{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:10:21Z","timestamp":1790727021539,"version":"4.1.0"},"reference-count":80,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,30]],"date-time":"2022-12-30T00:00:00Z","timestamp":1672358400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Sturgis Foundation Grant Award","award":["GR110030"],"award-info":[{"award-number":["GR110030"]}]},{"name":"Sturgis Foundation Grant Award","award":["GR102402"],"award-info":[{"award-number":["GR102402"]}]},{"name":"Sturgis Foundation Grant Award","award":["1R01AG071782"],"award-info":[{"award-number":["1R01AG071782"]}]},{"name":"UAMS Provost\u2019s Innovator Awards","award":["GR110030"],"award-info":[{"award-number":["GR110030"]}]},{"name":"UAMS Provost\u2019s Innovator Awards","award":["GR102402"],"award-info":[{"award-number":["GR102402"]}]},{"name":"UAMS Provost\u2019s Innovator Awards","award":["1R01AG071782"],"award-info":[{"award-number":["1R01AG071782"]}]},{"name":"UAMS College of Medicine Creativity Hub","award":["GR110030"],"award-info":[{"award-number":["GR110030"]}]},{"name":"UAMS College of Medicine Creativity Hub","award":["GR102402"],"award-info":[{"award-number":["GR102402"]}]},{"name":"UAMS College of Medicine Creativity Hub","award":["1R01AG071782"],"award-info":[{"award-number":["1R01AG071782"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>One feature of high-fat diet-induced neurodegeneration in the hypothalamus is an increased level of palmitate, which is associated with endoplasmic reticulum (ER) stress, loss of CoxIV, mitochondrial fragmentation, and decreased abundance of MC4R. To determine whether antidiabetic drugs protect against ER and\/or mitochondrial dysfunction by lipid stress, hypothalamic neurons derived from pre-adult mice and neuronal Neuro2A cells were exposed to elevated palmitate. In the hypothalamic neurons, palmitate exposure increased expression of ER resident proteins, including that of SERCA2, indicating ER stress. Liraglutide reverted such altered ER proteostasis, while metformin only normalized SERCA2 expression. In Neuro2A cells liraglutide, but not metformin, also blunted dilation of the ER induced by palmitate treatment, and enhanced abundance and expression of MC4R at the cell surface. Thus, liraglutide counteracts, more effectively than metformin, altered ER proteostasis, morphology, and folding capacity in neurons exposed to fat. In palmitate-treated hypothalamic neurons, mitochondrial fragmentation took place together with loss of CoxIV and decreased mitochondrial membrane potential (MMP). Metformin, but not liraglutide, reverted mitochondrial fragmentation, and both liraglutide and metformin did not protect against either loss of CoxIV abundance or MMP. Thus, ER recovery from lipid stress can take place in hypothalamic neurons in the absence of recovered mitochondrial homeostasis.<\/jats:p>","DOI":"10.3390\/ijms24010629","type":"journal-article","created":{"date-parts":[[2022,12,30]],"date-time":"2022-12-30T03:31:17Z","timestamp":1672371077000},"page":"629","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Liraglutide Counteracts Endoplasmic Reticulum Stress in Palmitate-Treated Hypothalamic Neurons without Restoring Mitochondrial Homeostasis"],"prefix":"10.3390","volume":"24","author":[{"given":"Haven","family":"Griffin","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah C.","family":"Sullivan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven W.","family":"Barger","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin D.","family":"Phelan","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Developmental Sciences, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Baldini","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1172\/JCI59660","article-title":"Obesity is associated with hypothalamic injury in rodents and humans","volume":"122","author":"Thaler","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4192","DOI":"10.1210\/en.2004-1520","article-title":"Consumption of a fat-rich diet activates a proinflammatory response and induces insulin resistance in the hypothalamus","volume":"146","author":"Araujo","year":"2005","journal-title":"Endocrinology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2124","DOI":"10.1016\/j.celrep.2014.11.018","article-title":"Microglia dictate the impact of saturated fat consumption on hypothalamic inflammation and neuronal function","volume":"9","author":"Valdearcos","year":"2014","journal-title":"Cell Rep."