PACAP ameliorates obesity-induced insulin resistance through FAIM/Rictor/AKT axis.

Autor: Feng J; Department of Cellular Biology, Institute of Biomedicine, Jinan University, Guangzhou, China.; Key Laboratory of Bioengineering Medicine of Guangdong Province, Jinan University, Guangzhou, China.; The National Demonstration Center for Experimental Education of Life Science and Technology, Jinan University, Guangzhou, China., Chen W; Department of Metabolic and Bariatric Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, China., Li S; Department of Cellular Biology, Institute of Biomedicine, Jinan University, Guangzhou, China.; Key Laboratory of Bioengineering Medicine of Guangdong Province, Jinan University, Guangzhou, China.; The National Demonstration Center for Experimental Education of Life Science and Technology, Jinan University, Guangzhou, China., Fang Q; Department of Cellular Biology, Institute of Biomedicine, Jinan University, Guangzhou, China.; Key Laboratory of Bioengineering Medicine of Guangdong Province, Jinan University, Guangzhou, China.; The National Demonstration Center for Experimental Education of Life Science and Technology, Jinan University, Guangzhou, China., Chen X; Department of Cellular Biology, Institute of Biomedicine, Jinan University, Guangzhou, China.; Key Laboratory of Bioengineering Medicine of Guangdong Province, Jinan University, Guangzhou, China.; The National Demonstration Center for Experimental Education of Life Science and Technology, Jinan University, Guangzhou, China., Bai G; Department of Cellular Biology, Institute of Biomedicine, Jinan University, Guangzhou, China.; Key Laboratory of Bioengineering Medicine of Guangdong Province, Jinan University, Guangzhou, China.; The National Demonstration Center for Experimental Education of Life Science and Technology, Jinan University, Guangzhou, China., Tian M; Department of Cellular Biology, Institute of Biomedicine, Jinan University, Guangzhou, China.; Key Laboratory of Bioengineering Medicine of Guangdong Province, Jinan University, Guangzhou, China.; The National Demonstration Center for Experimental Education of Life Science and Technology, Jinan University, Guangzhou, China., Huang Y; Department of Cellular Biology, Institute of Biomedicine, Jinan University, Guangzhou, China.; Key Laboratory of Bioengineering Medicine of Guangdong Province, Jinan University, Guangzhou, China.; The National Demonstration Center for Experimental Education of Life Science and Technology, Jinan University, Guangzhou, China., Xu P; Department of Cellular Biology, Institute of Biomedicine, Jinan University, Guangzhou, China.; Key Laboratory of Bioengineering Medicine of Guangdong Province, Jinan University, Guangzhou, China.; The National Demonstration Center for Experimental Education of Life Science and Technology, Jinan University, Guangzhou, China., Wang Z; Department of Cellular Biology, Institute of Biomedicine, Jinan University, Guangzhou, China.; Key Laboratory of Bioengineering Medicine of Guangdong Province, Jinan University, Guangzhou, China.; The National Demonstration Center for Experimental Education of Life Science and Technology, Jinan University, Guangzhou, China., Ma Y; Department of Cellular Biology, Institute of Biomedicine, Jinan University, Guangzhou, China.; Key Laboratory of Bioengineering Medicine of Guangdong Province, Jinan University, Guangzhou, China.; The National Demonstration Center for Experimental Education of Life Science and Technology, Jinan University, Guangzhou, China.
Jazyk: angličtina
Zdroj: The FEBS journal [FEBS J] 2024 Sep; Vol. 291 (18), pp. 4096-4110. Date of Electronic Publication: 2024 Jul 23.
DOI: 10.1111/febs.17228
Abstrakt: Obesity and obesity-related insulin resistance have been a research hotspot. Pituitary adenylate cyclase activating polypeptide (PACAP) has emerged as playing a significant role in energy metabolism, holding promising potential for attenuating insulin resistance. However, the precise mechanism is not fully understood. Palmitic acid and a high-fat diet (HFD) were used to establish insulin resistance model in Alpha mouse liver 12 cell line and C57BL/6 mice, respectively. Subsequently, we assessed the effects of PACAP both in vivo and in vitro. Lentivirus vectors were used to explore the signaling pathway through which PACAP may ameliorate insulin resistance. PACAP was found to selectively bind to the PACAP type I receptor receptor and ameliorate insulin resistance, which was characterized by increased glycogen synthesis and the suppression of gluconeogenesis in the insulin-resistant cell model and HFD-fed mice. These effects were linked to the activation of the Fas apoptotic inhibitory molecule/rapamycin-insensitive companion of mammalian target of rapamycin/RAC-alpha serine/threonine-protein kinase (FAIM/Rictor/AKT) axis. Furthermore, PACAP ameliorated insulin resistance by increasing solute carrier family 2, facilitated glucose transporter members 2/4 and inhibiting gluconeogenesis-related proteins glucose 6-phosphatase catalytic subunit 1 and phosphoenolpyruvate carboxykinase 2 expression. Meanwhile, the phosphorylation of hepatic AKT/glycogen synthase kinase 3β was promoted both in vivo and in vitro by PACAP. Additionally, PACAP treatment decreased body weight, food intake and blood glucose levels in obese mice. Our study shows that PACAP ameliorated insulin resistance through the FAIM/Rictor/AKT axis, presenting it as a promising drug candidate for the treatment of obesity-related insulin resistance.
(© 2024 Federation of European Biochemical Societies.)
Databáze: MEDLINE
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