Adipose ADM2 ameliorates NAFLD via promotion of ceramide catabolism.
10.1016/j.apsb.2024.09.010
- Author:
Pengcheng WANG
1
;
Song-Yang ZHANG
2
;
YongQiang DONG
3
;
Guangyi ZENG
2
;
Huiying LIU
2
;
Xian WANG
2
;
Changtao JIANG
1
;
Yin LI
2
Author Information
1. Center of Basic Medical Research, Institute of Medical Innovation and Research, Third Hospital, Peking University, Beijing 100191, China.
2. Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, State Key Laboratory of Vascular Homeostasis and Remodeling, Beijing 100191, China.
3. The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou 450052, China.
- Publication Type:Journal Article
- Keywords:
ACER2;
Adipose tissue;
Adrenomedullin 2;
Ceramide;
HIF2α;
Lipid metabolism;
Non-alcoholic fatty liver disease
- From:
Acta Pharmaceutica Sinica B
2024;14(11):4883-4898
- CountryChina
- Language:English
-
Abstract:
The adipose tissue of mammals represents an important energy-storing and endocrine organ, and its dysfunction is relevant to the onset of several health problems, including non-alcoholic fatty liver disease (NAFLD). However, whether treatments targeting adipose dysfunction could alleviate NAFLD has not been well-studied. Adrenomedullin 2 (ADM2), belonging to the CGRP superfamily, is a protective peptide that has been shown to inhibit adipose dysfunction. To investigate the adipose tissue-specific effects of ADM2 on NAFLD, adipose-specific ADM2-overexpressing transgenic (aADM2-tg) mice were developed. When fed a high-fat diet, aADM2-tg mice displayed decreased hepatic triglyceride accumulation compared to wild-type mice, which was attributable to the inhibition of hepatic de novo lipogenesis. Results from lipidomics studies showed that ADM2 decreased ceramide levels in adipocytes through the upregulation of ACER2, which catalyzes ceramide catabolism. Mechanically, activation of adipocyte HIF2α was required for ADM2 to promote ACER2-dependent adipose ceramide catabolism as well as to decrease hepatic lipid accumulation. This study highlights the role of ADM2 and adipose-derived ceramide in NAFLD and suggests that its therapeutic targeting could alleviate disease symptoms.
