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T266M variants of ANGPTL4 improve lipid metabolism by modifying their binding affinity to acetyl-CoA carboxylase in obstructive sleep apnea.
Li, Xinyi; Li, Chenyang; Xue, Wenjun; Wei, Zhicheng; Shen, Hangdong; Wu, Kejia; Zhu, Huaming; Xu, Huajun; Wu, Xiaolin; Yi, Hongliang; Guan, Jian; Yin, Shankai.
Afiliação
  • Li X; Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Sleep Disordered Breathing, Otorhinolaryngology Institute of Shanghai JiaoTong University, Shanghai, China.
  • Li C; Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Sleep Disordered Breathing, Otorhinolaryngology Institute of Shanghai JiaoTong University, Shanghai, China.
  • Xue W; Department of Otorhinolaryngology Head and Neck surgery, Shanghai Eighth People's Hospital Affiliated to Jiangsu University, Shanghai, China.
  • Wei Z; Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Sleep Disordered Breathing, Otorhinolaryngology Institute of Shanghai JiaoTong University, Shanghai, China.
  • Shen H; Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Sleep Disordered Breathing, Otorhinolaryngology Institute of Shanghai JiaoTong University, Shanghai, China.
  • Wu K; Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Sleep Disordered Breathing, Otorhinolaryngology Institute of Shanghai JiaoTong University, Shanghai, China.
  • Zhu H; Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Sleep Disordered Breathing, Otorhinolaryngology Institute of Shanghai JiaoTong University, Shanghai, China.
  • Xu H; Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Sleep Disordered Breathing, Otorhinolaryngology Institute of Shanghai JiaoTong University, Shanghai, China.
  • Wu X; Central Laboratory of Shanghai Eighth People's Hospital, Xuhui Branch of Shanghai Sixth People's Hospital, P. R. China.
  • Yi H; Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Sleep Disordered Breathing, Otorhinolaryngology Institute of Shanghai JiaoTong University, Shanghai, China.
  • Guan J; Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Sleep Disordered Breathing, Otorhinolaryngology Institute of Shanghai JiaoTong University, Shanghai, China.
  • Yin S; Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Sleep Disordered Breathing, Otorhinolaryngology Institute of Shanghai JiaoTong University, Shanghai, China.
Ann Med ; 56(1): 2337740, 2024 Dec.
Article em En | MEDLINE | ID: mdl-38574398
ABSTRACT

BACKGROUND:

Angiopoietin-like protein 4 (ANGPTL4) is recognized as a crucial regulator in lipid metabolism. Acetyl-CoA carboxylases (ACACAs) play a role in the ß-oxidation of fatty acids. Yet, the functions of ANGPTL4 and ACACA in dyslipidemia of obstructive sleep apnea (OSA) remain unclear.

METHODS:

This study included 125 male OSA subjects from the Shanghai Sleep Health Study (SSHS) who were matched for age, body mass index (BMI), and lipid profile. Serum ANGPTL4 levels were measured via ELISA. The ANGPTL4 T266M variants of 4455 subjects along with their anthropometric, fasting biochemical, and standard polysomnographic parameters were collected. Linear regression was used to analyze the associations between quantitative traits and ANGPTL4 T266M. Molecular docking and molecular dynamic simulation were employed to compare the effects of the wild-type ANGPTL4 and its T266M mutation on ACACA.

RESULTS:

Serum ANGPTL4 levels significantly decreased with increasing OSA severity (non-OSA 59.6 ± 17.4 ng/mL, mild OSA 50.0 ± 17.5 ng/mL, moderate OSA 46.3 ± 15.5 ng/mL, severe OSA 19.9 ± 14.3 ng/mL, respectively, p = 6.02 × 10-16). No associations were found between T266M and clinical characteristics. Molecular docking indicated that mutant ANGTPL4 T266M had stronger binding affinity for the ACACA protein, compared with wild-type ANGPTL4. In terms of protein secondary structure, mutant ANGTPL4 T266M demonstrated greater stability than wild-type ANGPTL4.

CONCLUSIONS:

Serum ANGTPL4 levels were significantly decreased in OSA patients, particularly among individuals with severe OSA. Although functional ANGTPL4 T266M variants were not associated with lipid levels in OSA, ANGTPL4 T266M could enhance binding affinity for the ACACA protein, potentially regulating lipid metabolism.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Acetil-CoA Carboxilase / Apneia Obstrutiva do Sono Limite: Humans / Male País/Região como assunto: Asia Idioma: En Revista: Ann Med Ano de publicação: 2024 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Acetil-CoA Carboxilase / Apneia Obstrutiva do Sono Limite: Humans / Male País/Região como assunto: Asia Idioma: En Revista: Ann Med Ano de publicação: 2024 Tipo de documento: Article