Depression Exacerbates Hepatic Steatosis in C57BL/6J Mice by Activating the Hypothalamic-Pituitary-Adrenal Axis.

Autor:	Su M; Department of Gastroenterology, the Affiliated Lihuili Hospital, Ningbo University, Ningbo, P.R. China.; Zhejiang Key Laboratory of Pathophysiology, Department of Physiology and Pharmacology, Health Science Center, Ningbo University, Ningbo, P.R. China., Yan Z; Zhejiang Key Laboratory of Pathophysiology, Department of Physiology and Pharmacology, Health Science Center, Ningbo University, Ningbo, P.R. China., Wang Y; Zhejiang Key Laboratory of Pathophysiology, Department of Physiology and Pharmacology, Health Science Center, Ningbo University, Ningbo, P.R. China., Cai J; Zhejiang Key Laboratory of Pathophysiology, Department of Physiology and Pharmacology, Health Science Center, Ningbo University, Ningbo, P.R. China., Dong J; Zhejiang Key Laboratory of Pathophysiology, Department of Physiology and Pharmacology, Health Science Center, Ningbo University, Ningbo, P.R. China., Luo J; Zhejiang Key Laboratory of Pathophysiology, Department of Physiology and Pharmacology, Health Science Center, Ningbo University, Ningbo, P.R. China., Chen D; Department of Gastroenterology, the Affiliated Lihuili Hospital, Ningbo University, Ningbo, P.R. China., Liu A; Zhejiang Key Laboratory of Pathophysiology, Department of Physiology and Pharmacology, Health Science Center, Ningbo University, Ningbo, P.R. China liuaiming@nbu.edu.cn., Ye H; Department of Gastroenterology, the Affiliated Lihuili Hospital, Ningbo University, Ningbo, P.R. China; yh-med@163.com.
Jazyk:	angličtina
Zdroj:	In vivo (Athens, Greece) [In Vivo] 2024 Jul-Aug; Vol. 38 (4), pp. 1677-1689.
DOI:	10.21873/invivo.13618
Abstrakt:	Background/aim: Depression is associated with metabolic disorders, including non-alcoholic fatty liver disease (NAFLD). However, the mechanisms underlying the interaction between them are still poorly known. Materials and Methods: In this study, mice on a choline deficiency, L-amino acid-defined, high-fat diet (CDAHFD) developing steatosis were challenged with chronic restraint stress (CRS), a protocol widely used to induce depression. The development of depression and steatosis was evaluated using histopathology analysis, ELISA, q-PCR and Western Blot. Results: The contribution of the activated HPA axis to hepatic steatosis progress was fully established, which was validated using a hepatocyte model. Histopathological and biochemical analysis indicated that steatosis was exacerbated by CRS challenge, and behavioral tests indicated that the mice developed depression. Among the screened endocrinal pathways, the hypothalamic-pituitary-adrenal (HPA) axis was significantly activated and the synergistic effect of CDAHFD and CRS in activating the HPA axis was observed. In the hypothalamus, expression of corticotropin-releasing hormone (CRH) was increased by 86% and the protein levels of hypothalamic CRH were upregulated by 25% to 33% by CRS treatment. Plasma CRH levels were elevated by 45-56% and plasma adrenocorticotropic hormone (ACTH) levels were elevated by 29-58% by CRS treatment. In the liver, target genes of the HPA axis were activated, accompanied by disruption of the lipid metabolism and progression of steatohepatitis. The lipid metabolism in the Hepa1-6 cell line treated with endogenous corticosterone (CORT) was in accordance with the aforementioned in vivo responses. Conclusion: Depression aggravated hepatic steatosis in CDAHFD-fed mice by activating the HPA axis. The risk of NAFLD development should be fully considered in depressive patients and improvement of psychotic disorders could be an etiological treatment strategy for them. (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)
Databáze:	MEDLINE
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