{"doi":"10.20944/preprints202306.0482.v1","title":"A Ketogenic Diet in Combination With Gemcitabine Mitigates Pancreatic Cancer Associated Cachexia in Male and Female KPC Mice","abstract":"Cancer associated cachexia (CAC) is a critical contributor to pancreatic ductal adenocarcinoma (PDAC) mortality. Thus, there is an urgent need for new strategies to mitigate PDAC-associated cachexia; and the exploration of dietary interventions is a critical component. We previously observed that a ketogenic diet (KD) combined with gemcitabine enhances overall survival in the autochthonous LSL-KrasG12D/+; LSL-Trp53 R172H/+; Pdx1-Cre (KPC) mouse model. In this study, we investigated the effect and cellular mechanisms of a KD in combination with gemcitabine on the maintenance of skeletal muscle mass in KPC mice. For this purpose, male and female pancreatic tumor-bearing KPC mice were allocated to a control diet (CD), a KD, a CD + gemcitabine (CG), or a KD + gemcitabine (KG) group. We observed that a KD or a KG mitigated muscle strength decline over time and presented higher gastrocnemius weights compared CD-fed mice. Mechanistically, we observed sex-dependent effects of KG treatment, including the inhibition of autophagy, and increased phosphorylation levels of eIF2α in KG-treated KPC mice when compared to CG-treated mice. Our data suggests that a KG results in preservation of skeletal muscle mass. Additional research is warranted to explore whether this diet-treatment combination can be clinically effective in combating CAC in PDAC patients.","journal":"Preprints.org","year":2023,"id":392430,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9529,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":699479,"name":"Suraj Pathak","orcid":"0000-0002-0009-1972","position":1,"is_corresponding":false},{"id":1165987,"name":"Cecilia Rodríguez Lanzi","orcid":"0000-0002-4878-0427","position":2,"is_corresponding":false},{"id":693412,"name":"Brian V. Hong","orcid":"0000-0001-7080-2744","position":3,"is_corresponding":false},{"id":935890,"name":"Rasheed Sule","orcid":"0000-0001-9759-0809","position":4,"is_corresponding":false},{"id":1165988,"name":"Ryman Crone","orcid":"0009-0007-8373-9095","position":5,"is_corresponding":false},{"id":1165989,"name":"Fangyi Wang","orcid":"0000-0003-2687-9909","position":6,"is_corresponding":false},{"id":930623,"name":"Shuai Chen","orcid":"0000-0002-4016-8217","position":7,"is_corresponding":false},{"id":266250,"name":"Aldrin V. Gomes","orcid":"0000-0002-9819-3036","position":8,"is_corresponding":false},{"id":413822,"name":"Keith Baar","orcid":"0000-0001-9337-6186","position":9,"is_corresponding":false},{"id":752434,"name":"Gerardo G. Mackenzie","orcid":"0000-0002-6460-7165","position":10,"is_corresponding":false},{"id":1165986,"name":"Natalia E. Cortez","orcid":"0000-0002-1571-2188","position":0,"is_corresponding":true}],"reference_count":59,"raw_metadata":null,"created_at":"2026-07-19T01:18:56.730121Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}