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Leon, S., Nadjar, A., and Quarta, C. (2021). Microglia-Neuron Crosstalk in Obesity: Melodious Interaction or Kiss of Death?. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22105243"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"17675","DOI":"10.1074\/jbc.M113.475343","article-title":"Obesity induces hypothalamic endoplasmic reticulum stress and impairs proopiomelanocortin (POMC) post-translational processing","volume":"288","author":"Cakir","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"4191","DOI":"10.1210\/en.2007-0173","article-title":"Regulation of prohormone convertases in hypothalamic neurons: Implications for prothyrotropin-releasing hormone and proopiomelanocortin","volume":"148","author":"Nillni","year":"2007","journal-title":"Endocrinology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"101114","DOI":"10.1016\/j.isci.2020.101114","article-title":"Selective Survival of Sim1\/MC4R Neurons in Diet-Induced Obesity","volume":"23","author":"Nyamugenda","year":"2020","journal-title":"iScience"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1111\/jnc.14662","article-title":"Injury to hypothalamic Sim1 neurons is a common feature of obesity by exposure to high-fat diet in male and female mice","volume":"149","author":"Nyamugenda","year":"2019","journal-title":"J. Neurochem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2180","DOI":"10.1016\/j.celrep.2020.01.072","article-title":"Palmitate Is Increased in the Cerebrospinal Fluid of Humans with Obesity and Induces Memory Impairment in Mice via Pro-inflammatory TNF-alpha","volume":"30","author":"Melo","year":"2020","journal-title":"Cell Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1038\/s41586-021-03960-y","article-title":"Neurotoxic reactive astrocytes induce cell death via saturated lipids","volume":"599","author":"Guttenplan","year":"2021","journal-title":"Nature"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"270","DOI":"10.3389\/fnins.2017.00270","article-title":"Effects of Fat and Sugar, Either Consumed or Infused toward the Brain, on Hypothalamic ER Stress Markers","volume":"11","author":"Belegri","year":"2017","journal-title":"Front. Neurosci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1210\/me.2013-1357","article-title":"Mild lipid stress induces profound loss of MC4R protein abundance and function","volume":"28","author":"Cragle","year":"2014","journal-title":"Mol. Endocrinol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1210\/en.2009-1122","article-title":"Palmitate attenuates insulin signaling and induces endoplasmic reticulum stress and apoptosis in hypothalamic neurons: Rescue of resistance and apoptosis through adenosine 5\u2032 monophosphate-activated protein kinase activation","volume":"151","author":"Mayer","year":"2010","journal-title":"Endocrinology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1678","DOI":"10.1016\/j.febslet.2015.04.025","article-title":"Hypothalamic ER stress: A bridge between leptin resistance and obesity","volume":"589","author":"Ramirez","year":"2015","journal-title":"FEBS Lett."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1194\/jlr.R067595","article-title":"The role of ER stress in lipid metabolism and lipotoxicity","volume":"57","author":"Han","year":"2016","journal-title":"J. Lipid Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"159219","DOI":"10.1016\/j.bbalip.2022.159219","article-title":"Palmitate and thapsigargin have contrasting effects on ER membrane lipid composition and ER proteostasis in neuronal cells","volume":"1867","author":"Jantti","year":"2022","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1038\/s41420-020-0241-z","article-title":"Delivery of phosphatidylethanolamine blunts stress in hepatoma cells exposed to elevated palmitate by targeting the endoplasmic reticulum","volume":"6","author":"Trentzsch","year":"2020","journal-title":"Cell Death Discov."