LAUSR

Healthy perivascular adipose tissue (PVAT) has anticontractile, anti-inflammatory and antioxidant actions that can be disrupted by cardiometabolic risk factors. In the present study we hypothesized that protein restriction in the early phases of development could result in PVAT dysfunction and tauroursodeoxycholic acid (TUDCA) could be beneficial by inhibiting endoplasmic reticulum stress (ERS). To test this hypothesis, post-weaning male and female mice fed a normoprotein (NP, 14% protein) or a low protein (LP, 6% protein, isocaloric) diet for 15 weeks. In the last 2 weeks, some NP and LP animals received TUDCA (300 mg/kg/day) or vehicle. At the end of treatment, thoracic aorta was isolated to assess vascular responses with or without adjacent PVAT, as well as PVAT gene expression and histology. As results, the presence of PVAT reduced the phenylephrine-induced contraction in aorta of female NP and LP and male NP but not in male LP, suggesting LP-induced PVAT dysfunction in males only. In males, aortic PVAT from LP group showed less lipid content and increased collagen deposition. Decreased expression of PRDM-16, PPAR-γ, PGC-1α and leptin was observed in PVAT of LP group. These functional and morphological PVAT alterations in males were reversed by TUDCA treatment. Because TUDCA inhibits ERS, next we evaluated gene expression of ERS markers. There was an increased expression of GRP78, ATF4/6, IRE1α, and CHOP in PVAT from LP group, which was normalized by TUDCA. Also, TUDCA treatment normalized the reduced PVAT expression of the TUDCA receptor FXR in LP group. In conclusion, our data suggest that post-weaning protein-restriction impairs PVAT function and structure in males. These changes were associated with decreased expression of adipogenesis and adipocyte differentiation factors, and increased ERS markers. TUDCA reversed protein-restriction-induced PVAT abnormalities. Therefore, TUDCA emerges as a potential therapy for vascular complications associated with early undernutrition. The authors have nothing to disclose. This is the full abstract presented at the American Physiology Summit 2023 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.