GLP-1/GLP-1RAs: New Options for the Drug Treatment of NAFLD

Jiang, Haoran; Zang, Linquan

doi:10.2174/0113816128283153231226103218

Cited by 2 publications

References 169 publications

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Guanidine‐Derived Polymeric Nanoinhibitors Target the Lysosomal V‐ATPase and Activate AMPK Pathway to Ameliorate Liver Lipid Accumulation

Zhao,

Hu,

Wang

et al. 2024

Advanced Science

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Current research efforts in polymer and nanotechnology applications are primarily focused on cargo delivery to enhance the therapeutic index, with limited attention being paid to self‐molecularly targeted nanoparticles, which may also exhibit significant therapeutic potential. Long‐term and anomalous lipid accumulation in the liver is a highly relevant factor contributing to liver diseases. However, the development of the reliable medications and their pharmacological mechanisms remain insufficient. Herein, a polyguanide nanoinhibitors (PGNI) depot is constructed by copolymerizing biguanide derivatives in different proportions onto prepolymers. The nanoinhibitors for their ability to ameliorate lipid accumulation in vitro and in vivo is screened, and subsequently demonstrated that covalently polymeric guanidine chains exhibit superior efficacy in ameliorating hepatic lipid accumulation via heterogeneous mechanisms compared to small‐molecule guanidine. It is found that PGNIs stabilize guanidine metabolism in the liver, preferably for biosafety. More importantly, PGNI is ingested and localized in hepatocyte lysosomes and is locked to interact with vesicular adenosine triphosphatase (V‐ATPase) on lysosomes, leading to the inhibition of V‐ATPase and lysosomal acidification, thereby activating the AMPK pathway, reducing fatty acid synthesis, and enhancing lipolysis and fatty acid oxidation. These results imply that polymer‐formed nanoparticles can serve as targeted inhibitors, offering a novel approach for therapeutic applications.

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Guanidine‐Derived Polymeric Nanoinhibitors Target the Lysosomal V‐ATPase and Activate AMPK Pathway to Ameliorate Liver Lipid Accumulation

Zhao,

Hu,

Wang

et al. 2024

Advanced Science

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Effect of High‑Fat-Diet and Semaglutide on Bladder Cancer in Mice

Liu,

Ban,

Yang

et al. 2024

Preprint

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Objective The aim of this study is to examine the proteomics of adipose tissue in mice with obesity induced by a high-fat diet, in order to investigate how obesity affects the protein expression profile of adipose tissue. Additionally, we seek to establish a foundation for understanding the mechanism through which semaglutide may impact bladder cancer (BLCA) associated with obesity.Methods Thirty-six male C57BL/6J mice, all in good health, were chosen and divided into three groups: a group fed a normal diet (referred to as the NCD group), a group fed a high-fat diet (known as the HFD group), and a group fed a high-fat diet along with semaglutide treatment (referred to as the Sema group). We examined how obesity affects serum markers and how semaglutide influences these markers. Additionally, we investigated changes in protein expression within BLCA using proteomics techniques. By employing bioinformatics methods, we identified differentially expressed proteins that may be associated with the hypothesized mechanism of semaglutide's potential for reducing bladder cancer risk.Results Our findings indicate that semaglutide has the potential to decrease body weight, enhance glucose metabolism, and improve blood lipid levels. The alterations observed in the expression of Lama2 ( laminin subunit alpha-2), Lama4 (laminin subunit alpha 4), Lamc1 (laminin subunit gamma 1), Thbs2 (thrombospondin 2) genes across the normal group, high fat group, and semaglutide group primarily involve the extracellular matrix (ECM) pathway. Following intervention with semaglutide, a significant reduction in the expression of various proteins was observed in BLCA. These results suggest that by modulating genes such as Lama2, Lama4, Lamc1, Thbs2 and others, semaglutide may potentially mitigate the risk associated with BLCA.Conclusion Semaglutide exhibits potential in mitigating obesity induced by a high-fat diet and delaying the onset and progression of bladder cancer. The activation of Lama2, Lama4, Lamc1, Thbs2, and their involvement in the ECM pathway may underlie the mechanism through which semaglutide exerts its effects on bladder cancer.

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GLP-1/GLP-1RAs: New Options for the Drug Treatment of NAFLD

Cited by 2 publications

References 169 publications

Guanidine‐Derived Polymeric Nanoinhibitors Target the Lysosomal V‐ATPase and Activate AMPK Pathway to Ameliorate Liver Lipid Accumulation

Guanidine‐Derived Polymeric Nanoinhibitors Target the Lysosomal V‐ATPase and Activate AMPK Pathway to Ameliorate Liver Lipid Accumulation

Effect of High‑Fat-Diet and Semaglutide on Bladder Cancer in Mice

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