Caloric Restriction Improves Hepatic Thyroid Hormone Signaling During Metabolic Syndrome

Thyroid hormone dysregulation has been associated with metabolic syndrome (MetS) risk factors: hypertension, atherogenic dyslipidemia, obesity, and glucose intolerance. Several pathways are regulated by thyroid hormones such as the insulin signaling pathway, lipid metabolism, and antioxidant production among others. Impairment of thyroid hormone production causes dysregulation of these pathways. Caloric restriction (CR) is a form of non-pharmaceutical approach that has been shown to ameliorate MetS cluster factor conditions. However, caloric restriction's effects on thyroid hormone signaling during MetS remains unclear. A cohort of 11-week-old Otsuka Long Evan Tokushima Fatty (OLETF) and lean-strain control Long Tokushima Evans Otsuka (LETO) rats were fed chow ad libitium for 4 weeks. At 15 weeks, the animals were fed a 50% CR diet (compared to their control) for 10 days and assigned to four groups: (1) LETO (n=14), (2) LETO CR (n=14), (3) OLETF (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 7 days and assigned to four groups: (1) LETO (n=7), (2) LETO post-recovery (LETO PR; n=7), (3) OLETF (n=7), and (4) OLETF PR (n=7). Mean body mass decreased 12% and 14% in LETO and OLETF, respectively, during the CR period compared to their ad lib controls. Hepatic deiodinase 1 (Dio1) protein expression was reduced by 41% in the OLETF compared to LETO. Dio1 protein expression was increased by 150% during CR and 88% by PR in OLETF. Deiodinase 2 (Dio2) showed a decreasing trend in OLETF rats compared to LETO and an increasing trend in the OLETF CR group compared to its ad lib control. Both free (fT4) and total T4 (tT4) had increasing trends in OLETF compared to LETO. CR induced a decreasing trend in fT4 and tT4 in OLETF compared to ad lib OLETF controls. These findings demonstrate that caloric restriction induces changes in hepatic thyroid hormone signaling that can improve impaired metabolism induced by MetS. Doctoral fellowship UC MEXUS-CONACYT 440553 National Institute on Minority Health and Health Disparities grant 9T37-MD001480 American Heart Association 23DIVSUP1066372. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.