Abstract
IntroductionCopeptin is the stable surrogate marker of vasopressin (VP), which is released in response to elevated plasma osmolality or low blood pressure. Elevated plasma copeptin levels are associated with higher risk of insulin resistance-related disorders, such as type 2 diabetes (T2DM), metabolic syndrome (MS), and cardiovascular disease, and experimental reduction of circulating VP levels is shown to significantly decrease hepatic fat content in obese rats, independently from body adiposity. However, the association between copeptin and non-alcoholic fatty liver disease and steatohepatitis (NAFLD/NASH) in humans has not been explored yet. The aim of this study was to explore the relationship between plasma copeptin and the presence/severity of NAFLD/NASH.MethodsFor this study, we recruited 60 obese patients candidate to bariatric surgery for clinical purposes in which intraoperative liver biopsies were performed for diagnosing NAFLD/NASH. Circulating copeptin levels were also assessed in 60 age- and sex-comparable non-obese individuals without NAFLD at liver ultrasonography. Plasma copeptin was measured by sandwich immunoluminometric assay (Thermo Fisher Scientific).ResultsObese patients with biopsy-proven NAFLD (53%) had significantly higher copeptin levels than both obese individuals without NAFLD and non-obese subjects (ob/NAFLD+ 9.5 ± 4.9; ob/NAFLD− 6.4 ± 2.6; and non-ob/NAFLD− 7.4 ± 5.1 pmol/L; p = 0.004 and p = 0.01 respectively). Plasma copeptin concentration positively correlated with hepatic macro- and micro-vesicular steatosis (r = 0.36, p = 0.026; r = 0.31, p = 0.05), lobular inflammation (r = 0.37, p = 0.024) and significantly increased throughout degrees of NASH severity, as expressed as absence, borderline, and overt NASH at the liver biopsy (r = 0.35, p = 0.01). Greater circulating copeptin predicted the presence of NASH with OR = 1.73 (95% CI = 1.02–2.93) after multivariate adjustment for age, sex, renal function and presence of T2DM and MS components.ConclusionsIncreased plasma copeptin is independently associated with the presence and severity of NAFLD and NASH, pointing to a novel mechanism behind human fatty liver disease potentially modifiable by pharmacological treatment and lifestyle intervention.
Highlights
Copeptin is the stable surrogate marker of vasopressin (VP), which is released in response to elevated plasma osmolality or low blood pressure
Plasma copeptin concentration positively correlated with hepatic macro- and micro-vesicular steatosis (r = 0.36, p = 0.026; r = 0.31, p = 0.05), lobular inflammation (r = 0.37, p = 0.024) and significantly increased throughout degrees of NAFLD development and progression to steatohepatitis (NASH) severity, as expressed as absence, borderline, and overt NASH at the liver biopsy (r = 0.35, p = 0.01)
Greater circulating copeptin predicted the presence of NASH with OR = 1.73 after multivariate adjustment for age, sex, renal function and presence of type 2 diabetes mellitus (T2DM) and metabolic syndrome (MS) components
Summary
Copeptin is the stable surrogate marker of vasopressin (VP), which is released in response to elevated plasma osmolality or low blood pressure. Elevated plasma copeptin levels are associated with higher risk of insulin resistance-related disorders, such as type 2 diabetes (T2DM), metabolic syndrome (MS), and cardiovascular disease, and experimental reduction of circulating VP levels is shown to significantly decrease hepatic fat content in obese rats, independently from body adiposity. In humans, elevated circulating copeptin levels have been independently associated with increased risk of type 2 diabetes mellitus (T2DM), cardiovascular morbidity and mortality [7,8,9,10,11,12,13,14], and clinical signatures of metabolic syndrome (MS), such as hyperinsulinemia [7], visceral fat deposition, systemic hypertension, high triglycerides, and impaired glucose regulation, independently from obesity [15, 16]. Obese rats with elevated VP develop glucose intolerance, whereas blocking of the VP 1a receptors (V1aR) improves glucose tolerance [17]
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