(961.1) A 24-Hour Fast Increases Liver Cytotoxic T Cell Populations in Genetically Obese Mice: A Preliminary Study

Poster Board Number: E627

Elliot Graham (Colorado State University), S.Raj Trikha (Colorado State University), Briana Risk (Colorado State University), Tiffany Weir (Colorado State University), Christopher Gentile (Colorado State University)

BACKGROUND

Recent data suggests that regulated fasting protocols can improve metabolic parameters associated with obesity. However, questions remain regarding the appropriate fasting duration needed to attenuate obesity-associated complications such as glucose intolerance, arterial stiffness, and immune cell dysfunction. Therefore, the primary purpose of this study was to examine if an acute 24-hour fast improves detrimental consequences of obesity and alters tissue-specific immune cell counts in obese mice. 

METHODS

Ten 12-week-old male and female genetically obese mice (Ob; n=20) and wild-type littermates (WT; n=20) were fed a standard diet and randomized to either ad libitum feeding or a 24-hour fast (WT-CON, WT-Fast, Ob-CON, Ob-Fast). Mouse weight was measured before and after feeding protocols. Following feeding protocols, arterial stiffness was assessed via arterial pulse wave velocity (aPWV); liver and mesenteric adipose tissue (MAT) immune cell populations were assessed via spectral flow cytometry and normalized by tissue weight. For statistical analyses, sex-adjusted regression models were fit to account for the confounding effects of sex. 

RESULTS

There was not a significant interaction between genotype and intervention on changes in body weight, plasma glucose concentrations, or aPWV (p=0.16; p=0.33; p=0.37, respectively). After adjusting for genotype, acute fasting did not significantly alter changes in plasma glucose concentrations or aPWV (p=0.95; p=0.22). However, after adjusting for genotype, acute fasting promoted significant weight loss (CON 0.4g ± 0.56; Fast -2.6g ± 0.72; plt;0.01). Compared to Ob-CON, Ob-Fast mice had significant increases in liver total immune and cytotoxic T cells (plt;0.01) yet no significant changes in either liver regulatory T or helper T cells nor in MAT total immune, cytotoxic T, helper T, and regulatory T cell populations. WT-Fast mice had significant reductions in liver total immune, cytotoxic T, helper T, and regulatory T cell populations while these same cell populations were increased in MAT when compared to WT-CON mice. 

CONCLUSIONS

An acute 24 hr. fast in mice was insufficient to significantly modulate glucose intolerance and aPWV in Ob mice compared to WT. However, fasting differentially affected liver and MAT T cell populations in mice. These results suggest acute fasting could be a robust mediator of T cell populations with a particular emphasis on expanding liver cytotoxic T cell communities in obese mice. 

Support or Funding Information

This work was supported by the National Heart, Lung, and Blood Institute [5R01HL144611].