Portal vein and systemic adiponectin concentrations are closely linked with hepatic glucose and lipoprotein kinetics in extremely obese subjects

Abstract

Objective Low systemic plasma adiponectin concentrations are associated with abnormalities in hepatic glucose and lipoprotein metabolism in obese people. However, the relationship between the delivery of adiponectin to the liver via the portal vein and hepatic glucose and lipoprotein metabolism is not known. Materials/Methods We examined the relationship between hepatic substrate metabolism (glucose rate of appearance (Ra) into plasma and hepatic very low density lipoprotein (VLDL)-triglyceride (TG) and apolipoprotein B-100 (apoB-100) secretion rates; determined by using stable isotope-labeled tracer techniques) and portal vein adiponectin concentration in 8 insulin-resistant, extremely obese subjects (body mass index: 65 ± 7 kg/m2). Results Portal vein adiponectin concentration was inversely associated with basal glucose Ra (r = −0.820, P = 0.013) and VLDL-TG (r = −0.823, P = 0.012) and VLDL-apoB-100 (r = −0.787, P = 0.020) secretion rates. Very similar correlations were obtained for radial artery adiponectin, as a result of a mirroring relationship between portal and arterial adiponectin concentrations (r = 0.899, P = 0.002) and the absence of significant arteriovenous concentration differences (P = 0.570). Insulin resistance, assessed with the homeostasis model assessment score, was also strongly associated with hepatic glucose and lipid metabolic parameters, as well as with adiponectin concentrations in the portal vein and radial artery. Conclusions These results suggest that adiponectin delivery to the liver, whether via the portal or the systemic circulation, may be an important regulator of basal hepatic glucose, VLDL-TG and VLDL-apoB-100 production rates in obese people, possibly through direct effects on the liver or changes in hepatic insulin sensitivity. However, portal vein adiponectin does not appear to be superior to arterial adiponectin as a marker of hepatic metabolic dysregulation. Additional studies are needed to elucidate the mechanism(s) responsible for the strong association we observed between adiponectin and hepatic substrate metabolism.

Kinetic and Related Determinants of Plasma Triglyceride Concentration in Abdominal Obesity

“…51 We neither found any correlation between adiponectin and VLDL kinetics, despite the fact that plasma adiponectin has been proposed to be an important regulator of basal VLDLtriglyceride secretion and catabolism. [52][53][54] The reason for this difference is unclear.…”

Circulating cytokines as determinants of weight loss-induced improvements in insulin sensitivity

“…However, HMW adiponectin concentrations decreased in response to weight loss in a manner that was correlated with improvements in insulin action. This finding in our overweight study participants was unexpected because in obese individuals adiponectin concentrations increase with weight loss [20–22] and because adiponectin enhances insulin action on skeletal muscle [9] and liver [10]. However, some studies have reported no change in adiponectin levels despite improvements in glucoregulation [23–25].…”

“…Leptin was measured as a sensor of adipose tissue energy status and because it may induce adiponectin [8]. Total and high molecular weight (HMW) adiponectin were measured because of their effects on insulin sensitivity [9,10]. Monocyte chemoattractant protein-1 (MCP1) was measured as a marker of adipose tissue inflammation [11].…”

Adiponectin as a tissue regenerating hormone: more than a metabolic function

“…Hepatic insulin sensitivity in humans is associated with circulating adiponectin concentration [30][31][32]. The amount of adiponectin in the plasma negatively correlates with endogenous glucose production in healthy [2], severely obese [3,33] and type 2 diabetic individuals [1,30,32].…”