Exercise-Induced Lowering of Fetuin-A May Increase Hepatic Insulin Sensitivity

Abstract

Introduction Fetuin-A is a novel hepatokine, and there is preliminary evidence that it may contribute to the pathogenesis of type 2 diabetes. Exercise reduces fetuin-A, but the specific metabolic effects particularly as they relate to the regulation of insulin resistance are unknown. This led us to examine the effect of exercise training on circulating fetuin-A in relation to skeletal muscle and/or hepatic insulin resistance in obese adults. Methods Twenty older adults (66.3 ± 0.9 yr; body mass index, 34.1 ± 1.2 kg·m−2) participated in this prospective 12-wk study and underwent supervised exercise training (5 d·wk−1, 60 min·d−1 at approximately 85% HRmax). Insulin resistance was assessed using the euglycemic–hyperinsulinemic clamp (40 mU·m−2·min−1) with isotope dilution ([6,6-2H2]-glucose). Skeletal muscle insulin sensitivity (rate of glucose disposal), hepatic insulin resistance (rate of glucose appearance × fasting insulin), metabolic flexibility (respiratory quotientclamp – respiratory quotientfasting), fetuin-A, high-molecular weight adiponectin, high-sensitivity C-reactive protein, leptin, and body fat (dual energy x-ray absorptiometry) were measured before and after the intervention. Results Exercise reduced body fat, high-sensitivity C-reactive protein, leptin and hepatic as well as skeletal muscle insulin resistance (each, P < 0.05). Fetuin-A was decreased by approximately 8% (pre, 1.01 ± 0.08, vs post, 0.89 ± 0.06 g·L−1; P < 0.05) after the intervention, and lower fetuin-A after exercise correlated with lower hepatic insulin resistance (r = −0.46, P < 0.01), increased metabolic flexibility (r = −0.70, P < 0.01) and high-molecular weight adiponectin (r = −0.57, P < 0.01). Conclusions Fetuin-A may contribute to exercise training-induced improvements in hepatic insulin resistance, CHO utilization, and inflammation in older obese adults. Further work is required to determine the cellular mechanism(s) of action for fetuin-A because this hepatokine is related to type 2 diabetes risk

Interaction between plasma fetuin‐A and free fatty acids predicts changes in insulin sensitivity in response to long‐term exercise

“…Although it has been demonstrated that exercise may reduce plasma fetuin‐A concentrations (Malin et al. ), and that interaction of fetuin‐A and FFAs can induce TLR4‐associated insulin resistance (Pal et al. ; Stefan and Haring ), we seem to be the first to demonstrate that changes in fetuin‐A and FFAs together may predict some of the benefits seen on insulin sensitivity after long‐term exercise.…”

Alterations of Serum Ser312‐Phosphorylated Fetuin‐A from Exercise‐Induced Moderate Body Weight Loss in Individuals with Obesity

“…Several studies have also shown that exercise alone , hypocaloric diets , gastric banding or bypass surgery , and medication exert beneficial effects and alter insulin sensitivity. Among older adults, a 12‐week supervised exercise training was shown to lower serum Fet‐A by 8%, which was correlated with hepatic insulin resistance and high‐molecular‐weight adiponectin . Further, a 16‐month longitudinal study of 75 patients with morbid obesity after gastric bypass demonstrated that changes of serum Fet‐A were significantly correlated with changes in fasting insulin, 2‐hour insulin, and HOMA‐IR .…”

“…Gastric bypass surgery that resulted in a 35% body weight loss decreased serum Fet‐A, which correlated with fasting insulin, postprandial insulin, and homeostasis model assessment of insulin resistance (HOMA‐IR) . High‐intensity exercise has led to significantly decreased serum Fet‐A, which is associated with lower hepatic insulin resistance .…”

Bariatric surgery insurance requirements independently predict surgery dropout

“…This finding is consistent with work by Harnisch et al who found no difference on post-surgery weight loss or disease resolution of T2D and hypertension at 12 and 24 months between patients with approximate 10 pound weight gain compared with those who lost 10 pounds preoperatively (19) . Thus, preoperative weight loss was not necessarily correlated with greater BMI change postoperatively, and more work is required to determine if optimizing cardiorespiratory fitness, with or without weight loss, can promote long term weight maintenance, insulin sensitivity and cardio-metabolic health (20, 21) .…”