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1578","DOI":"10.1523\/JNEUROSCI.3952-03.2004","article-title":"GABA release from proopiomelanocortin neurons","volume":"24","author":"Hentges","year":"2004","journal-title":"J. Neurosci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.cell.2013.09.003","article-title":"Mitofusin 2 in POMC neurons connects ER stress with leptin resistance and energy imbalance","volume":"155","author":"Schneeberger","year":"2013","journal-title":"Cell"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"101","DOI":"10.3389\/fnagi.2015.00101","article-title":"Implications of mitochondrial dynamics on neurodegeneration and on hypothalamic dysfunction","volume":"7","author":"Zorzano","year":"2015","journal-title":"Front. Aging Neurosci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3770","DOI":"10.1523\/JNEUROSCI.3173-18.2019","article-title":"The Divergent Roles of Dietary Saturated and Monounsaturated Fatty Acids on Nerve Function in Murine Models of Obesity","volume":"39","author":"Rumora","year":"2019","journal-title":"J. Neurosci."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Jo, D., Yoon, G., and Song, J. (2021). Role of Exendin-4 in Brain Insulin Resistance, Mitochondrial Function, and Neurite Outgrowth in Neurons under Palmitic Acid-Induced Oxidative Stress. Antioxidants, 10.","DOI":"10.3390\/antiox10010078"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"American Diabetes Association (2019). 8. Obesity Management for the Treatment of Type 2 Diabetes: Standards of Medical Care in Diabetes\u20142019. Diabetes Care, 42, S81\u2013S89.","DOI":"10.2337\/dc19-S008"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1016\/S0140-6736(17)30069-7","article-title":"3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: A randomised, double-blind trial","volume":"389","author":"Astrup","year":"2017","journal-title":"Lancet"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e291","DOI":"10.1038\/emm.2016.157","article-title":"Oxidative stress and calcium dysregulation by palmitate in type 2 diabetes","volume":"49","author":"Ly","year":"2017","journal-title":"Exp. Mol. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1626","DOI":"10.1242\/jcs.045625","article-title":"ATF6alpha induces XBP1-independent expansion of the endoplasmic reticulum","volume":"122","author":"Bommiasamy","year":"2009","journal-title":"J. Cell Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"104624","DOI":"10.1016\/j.neuint.2019.104624","article-title":"Protective effect of Liraglutide on diabetic retinal neurodegeneration via inhibiting oxidative stress and endoplasmic reticulum stress","volume":"133","author":"Liu","year":"2020","journal-title":"Neurochem. Int."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e1976","DOI":"10.1038\/cddis.2015.331","article-title":"Palmitate induces ER calcium depletion and apoptosis in mouse podocytes subsequent to mitochondrial oxidative stress","volume":"6","author":"Xu","year":"2015","journal-title":"Cell Death Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"R1","DOI":"10.1530\/JOE-18-0596","article-title":"The melanocortin pathway and control of appetite-progress and therapeutic implications","volume":"241","author":"Baldini","year":"2019","journal-title":"J. Endocrinol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1805","DOI":"10.1210\/me.2010-0071","article-title":"Obesity-linked variants of melanocortin-4 receptor are misfolded in the endoplasmic reticulum and can be rescued to the cell surface by a chemical chaperone","volume":"24","author":"Granell","year":"2010","journal-title":"Mol. Endocrinol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1080\/10520295.2017.1295169","article-title":"MAP2 IHC detection: A marker of antigenicity in CNS tissues","volume":"92","author":"Howanski","year":"2017","journal-title":"Biotech. Histochem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"6361","DOI":"10.1073\/pnas.93.13.6361","article-title":"Targeted deletion in astrocyte intermediate filament (Gfap) alters neuronal physiology","volume":"93","author":"McCall","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0169-328X(98)00040-0","article-title":"Microglia-specific localisation of a novel calcium binding protein, Iba1","volume":"57","author":"Ito","year":"1998","journal-title":"Mol. Brain Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"135850","DOI":"10.1016\/j.neulet.2021.135850","article-title":"The microtubule cytoskeleton at the synapse","volume":"753","author":"Parato","year":"2021","journal-title":"Neurosci. Lett."