{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T13:54:04Z","timestamp":1791381244700,"version":"4.3.3"},"reference-count":72,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,4,1]],"date-time":"2023-04-01T00:00:00Z","timestamp":1680307200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01CA136493"],"award-info":[{"award-number":["R01CA136493"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UL1TR000039"],"award-info":[{"award-number":["UL1TR000039"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"UAMS Translational Research Institute","doi-asserted-by":"publisher","award":["R01CA136493"],"award-info":[{"award-number":["R01CA136493"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"UAMS Translational Research Institute","doi-asserted-by":"publisher","award":["UL1TR000039"],"award-info":[{"award-number":["UL1TR000039"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Malic Enzyme 1 (ME1) supports lipogenesis, cholesterol synthesis, and cellular redox potential by catalyzing the decarboxylation of L-malate to pyruvate, and the concomitant reduction of NADP to NADPH. We examined the contribution of ME1 to the development of obesity by provision of an obesogenic diet to C57BL\/6 wild type (WT) and MOD-1 (lack ME1 protein) female mice. Adiposity, serum hormone levels, and adipose, mammary gland, liver, and small intestine gene expression patterns were compared between experimental groups after 10 weeks on a diet. Relative to WT female mice, MOD-1 female mice exhibited lower body weights and less adiposity; decreased concentrations of insulin, leptin, and estrogen; higher concentrations of adiponectin and progesterone; smaller-sized mammary gland adipocytes; and reduced hepatosteatosis. MOD-1 mice had diminished expression of Lep gene in abdominal fat; Lep, Pparg, Klf9, and Acaca genes in mammary glands; Pparg and Cdkn1a genes in liver; and Tlr9 and Ffar3 genes in the small intestine. By contrast, liver expression of Cdkn2a and Lepr genes was augmented in MOD-1, relative to WT mice. Results document an integrative role for ME1 in development of female obesity, suggest novel linkages with specific pathways\/genes, and further support the therapeutic targeting of ME1 for obesity, diabetes, and fatty liver disease.<\/jats:p>","DOI":"10.3390\/ijms24076613","type":"journal-article","created":{"date-parts":[[2023,4,3]],"date-time":"2023-04-03T03:08:31Z","timestamp":1680491311000},"page":"6613","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Malic Enzyme 1 (ME1) Promotes Adiposity and Hepatic Steatosis and Induces Circulating Insulin and Leptin in Obese Female Mice"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6842-7754","authenticated-orcid":false,"given":"Frank A.","family":"Simmen","sequence":"first","affiliation":[{"name":"Department of Physiology & Cell Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA"},{"name":"The Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John Mark P.","family":"Pabona","sequence":"additional","affiliation":[{"name":"Department of Physiology & Cell Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Al-Dwairi","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biochemistry, College of Medicine, Jordan University of Science and Technology, Irbid 22110, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iad","family":"Alhallak","sequence":"additional","affiliation":[{"name":"Department of Physiology & Cell Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Theresa E.","family":"Montales","sequence":"additional","affiliation":[{"name":"Department of Physiology & Cell Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosalia C. M.","family":"Simmen","sequence":"additional","affiliation":[{"name":"Department of Physiology & Cell Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA"},{"name":"The Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,1]]},"reference":[{"key":"ref_1","unstructured":"NCD Risk Factor Collaboration (NCD-RisC) (2017). Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: A pooled analysis of 2416 population-based measurement studies in 128\u00b79 million children, adolescents, and adults. Lancet, 390, 2627\u20132642."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1038\/s41576-021-00414-z","article-title":"The genetics of obesity: From discovery to biology","volume":"23","author":"Loos","year":"2021","journal-title":"Nat. Rev. Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1038\/382250a0","article-title":"Role of leptin in the neuroendocrine response to fasting","volume":"382","author":"Ahima","year":"1996","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Ke, W., Reed, J.N., Yang, C., Higgason, N., Rayyan, L., W\u00e4hlby, C., Carpenter, A.E., Civelek, M., and O\u2019Rourke, E.J. (2021). Genes in human obesity loci are causal obesity genes in C. elegans. PLOS Genet., 17.","DOI":"10.1371\/journal.pgen.1009736"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/ng.325","article-title":"Validation of candidate causal genes for obesity that affect shared metabolic pathways and networks","volume":"41","author":"Yang","year":"2009","journal-title":"Nat. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Al-Dwairi, A., Pabona, J.M.P., Simmen, R.C.M., and Simmen, F.A. (2012). Cytosolic malic enzyme 1 (ME1) mediates high fat diet-induced adiposity, endocrine profile, and gastrointestinal tract proliferation-associated biomarkers in male mice. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0046716"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Zhong, H., Beaulaurier, J., Lum, P.Y., Molony, C., Yang, X., MacNeil, D.J., Weingarth, D.T., Zhang, B., Greenawalt, D., and Dobrin, R. (2010). Liver and adipose expression associated SNPs are enriched for association to type 2 diabetes. PLoS Genet., 6.","DOI":"10.1371\/journal.pgen.1000932"},{"key":"ref_8","first-page":"46","article-title":"DECR1 and ME1 genotypes are associated with lipid composition traits in Duroc pigs","volume":"131","author":"Quintanilla","year":"2013","journal-title":"J. Anim. Breed. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1111\/jbg.12065","article-title":"Transcript level of the porcine ME1 gene is affected by SNP in its 3\u2019UTR, which is also associated with subcutaneous fat thickness","volume":"131","author":"Bartz","year":"2013","journal-title":"J. Anim. Breed. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"23219","DOI":"10.1038\/srep23219","article-title":"Identification of genes for controlling swine adipose deposition by integrating transcriptome, whole-genome resequencing, and quantitative trait loci data","volume":"6","author":"Xing","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"R77","DOI":"10.1530\/JME-20-0176","article-title":"Malic enzyme 1 (ME1) in the biology of cancer: It is not just intermediary metabolism","volume":"65","author":"Simmen","year":"2020","journal-title":"J. Mol. Endocrinol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1038\/oby.2003.30","article-title":"DNA microarray analysis of genes differentially expressed in diet-induced (cafeteria) obese rats","volume":"11","author":"Marti","year":"2003","journal-title":"Obes. Res."},{"key":"ref_13","first-page":"E1092","article-title":"Differential regulation of intestinal lipid metabolism-related genes in obesity-resistant A\/J vs. obesity-prone C57BL\/6J mice","volume":"291","author":"Kondo","year":"2006","journal-title":"Am. J. Physiol. Metab."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Desmarchelier, C., Dahlhoff, C., Keller, S., Sailer, M., Jahreis, G., and Daniel, H. (2012). C57Bl\/6 N mice on a western diet display reduced intestinal and hepatic cholesterol levels despite a plasma hypercholesterolemia. BMC Genom., 13.","DOI":"10.1186\/1471-2164-13-84"},{"key":"ref_15","first-page":"1833","article-title":"Free-choice high-fat diet alters circadian oscillation of energy intake in adolescent mice: Role of prefrontal cortex","volume":"56","author":"Stucchi","year":"2016","journal-title":"Eur. J. Nutr."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Russo, B., Menduni, M., Borboni, P., Picconi, F., and Frontoni, S. (2021). Autonomic Nervous System in Obesity and Insulin-Resistance-The Complex Interplay between Leptin and Central Nervous System. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22105187"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"10494","DOI":"10.1038\/ncomms10494","article-title":"Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels","volume":"7","author":"Carli","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2806","DOI":"10.2337\/db20-0070","article-title":"Genetic Studies of Leptin Concentrations Implicate Leptin in the Regulation of Early Adiposity","volume":"69","author":"Yaghootkar","year":"2020","journal-title":"Diabetes"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"596","DOI":"10.3389\/fonc.2019.00596","article-title":"Obesity and Breast Cancer: Role of Leptin","volume":"9","year":"2019","journal-title":"Front. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Buonaiuto, R., Napolitano, F., Parola, S., De Placido, P., Forestieri, V., Pecoraro, G., Servetto, A., Formisano, L., Formisano, P., and Giuliano, M. (2022). Insight on the Role of Leptin: A Bridge from Obesity to Breast Cancer. Biomolecules. iomolecules, 12.","DOI":"10.3390\/biom12101394"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"S\u0142abuszewska-J\u00f3\u017awiak, A., Lukaszuk, A., Janicka-Ko\u015bnik, M., Wdowiak, A., and Jakiel, G. (2022). Role of Leptin and Adiponectin in Endometrial Cancer. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23105307"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Socol, C.T., Chira, A., Martinez-Sanchez, M.A., Nu\u00f1ez-Sanchez, M.A., Maerescu, C.M., Mierlita, D., Rusu, A.V., Ruiz-Alcaraz, A.J., Trif, M., and Ramos-Molina, B. (2022). Leptin Signaling in Obesity and Colorectal Cancer. