Obesity is a major contributor to metabolic dysfunction,and its impact on pancreatic health has garnered increasing attention.Macrophages,as key regulators of inflammation and metabolism,play a central role in mediati...Obesity is a major contributor to metabolic dysfunction,and its impact on pancreatic health has garnered increasing attention.Macrophages,as key regulators of inflammation and metabolism,play a central role in mediating obesity-induced pancreatic damage.In obese individuals,excessive lipid accumulation and chronic low-grade inflammation drive the infiltration and polarization of macrophages within the pancreas.These macrophages,particularly the pro-inflammatory Macrophage,pro-inflammatory phenotype(M1)phenotype,secrete cytokines such as C-C motif ligand 2(CCL2)and transforming growth factor beta(TGF-β),which disrupt pancreaticβ-cell function and impair insulin secretion.Conversely,anti-inflammatory Macrophage,anti-inflammatory phenotype(M2)macrophages contribute to tissue repair but may also promote fibrotic changes under prolonged metabolic stress.Pancreatic macrophages are activated under high-fat diet conditions,promoting inflammation and impairingβ-cell function through the SUCLA2-HIF-1αaxis and mechanistic Target of Rapamycin Complex 1(mTORC1)/PD-1 pathway,thereby establishing a self-perpetuating"metabolicimmunosuppressive"vicious cycle.Targeted intervention strategies against macrophages—such as SUCLA2 inhibitors can ameliorate metabolic dysregulation.Meanwhile,exosome-mediated interorgan communication[e.g.,via microRNA-155(miR-155)and miR-30a]offers novel insights for multi-system synergistic therapies.Understanding the mechanisms by which macrophages mediate metabolic dysregulation in the pancreas under obese conditions provides critical insights into the pathogenesis of obesity-related pancreatic disorders.展开更多
基金Supported by National Natural Science Foundation of China Youth Science Fund Project,No.82305376the Young Talent Support Program of the China Association for Acupuncture-Moxibustion,No.2024-2026ZGZJXH-QNRC005+1 种基金the 2024 Jiangsu Provincial Young Scientific and Technological Talent Support Program,No.JSTJ-2024-380the 2025 Jiangsu Science and Technology Think Tank Program Project,No.JSKX0125035。
文摘Obesity is a major contributor to metabolic dysfunction,and its impact on pancreatic health has garnered increasing attention.Macrophages,as key regulators of inflammation and metabolism,play a central role in mediating obesity-induced pancreatic damage.In obese individuals,excessive lipid accumulation and chronic low-grade inflammation drive the infiltration and polarization of macrophages within the pancreas.These macrophages,particularly the pro-inflammatory Macrophage,pro-inflammatory phenotype(M1)phenotype,secrete cytokines such as C-C motif ligand 2(CCL2)and transforming growth factor beta(TGF-β),which disrupt pancreaticβ-cell function and impair insulin secretion.Conversely,anti-inflammatory Macrophage,anti-inflammatory phenotype(M2)macrophages contribute to tissue repair but may also promote fibrotic changes under prolonged metabolic stress.Pancreatic macrophages are activated under high-fat diet conditions,promoting inflammation and impairingβ-cell function through the SUCLA2-HIF-1αaxis and mechanistic Target of Rapamycin Complex 1(mTORC1)/PD-1 pathway,thereby establishing a self-perpetuating"metabolicimmunosuppressive"vicious cycle.Targeted intervention strategies against macrophages—such as SUCLA2 inhibitors can ameliorate metabolic dysregulation.Meanwhile,exosome-mediated interorgan communication[e.g.,via microRNA-155(miR-155)and miR-30a]offers novel insights for multi-system synergistic therapies.Understanding the mechanisms by which macrophages mediate metabolic dysregulation in the pancreas under obese conditions provides critical insights into the pathogenesis of obesity-related pancreatic disorders.
