Hyperadrenocorticism of calorie restriction contributes to its anti‐inflammatory action in mice. Issue 3 (1st April 2019)

• Record Type: Journal Article
• Authors: Allen, Brian D.; Liao, Chen‐Yu; Shu, Jianhua; Muglia, Louis J.; Majzoub, Joseph A.; Diaz, Vivian; Nelson, James F.
• Is Part Of: Aging cell. Volume 18:Issue 3(2019)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2019-04-01
• Subjects: aging -- calorie restriction -- corticosterone -- CRH -- inflammation -- mouse; Cells -- Aging -- Periodicals; 571.8783605
• DOI: 10.1111/acel.12944
• Languages: English
• ISSNs: 1474-9718

Abstract

Abstract: Calorie restriction (CR), which lengthens lifespan in many species, is associated with moderate hyperadrenocorticism and attenuated inflammation. Given the anti‐inflammatory action of glucocorticoids, we tested the hypothesis that the hyperadrenocorticism of CR contributes to its attenuated inflammatory response. We used a corticotropin‐releasing‐hormone knockout (CRHKO) mouse, which is glucocorticoid insufficient. There were four controls groups: CRHKO mice and wild‐type (WT) littermates fed either ad libitum (AL) or CR (60% of AL food intake), and three experimental groups: (a) AL‐fed CRHKO mice given corticosterone (CORT) in their drinking water titrated to match the integrated 24‐hr plasma CORT levels of AL‐fed WT mice, (b) CR‐fed CRHKO mice given CORT to match the 24‐hr CORT levels of AL‐fed WT mice, and (c) CR‐fed CHRKO mice given CORT to match the 24‐hr CORT levels of CR‐fed WT mice. Inflammation was measured volumetrically as footpad edema induced by carrageenan injection. As previously observed, CR attenuated footpad edema in WT mice. This attenuation was significantly blocked in CORT‐deficient CR‐fed CRHKO mice. Replacement of CORT in CR‐fed CRHKO mice to the elevated levels observed in CR‐fed WT mice, but not to the levels observed in AL‐fed WT mice, restored the anti‐inflammatory effect of CR. These results indicate that the hyperadrenocorticism of CR contributes to the anti‐inflammatory action of CR, which may in turn contribute to its life‐extending actions. Abstract : We tested the role of hyperadrenocorticism in the anti‐inflammatory action of calorie restriction (CR), using a corticosterone (CORT)‐deficient knockout (KO) mouse. The reduced inflammation of CR wild‐type (WT) mice was blocked in CR KO mice. Replacement of CORT in CR KO mice to the elevated levels of CR WT mice (but not to the lower levels of ad lib fed mice) rescued the anti‐inflammatory action of CR—indicating that the hyperadrenocorticism of CR contributes to its anti‐inflammatory action.