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23094713"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/S0021-9258(17)43697-0","article-title":"Cloning of cDNA sequences for murine malic enzyme and the identification of aberrantly large malic enzyme mRNA in MOD-1 null mice","volume":"259","author":"Sul","year":"1984","journal-title":"J. Biol. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4494","DOI":"10.1016\/S0021-9258(18)68953-7","article-title":"The molecular basis for a cytosolic malic enzyme null mutation. Malic enzyme mRNA from MOD-1 null mice contains an internal in-frame duplication that extends the coding sequence by 522 nucleotides","volume":"263","author":"Brown","year":"1988","journal-title":"J. Biol. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"RESEARCH0034","DOI":"10.1186\/gb-2002-3-7-research0034","article-title":"Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes","volume":"3","author":"Vandesompele","year":"2002","journal-title":"Genome Biol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Al-Dwairi, A., Brown, A.R., Pabona, J.M.P., Van, T.H., Hamdan, H., Mercado, C.P., Quick, C.M., Wight, P.A., Simmen, R.C.M., and Simmen, F.A. (2014). Enhanced gastrointestinal expression of cytosolic malic enzyme (ME1) induces intestinal and liver lipogenic gene expression and intestinal cell proliferation in mice. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0113058"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"5740","DOI":"10.1210\/en.2006-0365","article-title":"Genistein affects adipose tissue deposition in a dose-dependent and gender-specific manner","volume":"147","author":"Penza","year":"2006","journal-title":"Endocrinology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"29","DOI":"10.3892\/ol.2010.202","article-title":"Effects of high-isoflavone soy diet vs. casein protein diet and obesity on DMBA-induced mammary tumor development","volume":"2","author":"Hakkak","year":"2010","journal-title":"Oncol. Lett."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1093\/toxsci\/kft331","article-title":"Genistein exposure during the early postnatal period favors the development of obesity in female, but not male rats","volume":"138","author":"Strakovsky","year":"2013","journal-title":"Toxicol. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1007\/s00394-014-0786-9","article-title":"Soy and the soy isoflavone genistein promote adipose tissue development in male mice on a low-fat diet","volume":"54","author":"Zanella","year":"2014","journal-title":"Eur. J. Nutr."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Marraudino, M., Ponti, G., Moussu, C., Farinetti, A., Macchi, E., Accornero, P., Gotti, S., Collado, P., Keller, M., and Panzica, G. (2021). Early Postnatal Genistein Administration Affects Mice Metabolism and Reproduction in a Sexually Dimorphic Way. Metabolites, 11.","DOI":"10.3390\/metabo11070449"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2011","DOI":"10.2147\/DMSO.S216312","article-title":"Genistein diet improves body weight, serum glucose and triglyceride levels in both male and female ob\/ob mice","volume":"12","author":"Rockwood","year":"2019","journal-title":"Diabetes, Metab. Syndr. Obesity Targets Ther."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1111\/j.1463-1326.2011.01488.x","article-title":"Oestrogen alters adipocyte biology and protects female mice from adipocyte inflammation and insulin resistance","volume":"14","author":"Stubbins","year":"2011","journal-title":"Diabetes, Obes. Metab."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4447","DOI":"10.1210\/en.2014-1342","article-title":"Estradiol prevents fat accumulation and overcomes leptin resistance in female high-fat diet mice","volume":"155","author":"Litwak","year":"2014","journal-title":"Endocrinology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1111\/j.1600-0463.2005.apm_113502.x","article-title":"Estrogenic agonism and antagonism of the soy isoflavone genistein in uterus, bone and lymphopoiesis in mice","volume":"113","author":"Erlandsson","year":"2005","journal-title":"Apmis"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1093\/toxsci\/kfm036","article-title":"Genistein accumulates in body depots and is mobilized during fasting, reaching estrogenic levels in serum that counter the hormonal actions of estradiol and organochlorines","volume":"97","author":"Penza","year":"2007","journal-title":"Toxicol. Sci."},{"key":"ref_37","first-page":"265","article-title":"Positional and temporal regulation of lipogenic gene expression in mouse liver","volume":"3","author":"Cochary","year":"1993","journal-title":"Gene Expr."},{"key":"ref_38","first-page":"1361","article-title":"Insulin regulation of malic enzyme gene expression in rat liver: Evidence for nuclear proteins that bind to two putative insulin response elements","volume":"8","author":"Garcia","year":"1994","journal-title":"Mol. Endocrinol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1778","DOI":"10.1210\/mend.12.11.0199","article-title":"A phorbol ester-insensitive AP-1 motif mediates the stimulatory effect of insulin on rat malic enzyme gene transcription","volume":"12","author":"Streeper","year":"1998","journal-title":"Mol. Endocrinol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Luong, X.G., Stevens, S.K., Jekle, A., Lin, T.