{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T16:38:44Z","timestamp":1775061524609,"version":"3.50.1"},"reference-count":64,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"JSPS KAKENHI","award":["JP25560374"],"award-info":[{"award-number":["JP25560374"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Leptin receptor-deficient WBN\/Kob-Lepr fa\/fa (WKF) rats spontaneously developed chronic pancreatitis and severe diabetes with obesity. Here, we evaluated the protective effects of diet restriction and chronic exercise against fatty and inflammation-induced disorders in the vulnerable pancreas of WKF rats. Six-week-old male WKF rats were divided into obese control (Obese), diet restriction (DR), and diet restriction + exercise (DR + Ex) groups. WBN\/Kob (WK) rats were used as lean control (Lean). Lean and Obese rats had free access to food, whereas food intake for DR and DR + Ex rats was restricted to 69% and 70% of the Obese level, respectively. The DR + Ex rats exercised voluntarily on a wheel ergometer daily. After six weeks, the rats were euthanized with isoflurane after overnight fasting. Obese rats exhibited diabetes, early stages of pancreatitis, diffuse pancreatic islets, and ultrastructural deteriorations in the pancreatic acinar cells, such as lipid droplet accumulation and swollen mitochondria with destroyed cristae, whereas Lean rats did not. DR rats exhibited improved glucose metabolism and serum triglyceride levels, effectively preventing inflammatory processes in the pancreas. However, DR rats exhibited no amelioration in the serum free fatty acids (FFAs) level, and limited improvements in ultrastructural deterioration in pancreatic cells. Chronic exercise combined with diet restriction (DR + Ex) improved serum FFA levels, the boundary of pancreatic islets, and the ultrastructure of subcellular organelles. These results demonstrate that diet restriction suppresses pancreatic inflammation, and further additional exercise effectively improves fatty pancreas-related deterioration by skeletal muscle activity linked through the circulatory network in WKF rats.<\/jats:p>","DOI":"10.3390\/ijms27073210","type":"journal-article","created":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T14:59:01Z","timestamp":1775055541000},"page":"3210","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Non-Pharmaceutical Interventions Based on Diet Restriction and Exercise Improve Morphology and Function of Fatty Pancreas in Male WBN\/Kob-Lepr (Fa\/Fa) Rats"],"prefix":"10.3390","volume":"27","author":[{"given":"Kumiko","family":"Minato","sequence":"first","affiliation":[{"name":"Department of Molecular Physiology, Division of Physical Fitness, The Jikei University School of Medicine, Chofu 182-8570, Japan"},{"name":"Human Ecology, Graduate School, Wayo Women\u2019s University, Ichikawa 272-8533, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoko","family":"Shiroya","sequence":"additional","affiliation":[{"name":"Department of Molecular Physiology, Division of Physical Fitness, The Jikei University School of Medicine, Chofu 182-8570, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7509-6009","authenticated-orcid":false,"given":"Yuka","family":"Kurosaka","sequence":"additional","affiliation":[{"name":"Health and Sports Science, Juntendo University, Inzai 270-1695, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideki","family":"Yamauchi","sequence":"additional","affiliation":[{"name":"Department of Molecular Physiology, Division of Physical Fitness, The Jikei University School of Medicine, Chofu 182-8570, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shigeru","family":"Takemori","sequence":"additional","affiliation":[{"name":"Department of Molecular Physiology, Division of Physical Fitness, The Jikei University School of Medicine, Chofu 182-8570, Japan"},{"name":"Department of Molecular Physiology, The Jikei University School of Medicine, Tokyo 105-8461, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1161\/ATVBAHA.114.303034","article-title":"Ectopic fat, insulin resistance, and nonalcoholic fatty liver disease: Implications for cardiovascular disease","volume":"34","author":"Byrne","year":"2014","journal-title":"Arterioscler. 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