FBXO28 reduces high-fat diet-induced hyperlipidemia in mice by alleviating abnormal lipid metabolism and inflammatory responses

J Sun; B Du; M Chen; J Jia; X Wang; J Hong

doi:10.1007/s40618-024-02376-5

FBXO28 reduces high-fat diet-induced hyperlipidemia in mice by alleviating abnormal lipid metabolism and inflammatory responses

J Endocrinol Invest. 2024 May 2. doi: 10.1007/s40618-024-02376-5. Online ahead of print.

Authors

J Sun¹, B Du², M Chen³, J Jia³, X Wang³, J Hong⁴

Affiliations

¹ Cadre's Ward, The Fourth Clinical College of Xinjiang Medical University, Urumqi, 830000, Xinjiang Uygur Autonomous Region, China.
² Department of Neurology, Urumqi Midong District Hospital of Traditional Chinese Medicine, Urumqi, 830000, Xinjiang Uygur Autonomous Region, China.
³ Cadre's Ward, Traditional Chinese Medicine Hospital of Xinjiang Medical University, No.116, Huanghe Road, Urumqi, 830000, Xinjiang Uygur Autonomous Region, China.
⁴ Cadre's Ward, Traditional Chinese Medicine Hospital of Xinjiang Medical University, No.116, Huanghe Road, Urumqi, 830000, Xinjiang Uygur Autonomous Region, China. jun_h1107@163.com.

PMID: 38696123
DOI: 10.1007/s40618-024-02376-5

Abstract

Background: Hyperlipidemia is a lipid metabolism disorder with increasing incidence and prevalence worldwide. Abnormal lipid metabolism and inflammation are two significant characteristics of hyperlipidemia. The purpose of this study was to explore the role and mechanism of F-box only protein 28 (FBXO28) in hyperlipidemia.

Methods: Mice were fed with high-fat diet (HFD) to elicit obesity, and 3T3-L1 preadipocytes were stimulated with MDI cocktail (IBMX, DEX and insulin) to evoke differentiation. In vivo and in vitro role of FBXO28 in hyperlipidemia was investigated by hematoxylin-eosin and oil Red O staining, the lipid biochemistry measurement, enzyme-linked immunosorbent assay, reverse transcription quantitative polymerase chain reaction and western blotting assays. The mechanism of FBXO28 explored by co-immunoprecipitation, immunofluorescence, ubiquitination and cycloheximide assays.

Results: Low expression of FBXO28 was found in hyperlipidemia in silico, in vivo and in vitro. Upregulation of FBXO28 declined the body weight, fat accumulation, and serum lipid content in HFD-fed mice. Abnormal lipid accumulation, and the level of liposynthetic genes and beta-oxidation related genes were improved by overexpression of FBXO28 both in HFD-elicited mice and MDI-treated 3T3-L1 preadipocytes. Besides, overexpression of FBXO28 declined HFD-induced the level of proinflammatory factors and F4/80. Mechanically, FBXO28 directly bound RAB27A and promoted its ubiquitinated degradation. Thus, upregulation of RAB27A inverted the improved role of FBXO28 in abnormal lipid metabolism and inflammation in vivo and in vitro.

Conclusion: FBXO28 ameliorated abnormal lipid metabolism and inflammation through the ubiquitinated degradation of RAB27A, thereby attenuating HFD-induced hyperlipidemia. The results could promote the treatment of hyperlipidemia, and the relevant diseases.

Keywords: FBXO28; High-fat diet; Hyperlipidemia; Inflammation; Lipid metabolism.

Grants and funding

SZ2021ZZ06/State Key Laboratory of Dampness Syndrome of Traditional Chinese Medicine.