-I., Gupta, K., Misner, D., Chanda, S., Mukherjee, S., Williams, C., and Stoycheva, A. (2020). Regulation of gene transcription by thyroid hormone receptor \u03b2 agonists in clinical development for the treatment of non-alcoholic steatohepatitis (NASH). PLoS ONE, 15.","DOI":"10.1101\/2020.09.25.312934"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.cca.2012.12.007","article-title":"Role of leptin and adiponectin in insulin resistance","volume":"417","author":"Yadav","year":"2013","journal-title":"Clin. Chim. Acta"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1502","DOI":"10.1210\/endo.143.4.8715","article-title":"Exclusive action of transmembrane TNF alpha in adipose tissue leads to reduced adipose mass and local but not systemic insulin resistance","volume":"143","author":"Xu","year":"2002","journal-title":"Endocrinology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1111\/j.1749-6632.1999.tb07790.x","article-title":"Insulin signaling and action in fat cells: Associations with insulin resistance and type 2 diabetes","volume":"892","author":"Smith","year":"1999","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"S10","DOI":"10.1016\/j.amjmed.2006.01.009","article-title":"Etiology of insulin resistance","volume":"119","author":"Petersen","year":"2006","journal-title":"Am. J. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1080\/10408363.2019.1699498","article-title":"Acetylation and insulin resistance: A focus on metabolic and mitogenic cascades of insulin signaling","volume":"57","author":"Emamgholipour","year":"2020","journal-title":"Crit. Rev. Clin. Lab. Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"bvab010","DOI":"10.1210\/jendso\/bvab010","article-title":"Homeostatic Regulation of Estrus Cycle of Young Female Mice on Western Diet","volume":"5","author":"Chaparro","year":"2021","journal-title":"J. Endocr. Soc."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3820","DOI":"10.1096\/fj.201902289R","article-title":"Malic enzyme 1 is important for uterine decidualization in response to progesterone\/cAMP\/PKA\/HB-EGF pathway","volume":"34","author":"Yu","year":"2020","journal-title":"FASEB J."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"102","DOI":"10.3389\/fendo.2017.00102","article-title":"The Role of Peroxisome Proliferator-Activated Receptor Gamma (PPARG) in Adipogenesis: Applying Knowledge from the Fish Aquaculture Industry to Biomedical Research","volume":"8","author":"Wafer","year":"2017","journal-title":"Front. Endocrinol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1038\/cdd.2010.100","article-title":"Kr\u00fcppel-like factor KLF9 regulates PPAR\u03b3 transactivation at the middle stage of adipogenesis","volume":"18","author":"Pei","year":"2010","journal-title":"Cell Death Differ."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1530\/JME-21-0100","article-title":"Breast adipose regulation of premenopausal breast epithelial phenotype involves interleukin 10","volume":"67","author":"Alhallak","year":"2021","journal-title":"J. Mol. Endocrinol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/s00018-022-04629-z","article-title":"Hepatocyte PPAR\u03b3 contributes to the progression of non-alcoholic steatohepatitis in male and female obese mice","volume":"80","author":"Lee","year":"2023","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.livres.2018.12.001","article-title":"Hepatic lipid homeostasis by peroxisome proliferator-activated receptor gamma 2","volume":"2","author":"Lee","year":"2018","journal-title":"Liver Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"101412","DOI":"10.1016\/j.redox.2019.101412","article-title":"Hepatocyte-specific Nrf2 deficiency mitigates high-fat diet-induced hepatic steatosis: Involvement of reduced PPAR\u03b3 expression","volume":"30","author":"Li","year":"2019","journal-title":"Redox Biol."},{"key":"ref_54","first-page":"340731","article-title":"Hepatic gene expression profiling in Nrf2 knockout mice after long-term high-fat diet-induced obesity","volume":"2013","author":"Chartoumpekis","year":"2013","journal-title":"xidative Med. Cell. Longev."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1007\/s12020-009-9224-9","article-title":"Diet-induced obesity is associated with hyperleptinemia, hyperinsulinemia, hepatic steatosis, and glomerulopathy in C57Bl\/6J mice","volume":"36","author":"Hoffler","year":"2009","journal-title":"Endocrine"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1530\/JOE-16-0142","article-title":"Metformin increases hepatic leptin receptor and decreases steatosis in mice","volume":"230","author":"Tang","year":"2016","journal-title":"J. Endocrinol."},{"key":"ref_57","first-page":"S94","article-title":"Assessment of common and differentially expressed proteins between diabetes mellitus and fatty liver disease: A network analysis","volume":"14","author":"Saki","year":"2021","journal-title":"Gastroenterol. Hepatol. Bed Bench."