Michael E Ponte, John C Prom, Pradeep Devkota, Sireesha Yerrathota, Mea Carradine, Larry Ha, E Matthew Morris, Andrew J Lutkewitte
{"title":"The Impact of a Western Diet with High Salt on Metabolic Outcomes in Male C57bl/6J Mice.","authors":"Michael E Ponte, John C Prom, Pradeep Devkota, Sireesha Yerrathota, Mea Carradine, Larry Ha, E Matthew Morris, Andrew J Lutkewitte","doi":"10.1016/j.jnphys.2026.100025","DOIUrl":"https://doi.org/10.1016/j.jnphys.2026.100025","url":null,"abstract":"<p><p>The typical Western diet drives obesity and metabolic disease through high intake of saturated fats, sugars, and salt. However, common rodent diet models (High-Fat, High-Sucrose, or HFHS) are often low in salt. We aimed to investigate the chronic metabolic outcomes by feeding C57BL/6J male mice a Low-Fat Diet (LFD), HFHS, or a High-Salt HFHS diet (HFHS + 3% Salt) for 16 weeks, monitoring body composition, glucose tolerance, and tissue function. The HFHS group exhibited the most significant weight gain over 16 weeks. Surprisingly, the addition of salt mitigated hepatic lipid accumulation; the HFHS + Salt group had liver weights and triglyceride levels like the LFD group, while the HFHS group showed elevated levels. However, the high-salt component exacerbated other issues. The HFHS + Salt fed mice displayed the highest degree of glucose intolerance, followed by the HFHS group. Furthermore, gonadal adipose tissue was significantly larger in the HFHS + Salt mice, suggesting the salt component specifically drives expansion in this depot. Paradoxically, salt also appeared to dampen the expression of inflammation-related genes (<i>Ccl2</i> and <i>Adgre1</i>) in adipose tissue compared to HFHS alone. In terms of liver mitochondrial function, HFHS increased oxygen consumption, but the addition of salt appeared to dampen this effect. In conclusion, the dietary salt component within a high-fat/high-sucrose diet has differential and complex effects. While it reduced overall weight gain and hepatic steatosis, it significantly impaired glucose tolerance and specifically worsened gonadal adipose expansion, underscoring the need to better model the full complexity of the Western Diet.</p>","PeriodicalId":524249,"journal":{"name":"The journal of nutritional physiology","volume":"6 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657138/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149187817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}