Crosstalk between sleep disorders and adipokine secretory profiles: novel mechanisms for metabolic disease risk.
Sleep disorders-including sleep deprivation, obstructive sleep apnea (OSA), and circadian rhythm disruption-and metabolic diseases such as obesity and type 2 diabetes represent major, interconnected public health challenges. This review aims to synthesize current evidence on the bidirectional crosstalk between these conditions, with a focus on the mediating role of dysregulated adipokine secretion.
We elaborate a mechanistic framework wherein specific sleep disturbances disrupt circadian rhythms and alter the secretory profiles of key adipokines, including leptin, adiponectin, interleukin-6 (IL-6), and angiopoietin-like protein 4 (ANGPTL4). Sleep deprivation and fragmentation promote a state of leptin dysregulation and reduce adiponectin levels, while OSA-driven intermittent hypoxia potently upregulates IL-6 and ANGPTL4. These alterations collectively contribute to insulin resistance, dyslipidemia, and chronic low-grade inflammation, thereby elevating metabolic disease risk. Conversely, obesity and diabetes exacerbate sleep disorders through pathways involving visceral adiposity, neuroendocrine dysfunction (e.g. HPA-axis activation), and diabetes-related symptoms (e.g. nocturia, neuropathic pain), forming a vicious cycle. Clinical and preclinical evidence underscores that the synchronization of sleep-circadian biology is fundamental to maintaining adipokine homeostasis and metabolic health.
The evidence positions sleep and circadian health as critical, modifiable determinants of metabolic risk. Integrating sleep assessment and evidence-based interventions (e.g. CPAP for OSA, sleep extension, circadian realignment) into standard preventive and clinical frameworks for metabolic diseases is a promising strategy. Public health initiatives should elevate 'quality sleep' as a pillar of health alongside nutrition and physical activity to mitigate the intertwined epidemics of metabolic and sleep disorders.
We elaborate a mechanistic framework wherein specific sleep disturbances disrupt circadian rhythms and alter the secretory profiles of key adipokines, including leptin, adiponectin, interleukin-6 (IL-6), and angiopoietin-like protein 4 (ANGPTL4). Sleep deprivation and fragmentation promote a state of leptin dysregulation and reduce adiponectin levels, while OSA-driven intermittent hypoxia potently upregulates IL-6 and ANGPTL4. These alterations collectively contribute to insulin resistance, dyslipidemia, and chronic low-grade inflammation, thereby elevating metabolic disease risk. Conversely, obesity and diabetes exacerbate sleep disorders through pathways involving visceral adiposity, neuroendocrine dysfunction (e.g. HPA-axis activation), and diabetes-related symptoms (e.g. nocturia, neuropathic pain), forming a vicious cycle. Clinical and preclinical evidence underscores that the synchronization of sleep-circadian biology is fundamental to maintaining adipokine homeostasis and metabolic health.
The evidence positions sleep and circadian health as critical, modifiable determinants of metabolic risk. Integrating sleep assessment and evidence-based interventions (e.g. CPAP for OSA, sleep extension, circadian realignment) into standard preventive and clinical frameworks for metabolic diseases is a promising strategy. Public health initiatives should elevate 'quality sleep' as a pillar of health alongside nutrition and physical activity to mitigate the intertwined epidemics of metabolic and sleep disorders.