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1101\/gad.332643.119","article-title":"The senotherapeutic drug ABT-737 disrupts aberrant p21 expression to restore liver regeneration in adult mice","volume":"34","author":"Ritschka","year":"2020","journal-title":"Genes Dev."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e21230","DOI":"10.1096\/fj.202000683R","article-title":"CDKN2A deregulation in fatty liver disease and its accelerative role in the process of lipogenesis","volume":"35","author":"Zhang","year":"2021","journal-title":"FASEB J."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1002\/jcp.22830","article-title":"Induction of Paneth cell degranulation by orally administered Toll-like receptor ligands","volume":"227","author":"Rumio","year":"2011","journal-title":"J. Cell. Physiol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1002\/jemt.22831","article-title":"Three months of Western diet induces small intestinal mucosa alteration in TLR KO mice","volume":"80","author":"Sardi","year":"2017","journal-title":"Microsc. Res. Tech."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"3552","DOI":"10.1210\/en.2013-1142","article-title":"Offermanns S, Schwartz TW. GPR41\/FFAR3 and GPR43\/FFAR2 as cosensors for short-chain fatty acids in enteroendocrine cells vs FFAR3 in enteric neurons and FFAR2 in enteric leukocytes","volume":"154","author":"Pedersen","year":"2013","journal-title":"Endocrinology"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1177\/2042018810381066","article-title":"Free fatty acid receptors: Emerging targets for treatment of diabetes and its complications","volume":"1","author":"Kennedy","year":"2010","journal-title":"Ther. Adv. Endocrinol. Metab."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1073\/pnas.2637002100","article-title":"Short-chain fatty acids stimulate leptin production in adipocytes through the G protein-coupled receptor GPR41","volume":"101","author":"Xiong","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2381","DOI":"10.1016\/j.febslet.2010.04.027","article-title":"Roles of GPR41 and GPR43 in leptin secretory responses of murine adipocytes to short chain fatty acids","volume":"584","author":"Zaibi","year":"2010","journal-title":"FEBS Lett."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1017\/S0029665114001657","article-title":"Control of appetite and energy intake by SCFA: What are the potential underlying mechanisms?","volume":"74","author":"Chambers","year":"2015","journal-title":"Proc. Nutr. Soc."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"101350","DOI":"10.1016\/j.molmet.2021.101350","article-title":"Vagal neuron expression of the microbiota-derived metabolite receptor, free fatty acid receptor (FFAR3), is necessary for normal feeding behavior","volume":"54","author":"Cook","year":"2021","journal-title":"Mol. Metab."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1038\/s42255-020-00330-2","article-title":"NADPH levels affect cellular epigenetic state by inhibiting HDAC3-Ncor complex","volume":"3","author":"Li","year":"2021","journal-title":"Nat. Metab."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/j.bmcl.2005.10.065","article-title":"In silico design and synthesis of piperazine-1-pyrrolidine-2,5-dione scaffold-based novel malic enzyme inhibitors","volume":"16","author":"Zhang","year":"2006","journal-title":"Bioorganic Med. Chem. Lett."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.1021\/acs.biochem.2c00123","article-title":"Discovery and Characterization of a Novel Allosteric Small-Molecule Inhibitor of NADP+-Dependent Malic Enzyme 1","volume":"61","author":"Yoshida","year":"2022","journal-title":"Biochemistry"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2102","DOI":"10.1093\/carcin\/bgu106","article-title":"Maternal metabolic perturbations elicited by high-fat diet promote Wnt-1-induced mammary tumor risk in adult female offspring via long-term effects on mammary and systemic phenotypes","volume":"35","author":"Montales","year":"2014","journal-title":"Carcinogenesis"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"BBrown, A.R., Alhallak, I., Simmen, R.C.M., Melnyk, S.B., Heard-Lipsmeyer, M.E., Montales, M.T.E., Habenicht, D., Van, T.T., and Simmen, F.A. (2022). Kr\u00fcppel-like Factor 9 (KLF9) Suppresses Hepatocellular Carcinoma (HCC)-Promoting Oxidative Stress and Inflammation in Mice Fed High-Fat Diet. Cancers, 14.","DOI":"10.3390\/cancers14071737"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/7\/6613\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:08:13Z","timestamp":1760123293000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/7\/6613"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,1]]},"references-count":72,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["ijms24076613"],"URL":"https:\/\/doi.org\/10.3390\/ijms24076613","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,1]]}}}