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/j.molmet.2017.01.001","article-title":"Cholinergic neurons in the dorsomedial hypothalamus regulate food intake","volume":"6","author":"Jeong","year":"2017","journal-title":"Mol. Metab."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1093\/hmg\/9.1.101","article-title":"Profound obesity associated with a balanced translocation that disrupts the SIM1 gene","volume":"9","author":"Holder","year":"2000","journal-title":"Hum. Mol. Genet."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1210\/en.2019-00062","article-title":"Leptin Receptor Signaling in Sim1-Expressing Neurons Regulates Body Temperature and Adaptive Thermogenesis","volume":"160","author":"Cakir","year":"2019","journal-title":"Endocrinology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.cmet.2011.01.010","article-title":"Melanocortin-4 receptors expressed by cholinergic neurons regulate energy balance and glucose homeostasis","volume":"13","author":"Rossi","year":"2011","journal-title":"Cell Metab."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1016\/j.celrep.2018.07.031","article-title":"Interrogating the Spatiotemporal Landscape of Neuromodulatory GPCR Signaling by Real-Time Imaging of cAMP in Intact Neurons and Circuits","volume":"24","author":"Muntean","year":"2018","journal-title":"Cell Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"E1122","DOI":"10.1152\/ajpendo.00006.2010","article-title":"Cultured hypothalamic neurons are resistant to inflammation and insulin resistance induced by saturated fatty acids","volume":"298","author":"Choi","year":"2010","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1016\/j.celrep.2018.10.055","article-title":"KDEL Receptors Are Differentially Regulated to Maintain the ER Proteome under Calcium Deficiency","volume":"25","author":"Trychta","year":"2018","journal-title":"Cell Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1016\/j.jhep.2017.05.023","article-title":"High fat diet disrupts endoplasmic reticulum calcium homeostasis in the rat liver","volume":"67","author":"Wires","year":"2017","journal-title":"J. Hepatol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"19320","DOI":"10.1073\/pnas.1012044107","article-title":"Sarco(endo)plasmic reticulum Ca2+-ATPase 2b is a major regulator of endoplasmic reticulum stress and glucose homeostasis in obesity","volume":"107","author":"Park","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Hojmann Larsen, A., Frandsen, A., and Treiman, M. (2001). Upregulation of the SERCA-type Ca2+ pump activity in response to endoplasmic reticulum stress in PC12 cells. BMC Biochem., 2.","DOI":"10.1186\/1471-2091-2-4"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"175062","DOI":"10.1155\/2014\/175062","article-title":"Mitochondrial dysfunctions in neurodegenerative diseases: Relevance to Alzheimer\u2019s disease","volume":"2014","author":"Hroudova","year":"2014","journal-title":"Biomed. Res. Int."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2303","DOI":"10.2337\/db07-1781","article-title":"Mitochondrial networking protects beta-cells from nutrient-induced apoptosis","volume":"58","author":"Molina","year":"2009","journal-title":"Diabetes"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"193","DOI":"10.2337\/db16-0915","article-title":"Metformin Suppresses Diabetes-Accelerated Atherosclerosis via the Inhibition of Drp1-Mediated Mitochondrial Fission","volume":"66","author":"Wang","year":"2017","journal-title":"Diabetes"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/S0165-0270(00)00340-X","article-title":"MitoTracker labeling in primary neuronal and astrocytic cultures: Influence of mitochondrial membrane potential and oxidants","volume":"104","author":"Buckman","year":"2001","journal-title":"J. Neurosci. Methods"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Simon-Szabo, L., Kokas, M., Mandl, J., Keri, G., and Csala, M. (2014). Metformin attenuates palmitate-induced endoplasmic reticulum stress, serine phosphorylation of IRS-1 and apoptosis in rat insulinoma cells. