010","journal-title":"Gastroenterology"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/13\/1748\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:03:55Z","timestamp":1760126635000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/13\/1748"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,29]]},"references-count":73,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["cells12131748"],"URL":"https:\/\/doi.org\/10.3390\/cells12131748","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,29]]}}}