Effects of Body Mass Regain After Caloric Restriction on Markers of Liver Injury in a Model of Metabolic Syndrome

Metabolic syndrome (MetS) affects 1 in 3 adults in the United States and is defined as the presence of three or more of the following conditions: (1) abdominal obesity, (2) dyslipidemia, (3) glucose intolerance with or without insulin resistance, (4) hypertension, and (5) prothrombotic and proinflammatory condition. MetS can lead to the development of metabolic dysfunction-associated fatty liver disease (MAFLD) and hepatic injury due to an imbalance in redox signaling. Caloric restriction (CR) is a common intervention to attenuate MAFLD and fibrosis but has a high failure rate among obese individuals. To test the hypothesis that CR reduces oxidative injury associated with MetS, 11-week-old Otsuka Long Evan Tokushima Fatty (OLETF) and lean strain control Long Evans Tokushima Otsuka (LETO) rats were fed a 50% CR diet (compared to their control) for 2 weeks and assigned to four groups: 1) LETO CR Ctrl (n=14), 2) LETO CR (n=12), 3) OLETF CR Ctrl (n=14), and 4) OLETF CR (n=14). After the CR period, 7 animals from each group were then refed at pre-CR levels for 2 weeks and assigned to four groups: 1) LETO Ctrl (n=7), 2) LETO body mass regain (BMR) (n=7), 3) OLETF Ctrl (n=7), and 4) OLETF BMR (n=7). To assess oxidative injury, hepatic 4-hydroxynonenal (4-HNE), a product of lipid peroxidation, and 3-nitrotyrosine (3NT), a marker of protein oxidation were measured. We expect CR to reduce these levels in the liver and for the levels to return to pre-CR levels following partial body mass regain. These data have the potential to highlight the detriments of BM regain on liver health. EEJ: GRISE Bio-I-STeP 5T32GM141862-02 and AHA 23DIVSUP1066372.MC: UC MEXUS-CONACY T440553 and National Institute on Minority Health and Health Disparities 9T37-MD001480. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.