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0097868"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"174249","DOI":"10.1016\/j.ejphar.2021.174249","article-title":"Effect of anti-hyperglycemic drugs on endoplasmic reticulum (ER) stress in human coronary artery endothelial cells","volume":"907","author":"Kapadia","year":"2021","journal-title":"Eur. J. Pharmacol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1562","DOI":"10.1089\/ars.2017.7409","article-title":"Does Metformin Modulate Endoplasmic Reticulum Stress and Autophagy in Type 2 Diabetic Peripheral Blood Mononuclear Cells?","volume":"28","author":"Iannantuoni","year":"2018","journal-title":"Antioxid. Redox Signal."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/B978-0-12-385114-7.00004-0","article-title":"Measuring ER stress and the unfolded protein response using mammalian tissue culture system","volume":"490","author":"Oslowski","year":"2011","journal-title":"Methods Enzymol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1091\/mbc.e07-06-0587","article-title":"Sequestration of Mutated \u03b11-Antitrypsin into Inclusion Bodies Is a Cell-protective Mechanism to Maintain Endoplasmic Reticulum Function","volume":"19","author":"Granell","year":"2008","journal-title":"Mol. Biol. Cell"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Li, H., and Sun, S. (2021). Protein Aggregation in the ER: Calm behind the Storm. Cells, 10.","DOI":"10.3390\/cells10123337"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"5058","DOI":"10.1038\/s41467-019-12991-z","article-title":"ESCRT-III-driven piecemeal micro-ER-phagy remodels the ER during recovery from ER stress","volume":"10","author":"Loi","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/j.cell.2005.08.035","article-title":"Divergence of melanocortin pathways in the control of food intake and energy expenditure","volume":"123","author":"Balthasar","year":"2005","journal-title":"Cell"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e133429","DOI":"10.1172\/jci.insight.133429","article-title":"Semaglutide lowers body weight in rodents via distributed neural pathways","volume":"5","author":"Gabery","year":"2020","journal-title":"JCI Insight"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2456","DOI":"10.1172\/JCI72434","article-title":"Neuronal GLP1R mediates liraglutide\u2019s anorectic but not glucose-lowering effect","volume":"124","author":"Sisley","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"4473","DOI":"10.1172\/JCI75276","article-title":"The arcuate nucleus mediates GLP-1 receptor agonist liraglutide-dependent weight loss","volume":"124","author":"Secher","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.ceca.2014.08.006","article-title":"Endoplasmic reticulum stress in insulin resistance and diabetes","volume":"56","author":"DeJesus","year":"2014","journal-title":"Cell Calcium"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.ceca.2013.05.007","article-title":"Calcium-dependent protein folding in amyotrophic lateral sclerosis","volume":"54","author":"Prell","year":"2013","journal-title":"Cell Calcium"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1038\/nature09968","article-title":"Aberrant lipid metabolism disrupts calcium homeostasis causing liver endoplasmic reticulum stress in obesity","volume":"473","author":"Fu","year":"2011","journal-title":"Nature"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1002\/glia.24082","article-title":"The role of endoplasmic reticulum stress in astrocytes","volume":"70","author":"Sims","year":"2022","journal-title":"GLIA"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.cmet.2017.05.015","article-title":"Microglial Inflammatory Signaling Orchestrates the Hypothalamic Immune Response to Dietary Excess and Mediates Obesity Susceptibility","volume":"26","author":"Valdearcos","year":"2017","journal-title":"Cell Metab."