{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T01:38:07Z","timestamp":1789090687010,"version":"build-2803163510"},"reference-count":48,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,11,18]],"date-time":"2024-11-18T00:00:00Z","timestamp":1731888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Veteran\u2019s Affairs","award":["VAMR I01BX003836 (NAP)"],"award-info":[{"award-number":["VAMR I01BX003836 (NAP)"]}]},{"name":"Department of Veteran\u2019s Affairs","award":["VA RCS IK6BX005387 (NAP)"],"award-info":[{"award-number":["VA RCS IK6BX005387 (NAP)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Obesity promotes metabolic diseases such as type 2 diabetes and cardiovascular disease. PKC\u03b4I is a serine\/threonine kinase which regulates cell growth, differentiation, and survival. Caspase-3 cleavage of PKC\u03b4I releases the C-terminal catalytic fragment (PKC\u03b4I_C), which promotes inflammation and apoptosis. We previously demonstrated an increase in PKC\u03b4I_C in human obese adipose tissue (AT) and adipocytes. Subsequently, we designed a small molecule drug called NP627 and demonstrated that NP627 specifically inhibited the release of PKC\u03b4I_C in vitro. Here, we evaluate the in vivo safety and efficacy of NP627 in a diet-induced obese (DIO) mouse model. The results demonstrate that NP627 treatment in DIO mice increased glucose uptake and inhibited the cleavage of PKC\u03b4I_C in the AT as well as in the kidney, spleen, and liver. Next, RNAseq analysis was performed on the AT from the NP627-treated DIO mice. The results show increases in ADIPOQ and CIDEC, upregulation of AMPK, PI3K-AKT, and insulin signaling pathways, while inflammatory pathways were decreased post-NP627 administration. Further, levels of lncRNAs associated with metabolic pathways were affected by NP627 treatment. In conclusion, the study demonstrates that NP627, a small-molecule inhibitor of PKC\u03b4I activity, is not toxic and that it improves the metabolic function of DIO mice in vivo.<\/jats:p>","DOI":"10.3390\/biology13110943","type":"journal-article","created":{"date-parts":[[2024,11,19]],"date-time":"2024-11-19T11:58:07Z","timestamp":1732017487000},"page":"943","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Small Molecule Inhibitor of Protein Kinase C DeltaI (PKC\u03b4I) Decreases Inflammatory Pathways and Gene Expression and Improves Metabolic Function in Diet-Induced Obese Mouse Model"],"prefix":"10.3390","volume":"13","author":[{"given":"Brenna","family":"Osborne","sequence":"first","affiliation":[{"name":"Research Service, James A. Haley Veteran\u2019s Hospital, 13000 Bruce B Downs Blvd, Tampa, FL 33612, USA"},{"name":"Department of Molecular Medicine, University of South Florida, Tampa, FL 33612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rekha S.","family":"Patel","sequence":"additional","affiliation":[{"name":"Research Service, James A. Haley Veteran\u2019s Hospital, 13000 Bruce B Downs Blvd, Tampa, FL 33612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4591-9286","authenticated-orcid":false,"given":"Meredith","family":"Krause-Hauch","sequence":"additional","affiliation":[{"name":"Research Service, James A. Haley Veteran\u2019s Hospital, 13000 Bruce B Downs Blvd, Tampa, FL 33612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4090-4680","authenticated-orcid":false,"given":"Ashley","family":"Lui","sequence":"additional","affiliation":[{"name":"Department of Molecular Oncology, Moffitt Cancer Center, Tampa, FL 33612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gitanjali","family":"Vidyarthi","sequence":"additional","affiliation":[{"name":"Research Service, James A. Haley Veteran\u2019s Hospital, 13000 Bruce B Downs Blvd, Tampa, FL 33612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4811-8596","authenticated-orcid":false,"given":"Niketa A.","family":"Patel","sequence":"additional","affiliation":[{"name":"Research Service, James A. Haley Veteran\u2019s Hospital, 13000 Bruce B Downs Blvd, Tampa, FL 33612, USA"},{"name":"Department of Molecular Medicine, University of South Florida, Tampa, FL 33612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,18]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2024). Obesity and Overweight, World Health Organization."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1038\/s41418-022-01062-4","article-title":"Cell death and inflammation during obesity: \u201cKnow my methods, WAT (son)\u201d","volume":"30","author":"Hildebrandt","year":"2023","journal-title":"Cell Death Differ."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Renovato-Martins, M., Moreira-Nunes, C., Atella, G.C., Barja-Fidalgo, C., and Moraes, J.A. (2020). Obese Adipose Tissue Secretion Induces Inflammation in Preadipocytes: Role of Toll-like Receptor-4. 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