{"id":3305,"date":"2026-03-11T01:52:41","date_gmt":"2026-03-11T01:52:41","guid":{"rendered":"https:\/\/medicine.nus.edu.sg\/medphc\/?p=3305"},"modified":"2026-03-11T01:52:41","modified_gmt":"2026-03-11T01:52:41","slug":"autophagy-as-a-therapeutic-linchpin-in-metabolic-diseases-and-obesity-associated-diabetes","status":"publish","type":"post","link":"https:\/\/medicine.nus.edu.sg\/medphc\/publications\/autophagy-as-a-therapeutic-linchpin-in-metabolic-diseases-and-obesity-associated-diabetes\/","title":{"rendered":"Autophagy as a therapeutic linchpin in metabolic diseases and obesity-associated diabetes"},"content":{"rendered":"

\"\"<\/p>\n

ABSTRACT<\/h2>\n

Autophagy, a conserved lysosomal degradation pathway, is increasingly recognized as a central regulator of metabolic health. Its impairment contributes directly to obesity and type 2 diabetes by disrupting nutrient sensing, stress adaptation, and organelle quality control. Hyperactivation of MTORC1 with insufficient AMPK and SIRT1 signaling suppresses autophagic flux, driving lipid accumulation, insulin resistance, and mitochondrial dysfunction. Clinically relevant consequences include adipose inflammation and hypertrophy, hepatic steatosis with impaired \u03b2-oxidation, pancreatic \u03b2-cell failure from unresolved ER stress, and skeletal muscle atrophy due to loss of proteostasis. Moreover, defective autophagy across the gut \u2013 liver \u2013 brain axis exacerbates intestinal barrier dysfunction, endotoxemia, and neuroendocrine imbalance, amplifying systemic metabolic deterioration. Emerging interventions that restore autophagic capacity, including exercise-induced AMPK activation, dietary modulation of unsaturated fatty acids, pharmacological inducers, and nanotechnology-based lysosomal re-acidification show promise in preclinical models. However, the tissue-specific duality of autophagy, where suppression may be beneficial in some contexts but harmful in others, highlights the complexity of therapeutic targeting. This review highlights current mechanistic and translational insights to position autophagy as a therapeutic linchpin in obesity-associated metabolic disease. By aligning molecular pathways with clinical outcomes, we herein highlight opportunities to develop precision strategies that harness autophagy to combat the global burden of obesity and metabolic disorders.<\/p>\n

Full Article:\u00a0https:\/\/www.tandfonline.com\/doi\/full\/10.1080\/15548627.2026.2636096<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

ABSTRACT Autophagy, a conserved lysosomal degradation pathway, is increasingly recognized as a central regulator of metabolic health. Its impairment contributes directly to obesity and type 2 diabetes by disrupting nutrient sensing, stress adaptation, and organelle quality control. Hyperactivation of MTORC1 with insufficient AMPK and SIRT1 signaling suppresses autophagic flux, driving lipid accumulation, insulin resistance, and […]<\/p>\n","protected":false},"author":9345,"featured_media":3306,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"default","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","ast-disable-related-posts":"","theme-transparent-header-meta":"default","adv-header-id-meta":"","stick-header-meta":"default","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"set","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"footnotes":""},"categories":[5],"tags":[],"class_list":["post-3305","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-publications"],"acf":[],"yoast_head":"\nAutophagy as a therapeutic linchpin in metabolic diseases and obesity-associated diabetes - Pharmacology<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/medicine.nus.edu.sg\/medphc\/publications\/autophagy-as-a-therapeutic-linchpin-in-metabolic-diseases-and-obesity-associated-diabetes\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Autophagy as a therapeutic linchpin in metabolic diseases and obesity-associated diabetes - Pharmacology\" \/>\n<meta property=\"og:description\" content=\"ABSTRACT Autophagy, a conserved lysosomal degradation pathway, is increasingly recognized as a central regulator of metabolic health. 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