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"14556","DOI":"10.1038\/ncomms14556","article-title":"Sex differences in microglial CX3CR1 signalling determine obesity susceptibility in mice","volume":"8","author":"Dorfman","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1384","DOI":"10.1016\/j.neuroimage.2010.01.057","article-title":"The combined effects on neuronal activation and blood-brain barrier permeability of time and n-3 polyunsaturated fatty acids in mice, as measured in vivo using MEMRI","volume":"50","author":"Kuo","year":"2010","journal-title":"Neuroimage"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Song, J.E., Alves, T.C., Stutz, B., Sestan-Pesa, M., Kilian, N., Jin, S., Diano, S., Kibbey, R.G., and Horvath, T.L. (2021). Mitochondrial Fission Governed by Drp1 Regulates Exogenous Fatty Acid Usage and Storage in Hela Cells. Metabolites, 11.","DOI":"10.3390\/metabo11050322"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"e13086","DOI":"10.15252\/emmm.202013086","article-title":"Drug-like sphingolipid SH-BC-893 opposes ceramide-induced mitochondrial fission and corrects diet-induced obesity","volume":"13","author":"Jayashankar","year":"2021","journal-title":"EMBO Mol. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1016\/j.cell.2016.02.010","article-title":"UCP2 Regulates Mitochondrial Fission and Ventromedial Nucleus Control of Glucose Responsiveness","volume":"164","author":"Toda","year":"2016","journal-title":"Cell"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/j.cmet.2013.03.002","article-title":"Mitochondrial dynamics in the regulation of nutrient utilization and energy expenditure","volume":"17","author":"Liesa","year":"2013","journal-title":"Cell Metab."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.celrep.2018.09.034","article-title":"Mild Impairment of Mitochondrial OXPHOS Promotes Fatty Acid Utilization in POMC Neurons and Improves Glucose Homeostasis in Obesity","volume":"25","author":"Timper","year":"2018","journal-title":"Cell Rep."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Wicinski, M., Socha, M., Malinowski, B., Wodkiewicz, E., Walczak, M., Gorski, K., Slupski, M., and Pawlak-Osinska, K. (2019). Liraglutide and its Neuroprotective Properties-Focus on Possible Biochemical Mechanisms in Alzheimer\u2019s Disease and Cerebral Ischemic Events. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20051050"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1097\/FJC.0000000000000087","article-title":"GLP-1 agonists inhibit ox-LDL uptake in macrophages by activating protein kinase A","volume":"64","author":"Dai","year":"2014","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2709","DOI":"10.2337\/db12-1689","article-title":"FAT\/CD36: A major regulator of neuronal fatty acid sensing and energy homeostasis in rats and mice","volume":"62","author":"Musatov","year":"2013","journal-title":"Diabetes"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Urso, C.J., and Zhou, H. (2021). Role of CD36 in Palmitic Acid Lipotoxicity in Neuro-2a Neuroblastoma Cells. Biomolecules., 11.","DOI":"10.3390\/biom11111567"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Zeeshan, H.M., Lee, G.H., Kim, H.R., and Chae, H.J. (2016). Endoplasmic Reticulum Stress and Associated ROS. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17030327"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.mam.2018.03.002","article-title":"ROS signaling and ER stress in cardiovascular disease","volume":"63","author":"Ochoa","year":"2018","journal-title":"Mol. Asp. Med."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1172\/JCI43134","article-title":"Remodeling of the arcuate nucleus energy-balance circuit is inhibited in obese mice","volume":"122","author":"McNay","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Moraes, J.C., Coope, A., Morari, J., Cintra, D.E., Roman, E.A., Pauli, J.R., Romanatto, T., Carvalheira, J.B., Oliveira, A.L., and Saad, M.J. (2009). High-fat diet induces apoptosis of hypothalamic neurons. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0005045"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"4963","DOI":"10.1074\/jbc.M608283200","article-title":"Constitutive traffic of melanocortin-4 receptor in Neuro2A cells and immortalized hypothalamic neurons","volume":"282","author":"Mohammad","year":"2007","journal-title":"J. Biol. Chem."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/1\/629\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:56:05Z","timestamp":1760147765000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/1\/629"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,30]]},"references-count":80,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,1]]}},"alternative-id":["ijms24010629"],"URL":"https:\/\/doi.org\/10.3390\/ijms24010629","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,30]]}}}