{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T11:00:39Z","timestamp":1790593239463,"version":"4.1.0"},"reference-count":21,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2023YFC2706300"],"award-info":[{"award-number":["2023YFC2706300"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Glycogen storage disease type IIIa (GSDIIIa) causes progressive cardiomyopathy, and current high\u2010fat dietary strategies lack consensus regarding long\u2010term cardiovascular safety. We evaluated the efficacy and safety of high\u2010protein versus high\u2010fat diets in a novel cardiac\u2010specific\n                    <jats:italic>AGL<\/jats:italic>\n                    knockout (CKO;\n                    <jats:italic>AGL<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>flox\/flox<\/jats:italic>\n                    <\/jats:sup>\n                    \/\n                    <jats:italic>MHC\u2010Cre<\/jats:italic>\n                    ) mouse model to specifically assess isolated cardiac responses. CKO mice were randomized at weaning to High\u2010Protein (HPD), High\u2010Protein High\u2010Fat (HPHFD), or Low\u2010Protein (LPD) diets, with approximate protein\/fat\/carbohydrate distributions of 40%\/4%\/50%, 40%\/50%\/10%, and 10%\/4%\/80%, respectively; CKO mice on normal diet (ND) and\n                    <jats:italic>AGL<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>flox\/flox<\/jats:italic>\n                    <\/jats:sup>\n                    mice served as controls. Cardiac phenotypes and hepatic gluconeogenic enzymes were evaluated longitudinally up to 24\u2009weeks. CKO\u2010ND mice developed progressive cardiomyopathy with elevated myocardial glycogen at 24\u2009weeks (32.01\u2009\u00b1\u20093.22 vs. 5.90\u2009\u00b1\u20092.21\u2009mg\/g in controls,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001), reduced left ventricular ejection fraction, and elevated serum creatine kinase. Both HPD and HPHFD significantly reduced myocardial glycogen burden (12.82\u2009\u00b1\u20093.58 and 15.07\u2009\u00b1\u20094.40\u2009mg\/g,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001), restored systolic function, and normalized hypertrophy. However, HPHFD induced distinct hyperlipidemia, whereas HPD maintained a stable lipid profile. Furthermore, therapeutic benefits in high\u2010protein groups were associated with upregulated hepatic rate\u2010limiting gluconeogenic enzymes (FBP2, PCK1). In this cardiac\u2010specific\n                    <jats:italic>AGL<\/jats:italic>\n                    knockout model, a high\u2010protein, non\u2010high\u2010fat diet attenuated cardiac glycogen accumulation and systolic dysfunction without the hyperlipidemia observed with the high\u2010fat regimen. These preclinical findings support further evaluation of high\u2010protein dietary strategies for GSDIIIa cardiomyopathy and suggest a possible liver\u2010heart metabolic axis involving hepatic gluconeogenesis.\n                  <\/jats:p>","DOI":"10.1002\/jimd.70237","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T23:47:34Z","timestamp":1786405654000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["High\u2010Protein Diet Ameliorates Cardiomyopathy in a Cardiac\u2010Specific\n                    <scp>\n                      <i>AGL<\/i>\n                    <\/scp>\n                    Knockout Mouse Model: Association With Upregulated Hepatic Gluconeogenesis"],"prefix":"10.1002","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2306-0298","authenticated-orcid":false,"given":"Caiqi","family":"Du","sequence":"first","affiliation":[{"name":"Department of Pediatrics Tongji Children's Hospital, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology  Wuhan China"},{"name":"Hubei Key Laboratory of Pediatric Genetic Metabolic and Endocrine Rare Diseases  Wuhan China"},{"name":"Hubei Provincial Clinical Research Center for Child Growth, Development, and Metabolic Diseases  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9149-2382","authenticated-orcid":false,"given":"Hao","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Tongji Children's Hospital, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology  Wuhan China"},{"name":"Hubei Key Laboratory of Pediatric Genetic Metabolic and Endocrine Rare Diseases  Wuhan China"},{"name":"Hubei Provincial Clinical Research Center for Child Growth, Development, and Metabolic Diseases  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Tongji Children's Hospital, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology  Wuhan China"},{"name":"Hubei Key Laboratory of Pediatric Genetic Metabolic and Endocrine Rare Diseases  Wuhan China"},{"name":"Hubei Provincial Clinical Research Center for Child Growth, Development, and Metabolic Diseases  Wuhan China"},{"name":"Department of Pediatrics Jiujiang Maternal and Child Health Hospital  Jiujiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1125-6827","authenticated-orcid":false,"given":"Sisi","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Tongji Children's Hospital, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology  Wuhan China"},{"name":"Hubei Key Laboratory of Pediatric Genetic Metabolic and Endocrine Rare Diseases  Wuhan China"},{"name":"Hubei Provincial Clinical Research Center for Child Growth, Development, and Metabolic Diseases  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9715-9231","authenticated-orcid":false,"given":"Haotian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Tongji Children's Hospital, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology  Wuhan China"},{"name":"Hubei Key Laboratory of Pediatric Genetic Metabolic and Endocrine Rare Diseases  Wuhan China"},{"name":"Hubei Provincial Clinical Research Center for Child Growth, Development, and Metabolic Diseases  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boda","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Tongji Children's Hospital, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology  Wuhan China"},{"name":"Hubei Key Laboratory of Pediatric Genetic Metabolic and Endocrine Rare Diseases  Wuhan China"},{"name":"Hubei Provincial Clinical Research Center for Child Growth, Development, and Metabolic Diseases  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6005-0905","authenticated-orcid":false,"given":"Cai","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Tongji Children's Hospital, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology  Wuhan China"},{"name":"Hubei Key Laboratory of Pediatric Genetic Metabolic and Endocrine Rare Diseases  Wuhan China"},{"name":"Hubei Provincial Clinical Research Center for Child Growth, Development, and Metabolic Diseases  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5741-4867","authenticated-orcid":false,"given":"Juan","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Tongji Children's Hospital, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology  Wuhan China"},{"name":"Hubei Key Laboratory of Pediatric Genetic Metabolic and Endocrine Rare Diseases  Wuhan China"},{"name":"Hubei Provincial Clinical Research Center for Child Growth, Development, and Metabolic Diseases  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2889-0910","authenticated-orcid":false,"given":"Wenjun","family":"Long","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Tongji Children's Hospital, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology  Wuhan China"},{"name":"Hubei Key Laboratory of Pediatric Genetic Metabolic and Endocrine Rare Diseases  Wuhan China"},{"name":"Hubei Provincial Clinical Research Center for Child Growth, Development, and Metabolic Diseases  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3748-4817","authenticated-orcid":false,"given":"Xiaoping","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Tongji Children's Hospital, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology  Wuhan China"},{"name":"Hubei Key Laboratory of Pediatric Genetic Metabolic and Endocrine Rare Diseases  Wuhan China"},{"name":"Hubei Provincial Clinical Research Center for Child Growth, Development, and Metabolic Diseases  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9009-3284","authenticated-orcid":false,"given":"Yan","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Tongji Children's Hospital, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology  Wuhan China"},{"name":"Hubei Key Laboratory of Pediatric Genetic Metabolic and Endocrine Rare Diseases  Wuhan China"},{"name":"Hubei Provincial Clinical Research Center for Child Growth, Development, and Metabolic Diseases  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,10]]},"reference":[{"key":"e_1_2_12_2_1","first-page":"1993","volume-title":"Glycogen Storage Disease Type III. 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